2AC Heartjnl BCS Abstracts 2011

97
June 2011 Volume 97 Supplement I
heart
British Cardiovascular Society Annual Conference 1315 June 2011 Manchester Central
heart.bmj.com www.bcs.com
Volume 97 Supplement I Pages A1A104 HEART June 2011
Young Research Workers Prize

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ENDOTHELIAL CELL NITRIC OXIDE BIOAVAILABILITY AND INSULIN SENSITIVITY ARE REGULATED BY IGF-1 AND INSULIN RECEPTOR LEVELS
doi:10.1136/heartjnl-2011-300110.1 A Abbas, H Viswambharan, H Imrie, A Rajwani, M Kahn, M Gage, R Cubbon, J Surr, S Wheatcroft, M Kearney. Leeds Institute of Genetics Health and Therapeutics, Leeds, UK
Background In a similar manner to insulin, the growth promoting hormone Insulin-like Growth Factor-1 (IGF-1), may be an important regulator of endothelial nitric oxide (NO) bioavailability. We have previously reported evidence of increased basal NO production in the vasculature in two murine models of reduced IGF-1 receptor (global hemizygous knockout (IGFRKO) and endothelial cell specic IGF-1R knockout (ECIGFRKO)). Augmentation of this increase in NO is relative to progressive decrease in IGF-1R number (WT vs ECIGFRKO hemizygotes p0.01, WT vs ECIGFRKO homozygotes p0.001). Furthermore, by decreasing IGF-1R numbers in the insulin resistant hemizygous insulin receptor knockout (IRKO) model (IRKO 3 IGFRKO) we have shown insulin sensitivity in the vasculature can be restored. In this study, we have investigated further these receptor interactions with the generation of a mouse overexpressing the human IGF-1R specically in the endothelium under control of the Tie-2 promoter-enhancer (hIGFREO), and by targeted knockdown of the IGF-1R in human umbilical vein endothelial cells (HUVECs). Methods Metabolic function was assessed in mice by tolerance tests using whole-blood micro-sampling after insulin or glucose intraperitoneal injection. Cardiovascular function was assessed by thoracic aortic vasomotion ex vivo in the organbath. Complimentary in vitro studies were conducted by siRNA mediated downregulation of the IGF-1 receptor in HUVECs with and wihout insulin stimulation. Nitric oxide synthase activity was measured using an assay measuring conversion of [14C]-L-arginine to [14 C]-L-citrulline. Results Glucose and insulin tolerance testing showed no difference between hIGFREO mice and wild-type (WT) littermates. Murine thoracic aorta from hIGFREO mice were hypercontractile to phenylepherine (PE) compared to WT (Emax hIGFREO 0.9160.045 g; WT0.6260.045 g, p0.0036) with decreased response to LNMMA (Emax hIGFREO47.7069.87 g; WT106.1630.10 g, p0.048). These data indicate reduced endothelial NO bioavailability in hIGFREO mice compared to WT. HUVECs transfected with IGF1R-siRNA showed increased basal and insulin mediated eNOS phosphorylation in the presence of insulin (Ins: 16464.9% vs siRNA+Ins: 19260.7%, p<0.05). eNOS activity (L-arginine, L-citrulline assay) was enhanced upon trans-
Abstract A Figure 2
Abstract A Figure 3
Abstract A Figure 4
Abstract A Figure 1
Heart June 2011 Vol 97 Suppl 1
fection with IGF1R-siRNA (Scrambled siRNA: 95.7613.7% vs IGF1R-siRNA: 188.7648.3%, p<0.05). Implications These data demonstrate that increasing numbers of IGF-1R specically in murine endothelium leads to reduced NO bioavailability. Complementary siRNA studies conrm results of previous murine studies that reducing IGF-1R numbers enhance NO bioavailability. Therefore this raises the intriguing possibility that manipulation of IGF-1R numbers may represent a novel therapeutic
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intervention (PCI) were prospectively enrolled and underwent full 3-vessel VH-IVUS pre-PCI. Troponin-I (cTnI), IL-6, IL-18, hsCRP, neopterin, MCP-1 and sICAM-1 were measured pre-PCI and 24-h post-PCI. LTL was determined by qPCR. The combined primary endpoint (MACE) included unplanned revascularisation, myocardial infarction (MI) and death, with a secondary endpoint of post-PCI MI (MI 4a). Results 18 MACE occurred in 16 patients (median follow-up: 625 (463e990) days). 30 372 mm of VH-IVUS were analysed and 1106 plaques classied (Abstract B Figure 1) locally and via a core-lab. After multivariable regression:
Abstract A Figure 5
1. Total number of non-calcied VH-IVUS-identied thin capped broatheromata (VHTCFA) was the only factor independently associated with MACE (HR3.16, (95% CI1.16 to 8.64), p0.025). 2. Total VHTCFA number (OR1.26 (1.03 to 1.53) p0.021) and total stent length (OR1.04 (1.01 to 1.08), p0.01) were the only factors independently associated with MI 4a. 3. A novel 3-vessel vulnerability index (necrotic core: brous tissue ratio) and side branch loss were independently associated with stenting-related cTnI rise (standardised beta coefcient (sb)0.29, p0.004 and sb0.23, p0.019 respectively). 4. Necrotic core area at the minimum luminal area frame was the only factor independently associated with ACS presentation (OR1.59, p0.030). 5. Stented vessel VHTCFA number (OR1.75 (1.22 to 2.51), p0.002) was independently associated with the lower LTL tertile (DNA-based cardiovascular risk predictor). 6. Stenting-related IL-6 rise was the only biomarker independently associated with MACE (HR1.03 (1.01e1.05), p0.007).
Abstract A Figure 6
strategy by which to modify vascular NO bioavailability and endothelial cell insulin sensitivity.
Conclusion We present the rst report of an association between VHTCFA and MACE. This provides novel evidence that VHTCFA denitions are important in their own right (rather than as analogues of histological TFCA denitions). We also present the rst report of associations between VHTCFA and MI 4a as well as a novel vulnerability index that is association with stenting-related troponin rise. Finally, we report a novel association between VHTCFA and DNA-based cardiovascular risk prediction (LTL).
VH-IVUS FINDINGS PREDICT MAJOR ADVERSE CARDIOVASCULAR EVENTS. THE VIVA STUDY (VIRTUAL HISTOLOGY INTRAVASCULAR ULTRASOUND IN VULNERABLE ATHEROSCLEROSIS)
doi:10.1136/heartjnl-2011-300110.2
P A Calvert, 1D R Obaid, 2N E J West, 2L M Shapiro, 2D McNab, 2C G Densem, P M Schoeld, 2D Braganza, 2S C Clarke, 2M OSullivan, 3K K Ray, 1M R Bennett. 1 University of Cambridge, Cambridge, UK; 2Papworth Hospital NHS Foundation Trust, Cambridge, UK; 3St Georges University of London, London, UK
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Background Identication of high-risk atherosclerotic plaques offers opportunities for risk stratication and targeted intensive treatment of patients with coronary artery disease. Virtual Histology intravascular ultrasound (VH-IVUS) has been validated in human atherectomy and post-mortem studies and can classify plaques into presumed high- and low-risk groups. However, VH-IVUS-dened plaques have not been shown to be associated with major adverse cardiovascular events (MACE), or biomarkers that confer increased cardiovascular risk, such as serum cytokines or shortened leukocyte telomere length (LTL). Methods 170 patients with stable angina or troponin-positive acute coronary syndrome (ACS), referred for percutaneous coronary
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Abstract B Figure 1

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INSULIN RESISTANCE IMPAIRS ANGIOGENIC PROGENITOR CELL FUNCTION AND DELAYS ENDOTHELIAL REPAIR FOLLOWING VASCULAR INJURY
doi:10.1136/heartjnl-2011-300110.3 M B Kahn, N Yuldasheva, R Cubbon, J Surr, S Rashid, H Viswambharan, H Imrie, A Abbas, A Rajwani, M Gage, M T Kearney, S Wheatcroft. Leeds University, Leeds, UK
may be normalised by transfusion of APCs from insulin-sensitive animals but not from insulin-resistant animals. These data may have important implications for the development of therapeutic strategies for insulin-resistance associated cardiovascular disease.
Introduction Insulin-resistance, the primary metabolic abnormality underpinning type-2-diabetes mellitus (T2DM) and obesity, is an important risk factor for the development of atherosclerotic cardiovascular disease. Circulating-angiogenic-progenitor-cells (APCs) participate in endothelial-repair following arterial injury. Type-2 diabetes is associated with fewer circulating APCs, APC dysfunction and impaired endothelial-repair. We set out to determine whether insulin-resistance per se adversely affects APCs and endothelialregeneration. Research Design and Methods We quantied APCs and assessed APC-mobilisation and function in mice hemizygous for knockout of the insulin receptor (IRKO) and wild-type (WT) littermate controls. Endothelial-regeneration following femoral artery wire-injury was also quantied at time intervals after denudation and following APC transfusion. Results The metabolic phenotype of IRKO mice was consistent with compensated insulin resistance, with hyperinsulinaemia after a glucose challenge but a normal blood glucose response to a glucose tolerance test. IRKO mice had fewer circulating Sca-1+/Flk-1+ APCs than WT mice at baseline. Culture of mononuclear-cells demonstrated that IRKO mice had fewer APCs in peripheral-blood, but not in bone-marrow or spleen, suggestive of a mobilisation defect. Defective VEGF-stimulated APC mobilisation was conrmed in IRKO mice, consistent with reduced eNOS expression in bone marrow and impaired vascular eNOS activity. Paracrine-angiogenicactivity of APCs from IRKO mice was impaired compared to those from WT animals. Endothelial-regeneration of the femoral artery following denuding wire-injury was delayed in IRKO mice compared to WT (re-endothelialised area 35.864.8% vs 66.665.2% at day 5 following injury and 35.664.8% vs 59.866.6% at day 7; P<0.05) (Abstract C Figure 1A). Transfusion of mononuclear-cells from WT mice normalised the impaired endothelial-regeneration in IRKO mice (5764% vs 2565%; p<0.002). Transfusion of c-kit+ bone-marrow cells from WT mice also restored endothelial-regeneration in IRKO mice (6262% vs 2565%; p<0.002). However, transfusion of c-kit+ cells from IRKO mice was less effective at improving endothelial-repair (6262% vs 4564%; p<0.02) (Abstract C Figure 1B). Conclusions Insulin-resistance impairs APC function and delays endothelial-regeneration following arterial injury. These ndings support the hypothesis that insulin-resistance per se is sufcient to jeopardise endogenous vascular repair. Defective endothelial-repair
UPTAKE OF ULTRASMALL SUPERPARAMAGNETIC PARTICLES OF IRON OXIDE PREDICTS GROWTH IN ABDOMINAL AORTIC ANEURYSMS: A PILOT STUDY
doi:10.1136/heartjnl-2011-300110.4
J M J Richards, S I Semple, T J Mac Gillivray, C Gray, J P Langrish, M Williams, M Dweck, W Wallace, G McKillop, R T A Chalmers, O J Garden, D E Newby. University of Edinburgh, Edinburgh, UK
Background Prediction of abdominal aortic aneurysm (AAA) expansion and rupture is challenging and currently relies on serial measurements of maximum aneurysm diameter. Using ultrasmall superparamagnetic particles of iron oxide (USPIO) and MRI, we aimed to assess whether areas of cellular inammation correlated with the rate of abdominal aortic aneurysm expansion. Methods and Results An image acquisition and data analysis algorithm for the detection of focal USPIO accumulation in tissues was developed. Patients (n29; 27 male; aged 7065 years) with asymptomatic AAA (4.0e6.6 cm) were recruited from an outpatient surveillance programme and underwent 3T MRI before and 24e36 h after administration of USPIO. The change in T2* value on T2*weighted imaging was used to detect accumulation of USPIO within the abdominal aortic aneurysm. Histology of aortic wall tissue samples conrmed co-localisation and uptake of USPIO in areas with macrophage inltration. Patients were classied into one of three groups on the basis of imaging ndings (Abstract D Figure 1). Group 1: periluminal USPIO uptake only. Group 2: USPIO uptake throughout the thrombus. Group 3: USPIO uptake in the aortic wall. Patients in group 3 with distinct mural uptake of USPIO had a threefold higher growth rate (n13; 0.66 cm/yr; p0.020) than those with no (Group 1; n7; 0.22 cm/yr) or non-specic USPIO uptake (Group 2; n9; 0.24 cm/yr) despite having similar aneurysm diameters (5.460.6, 5.160.5 and 5.060.5 cm respectively; p>0.05) and patient characteristics (p>0.05). In one patient with an inammatory aneurysm, USPIO uptake and inammation extended beyond the aortic wall into surrounding tissues. Conclusion USPIO uptake in the aortic wall detects cellular inammation in patients with AAA and appears to predict more rapidly progressive AAA expansion. This technique therefore holds major promise as a new method of risk-stratifying patients with AAA that extends beyond the simple anatomical measure of aneurysm diameter.
Abstract C Figure 1 (A) Time-dependent endothelial regeneration following vascular injury (n=5 mice per group; *denotes p<0.05). (B) Effects on endothelial regeneration 5 days after wire-injury of transfusion of spleenderived MNCs or BM-derived c-kit (CD117)+ve cells from WT or IRKO mice (n=4 mice per group).
Abstract D Figure 1
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(Abstract E Figure 2B) and potentially causative sequence variants in these 3 candidate genes have been identied. We have translated these ndings to humans using data from a genome-wide association study population. Conclusions We have identied a new genomic locus for HR, which does not contain genes in pathways already known to determine HR. We prioritised three candidate genes at the locus, which may be targets for therapeutic modulation of HR in patients with heart disease.
Abstract D Figure 2
INTEGRATIVE GENOMICS APPROACHES IDENTIFY NEW GENES CONTROLLING HEART RATE

doi:10.1136/heartjnl-2011-300110.5
J S Ware, 3H Dobrzynski, 4M Pravanec, 1P J Muckett, 1S Wilkinson, Y Jamshidi, 1T J Aitma, 6N S Peters, 1,2S A Cook. 1MRC Clinical Sciences Centre, Imperial College London, London, UK; 2National Heart & Lung Institute, Imperial College London, London, UK; 3School of Medicine, University of Manchester, Manchester, UK; 4Institute of Physiology, Czech Academy of Science, Prague, UK; 5 Division of Clinical Developmental Sciences, St. Georges University of London, London, UK; 6National Heart & Lung Institute, Imperial College London, London, UK
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1,2
Introduction Heart rate (HR) is a fundamental measure of cardiac function, and is of prognostic and therapeutic signicance. We applied genetic and genomic approaches to identify new loci and genes controlling HR in a rat model that has previously been used to nd human cardiovascular disease genes. Methods Telemetric aortic pressure transducers were implanted into 226 animals from 33 rat strains: the Brown Norway, the Spontaneously Hypertensive Rat, and 31 strains from a recombinant inbred panel derived from these parental strains and HR was measured over several weeks. Statistical analyses were carried out using the R package, and quantitative trait loci (QTL) identied by linkage mapping using QTL Reaper. Potential covariates of HR were analysed in SPSS. The sinus node (SN) and right atria (RA) of 20 rats were microdissected (Abstract E Figure 1). Gene expression data were generated with the Affymetrix Rat Gene 1.0 ST microarray and analysed using Bioconductor. Differentially expressed genes were identied using SAM & Limma. Genes in the QTL that were expressed in the SN were resequenced to identify potential causative sequence variants. Results Narrow sense heritability of HR in this population was 51%, suggesting a large genetic contribution to HR. Linkage mapping identied a region on rat chromosome 13 controlling HR, with peak LOD score 6.7 (Abstract E Figure 2A). This QTL has not previously been identied in human, rat or mouse. Mean nocturnal HR in strains carrying the SHR allele was 388, compared with 357 in BN-like strains; an allelic effect of 31bpm (8.7%, p<0.00005) that is equivalent to 5e9 bpm in humans, corresponding to a decreased risk of cardiovascular death of 10%e29%. Two independent approaches (linear regression modelling & correlation analysis) conrmed that this effect was independent of potential physiological covariates, suggesting that the effect may be intrinsic to the heart, rather than due to neurohumeral inuences.We have generated the rst genomewide transcript expression prole of the SN. Three genes at the new HR locus were enriched in the SN
Abstract E Figure 1 Small (1 mm2) pieces of tissue were isolated from the rat SN and distant trabeculated RA and RNA extracted for gene expression proling.
Abstract E Figure 2 (A) Interval mapping revealed a linkage peak on chr13. Linkage was strongest for nocturnal HR, with a LOD score of 6.7 (p>0.00005). The horizontal line approximates to genomewide signicance. (B) A volcano plot showing 3 genes signicantly enriched in SN compared with RA.
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BCS Abstracts 2011
Abstracts
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ROUTE OF ADMISSION IN STEMI: DO PATIENTS WHO PRESENT DIRECTLY TO A PCI-CAPABLE HOSPITAL DIFFER FROM INTER-HOSPITAL TRANSFERS?
doi:10.1136/heartjnl-2011-300198.1 D Austin, Z Adam, J Shome, M Awan, A G C Sutton, J A Hall, R A Wright, D F Muir, N M Swanson, J Carter, MA de Belder. James Cook University Hospital, Middlesbrough, UK
difference in outcome was noted by route of admission for either inhospital or 1-year events.
Abstract 1 Table 2
Direct In-hospital MACCE Adjusted in-hospital MACCE (model 1) Adjusted in-hospital MACCE (model 2) Direct 1-year mortality Adjusted 1-year mortality (model 3) Adjusted 1-year mortality (model 4) 7% Transfer 9.7% 4.3% Transfer 6.7% OR (95% CI) 1.58 (1.04 to 2.39) 1.64 (1.00 to 2.28) 1.34 (0.79 to 2.29) p 0.03 0.05 0.27
Background Rapid delivery of reperfusion therapy with PPCI is the gold standard treatment in STEMI. Systems have been developed, such as direct admission to a PCI-capable hospital, to minimise the time from diagnosis to PPCI. Despite this, a signicant minority of patients are initially admitted to non-PCI capable hospitals. The aim of this study was to determine whether patients differed in their characteristics, time to PPCI, and outcome by route of admission. Methods The study was performed in a single tertiary centre in North England. Data are collected routinely on all patients undergoing PPCI and include demographic, clinical and procedural variables. In-hospital MACCE (death, re-infarction or CVA) and mortality are collected providing relevant outcome measures. Baseline clinical variables by route of admission were compared and unadjusted inhospital MACCE rates determined. One-year mortality by route of admission was calculated using the K-M product limit estimate. Inhospital and 1-year outcomes were analysed after adjustment for factors known to be predictors of early mortality following STEMI (models 1 and 3). To determine the relative importance of delays in treatment, call-to-balloon time was added (models 2 and 4). Logistic regression was used for the adjusted in-hospital outcomes, and Coxproportional regression for adjusted 1-year mortality. Results 2268 patients were included in the analysis. 510 patients (22.5%) were treated with PPCI following transfer from a non-PCI capable centre. Analysis of baseline variables (Abstract 1 table 1) showed the transfer group were more likely to have an LAD occlusion treated, and previous MI. Despite shorter DTB times, the transfer group had a greater median CTB time (52 minutes longer) compared with direct admissions. Other baseline variables were statistically no different between groups. There were 110 in-hospital MACCE events, and 168 deaths within 1-year follow-up. The transfer group had signicantly higher unadjusted in-hospital MACCE rates (2.4% absolute, 58% relative increase (Abstract 1 table 2)). At 1 year, the transfer group had signicantly higher unadjusted mortality (2.7% absolute, 48% relative increase (Abstract 1 table 2)). After adjustment for relevant co-variates (models 1 and 3) route of admission remained a signicant predictor of in-hospital and 1-year mortality. With the addition of call-to-balloon time, no signicant
HR (95% CI) 1.48 (1.06 to 2.07) 1.41 (0.99 to 2.01) 1.29 (0.87 to 1.89)
p 0.02 0.05 0.20
Conclusion In this study, patients who presented directly had superior in-hospital and 1-year outcomes compared with those who required transfer from other hospitals. Adjustment for longer call-toballoon times attenuated the nding of poorer outcomes in these patients, suggesting that delays in treatment are critical. Systems of care should be designed to avoid admission of STEMI patients to non-PCI hospitals, and facilitate more rapid transfer of patients where this has not been possible.
A DIRECT TRANSFER PROTOCOL FOR PATIENTS WITH NON ST-ELEVATION MYOCARDIAL INFARCTION REDUCES TIME TO CORONARY ANGIOGRAPHY
doi:10.1136/heartjnl-2011-300198.2
S M Gallagher, M J Lovell, D Jones, E Ferguson, S Antoniou, S Mohiddin, M Westwood, A Mathur, R A Archbold, C Knight, A K Jain. London Chest Hospital, Barts and the London NHS Trust, London, UK
Abstract 1 Table 1
Direct Age (years6SD) Male Diabetes Previous MI Treated vessel LMS LAD LCx RCA Graft Cardiogenic shock Smoking (ex/current) Call-to-balloon time Door-to-balloon time 24 (1.4) 630 (36.1) 249 (14.3) 812 (46.6) 28 (1.7) 28 (1.7) 1331 (75.7) 102 (82e135) 44 (29e76) 13 (2.5) 218 (42.9) 83 (16.3) 188 (37.0) 5 (1.1) 35 (6.9) 377 (73.9) 154 (107e235) 34 (24e50) 0.61 0.42 <0.001 <0.001 64.3 (12.7) 1252 (71.2) 177 (10.1) 225 (12.6) Transfer 63.9 (12.4) 367 (72.0) 55 (10.8) 89 (17.3) p 0.17 0.74 0.68 0.001 0.001
Introduction Patients with non-ST elevation myocardial infarctions (NSTEMI) are at high risk of further cardiac events. National guidelines recommend early coronary angiography within 96 h of presentation. Most patients with NSTEMI present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of early angiography is problematic. Methods A novel clinical care pathway for the management of NSTEMI, known locally as the Heart Attack Centre-Extension or HAC-X, has been investigated. This pathway identies patients with NSTEMI by clinical assessment and rapid point-of-care troponin testing while in the emergency department (ED). Patients meeting criteria for urgent transfer receive evidence based medical therapy for NSTEMI (see Abstract 2 table 1) in the ED, and are transferred to the tertiary centre within 1 h without referral. All unstable patients are taken straight to the cardiac catheterisation laboratory. For stable patients, coronary angiography is undertaken on the same day, or if patients arrive after 17:00 on the next available routine list. The study group consists of 775 patients divided into two groups; 464 patients treated before the instigation of the HAC-X pathway (Pre-HACX), and 311 patients treated via the novel pathway (Post-HACX). We have undertaken a prospective observational study of post-HAC-X patients, assessing need for angiography and or revascularisation along with discharge diagnosis. We have also compared the waiting time for angiography of pre-HAC-X and post-HAC-X groups. Results 250/311 (80.4%) of HACX patients underwent angiography. Following angiography, 144/250 (57.6%) were treated with coronary revascularisation (108 (75%) PCI and 36 (25%) CABG). 106/250
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BCS Abstracts 2011

Abstract 2 Table 1
Inclusion criteria
Inclusion and exclusion criteria for HACX

Symptoms suggestive of myocardial ischaemia With ECG changes including: ST depression; T wave inversion in V1-4; Dynamic T wave changes OR positive troponin I assay
Exclusion criteria
Unexplained anaemia (Hb<10) Hypoxia Acute renal failure Loss of consciousness Recent trauma Overt sepsis
wait for transfer to tertiary centre was 4.1 (64.7) days. Median length of stay for HACX patients was 3 days. HAC-X has reduced wait for coronary angiography by 3.4 days per patient. Conclusions This novel care pathway allows delivery of early angiography to NSTEMI patients in accordance with national guidance. Importantly, the pathway allows accurate diagnosis of NSTEMI, and inappropriate transfers are infrequent. Its introduction has resulted in a signicant reduction in time to angiography for NSTEMI patients, and signicant reductions in total hospital bed occupancy for patients with NSTEMI.
Immediate medical therapy includes Aspirin 300 mg Clopidogrel 600 mg Fondaparinux 2.5 mg Eptibatide bolus (180 mg/kg) as long as no bleeding contraindications
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SURVIVAL FOLLOWING ACUTE MYOCARDIAL INFARCTION IN PATIENTS OF SOUTH ASIAN AND WHITE EUROPEAN ETHNICITY IN THE UK
doi:10.1136/heartjnl-2011-300198.3
N N Gholap, R L Mehta, K Khunti, M J Davies, 2I B Squire. 1University Hospitals of Leicester, Leicester, UK; 2University of Leicester, Leicester, UK
(42.4%) of patients were treated with medical therapy alone. NSTEACS (encompassing NSTEMI and unstable angina) was the discharge diagnosis for 75.4% of HACX patients. 10% of patients had another cause for chest pain symptoms (including pericarditis and, myocarditis); 14.6% had a non-cardiac diagnosis. Mean time from presentation to angiography was pre-HAC-X 7349 mins (66836) and post HAC-X 754 mins (6458) (p<0.0001) (see Abstract gure 1). Pre-HAC-X mean
Abstract 2 Figure 1 angiography.

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Time from ED presentation to coronary
Introduction Some UK studies have suggested higher case-fatality rates following acute myocardial infarction (AMI) in British South Asian (SA), compared to white European (WE) people, driven by higher prevalence of diabetes in the SA ethnic group. However other studies have suggested similar or even better adjusted overall post-AMI survival for these ethnic groups. In patients with AMI, both prior diagnosis of diabetes as well as acutely elevated blood glucose regardless of diabetes status are associated with adverse outcomes. The aim of this study was to compare survival rates following AMI in SA and WE patients drawn from a contemporary, multi-ethnic UK population. Methods: We conducted a retrospective cohort study of total 4111 (SA 18%) consecutive patients with AMI admitted between October 2002 and September 2008. Baseline differences between the ethnic subgroups were examined using independent two-sample t tests for continuous and c2 tests for categorical variables. Cox regression models were constructed to identify determinants of 30-days and 1year mortality, entering ethnicity, random admission blood glucose and antecedent diabetes individually and together along with other relevant variables. Results: SA patients were younger (62 vs 67 years, p<0.005) and less likely to have smoked (16% vs 40%, p<0.005) but more likely to have hypertension (55% vs 49%, p0.004) or diabetes (40% vs 16%, p<0.005) at presentation compared to WE patients. All cause 30-day and 1-year mortality proportions were 10.0 % and 15.2% in SA compared to respectively 9.9 % and 16.7 % in WE patients. For SA ethnicity, the univariate HR of 30-day mortality was 1.01 (95% CI 0.79 to 1.30) compared to WE ethnicity. On multivariate analysis (excluding antecedent diabetes and admission blood glucose) this association of SA ethnicity and mortality became signicant (HR 1.56, CI 1.10 to 2.23) and remained so when antecedent diabetes was added to the analysis (HR 1.48, CI 1.03 to 2.13). However when admission blood glucose was added to the model, association of ethnicity with mortality became non-signicant (HR 1.31, CI 0.86 to 1.99). Conversely each unit (mmol/l) increase in admission blood glucose was associated with 7% increase in mortality (HR 1.07, CI 1.04 to 1.10) in this model, after adjusting for all the covariates. Furthermore exclusion of ethnicity and antecedent diabetes from the model did not alter the predictive value of admission blood glucose (HR 1.08, CI 1.05 to 1.10). Similar associations were observed for 1-year mortality. Conclusions Despite higher prevalence of diabetes in SA patients, their mortality post AMI was similar to WE patients. Furthermore, admission hyperglycaemia more so than antecedent diabetes was an important predictor of increased mortality post AMI. To improve survival, active management of admission hyperglycaemia should be considered in patients admitted with AMI, regardless of their diabetes status or ethnicity.
BCS Abstracts 2011

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A RATIONAL APPROACH TO RAISED TROPONINS ON A HYPERACUTE STROKE UNIT: COPING WITH THE IMPACT ON CARDIOLOGY SERVICES
doi:10.1136/heartjnl-2011-300198.4 S S Nijjer, G Banerjee, J Barker, S Banerjee, S Connolly, K F Fox. Imperial College Healthcare NHS Trust, London, UK Cardiovascular Science, Edinburgh University, Edinburgh, UK; 2Edinburgh Heart Centre, Royal Inrmary of Edinburgh, Edinburgh, UK; 3Epidemiology and Statistics Core, Wellcome Trust Clinical Research Facility, Edinburgh, UK; 4Department of Clinical Biochemistry, Royal Inrmary of Edinburgh, Edinburgh, UK
Introduction Troponin is frequently measured on admission to hyperacute stroke units (HASUs). Modest elevations in stroke are common but whether patient management changes in response to the blood test is unclear. Raised troponin without chest pain or dynamic ECG changes create diagnostic dilemmas. Management strategies were assessed with the introduction of the Imperial HASU covering North West London. Methods Consecutive HASU admissions over 6 months were assessed for measurement of troponin, the result, and the cardiac investigations performed. Clinical parameters guided investigations lead by two Consultant Cardiologists (KF, SC) rather than strict research protocol. Results 412 patients were admitted: 245 patients had a total of 435 troponin-I levels measured, without chest pain or dynamic ischaemic ECG changes. 70 (29%) patients had positive levels (>0.032 ng/l): 53 (22%) were low (0.032e0.3 ng/l), 17 (7%) were high (>0.3 ng/l). 237 had diagnoses readily available: 170 had stroke (ischaemic or haemorrhagic), 67 had non-stroke (eg, seizure). Troponin was more likely to be raised if stroke, OR 4.3 (2.0e9.7, p0.0001). Five patients with high troponins had non-invasive stress testing (1 perfusion scan and 4 stress echos): all were negative. All positive troponins had echocardiography and cardiology review with no change in management in 91% of cases. 6 patients had invasive coronary angiography: 3 high and 3 low troponin. Only 2 patients (3% of those with positive troponin) required percutaneous coronary intervention (PCI); both had troponin >0.3 and multiple cardiac risk factors. Patients with troponin <0.3 did not require PCIeall three had normal coronary arteries. Conclusions Every positive troponin necessitated a review and additional tests, increasing demand on cardiology services without increase in resources. However only 2 patients required PCI with the majority medically managed. We propose a pragmatic pathway for when troponin is performed as a routine test. Raised troponins >0.3 ng/l should be assessed for chest pain and ECG changes suggesting true myocardial infarction. Without these, non-invasive assessment and optimal medical therapy is sufcient in the majority. Minor troponin rise (0.032e0.3 ng/l) represents myocytolysis: cerebral insular damage causes sympathoadrenal activation and patchy myocyte damage. Without chest pain or ECG changes, optimal medical management without further investigation is appropriate. Since this does not represent true acute coronary syndrome, an early invasive strategy confers no additional benet over medical therapy. In contrast, aspirin and statins benet both stroke and any coronary disease present. The nancial and medical implications of performing non-indicated tests in a routine manner when the result will be disregarded is signicant. Therefore, we caution against routine measurement of troponin in stroke.
Introduction Although troponin assays have become increasingly more sensitive, it is unclear whether further reductions in the threshold of detection for plasma troponin concentrations impact on clinical outcomes in patients with suspected acute coronary syndrome. The aim of this study was to determine whether lowering the diagnostic threshold for myocardial infarction with a sensitive troponin assay will improve clinical outcomes. Methods Consecutive patients admitted with suspected acute coronary syndrome before (n1038; validation phase) and after (n1054; implementation phase) lowering the threshold of detection for myocardial necrosis from 0.20 to 0.05 ng/ml with a sensitive troponin I assay were stratied into three groups: <0.05, 0.05e0.19 and $0.20 ng/ml. During the validation phase, only concentrations above the original diagnostic threshold of $0.20 ng/ml were reported to clinicians. Event-free survival (reinfarction and death) at 1 year were compared in patients grouped by plasma troponin concentrations. Results Plasma troponin concentrations were <0.05 ng/ml in 1340 (64%), 0.05e0.19 ng/ml in 170 (8%) and $0.20 ng/ml in 582 (28%) patients. During the validation phase, 39% of patients with undisclosed plasma troponin concentrations of 0.05e0.19 ng/ml were dead or had recurrent myocardial infarction at 1 year, compared to 7% and 24% of those with troponin concentrations <0.05 ng/ml (p<0.001) or $0.20 ng/ml (p0.007) respectively. During the implementation phase, lowering the diagnostic threshold to 0.05 ng/ml reduced 1-year death and recurrent myocardial infarction from 39% to 21% in patients with troponin concentrations of 0.05e0.19 ng/ml (OR 0.42, 95%CI 0.24 to 0.84, p0.013), whereas clinical outcomes were unchanged in patients with troponin concentrations <0.05 ng/ml or $0.20 ng/ml (Abstract 5 gure 1).
IMPLEMENTATION OF A SENSITIVE TROPONIN I ASSAY REDUCES DEATH AND RECURRENT MYOCARDIAL INFARCTION IN PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME
doi:10.1136/heartjnl-2011-300198.5
Abstract 5 Figure 1
Conclusions In patients with suspected acute coronary syndrome, implementation of a sensitive troponin assay increases the diagnosis of myocardial infarction by a third, and identies those at high-risk of reinfarction and death. Lowering the diagnostic threshold of plasma troponin is associated with major reductions in morbidity and mortality.
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K K Lee, N L Mills, A M D Churchhouse, A Anand, 1D Gamble, 1A Shah, 1E Paterson, M MacLeod, 3C Graham, 4S Walker, 1M A Denvir, 1K A A Fox, 1D E Newby. 1Centre for
BCS Abstracts 2011

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CARDIAC MORBIDITY AND MORTALITY CAN BE ACCURATELY PREDICTED IN PATIENTS PRESENTING WITH ACS USING MULTIPLE BIOMARKERS MEASURED ON AN ADMISSION BLOOD SAMPLE
doi:10.1136/heartjnl-2011-300198.6 I R Pearson, K Viswanathan, N Kilcullen, A S Hall, C P Gale, U M Sivananthan, J H Barth, 2C Morrell. 1Leeds Teaching Hospitals, Leeds, UK; 2University of Leeds, Leeds, UK
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IN ACUTE CORONARY SYNDROMES, HEART-TYPE FATTY ACID BINDING PROTEIN IS A MORE ACCURATE PREDICTOR OF LONG TERM PROGNOSIS THAN TROPONIN
doi:10.1136/heartjnl-2011-300198.7
I R Pearson, A S Hall, C P Gale, U M Sivananthan, 1K Viswanathan, 1N Kilcullen, C Morrell, 1J H Barth. 1Leeds Teaching Hospitals, Leeds, UK; 2University of Leeds, Leeds, UK
Background Rapid assessment of patients with suspected acute coronary syndrome (ACS) allows the right patients to receive the right treatment at the right time. Discrimination of risk permits clinical triage into pathways of immediate inpatient or deferred outpatient care. It is known that a signicant proportion of the ACS patients sent home following an MI screen, based on a negative 12-h troponin level, are misdiagnosed as having noncardiac chest pain when in fact they are at high risk of cardiac events. It has been shown that the novel biomarker H-FABP can detect myocardial ischaemia even in the absence of myocyte necrosis. We hypothesise that a multi biomarker blood test incorporating troponin I, CK-MB and H-FABP, taken on admission, can accurately discriminate those patients with a non-cardiac cause of chest pain who are at low risk of cardiac morbidity or mortality. Methods We studied 519 patients with suspected ACS admitted to a single UK Teaching Hospital. A risk scoring model was constructed based on tertile values for Randox Cardiac-Array measurement of troponin I, H-FABP and CK-MB. These were measured on a blood sample taken at the time of hospital admission. The lowest two lower tertiles were each given a score of 1 and the top tertile a score of 3. The scores were then combined by summation resulting in an overall score of between 3 and 9. Outcome measures up to 12 months were: (i) death from all causes; (ii) repeat acute coronary syndrome (ACS) (iii); readmission for heart failure; (iv) readmission for cerebrovascular event (CVA); (v) coronary revascularisation. Results The distribution of Cardio-Array scores was: 3 (n164; 31.6%); 5 (n134; 25.8%); 7 (n110; 21.2%); 9 (n111; 21.4%). The cumulative incidence of events according to the Cardiac-Array score is shown in Abstract 6 table 1.
Introduction We have previously shown that heart-type fatty acid binding protein (H-FABP) has a role in predicting all-cause mortality after acute coronary syndromes (ACS) and after multivariable analysis, provides additional information to that gained from the GRACE clinical risk factor score, troponin and highly sensitive CRP. H-FABP is released into the circulation during myocardial ischaemia and after myocardial necrosis, in contrast to troponin which is released after myocardial necrosis only. We have also shown that there is a group of ACS patients who are at high risk of cardiac events and death despite normal troponin levels on admission. This group may benet from an early invasive strategy. Hypothesis Plasma H-FABP level, taken between 12 and 24 h after admission, can identify troponin negative ACS patients who are at a high long term risk of death. Methods Six-year mortality data is now available for patients enrolled in the FAB 1 study, for which 1-year mortality data was published in 2007. In this study, 1448 unselected patients admitted to hospital with ACS had serum H-FABP level measured in addition to usual care. Mortality was tracked by the UK Ofce of National Statistics. Results At 6 years overall all-cause mortality, available for 1421 patients (98.1%), was 43.5%. If troponin ve/H-FABP ve mortality was 20.9%; troponin ve/H-FABP +ve 56.4%; troponin +ve/H-FABP ve 20.2%; troponin +ve/H-FABP +ve 49.1%. Mortality rate was independent of troponin status but strongly related to H-FABP status. Conclusion The current system of stratication of ACS patients for early invasive management if troponin positive will miss a cohort of patients who are at high risk of death despite being troponin negative, and who may benet from invasive investigation. Conversely, it is likely that some ACS patients undergo angiography based on a false positive troponin level. The addition of H-FABP measurement to the management of ACS could avoid this.
Abstract 6 Table 1 The cumulative incidence of events according to the Cardiac-Array Score
Score 3 5 7 9 Ratio (9/3) p Value Death 0.61% 3.21% 11.11% 12.98% 21.28 <0.0001 or ACS 3.07% 5.77% 17.78% 16.23% 5.29 <0.0001 or HF 3.11% 5.81% 19.05% 18.37% 5.91 <0.0001 or CVA 3.11% 5.81% 20.93% 18.92% 6.08 <0.0001 or Revasc 4.28% 6.41% 24.44% 22.08% 5.16 <0.0001
Conclusion Patients presenting with possible ACS who have a Cardiac-Array biomarker score of 3 or 5, as measured on their admission blood sample, have a very low rate of cardiovascular events. This tool could be used to safely triage patients towards early discharge and outpatient care, based upon available resources. A score of 7 or 9 would merit admission to hospital, and consideration of early cardiac catheterisation.
Abstract 7 Figure 1
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DOES THE ADDITION OF A RADIAL ARTERY GRAFT IMPROVE SURVIVAL AFTER HIGHER RISK CORONARY SURGERY? A PROPENSITY-SCORE ANALYSIS
doi:10.1136/heartjnl-2011-300198.8 C H Yap, P A Hayward, W Y Shi, D T Dinh, 1C M Reid, 3,4G C Shardey, J A Smith. 1Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, UK; 2Department of Cardiac Surgery, Austin Hospital, University of Melbourne, Melbourne, UK; 3Department of Cardiothoracic Surgery and Surgery, Monash Medical Centre, Monash University, Melbourne, UK; 4Department of Surgery, Monash Medical Centre, Monash University, Melbourne, UK
3,4 1 2 2 1
Introduction The use of the radial artery as a second arterial graft during coronary surgery has become popular due to high patency, encouraging clinical outcomes and low harvest site complication rates. However it is not clear whether higher risk patients derive such benets. We sought to assess this by examining outcomes in higher risk subgroups. Methods A multicentre database was analysed. From 2001 to 2009, 11 388 patients underwent isolated multivessel coronary surgery. We identied a higher risk subgroup (n3149) according to emergent status, coronary instability, low ejection fraction, aortic counterpulsation or anticoagulant status. Among these, 2231 (71%) received at least 1 radial artery graft in addition to a left internal thoracic artery (LITA). The remaining 918 (29%) received LITA and veins only. Propensity-score matching and adjustment was performed to correct for group differences. Results Patients who did not receive a radial artery were more likely to be older (mean age, radial: 66610 years vs vein: 71610, p<0.0001) female (22% vs 27%, p0.002), have poor left ventricular function (16% vs 23%, p<0.0001), left main stenosis (35% vs 41%, p0.002) or be of emergent status (11% vs 24%, p<0.0001). These patients experienced higher unadjusted 30-day mortality (2.2% vs 7.1%, p<0.0001) and poorer 7-year survival (p<0.0001). Furthermore, 548 patients in the radial group were propensity-score matched to 548 receiving LITA and veins. At 30 days, there were comparable rates of mortality (radial: 2% vs vein: 3%, p0.19), stroke (1% vs 1%, p0.51), myocardial infarction (1% vs 1%, p0.77), major adverse cardiac or cerebrovascular events (MACCE) (2% vs 4%, p0.12), return to theatre (5% vs 7%, p0.19), hospital readmissions (12% vs 12%, p>0.99) and combined any mortality/morbidity (30% vs 32%, p0.33). At 7 years, survival between radial and vein groups was similar (7962.5% vs 8062.5%, p0.74). Propensity-adjusted multivariable regression did not show radial artery to be protective from 30-day mortality (p0.14, OR 0.67, 0.40 to 1.13), 30-day MACCE (p0.23, OR 0.76, 0.48 to 1.20), or mid-term mortality (p0.79, HR 0.97, 0.78 to 1.20). Conclusions This multicentre analysis suggests that patients with the greatest coronary instability, urgency of surgery, or impairment of ventricular function are not disadvantaged in the early and midterm by use of a single arterial graft. Limitations include the inability to correct for unquantiable variables retrospectively. Despite this, surgeons may utilise clinical judgement to select radial or venous conduits to supplement the LITA according to other patient factors or technical preference without prejudicing outcome.
elevation myocardial infarction (STEMI), resulting in shorter hospital stays. Discharge at 72 h in selected patients has been suggested. We investigated the feasibility and safety of very early discharge (<48 h) coupled with regular outpatient support for lowrisk patients following PPCI. Methods 2317 patients underwent PPCI for STEMI between October 2003 and May 2010 at a regional Heart Attack Centre (HAC). Demographic and procedural data were documented at the time of intervention. Patients with TIMI 3 ow, ST segment resolution, good or moderate left ventricular function, and no dysrhythmia were stratied to 48 h discharge. Remaining patients were discharged according to physician preference. All patients were reviewed at 1, 8 and 52 weeks with a multidisciplinary team including rehabilitation, heart failure, and psychology. The primary endpoint was major adverse cardiac events (MACE) included death, myocardial infarction (MI), stroke and target vessel revascularisation (TVR). All-cause mortality data were provided by the Ofce of National Statistics via the BCIS CCAD national audit. Outcomes were compared between those discharged at #48 h, 72 h, and >72 h, out to 5 years of follow-up. Results 1079 patients (46.5%) were stratied to 48-h discharge, 14% discharged at 72 h and the remainder discharged at a median of 6 days (4.3e10), including those with complications. Patients discharged at #48 h were signicantly younger and had a lower incidence of multi-vessel disease than those discharged at 72 h (Abstract 9 table 1). Remaining baseline characteristics were similar. MACE at 3 years was similar between 48-h discharge patients and 72- h discharge (9.1% vs 8.7%, p0.7). This persisted out to 5 years (9.6% vs 9%, p0.55). As expected patients with length of stays >72 h had signicantly worse outcomes (Abstract 9 gure 1).
Abstract 9 Table 1
48 h (n[1079) Age Previous MI Previous CABG Previous PCI DM HTN Hchol 3 vessel disease 60.7 130 (12.0%) 21 (1.9%) 102 (9.4%) 156 (14.4%) 455 (42.1%) 403 (37.3%) 448 (46.4%) 72 h (n[323) 64.0 35 (10.8%) 7 (2.2%) 29 (9.0%) 52 (16.1%) 148 (45.8%) 124 (38.4%) 156 (54.9%) p Value 0.0002 0.5569 0.8019 0.8007 0.4632 0.2854 0.7858 0.0112
EARLY HOSPITAL DISCHARGE AT 48 H FOLLOWING PRIMARY PCI FOR MYOCARDIAL INFARCTION IS BOTH SAFE AND FEASIBLE
doi:10.1136/heartjnl-2011-300198.9
O Guttmann, D A Jones, K S Rathod, M Akhtar, A Ludman, A K Jain, C Knight, A Mathur, S Mohiddin, A Wragg, E J Smith. Barts and the London NHS trust, London, UK
Abstract 9 Figure 1
MACE after primary PCI.
Introduction Reperfusion therapy with primary PCI (PPCI) has reduced rates of recurrent ischaemia and arrhythmia following ST
Conclusion Early discharge at 48 h is feasible and appears to be safe for patients undergoing contemporary Primary PCI.
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EVALUATING A NURSE LED TRIAGE PROCESS IN TREATING PATIENTS WITH LEFT BUNDLE BRANCH BLOCK (LBBB) REFERRED FOR PRIMARY PERCUTANEOUS CORONARY INTERVENTION (PPCI)
doi:10.1136/heartjnl-2011-300198.10 N V Joshi, B R Bawamia, S Jamieson, A Zaman, R Edwards. Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK; 2The Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne, UK
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COPEPTIN IMPROVES EARLY RISK STRATIFICATION BY GRACE SCORE IN NON ST-ELEVATION MYOCARDIAL INFARCTION; NT-PROBNP DOES NOT
doi:10.1136/heartjnl-2011-300198.11
O S Dhillon, H K Narayan, P A Quinn, J Struck, 1I B Squire, 1J E Davies, 1L L Ng. University of Leicester, Leicester, UK; 2Brahms, Hennigsdorf, UK
Background The Freeman Hospital (FRH) performs over 900 pPCI a year. Patients with suspected Acute Myocardial Infarction (AMI) are referred either by paramedics or networked hospitals for consideration of pPCI via a Telmed system, which is triaged by experienced CCU nurses. The pPCI Pathway can be activated in patients with LBBB suspected of having an AMI. However, there remains considerable variation in the clinical utility of new or presumed new LBBB as a ST-elevation myocardial infarction (STEMI)-equivalent ECG diagnostic criterion. The major discriminators the triage staff use in this population are ECG ndings and symptoms suggestive of AMI. Our aim was to evaluate outcomes in patients with LBBB accepted to FRH or referred to local hospitals for assessment. Methods Consecutive patients referred to FRH with LBBB and suspected AMI from 1st August 2009 to 30th November 2009 were analysed by recording: 1) Peak Troponin Level 2) Angiographic ndings 3) Revascularisation rates. Results 1069 patients were referred for consideration of pPCI. 177 (16.6%) of patients had new or presumed new LBBB. 33 (18.6%) patients were accepted by FRH and 144 patients (81.4%) were declined and referred to their local hospitals for assessment. Abstract 10 Table 1 Troponin levels in patients with LBBB referred for consideration of pPCI. 26.5% of patients with LBBB referred for consideration of pPCI had moderately to highly raised troponin. Of the 33 patients admitted to FRH, 13 underwent inpatient angiography and 9 patients had signicant coronary disease (coronary stenosis 70%e100% in at least one coronary artery). Of those, 5 had PCI and 1 required urgent CABG. Only one patient had a 100% coronary occlusion believed to be an acute occlusion. 4 patients had unobstructed coronaries and were managed medically. Of the 132 patients declined for pPCI only 2 (1.5%) were referred back to FRH for PCI. Neither of these patients was found to have a 100% acute occlusion of a coronary artery.
Abstract 10 Table 1
FRH Assessed Number of patients Number analysed 33 33 FRH Declined 144 132 (Biochemistry data not found for 12 patients) 84 (63.6%) 25 (18.9%) 17 (12.9%) 6 (4.5%)
Background Risk stratication is vital to the optimal management of patients with non ST-elevation myocardial infarction (NSTEMI) however, current tools are not fully discriminatory. Copeptin, the stable 39 amino acid C-terminal portion of pro-vasopressin, is a recognised prognostic marker in ST elevation myocardial infarction (STEMI) that is also useful to exclude MI as levels rise early after onset. Copeptin has not been evaluated in a NSTEMI population to date. Aims We hypothesised that copeptin is an independent predictor of mortality following NSTEMI and, in accordance with AHA criteria for the evaluation of novel biomarkers, assess whether copeptin adds prognostic information to GRACE risk score (GRACE-RS). We use NT-proBNP for comparison. Methods and Results In this prospective observational study plasma copeptin and NT-proBNP was measured in 754 NSTEMI patients (519 men, median age 70613 years) within 36 h of symptoms. The primary endpoint of all-cause mortality at 6 months was reached by 56 (7.4%) patients. Median copeptin levels were 7.9 range 0.3 to 523.0 pmol/l and were signicantly higher in those that reached the primary endpoint than the event free survivors; median (IQR), 32.0 (12.0e88.7) vs 7.2 (4.0e16.7) respectively p<0.001. Both copeptin and NT-proBNP were predictive of the primary endpoint on univariate Cox regression analysis (HR 5.98 p<0.0005 and HR 6.07 p<0.0005 respectively). On adjustment for baseline clinical and biochemical variables copeptin remained predictive (HR 3.03 p0.009) but NTproBNP did not (p0.70). Kaplan-Meier analysis revealed that supramedian levels of copeptin were associated with increased mortality (log rank 28.4 p<0.001). ROC curve c-statistics for GRACE-RS of 0.799 increased to 0.835 when combined with copeptin (0.785), when combined with NT-proBNP (0.730) increased to 0.802. Re-classication analysis shows that copeptin improves accuracy of risk stratication when combined with the GRACE-RS as determined by net reclassication improvement (NRI 13.3% p0.008) whereas, NTproBNP does not (NRI 4.9% p0.21). The relative utilities for logistic regression models using GRACE-RS alone, GRACE-RS + copeptin and GRACE-RS + NTproBNP as covariates are shown in Abstract 11 gure 1. The relevant region was the region to the right of the sample risk for 6 months mortality, 0.074. The relative utility for GRACE-RS + copeptin was consistently more than the relative utility for GRACE-RS + NTproBNP across a range of risks; for example at a risk threshold of 15% the additional utility of adding copeptin to the GRACE-RS was 0.097 compared to 0.009 for NTproBNP.
Troponin levels Trop I<0.04 or Trop T<0.01 (Normal) Trop I 0.04e0.1 or Trop T 0.01e0.1 (Mildly raised) Trop I or Trop T 0.1e1.0 (Moderately raised) Trop I or Trop T>1.0 (High)
19 (57.6%) 2 (6.1%) 1 (3.0%) 11 (33.3%)
Conclusion Revascularisation was performed in only 6/33 (18.2%) accepted for assessment and only 2/132 (1.5%) were referred back to the centre for PCI. The sensitivity of the triage process in detecting patients with LBBB requiring urgent revascularisation is 75% and the specicity is 83%. The sensitivity of detecting patients with an acutely occluded artery diagnosed at angiography is 100% with a specicity of 81%. In a high volume Heart Attack Centre a nurse led triage is effective at discriminating patients with LBBB requiring immediate coronary intervention.
Abstract 11 Figure 1
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Conclusions High plasma copeptin levels indicate a worse outcome in NSTEMI patients. We have demonstrated that copeptin fulls AHA criteria by improving risk stratication over established markers GRACE score and NT-proBNP. Copeptin is also useful for rapid rule-out of MI and the current ndings further support clinical uptake.
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NEUTROPHIL ACTIVATION AT THE CULPRIT LESION IN ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION WITH MULTIPLE COMPLEX CORONARY PLAQUES
doi:10.1136/heartjnl-2011-300198.13
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C J Marshall, 1J L Mckenzie, 2T Moccata, 3M Nallaratnam, 3J Blake, 3C Frampton, M Richards, 2A J Kettle, 3D R Mcclean. 1Sunderland Royal Hospital, Sunderland, UK; 2 Free Radical Research Group, University of Otago, Christchurch, New Zealand; 3 Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand
THE RELATIONSHIP BETWEEN PSYCHOLOGICAL FACTORS AND IMPAIRED HEALTH-RELATED QUALITY OF LIFE POST ST-ELEVATION MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.12
1 1
L McGowan, H Iles-Smith, C Dickens, M Campbell, 1C Rogers, 2F Fath-Ordoubadi. University of Manchester, Manchester, UKI; 2CMFT, Manchester, UK
Introduction Evidence suggests that psychological factors, such as depression and anxiety, are independent risk factors for increased morbidity and mortality post ST-elevation myocardial infarction (STEMI). Since improved treatments have increased survival rates post STEMI the emphasis has turned to more patient related outcome measures such as health-related quality of life (HRQoL). The aim of the study was to assess the contribution of anxiety and depression to HRQoL in post STEMI patients, after controlling for possible confounding factors, including type of treatment. Methods We conducted a prospective cohort study of 385 postSTEMI patients who had undergone either lysis (183) or PPCI (202). The mean age was 60.0 years (SD 11.8) and 78% were male. Patients were assessed on a range of demographic, clinical and psychosocial variables, including measures of cardiac risk, cardiac severity and comorbidity (Charlson Comorbidity Indexd CCI). Psychosocial assessment included anxiety and depression (Hospital Anxiety and Depression Scale), illness perceptions (brief IPQ), and health-related quality of life (SF-36). The main outcome was the SF-36 Physical Component Score (PCS) at 6 months postSTEMI. Results Baseline results revealed a small number signicant differences between groups on a range of clinical variables, including higher GRACE scores for PPCI group (p0.007) but no differences in LV function. Lysis patients had more comorbid illness as measured by the CCI (p0.037). Regarding psychological variables the total HADS score was signicantly higher in the PPCI vs lysis group at baseline (means 13.2 (SD 7.9) and 11.4 (SD 8.9), p0.035), while anxiety and depression almost reached signicance, with raised anxiety and depression scores in the PPCI group. In order to identify variables at baseline that may contribute to SF-36 PCS at 6 months, we conducted a hierarchical multiple regression with four blocks of independent variablesddemographic, comorbidity-related, clinical and psychological. Factors which contributed to the nal model were cholesterol levels (p0.031) and depression (p<0.001). Treatment group did not play a role (p0.199). The addition of anxiety and depression contributed signicantly to the reporting of lower physical health-related quality of life (PCS) at 6 months (R20.12, p<0.001). Conclusion The ndings have shown that raised levels of depression and anxiety predicted impairment in health-related quality of life at 6 months post-STEMI, regardless of mode of treatment. The results indicate that the assessment of psychological factors is important in both groups. Despite PPCI having improved clinical outcomes, there will always be a group of patients receiving lysis. As such it is important to assess anxiety and depression in post STEMI patients, and to include these potentially modiable factors in the design of suitable interventions for this patient group.
Introduction The activation of neutrophils at the culprit coronary lesion following acute plaque disruption has not been reported. We hypothesised that neutrophil activation occurs in ST elevation myocardial infarction (STEMI) prior to percutaneous intervention (PCI), and that differences in activation may be detectable locally at the culprit lesion, particularly in patients with multiple complex coronary plaques. Methods Forty STEMI patients having primary PCI were compared to 10 controls with chronic stable angina (CSA) undergoing elective PCI. The clinical, demographic and angiographic characteristics of patients and controls are shown in Abstract 13 table 1. The culprit lesion was sampled after passage of a guide wire across the lesion and use of a low prole sampling catheter (Multifunctional probing catheter, Boston Scientic Corporation, Natick, Massachusetts, USA) at the site of occlusion, prior to further mechanical intervention. Neutrophil activation was measured by ow cytometry using neutrophil intracellular myeloperoxidase content (MPO Index) and the expression of the b2- integrin CD11b, a leukocyte adhesion and activation marker at the culprit coronary lesion (CA), the aorta at the coronary ostium (Ao), the coronary sinus (CS), and femoral artery (FA) prior to primary PCI. A lower MPO content indicates the depletion of intracellular MPO and cell activation.
Abstract 13 Table 1
Variable Age (years) mean6SD Male (%) Culprit coronary artery lesion treated (%) Left anterior descending Diagonal Circumex Right coronary Time to presentation (mins) mean6SD Baseline TIMI ow 0e1 STEMI (n[40) 62612 28 (70) 17 (42) 2 (5) 1 (3) 20 (50) 2226155 28 (70) Elective PCI (n[10) 6869.1 7 (70) 5 (50) 1 (10) 2 (20) 2 (20) NA 0 p Value 0.9 1 0.73 0.5 0.1 0.15 <0.001
Results A marked decrease in MPO content occurred at the CA, Ao and FA in STEMI compared to elective controls (p<0.01). Furthermore, MPO content was lower at the CA (23.1, (25.6 to 17.1), n37) compared to Ao (22.0, (24.7 to 16.2), n37), CS (20.6, (24.8 to 16.9), n30) and FA (20.4, (24.4 to 13.1), n40), all p<0.001 (Abstract 13 gure 1). Neutrophil MPO content was correlated with CD11b expression only at the culprit CA in STEMI (r0.4, p0.03, n31) (Abstract 13 gure 2). Neutrophil MPO content at the CA in patients with multiple complex plaques was similar to those with a single culprit however only in those with multiple complex plaques was a correlation between MPO content and CD11b (r0.7, p0.02) shown. Conclusion: In acute STEMI, neutrophils are activated systemically, regionally and locally at the culprit coronary lesion. In patients with multiple complex plaques, there may be an extended local role for the activated neutrophil following acute plaque destabilisation.
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MI, relating these to global and segmental myocardial function at 6 months. Methods and Results CMR scans were performed on 30 patients with ST elevation MI (STEMI) treated by primary PCI at each of 4 time points: 12e48 h (TP1); 5e7 days (TP2); 14e17 days (TP3); and 6 months (TP4). All patients showed oedema at TP1. The mean volume of oedema (% LV) was 37616 at TP1 and 39617 at TP2
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DYNAMIC CHANGES OF OEDEMA AND LATE GADOLINIUM ENHANCEMENT AFTER ACUTE MYOCARDIAL INFARCTION AND THEIR RELATIONSHIP TO FUNCTIONAL RECOVERY AND SALVAGE INDEX
doi:10.1136/heartjnl-2011-300198.14
E DallArmellina, N Karia, A Lindsay, T D Karamitsos, 1V Ferreira, 1M D Robson, P Kellman, 1J M Francis, 3C Forfar, 3B Prendergast, 3A P Banning, 1K Channon, 3 R J Kharbanda, 1S Neubauer, 1R P Choudhury. 1NIHR Biomedical Research Centre, Department of Cardiovascular Medicine, University of Oxford, Oxford, UK; 2NIH, Bethesda, USA; 3NIHR Biomedical Research Centre, Department of Cardiology, John Radcliffe Hospital, Oxford, UK
2
Introduction Changes in myocardial tissue in acute ischaemia are dynamic and complex and the characteristics of myocardial tissue on cardiovascular magnetic resonance (CMR) in the acute setting are not fully dened. We investigated changes in oedema and late gadolinium enhancement (LGE) with serial imaging early after acute
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with a reduction to 24613 (p<0.01) by TP 3. Myocardial segments with oedema also had increased signal on LGE at TP1 (k0.77; p<0.001). At TP1, the proportion of segments with wall motion impairment increased in relation to the extent of both myocardial oedema (p<0.01) and LGE (p<0.01). The volume of LGE decreased signicantly between TP1 and TP4 (27615% vs 22612%; p0.002). Of segments showing LGE at 48 h, 50% showed resolution by 6 months. In segments with such a reduction in LGE, 65% also showed improved wall motion (p<0.0001). The area of LGE measured at 6 months correlated more strongly with 48-h troponin (R20.84; p<0.01) than at TP1 (R20.5). The difference in LGE between TP1 and TP4 had profound effects on the calculation of salvage index (26621% at TP1 vs 42623% at TP4; p<0.02). Conclusions (1) Myocardial oedema was unchanged over the rst week but decreased by 15 days; (2) a large majority of segments that were positive for oedema also showed LGE, assessed at 12e48 h; (3) In 46% of patients, LGE present on early scans had diminished in size by 6 months, (4) resolution of LGE was associated with improvement in function; (5) the reduction in LGE at the later time had a profound effect on the calculation of salvage index, which varied by up to w60%, depending on the time point used. (6) From a clinical perspective, the use of acute LGE may severely underestimate salvaged myocardium and should not be used to predict recovery of myocardial function.
Abstract 15 Table 1 secondary outcomes

Variable hsCRP AUC (days 1e7) hsCRP at day 7 hsCRP at day 14 hsCRP at day 30 Troponin AUC (days 1e7) Troponin at day 14 Troponin at day 30 vWF AUC (days 1e3) vWF at day 14 vWF at day 30 IL-6 AUC (days 1e3) IL-6 at day 14 IL-6 at day 30
Log transformed values for the primary and

Active n 82 78 77 76 82 77 76 89 77 78 86 77 73 Active mean (SD) 3.51 (1.42) 1.03 (1.46) 1.14 (1.54) 1.13 (0.32) 1.35 (1.88) 3.73 (2.31) 4.83 (2.44) 1.33 (0.35) 0.36 (0.35) 0.37 (0.34) 2.62 (1.13) 1.32 (1.35) 1.22 (0.92) Placebo n 78 78 76 76 78 76 76 84 84 75 83 77 75 Placebo mean (SD) 3.55 (1.46) 1.09 (1.91) 0.89 (1.56) 0.92 (1.15) 1.50 (1.96) 4.14 (2.35) 4.74 (2.51) 1.31 (0.35) 0.28 (0.41) 0.29 (0.43) 2.56 (1.02) 0.92 (0.75) 1.08 (0.77)
p 0.86 0.83 0.32 0.30 0.61 0.27 0.82 0.66 0.23 0.19 0.74 0.028 0.31
15
INVESTIGATION OF IL-1 INHIBITION IN PATIENTS PRESENTING WITH NON-ST ELEVATION MYOCARDIAL INFARCTION ACUTE CORONARY SYNDROMES (THE MRC ILA HEART STUDY)
doi:10.1136/heartjnl-2011-300198.15
Results Five UK centres randomised 182 patients with non-ST elevation (NSTEMI) ACS to IL-1ra or placebo. Enrolment completed in March 2010. Mean age was 61 years, 32% female, 28% prior MI, 15% diabetes, 90% were receiving a statin at the time of randomisation and 64% had early PCI or CABG. Compliance was good with 85% of patients receiving daily injections during the rst 7 days, and 70% of patients were able to self-administer the injections. Injection site reactions reported as adverse events occurred in 14% of patients. There was no signicant difference in area under the curve for hsCRP between active and placebo groups. The MACE and serious adverse event rates are shown in Abstract 15 table 2.
A C Morton, 2C Foley, 1A Rothman, 1J Gunn, 3J P Greenwood, 3A Hall, 4K Fox, B Lees, 2M Flather, 1D Crossman. 1NIHR Cardiovascular Biomedical Research Unit, Shefeld, UK; 2CTEU, Royal Brompton and Hareelds NHS Trust, London, UK; 3 Academic Unit of Cardiovascular Medicine, Leeds, UK; 4Royal Inrmary of Edinburgh, Edinburgh, UK
2
Abstract 15 Table 2
Event MACE at 30 days MACE at 3 months MACE at 1 year MI (%) Stroke (%) Death (%) CV hospitalisation (%) Revascularisation (%) Injection site reactions (%) Other SAE (%)
MACE and other SAE

Active (n (95% CI)) 6 (0.19 to 1.79) 10 (0.32 to 1.84) 20 (0.59 to 2.22) 3.26 1.09 4.35 19.86 69.56 15.22 47.83 Placebo (n (95% CI)) 10 (1) 13 (1) 18 (1) 7.78 0 4.44 25 60 15.56 44.44 p 0.35 0.54 0.69 0.18 1.00 1.00 0.31 0.8 0.95 0.65
Background Inammatory mechanisms are involved in both coronary atherogenesis and its presentation as acute coronary syndromes (ACS). To date, drugs used at the time of ACS, or for primary and secondary prevention have not primarily targeted inammatory mechanisms. Studies with aspirin and statin drugs indicate that anti-inammatory properties of these compounds may contribute to their benecial effects. Pre-clinical studies from our group have indicated that the pro-inammatory cytokine IL-1 drives a number of vascular events relevant to coronary artery disease and ACS. IL-1 can be inhibited by IL-1 receptor antagonist (IL-1ra, Anakinra, Amgen) which is licensed for the treatment of rheumatoid arthritis. Aims To investigate the effects of interleukin-1 receptor antagonist (IL-1ra) on inammatory biomarkers in patients with ACS <48 h from symptom onset, and to evaluate the safety and tolerability of treatment. Design and methods The UK MRC ILA-HEART study is an investigator-initiated, non-industry sponsored, phase 2, multi-centre, placebo-controlled trial, comparing the IL-1ra (100 mg) with matching placebo given as a single, daily subcutaneous injection over 2 weeks. The primary outcome of the study was area under the curve (AUC) of high sensitivity CRP (hs-CRP) over the rst 7 days of treatment, and the main secondary outcomes are AUC of troponin and safety and compliance of trial treatment. Patients were encouraged to self-administer trial treatment, and underwent daily assessment of hs-CRP, troponin, von Willebrand factor and other biomarkers up to 7 days, and again at 2 weeks and 30 days. Patients were followed up to 12 months for safety (Abstract 15 table 1).
Discussion NSTEMI ACS treated with all the current evidencedbased therapies still has signicant recurrent events. MRC ILAHEART is the rst study to evaluate the effects of the anti-inammatory IL-1ra in ACS. The data indicates that despite encouraging pre-clinical evidence, the inammatory driver for NSTEMI-ACS is not IL-1 mediated.
16
ACUTE STENT THROMBOSIS RESULTING IN ST ELEVATION MYOCARDIAL INFARCTION (STEMI) IS ASSOCIATED WITH WORSE CLINICAL OUTCOMES THAN STEMI DUE TO NATIVE CORONARY THROMBOSIS
doi:10.1136/heartjnl-2011-300198.16
E C Sammut, A Graham, D A Jones, K Rathod, S May, A Jain, S Mohiddin, C Knight, A Mathur, A Wragg. The London Chest Hospital, London, UK
Background Stent thrombosis (ST) is a recognised cause of ST Elevation Myocardial infarction (STEMI) in patients with previous
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percutaneous coronary interventions (PCI). The incidence is increasing and to date outcomes are not well characterised, though there is a suggestion that there is a worse clinical outcome. We therefore sought to compare STEMI caused by ST vs de novo coronary thrombosis to evaluate procedural risk and clinical outcome. Methods Clinical information was analysed from a prospective database on 2421 patients who underwent Primary PCI following STEMI between October 2003 and May 2010 at a London centre. Information was entered at the time of procedure, diagnosis of stent thrombosis made at the time by primary operator and outcome assessed by all-cause mortality information provided by the Ofce of National Statistics via the BCIS CCAD national audit. Results Stent thrombosis (ST) accounted for 7.4% (180/2421) of all STEMIs with a frequency that has increased over time (5.4% in 2005 to 9.8% 2009). ST occurred early (0e30 days) in 36% (65/180), late (30 dayse1 year) in 22% (40/180) and very late (>1 year) in 42% (75/ 180) of pts. Drug-eluting stents (DES) accounted for 48% of SToverall and 70% over the past 3 years. Proposed mechanisms included premature discontinuation of anti-platelets (11%), under-deployment of previous stent insertion (22%) and underlying prothrombotic conditions (eg, SLE) (6%). Pts with ST compared to native artery occlusion had higher rates of previous MI (53.9% vs 11%, p<0.0001) and incidence of multi-vessel disease (59.8% vs 51.7%, p0.04 There was no difference in age, diabetes or cardiogenic shock. See Abstract 16 table 1. Infarct size based on peak enzyme markers was similar (2.5 vs 2.2, p0.45). In patients with ST, angiographic success (postprocedural Thrombolysis In Myocardial Infarction grade III ow) was worse than in patients with de novo STEMI (87.2% vs 93.7%, p0.02). Pts with STEMI due to ST had higher in-hospital MACE (11% vs 3%, p0.0001), MACE at 30 days (19% vs 6%, p<0.0001), this persisted up to 3 years (41% vs 12%, p<0.0001). See Abstract 16 gure 1. MACE was driven by higher rates of MI (7% vs 2%, p<0.0001), TVR (14% vs 3%, p<0.0001) and death (18% vs 6%, p0.0001). After adjusting for comorbidities, stent thrombosis was an independent predictor of long-term adverse outcome (OR2.1, 95% CI1.3 to 2.8, p<0.001). Conclusion Primary PCI for treatment of ST is less effective, and these patients are at increased risk for in-hospital and long-term mortality compared with patients undergoing primary PCI due to de novo STEMI.
17
SUDDEN CARDIAC DEATH AND ACUTE MYOCARDIAL INFARCTION: HOW HAS THE PICTURE CHANGED?
doi:10.1136/heartjnl-2011-300198.17
G Mole, 2D Watson, 3C Davidson. 1Brighton & Sussex Medical School, Brighton, UK; Deprtment of Informatics, University of Sussex, Brighton, UK; 3Brighton & Sussex University Hospital, Brighton, UK
2
Abstract 16 Table 1
AST (n[180) Age Multi-vessel disease Previous MI Previous CABG Diabetes mellitus Hypertension Hypercholesterolaemia Cardiogenic shock 63.9618 101 (59.76%) 96 (53.93%) 9 (5.06%) 46 (25.84%) 101 (56.74%) 108 (60.67%) 108 (60.67%) No AST (n[2241) 62.964 1011 (51.74%) 246 (10.96%) 60 (2.67%) 407 (18.14%) 975 (43.45%) 768 (34.30%) 768 (34.30%) Signicance (p value) 0.406 0.045 <0.0001 0.020 0.061 0.002 <0.0001 <0.0001
Introduction Coronary heart disease (CHD) is a major burden worldwide, particularly in economically developed countries such as the UK. Between 1980 and 2000, deaths from CHD fell by over 50%, and have continued to fall. The cost of CHD manifests itself in mortality, disability and economic impact: this should be looked at in the context of a disease that is preventable. Methods Data from death certicates and studies with strict clinicopathological criteria on mortality from CHD were accessed. These were analysed in terms of hospital admissions, revascularisation rates and index of multiple deprivation (IMD). Trends in mortality overall and for different age groups were analysed over time to determine how the picture has changed and predict what may happen going into the future. The mortality rates from the catchment area of the Royal Sussex County Hospital and York Hospital were analysed to assess reliability of ofcial gures against strict clinico-pathological inclusion criteria. A range of statistical tests including, linear regression, ANOVA and JoinPoint regression were employed. Results Between 1993 and 2008 deaths from CHD have fallen by over 50%. The decline has been greater in older age groups particularly the 65e74 age group (the oldest age group analysed). Comparison with data from studies with strict clinico-pathological criteria showed this to be the age group in which ofcial statistics were least accurate. Regression analysis demonstrated that a higher IMD is associated with increased mortality from CHD (r20.69, p<0.001). Increased admission rates was not signicantly associated with decreased mortality from CHD (r20.004, p0.239). Increased revascularisation was signicantly associated with decreased mortality from CHD (r20.99, p<0.001). JoinPoint regression analysis shows a constant rate of decline in mortality from 1993 to 2001 which then decreases faster between 2001 and 2006 before
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slowing dramatically from 2006 to 2008. JoinPoint regression analysis of different age groups demonstrates that the slower rate of decline from 2006 may be due to stubbornly high numbers of deaths in the 35e44 age group. Lastly the National gures on mortality from CHD are shown to be misleading as many people are still dying from CHD just when they have crossed the 75-year old exclusion criteria; as a result a delay in mortality is presented as prevention of mortality from CHD. Discussion There is a danger that previous successes are being offset by high rates in the younger cohorts, and that the overall trend may be eventually be reversed. There is still work to be done in reducing risk factors and also applying treatments that have had a proven positive impact (such as revascularisation) more effectively. Statistically signicant changes in declining CHD mortality rates. Future work This 10 000 word report formed the basis of a funding application to the British Heart Foundation for a follow-up to the United Kingdom Heart Attack Study. gure 1. After adjusting for comorbidities, anaemia remained an independent predictor of long-term adverse outcome (OR2.4, 95% CI1.1 to 3.7, p<0.001). Patients with baseline anaemia who received a blood transfusion were signicantly more likely to suffer an adverse outcome than those that did not receive a transfusion (21% vs 6%, p<0.0001).
All cause mortality after PCI for STEMI.
Conclusion Patients presenting with anaemia undergoing primary PCI appear at signicantly higher risk of an adverse outcome. This risk increases further in population receiving RBC transfusions during index hospitalisation.
19
TREATMENT OF MULTIVESSEL CORONARY ARTERY DISEASE IN PRIMARY PCI FOR ST ELEVATION MYOCARDIAL INFARCTION: CULPRIT ONLY REVASCULARISATION IS ASSOCIATED WITH HIGHER MACE RATES
doi:10.1136/heartjnl-2011-300198.19
K S Rathod, L A McGill, E Sammut, V S Rathod, D A Jones, R Weerackody, A Jain, C Knight, A Mathur, A Wragg. London Chest Hospital NHS Trust, London, UK
18
PATIENTS PRESENTING WITH ANAEMIA UNDERGOING PRIMARY PCI APPEAR AT SIGNIFICANTLY HIGHER RISK OF AN ADVERSE OUTCOME
doi:10.1136/heartjnl-2011-300198.18
K R Rathod, D A Jones, B Rathod, A Graham, E Sammut, S Gallagher, J Behar, A K Jain, C Knight, A Mathur, A Wragg, R Amersey. Barts and the London NHS trust, London, UK
Background Previous studies have demonstrated a relationship between pre-existing anaemia and inpatient mortality after percutaneous coronary intervention (PCI). There is limited data looking at the impact of baseline Haemoglobin and long term outcome after primary PCI. Methods Clinical information was analysed from a prospective database on 2357 STEMI patients who underwent Primary PCI between January 2004 and May 2010 at a London centre. Information was entered at the time of procedure and outcome assessed by all-cause mortality information provided by the Ofce of National Statistics via the BCIS/CCAD national audit. Anaemia was dened according to WHO denition of Hb greater than or equal to 12 g/dl for females and 13 g/dl for males. Results 471 (20%) patients were anaemic at presentation. The anaemic cohort, were older (72.2 vs 62.4, p<0.0001), had higher incidence of diabetes (27% vs 15%, p<0.0001), hypertension (42 vs 35%, p0.01), hypercholesterolaemia (40 vs 30%, p0.007), previous PCI (13 vs 7%, p0.01), and previous MI (23% vs 12%, p<0.0001). There were similar incidences of three-vessel disease and cardiogenic shock. Over a 3-year follow-up period there was significantly higher all cause mortality in the anaemic group compared to the normal Hb group (20.4% vs 13.5%, p<0.0001). See Abstract 18
Background Multi-vessel disease occurs in 40%e65% of patients undergoing Primary PCI for STEMI and is associated with adverse prognosis. Contemporary guidelines recommend treating the infarct related artery alone (culprit) during the urgent procedure. There is limited data comparing outcomes of complete with infarct-related artery (IRA)-only revascularisation in primary PCI for STEMI with few studies including the option of later date elective procedures for the other lesions (staged revascularisation). We therefore sought to clarify the outcome of patients with multi-vessel disease undergoing primary PCI dependent on management strategy. Methods Clinical information was analysed from a prospective data base on 2131 STEMI patients who underwent Primary PCI between January 2004 and May 2010 at a London centre. Patients with previous CABG were excluded. Information was entered at the time of procedure and outcome assessed by all-cause mortality information provided by the Ofce of National Statistics via the BCIS/ CCAD national audit. Patients were split into three different treatment groups: culprit vessel angioplasty-only (COR group); staged revascularisation (SR group) and simultaneous treatment of non-IRA (CR group). The primary end point used was major adverse cardiac events (MACE), dened as death, myocardial infarction (MI), stroke and target vessel revascularisation (TVR). Results There were 963 (45%) consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty. There were similar baseline characteristics between the 3 groups, aside from cardiogenic shock, which was signicantly higher in the complete revascularisation group. See Abstract 19 table 1. At 30-days of follow-up, 23/263 (9%) patients in the CR group experienced at least one major adverse cardiac event (MACE), 1 (1%) in the SR group and 35 (5%) in the COR group, p0.01. This trend continued
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up to 1-year of follow-up with the lowest rates of events in the SR group. However after 3 years MACE rates are signicantly increased in the COR group (24%) but were similar in the CR (18%) and SR (17%) groups. See Abstract gure 1. MACE rates were driven mainly by death in the CR with high rates of TVR in the COR and SR groups. See Abstract gure 2.
20
WHAT HAPPENS TO PLATELET FUNCTION AND VASCULAR INFLAMMATION WHEN CLOPIDOGREL IS WITHDRAWN? INSIGHTS USING SHORT THROMBELASTOGRAPHY
doi:10.1136/heartjnl-2011-300198.20
Abstract 19 Table 1
COR N[638 Age Gender (female) Ethnicity (Caucasian) Previous MI Previous CABG Previous PCI Diabetes Mellitus Hypertension Hypercholestrolaemia GPIIb/IIIa Inhibitor Cardiogenic Shock 64.77 156 (23.7%) 441 (67.0%) 109 (16.6%) 15 (2.3%) 83 (12.6%) 129 (19.6%) 312 (48.1%) 269 (41.5%) 572 (87.7%) 29 (4.7%) SR N[100 61.46 13 (13.0%) 79 (79.0%) 11 (11.0%) 2 (2.0%) 5 (5.0%) 16 (16.0%) 40 (40.0%) 37 (37.0%) 93 (93.0%) 2 (2.0%) CR N[263 64.32 74 (27.9%) 185 (69.8%) 36 (13.6%) 3 (1.1%) 23 (8.7%) 55 (20.8%) 91 (41.2%) 92 (41.6%) 231 (89.5%) 31 (12.26%) Signicance 0.144 0.0114 0.0511 0.2414 0.5231 0.031 0.5932 0.1205 0.7751 0.1724 p<0.0001
N Sambu, H Dent, T Warner, N Englyst, P Leadbeater, 1A Hobson, 1A Calver, S Corbett, 1H Gray, 1I Simpson, 1N Curzen. 1Southampton University Hospitals NHS Trust, Southampton, UK; 2University of Southampton, School of Medicine, Southampton, UK; 3The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK
1
Introduction A clustering of adverse events, in particular stent thrombosis (ST) has been observed following clopidogrel cessation 1-year after drug-eluting stenting (DES), the aetiology of which is poorly understood. We investigated the effect of withdrawing clopidogrel in DES patients using a simple, rapid, reproducible nearpatient platelet function test known as short Thrombelastography (s-TEG) that has been developed and validated by this group. Methods 33 patients on aspirin and due to stop clopidogrel at 1 year following DES were investigated. Venesection was performed at (i) 4 weeks and 24 h pre clopidogrel cessation (ii) 24 h, 48 h, 1, 2 and 4 weeks post clopidogrel cessation. At all time-points, platelet reactivity was determined using s-TEG and thromboxane (TX) B2, IL-6, CD40 ligand and high sensitivity CRP were measured. Results Clopidogrel cessation produced (i) a predictable increase in ADP-induced platelet aggregation, and (ii) an unexpected and signicant rise in AA-induced platelet aggregation. TXB2 was consistently suppressed conrming inhibition of COX by aspirin.
Conclusion We have described for the rst time an aspirin-independent increase in AA-induced clotting following clopidogrel withdrawal in DES patients. As well as potentially helping to explain the observed clustering of ST events early after clopidogrel withdrawal, these ndings raise the question as to whether AAinduced clotting is an appropriate test of aspirin sensitivity. Our results also conrm s-TEG as a plausible candidate for near-patient platelet function testing in this eld.
Abstract 19 Figure 1 disease.
Comparison of MACE between multivessel
21
INFLUENCE OF FRACTIONAL FLOW RESERVE MEASUREMENT ON TREATMENT-DECISIONS IN PATIENTS WITH RECENT ACUTE NON-ST ELEVATION MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.21
1 D Carrick, 1M Behan, 1F Foo, 1J Christie, 2J Norrie, 1K Oldroyd, 1C Berry. 1Department of Cardiology, Golden Jubilee National Hospital, Glasgow, UK; 2Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
Breakdown of MACE at 5 years.
Conclusions Culprit vessel-only angioplasty was associated with the highest rate of long-term MACE compared with multivessel treatment. Patients scheduled for staged revascularisation experienced a similar rate of MACE to patients undergoing complete simultaneous treatment of non-IRA.
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Introduction Non-ST elevation acute myocardial infarction (NSTEMI) is the most common form of acute coronary syndrome and has a relatively poor prognosis. Visual interpretation of the coronary angiogram is the standard approach to guide treatment decisions in patients with recent acute NSTEMI. The aim of our study was to determine whether measurement of coronary pressure derived fractional ow reserve (FFR), compared to coronary angiography alone, might inuence treatment decisions.
BCS Abstracts 2011

Setting The cardiac catheterisation laboratory in a regional heart centre in the UK. Denitions The clinical indication for FFR measurement was the presence of an intermediate coronary stenosis (50%e75% of the reference vessel diameter) which resulted in diagnostic and treatment uncertainty. FFR measurement was used to provide functional information on lesion severity and an FFR <0.80 was taken to represent a ow-limiting stenosis. Methods The study involved three accredited interventional cardiologists and a study coordinator. The cardiologists separately reviewed the coronary angiograms and together with the clinical history, made a decision for medical therapy, PCI, CABG/MDT, or deferred management. The FFR results were then disclosed and the initial management decision was reviewed in light of the FFR result and changed as appropriate. Results Of 1621 acute NSTEMI patients (January 2009eMarch 2010) in our hospital, 100 (6.2%) had FFR recorded. The treatment decisions for each cardiologist were: medical therapy 7%, 10%, 1%; PCI 64%, 70%, 60%; CABG/MDT 13%, 12%, 15%; deferred management 16%, 8%, 24%). The proportion of patients allocated to each treatment group differed between the 2nd and 3rd Cardiologist (p0.02). Following FFR disclosure, each cardiologist changed his/her treatment decision in 58%, 50% and 62% of patients (p<0.05). Of the new decisions made following FFR disclosure, the proportion of patients allocated to medical therapy increased by 26%, 19% and 29%, whereas the proportion of patients allocated to deferred management or multivessel PCI decreased by 16%, 8%, 24% and by 5%, 7% and 5%, respectively (all p<0.05). The number of patients in whom the treatment decisions made by each cardiologist independently conformed (and so represented a consensus in at least 2 of the 3 decisions) increased from 74% to 92% as a result of FFR disclosure (p<0.001). Conclusion In our hospital about 1 in 20 NSTEMI had a coronary pressure wire study because of diagnostic uncertainty based on coronary angiography alone. In NSTEMI patients selected for FFR measurement, the FFR resulted in a change in management in at least half of the patients. FFR use increased the proportion of patients in whom treatment decisions conformed suggesting FFR use may also help to reduce the variation in treatment decisions using angiography alone. These results support further studies of the clinical utility and prognostic implications of FFR measurement in patients with NSTEMI. Methods We studied 94 patients with ACS admitted to a single UK Teaching Hospital for PCI. We used the Randox Cardiac-Array to measure H-FABP at 4 hrs after PCI and troponin I at 12 h after PCI. Comparison of specicity and sensitivity of each biomarker for adverse cardiac events was made. Endpoint assessment consisted of one of the following three events (i) PC-induced MI (ii) readmission with MI by 6 months (iii) death by 6 months. Results The area under the receiver operator curve was 0.73 for H-FABP measured at 4 h as compared to 0.72 for TnI measured as 12 h. Conclusion Early assessment of PCI-induced myocardial injury using the Randox Cardiac-Array to measure H-FABP is as sensitive and specic for adverse prognosis as is TnI measurement taken at 12 h post PCI. This approach should help to expedite early, safe hospital discharge following PCI.
23
SERUM NGAL IDENTIFIES CONTRAST NEPHROPATHY EARLY IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE UNDERGOING CORONARY ANGIOGRAPHY AND ANGIOPLASTY
doi:10.1136/heartjnl-2011-300198.23
22
COMPARISON OF 4-H HEART FATTY ACID BINDING PROTEIN WITH 12-H TROPONIN I TO ASSESS 6-MONTH RISK FOLLOWING PERCUTANEOUS CORONARY INTERVENTION IN ACUTE CORONARY SYNDROMES
doi:10.1136/heartjnl-2011-300198.22
A C Qureshi, R Rampat, S M Harwood, M Roughton, 2M M Yaqoob, 1A Kapur. The London Chest Hospital, Barts and The London NHS Trust, London, UK; 2The Royal London Hospital, Barts and The London NHS Trust, London, UK; 3The William Harvey Research Institute, London, UK; 4The Royal College of Physicians, London, UK
1
I R Pearson, U M Sivananthan, J H Barth, C P Gale, 1A S Hall. 1Leeds Teaching Hospitals, Leeds, UK; 2Division of Biostatistics, University of Leeds, Leeds, UK
Background It is known that PCI can cause myocardial injury leading to the release of cardiac biomarkers into the circulation (procedural MI). This occurs in approximately one third of procedures and has been shown to impact negatively on prognosis. Monitoring for procedural MI, although not yet standard practice, is increasingly undertaken as a measure of quality control, and may be a factor when deciding time of discharge from hospital following the procedure. The use of TnI to screen for procedural MI requires a wait of 12-h post procedure before the blood sample may be taken, and an impact on length of hospital stay is inevitable. Heart-type Fatty Acid Binding Protein (H-FABP) is a small protein released rapidly and in large quantities from the myocardium into the circulation, both during ischaemia and following necrosis. It allows detection of myocardial injury associated with PCI earlier than with TnI. Hypothesis H-FABP at 4 h provides equivalent prognostic information to TnI at 12 h following PCI-induced myocardial injury.
Background The incidence of contrast nephropathy (CIN) following coronary angiography or percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) may be up to 30% and is associated with increased long term morbidity and mortality. Methods We recruited 208 consecutive patients undergoing elective or urgent coronary angiography or PCI with known DM and chronic kidney disease (CKD) (dened as eGFR <60 ml/min). CIN was dened as a post procedure rise in creatinine at day 3 of >25% from baseline or an absolute rise of 44.5 mmol/l. Severity of coronary disease was assessed using the SYNTAX Score and risk of CIN using the Mehran risk score. We evaluated serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and albuminuria for additional information about CIN risk. N-acetylcysteine and intravenous hydration were given to all patients with eGFR <50 ml in accordance with local guidelines. Results Baseline characteristics are summarised in table 1. 116 patients underwent coronary angiography and 92 underwent PCI. 39 patients (18.8%) developed CIN. Contrast dose was similar in the CIN and non-CIN group (p0.249). The Mehran risk score was strongly
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predictive of CIN development (p<0.001). The SYNTAX score did not differ between those who did or did not develop CIN (p0.188). A signicant rise in serum NGAL was seen as early as 2 h post procedure in the CIN arm (p0.03) and this persisted at 4 h (p0.007) and 12e24 h (p0.0015). Urine NGAL levels did not change signicantly during the rst 24 h. Neither albumin:creatinine ratio (p0.149) or protein:creatinine ratio (p0.635) predicted development of CIN. follow-up to date, 10 patients (59%) had a reduction in MR to # grade 2+ and 8 patients (47%) had $2 grade reduction in MR (p0.001). The reduction in MR grade remained signicant for the 8 patients with echo data at 6-month follow-up (p0.038). One patient had persistent grade 3+ MR at 1-month follow-up due to late partial detachment of one of the 2 clips deployed. NYHA class reduced signicantly following intervention. Prior to Mitraclip, 63% of patients were in NYHA class III/IV. At 1-month follow-up postMitraclip only one patient (4%) was in NYHA class III (p0.042) and 15 patients (83%) had at least 1 grade reduction in NYHA class. There was no signicant change in left ventricular size following intervention, although there was a trend towards reduced left ventricular volumes at 1-month follow-up (end diastolic volume 175 vs 160 ml, p0.102; end systolic volume 92 vs 79 ml, p0.076). Conclusion In selected patients Mitraclip edge-to-edge repair successfully reduces the severity of mitral regurgitation and improves symptoms. Further studies are needed to examine whether these results are durable and associated with improved outcome.
Abstract 23 Table 1
No CIN outcome (n[169) Age, (mean, SD) Hypertension (%) Hyperlipidaemia (%) Previous MI (%) Ex or current smoker (%) Heart failure (%) Valvular heart disease (%) Family history IHD (%) BMI, (mean, SD) 70.8 (8.5) 155 (91.7) 165 (97.6) 66 (39.1) 96 (55.9) 32 (19.1) 28 (16.6) 84 (49.7) 28.6 (5.4) CIN outcome (n[39) 71.5 (9.5) 33 (86.8) 37 (97.4) 15 (39.5) 19 (50.0) 7 (18.4) 7 (18.4) 20 (52.6) 29.2 (6.1) p Value 0.64 0.35 0.92 0.96 0.75 0.93 0.78 0.74 0.54
Conclusions The current gold standard for measuring CIN is a rise in serum creatinine but this is of limited value as it does not increase until 48e72 h post renal injury. Neither the SYNTAX score, nor urinary albuminuria or proteinuria are predictive of CIN development. A rise in serum NGAL levels within the rst 12 h following coronary angiography or PCI appears to be a very promising marker in the early diagnosis of CIN.
24
PERCUTANEOUS MITRAL VALVE REPAIR WITH THE MITRACLIP DEVICE: A TERTIARY CARDIAC UK EXPERIENCE
doi:10.1136/heartjnl-2011-300198.24
J Dungu, C S R Baker, M F Bellamy. Hammersmith Hospital, Imperial College London, London, UK
Introduction Percutaneous mitral valve repair using the transcatheter Mitraclip device is a novel therapy for patients with severe mitral regurgitation (MR) who are too high risk for conventional surgery. We report the largest UK series to date. Methods Patients were screened with transthoracic (TTE) and transoesophageal echocardiography (TOE). Mitral regurgitation was graded by British Society of Echocardiography criteria. Twenty-four patients with $ grade 3+ symptomatic MR underwent percutaneous mitral valve repair under general anaesthesia between February 2009 and October 2010. The Mitraclip device was deployed under 2- and 3-Dimensional TOE and uoroscopic guidance. All patients were discussed with the manufacturing company (Evalve) and in a multidisciplinary meeting including >2 cardiologists and 2 cardiothoracic surgeons with a special interest in mitral valve surgery prior to being accepted. Results Mitraclip therapy was attempted in 24 patients aged 71611 years with an average Euroscore of 16%. The indication for intervention was functional MR in 10 patients (42%), ischaemic MR in 7 patients (29%) and degenerative MR in 7 patients (29%). Twenty patients had successful deployment of the Mitraclip device (83%). Fifteen patients (75%) had 2 clips deployed. There were no vascular complications or strokes. We were unable to grasp the mitral valve leaets in 2 patients due to an excessive coaptation gap. There was 1 procedural death due to leaet tear in a patient with end-stage ischaemic cardiomyopathy and a grossly dilated left ventricle. All patients (100%) treated with the Mitraclip had severe MR (grade 3 +/4+) prior to intervention. Mitral regurgitation was graded by colour Doppler alone following intervention as standard quantitative analyses are not validated in the presence of a Mitraclip. At 1-month
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Abstract Figure 1
Change in MR grade post-Mitraclip.
Abstract Figure 2
Change in NYHA class post-Mitraclip.

BCS Abstracts 2011

25
TAVI OPERATOR RADIATION DOSE COMPARED TO PCI AND ICD OPERATORS: DO WE NEED ADDITIONAL RADIATION PROTECTION FOR TRANS-CATHETER STRUCTURAL HEART INTERVENTIONS
doi:10.1136/heartjnl-2011-300198.25 M Drury-Smith, A Maher, C Douglas-Hill, R Singh, M Bhabra, J Cotton, S Khogali. Heart and Lung Centre, New Cross Hospital, Wolverhampton, UK
1 1
26
THE EFFECTS OF PRE-EXISTING SIGNIFICANT CORONARY ARTERY DISEASE UPON OUTCOME AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION USING THE EDWARDS BIOPROSTHESIS
doi:10.1136/heartjnl-2011-300198.26
M Z Khawaja, 2H Haran, 1I Nadra, 1K Wilson, 1L Clack, 1K Macgillivray, 1J Hancock, C Young, 1V Bapat, 1M Thomas, 1S Redwood. 1Guys & St. Thomas Hospitals NHS Foundation Trust, London, UK; 2Kings College School Of Medicine & Dentristry, London, UK
Introduction Trans-catheter cardiac aortic valve implantation (TAVI), implantable cardiac debrillators (ICD), and percutaneous coronary intervention (PCI), are common procedures associated with radiation exposure to the operator and the patient. Radiation dose exposure is cumulative and if above the recommended annual levels may have signicant consequences for the operator. The radiation dose TAVI operators are exposed to is not widely known, but it is an important consideration in view of the increasing volume of procedures and the potential risks of over-exposure. Our aim was to monitor and compare, radiation exposure time, dose, and individual operator dose, in TAVI, PCI and ICD. Method Ten TAVIs were performed, 6 via the trans-femoral route and 4 via the subclavian approach. Radiation protection was employed in all cases using standard lead skirts and screens. During each procedure the radiation dose exposure was monitored for each operator using ThermoLuscent Dosemeters (TLD) on the left nger (LF), right nger (RF) and forehead. The six TAVI procedures performed via the transfemoral approach used only two operators, while the subclavian approach involved three operators. The third operator was a surgeon who was nearest to the x-ray images. Radiation exposure doses were also collected from ICD and PCI operators during the same period, using the same type of TLDs on LF and RF. Operator specic radiation doses were obtained from a central RRPPS Approved Dosimetry Service. PCI was considered a standard trans-catheter procedure. TAVI and ICD operator doses were compared to the mean standardised PCI operator dose. Results The mean exposure times and doses for the different types of trans-catheter procedures performed are detailed in the tables below. Despite the use of standard radiation protection measures, the mean dose to operators undertaking TAVI was 6 times higher than the trans-femoral PCI operator (p0.008). The mean radiation exposure time of TAVI was seven times more than PCI. Although subclavian TAVI and ICD procedures were expected to be comparable with respect to operator dose, subclavian TAVI operators have an unexpectedly higher dose (p0.03). Conclusions Overall TAVI operators are exposed to signicantly higher radiation doses compared to PCI and ICD operators. Additional radiation protection for TAVI operators is strongly advocated. We are currently evaluating the impact of using a RADPAD as additional protection during TAVI procedures.
Introduction Patients undergoing surgical aortic valve replacement (sAVR) routinely undergo simultaneous coronary artery bypass grafting (CABG) for signicant coronary artery disease (CAD) due to adverse prognostic impact. While manufacturers advise percutaneous intervention (PCI) of signicant CAD prior to transcatheter aortic valve implantation (TAVI) there is considerable variation among operators. Methods We performed a retrospective analysis of 168 patients who underwent TAVI using the Edwards bioprosthesis from March 2008 to October 2010 at St. Thomas Hospital, London. They were divided into two groups according to the results of the pre-TAVI coronary angiogram: (Group 1) patients with $1 coronary stenosis of $70% severity and those without (Group 2). The end-point was all-cause mortality. Results In total, 70 patients (41.7%) had signicant CAD prior to TAVI, with 10 (6.0%) undergoing PCI prior to their procedure. There were no signicant differences in either the baseline characteristics or access approach between the two groups (Abstract 26 tables 1 and 2). At a mean follow-up of 3356277 days (mean6SD), the overall mortality was 22.6%; Group 1 mortality was 30% and in group 2 was 17.3% (p0.124) (see Abstract 26 gure 1) There was no difference seen in the length of stay in the intensive care unit (2.766.2 vs 4.1614.9 days, p0.462) nor in the number of days to discharge (12.6610.1 vs 12.8613, p0.928). Among those patients who underwent PCI in Group 1, 8 had single vessel intervention and 2 had PCI to 2 vessels. The target vessels were left main stem (LMS) (n2), proximal left anterior descending artery (LAD) (n5), circumex (n1), right coronary artery (RCA) (n2), saphenous vein graft (SVG) to LAD (n1) and SVG to circumex (n1). Mortality in this sub-group was not signicantly different from the CAD patients who did not receive PCI (50% vs 26.7%, p0.272).
Abstract 26 Table 1
Group 1 Signicant CAD (n[70) Age (years6SD) Diabetes Mellitus Cerebrovascular disease Peripheral vascular disease Glomerular ltration rate 83.767.5 16 (22.9) 11 (15.7%) 15 (21.4%) 48.4627.9 23.5612.9 48.8611.3 0.6360.20 18 (25.7%) 16 (22.9%) Group 2 No signicant CAD (n[98) 81.768.5 27 (27.6%) 17 (17.3%) 12 (12.2%) 46.8623.1 21.5616.2 47.9612.4 0.6760.22 27 (27.6%) 12 (12.2%) p Value 0.112 0.492 0.780 0.110 0.685 0.399 0.658 0.219 0.791 0.070
Abstract 25 Table 1
Variable Mean exposure Time (mins) Mean exposure Dose (Gy/cmq) 6 SD TAVI 27.0* 196.256150.96y ICD 3.26 11.0369.01 PCI 3.825 33.09611.5 p Value <0.001* 0.008y
Logistic Euroscore (%6SD) LV ejection fraction (%6SD) Aortic valve area (cm26SD) Previous CABG Previous PCI
*Signicantly increased radiation exposure time in TAVI procedures compared to ICD and PCI. ySignicantly increased radiation exposure dose in TAVI procedures compared to ICD and PCI.
Abstract 25 Table 2
Mean radiation dose (Gy/cmq) per operator Trans-femoral TAVI Subclavian TAVI ICD PCI 1.67 2.53 1.95 0.18 SD 1.23 3.09 0.14 p value
Abstract 26 Table 2
Group 1 Signicant CAD (n[70) Transfemoral 44 (44.9%) 47 (48.0%) 7 (7.1%) Group 2 No signicant CAD (n[98) 29 (41.4%) 37 (52.9%) 4 (5.7%) p value 0.778
0.03 0.03 0.03 0.36
Transapical Transaortic
Conclusion The presence of signicant CAD had no signicant impact upon the all-cause mortality of patients after TAVI in our
Heart June 2011 Vol 97 Suppl 1 A19
BCS Abstracts 2011

Results As expected CwP was higher in patients with NSTEMI (46.5 (SD) 18.8) compared with the stable angina patients (Mean (SD) 21.1 (9.3) p0.01). IMR was also higher in patients with NSTEMI (Mean (SD) 27.6 (12.6)) compared with patients with stable angina (Mean (SD) 20.7 (5.4) p0.2). Total PMAs were nonsignicantly higher in patients with NSTEMI (Mean (SD) 14 (4.8)) compared with stable angina (Mean (SD) 10.9 (4.3) p0.07). CD62+ PMAs were signicantly higher in patients with NSTEMI (Mean (SD) 26.9 (12.2)) compared with stable angina (Mean (SD) 13.7 (5.1) p0.02) Abstract 27 gure 1. CwP correlated positively with total PMA (p0.01) in NSTEMI but not in stable angina patients. However, IMR correlated positively with total PMAs in both stable angina (p0.02) and NSTEMI (p0.08) Abstract 27 gure 2.
study. As yet, the impact of PCI to signicant CAD upon outcome after TAVI is not known and will be assessed in a prospective, randomised controlled trial currently underway.
27
PLATELET MONOCYTE AGGREGATES ARE DETERMINANTS OF MICROVASCULAR DYSFUNCTION DURING PERCUTANEOUS CORONARY INTERVENTION FOR STABLE ANGINA AND NON-ST SEGMENT ELEVATION MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.27
C A Mavroudis, B Majumder, M Lowdell, R D Rakhit. 1Cardiology Department, Royal Free Hospital, London, UK; 2Haematology Department, Royal Free Hospital, London, UK
Background Microvascular dysfunction is associated with adverse outcome in patients with acute coronary syndrome (ACS). During ACS platelet and monocyte derived chemokines, in conjunction with adhesion molecule expression, promote the inammatory process. Activated platelets express p-selectin which binds to the pselectin glycoprotein ligand on the monocyte forming platelet monocyte aggregates (PMA). PMA expression is a sensitive marker of platelet activation and inammation. Although platelet monocyte interaction is a normal physiological process, in the presence of platelet activation, activated (CD62+ PMA) may be directly involved in the pathophysiology of intracoronary inammation and microvascular dysfunction in ACS. Aim To investigate the relationship between microvascular dysfunction and PMA expression in patients with stable angina and non-ST elevation myocardial infarction (NSTEMI). Methods Six patients with stable angina undergoing elective PCI and six patients with NSTEMI undergoing non-elective PCI were recruited. Microvascular dysfunction was assessed by measuring the coronary wedge pressure (CwP) and the index of Microvascular resistance (IMR) using a single pressure-temperature sensor-tipped coronary wire from the simultaneous measurement of distal coronary pressure and thermodilution derived mean transit time (Tmn) of a bolus of saline injected at room temperature into the coronary artery during maximum hyperaemia. Blood samples were taken from the coronary artery (distal to the culprit lesion), aorta and the right atrium for PMA estimation. PMAs were assessed using uorescent monoclonal antibodies and ow cytometry. Total PMAs were calculated and expressed as a percentage of the total monocyte count. Activated CD62+ PMAs were expressed as a percentage of total PMAs.
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Conclusions PMAs are elevated in stable coronary disease and ACS with elevated activated CD62+ PMA a hallmark of ACS. PMAs correlate with measured microvascular dysfunction during PCI in stable angina and NSTEMI. This study supports the hypothesis that PMA formation may be important determinants of platelet activation, inammation and microvascular dysfunction in coronary disease.
28
LOW FRAME RATE SCREENING DURING PERCUTANEOUS CORONARY ANGIOPLASTY SIGNIFICANTLY REDUCES RADIATION EXPOSURE, GIVES GOOD IMAGE QUALITY WITHOUT AFFECTING PATIENT OUTCOME
doi:10.1136/heartjnl-2011-300198.28
S J Wilson, P Venables, O Gosling, V Suresh. 1South West Cardiothoracic Centre, Plymouth, UK; 2Royal Devon and Exeter Hospital, Exeter, UK
Introduction Minimisation of radiation exposure during cardiac procedures is required by statute (IRMER 2000). During coronary angioplasty 47% of radiation dose is related to screening at standard
BCS Abstracts 2011

Abstract 28 Table 1
Screening DAP (mGycm2) Standard (15 fps) Low (7.5 fps) Mean DAP reduction Signicance 28564.5 19248.5 33% p<0.01 Total DAP (mGycm2) 60746.9 50953.4 16% n/s Fluoro time (seconds) 770 800 e n/s Number of acquisitions 26.7 26.8 e n/s
frame rate (15 frames per second). Digital uoroscopic technology has improved imaging making the use of lower frame rates feasible. This study assessed whether low frame rate screening (7.5 frames per second) reduced radiation without affecting patient outcomes. Method We prospectively collected data from consecutive coronary angioplasty procedures performed at reduced screening frame rate (7.5 frames per second). We included elective, urgent and emergency procedures. Audit data from procedures performed at standard frame rate with the same inclusion criteria were used as a control group. Phillips Allura at plate XPER FD10 catheterisation equipment was used. The frame rate could be increased at the operators request, and any safety concerns were reported immediately. Data collection Patient data:
times and number of acquisition runs were similar in each group. In every case image quality was acceptable, with no requirement for increased screening frame rate. No safety concerns were reported. 30-day incidence of major adverse cardiovascular events (MACE) was similar in both groups. In the screening group there was 1 MACE event at 30 days (2%), with 2 MACE events (2%) in the control group. Screening and Total DAPs (mean mGycm2) were 33% and 16% lower respectively in the low frame rate group. Statistical comparison was made with the Man-Whitney U-test. This showed a signicant reduction in the Screening DAP (p#0.01) with low frame rate screening. See Abstract 28 table 1 and graph. Conclusions Low frame rate screening is a practical way of reducing radiation exposure in line with the ALARA As Low As Reasonably Acheivable principle. Having shown that low frame rate screening for coronary angiography gives good imaging quality and is safe, we now demonstrate that low frame rate screening coronary angioplasty is also safe. Radiation exposure from screening is signicantly reduced by 33% and total exposure is reduced by 16%. Low frame rate screening should be standard practice where modern facilities allow. We suggest that centres currently using 15 frames per second screening should undertake a similar assessment in order to minimise radiation.
< Age < Weight (Kg) < Height (cm)

Radiation data:
29
< < < <
Screening DAP (mGycm2) Total DAP (mGycm2) Total Fluoroscopy time (mm:ss) Number of acquisition runs
Operator outcome:
BIVALIRUDIN IN PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE ST-ELEVATION MYOCARDIAL INFARCTION: OUTCOMES IN A LARGE REAL-WORLD UK POPULATION
doi:10.1136/heartjnl-2011-300198.29
1 1
< Need to increase screening frame rate

Patient outcome:
C Eftychiou, 1R J Shelton, 1A Liu, 1K Somers, 1P Tooze, 2L Makri, 1D Barmby, J M McLenachan, 1J M Blaxill, 1S B Wheatcroft, 1J P Greenwood, 1D J Blackman. 1 Leeds General Inrmary, Leeds, UK; 2Statistical service of Cyprus, Nicosia, Cyprus
< 30 day incidence of major adverse cardiovascular event (MACE): death, non-fatal myocardial infarction or need for urgent revascularisation.
Results 55 consecutive studies were examined at low-frame rate and compared with the audit control group (n105). Mean age was 67 in the low screening rate group and 65 in the control group. Weight was similar in both groups (83 kg vs 82 kg). The screening
Background The HORIZONS-AMI trial demonstrated a signicantly lower early and late mortality in patients undergoing primary PCI (PPCI) treated with bivalirudin compared to a Glycoprotein IIb/ IIIa inhibitor (GPI) + heparin. However, concerns remain regarding the increased incidence of acute stent thrombosis (ST) with bivalirudin, the apparently worse outcomes in the absence of additional pre-procedural heparin, and the translation of trial results into a real-world population. We evaluated the outcomes of patients undergoing PPCI with bivalirudin in a large all-comers UK setting. Methods All patients who underwent PPCI in Leeds General Inrmary from 1 January 2009 to 31 December 2009 were prospectively entered into a dedicated registry. Demographic, procedural, and 30day outcome data were obtained by abstraction from the ONS mortality database and BCIS PCI database, review of hospital notes, and telephone follow-up. Bivalirudin was administered as a bolus, high-dose intra-procedural infusion, and low-dose infusion for 4 h post-PCI. Additional heparin was not routinely given, but was favoured by some operators. Bail-out GPI was administered according to physician judgement. Primary endpoints were death, MACE (death, re-infarction, stroke, unplanned target vessel revascularisation (TVR)), and stent thrombosis (ST) (ARC denition denite/probable) at 30-days follow-up. Results 968 patients (age 63.5613 years, 71.9% male, 13.2% diabetics) underwent PPCI. Bivalirudin was given in 882 patients (91.1%), and GPI + heparin in 85 (8.8%). Of bivalirudin-treated patients 100 (11.3%) also received heparin (29 pre-PCI and 80 during) while bail-out GPI was used in 91 (10.3%). Thirty-day outcomes are shown in Abstract 29 table 1. All-cause mortality was 5.2% in the bivalirudin treated patients. Acute SToccurred in 1.0%, a median of 2 h post-PCI, and within 6 h in 90%. Mortality in
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BCS Abstracts 2011

patients who suffered acute ST was 20%, compared to 80% following subacute ST. There was no difference in outcomes between bivalirudin treated patients who also received heparin compared to those who didn9 t (death 7.0% vs 5.0%, p value: 0.80; MACE 14.0% vs 10.8%, p value: 0.32; acute ST 0% vs 1.2%, p: 0.61). p1.0 respectively). Even though the bleeding risk was higher in the abciximab group when compared with bivalirudin, this was not signicant (5.8% vs 3.1%, p0.27). There was also no difference in the outcomes between the bivalirudin and UFH only groups for mortality, stent thromboses (acute and 30-day) and major bleeding. The abciximab group had signicantly higher major bleeding rates than the UFH only group (5.8% vs 2.4%, p0.04); all other outcomes were similar.
Abstract 29 Table 1
Outcomes at 30 days
All patients Bivalirudin GPI + heparin p value 85 6 (7.1%) 6 (7.1%) 2 (2.4%) 2 (2.4%) 2 (2.4%)
No. of patients Death Cardiac death Re-infarction Unplanned TVR Stroke
968 52 (5.4%) 45 (4.7%) 16 (1.7%) 12 (1.2%) 56 (5.8%)
882 46 (5.2%) 39 (4.4%) 14 (1.6%) 10 (1.1%) 54 (6.1%)
Abstract 30 Table 1
0.450 0.277 0.645 0.286 0.222 0.906 0.604 0.386 Age in yrs (range) Male (%) Diabetes (%) Pre-procedure cardiogenic shock (%) Drug eluting stent (at least one) (%) No of stents Single vessel PCI (%) Three vessel PCI (%) Radial procedure (%) Abciximab + UFH (n[346) 64614.1 (25e99) 77.7 12.4 7.8 56.1 1.460.9 91.3 1.4 28 Bivalirudin + UFH (n[162) 65613.0 (31e94) 72.2 6.2 6.2 56.8 1.460.8 87 1.9 26.5 UFH only (n[253) 67613.2 (30e96) 66.8 11.5 4.7 53.8 1.460.9 89.3 2 31.2
Death, re-infarction, stroke or TVR 110 (11.4%) 100 (11.3%) 10 (11.8%) Acute stent thrombosis 10 (1.0%) 9 (1.0%) 1 (1.2%) Subacute stent thrombosis 15 (1.6%) 13 (1.5%) 2 (2.4%)
Conclusion Routine use of bivalirudin in a large UK all-comers primary PCI population was associated with excellent 30-day outcomes, including all-cause and cardiac mortality. Acute stent thrombosis was infrequent, despite the absence of routine additional heparin.
Abstract 30 Table 2
30
COMPARISON OF BIVALIRUDIN VS ABCIXIMAB VS UNFRACTIONATED HEPARIN ONLY FOR PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN A HIGHVOLUME CENTRE
doi:10.1136/heartjnl-2011-300198.30
% In-hospital Mortality (including cardiogenic shock) 30 day Mortality (including cardiogenic shock) 30 day Mortality (excluding cardiogenic shock) Stent Thrombosis (within 30 days) Acute stent Thrombosis (24 h) # Major bleed requiring blood transfusion (non CABG related) Access related bleed requiring transfusion (includes IABP related)
Abciximab + UFH (n[346) 3.8 5.2 3.5 0.9 0 5.8 3.8
Bivalirudin + UFH (n[162) 5.6 6.8 4.9 0.6 0.6 3.1 1.9
UFH only (n[253) 5.1 7.1 5.5 1.2 0.4 2.4 1.2
R Showkathali, J Davies, N Malik, W Taggu, J Sayer, R Aggarwal, P Kelly. The Essex Cardiothoracic Centre, Basildon, UK
Introduction Primary percutaneous coronary intervention (PPCI) has been established as a standard therapy for ST elevation myocardial infarction (STEMI). In addition to thrombectomy and unfractionated heparin (UFH), thrombus burden in STEMI may require use of more potent antithrombotic agents. Bivalirudin is shown to be superior to abciximab in reducing the net adverse clinical events and major bleeding in STEMI in the HORIZONS-AMI trial (Stone et al NEJM, 2008). We aimed to carry out a real world comparison of different anti-thrombotic regimes in patients undergoing PPCI in our unit. Methods Our PPCI service started in September 2009 and we included all patients undergoing PPCI between September 2009 and September 2010. Prospectively entered data were obtained from our dedicated cardiac service database system (Philips CVIS). Mortality data were obtained from the summary care record (SCR) database. We used Fisher9 s exact test to compare clinical outcomes between the groups. Results Of the 998 patients admitted with suspected STEMI to our unit during the study period, 776 (77.8%) underwent PPCI. After excluding patients who had both bivalirudin and abciximab during their procedure (n15), we divided the others (n761) into 3 groups according to the anti-thrombotic regime used (Grp 1- Abciximab +UFH, Grp 2- Bivairudin+UFH and Grp 3- UFH only). Patient demographics and procedural information are given in Abstract 30 table 1. Continuous data are presented as mean6 SD. Clinical outcomes are shown in Abstract 30 table 2. In-hospital and 30-day mortality did not differ between patients who had bivalirudin vs abciximab (5.6% vs 3.8%, p0.35 and 6.8% vs 5.2% p0.53 respectively). Both acute and 30 day stent thrombosis rates were also similar in the two groups (0.6% vs none, p0.3, 0.6% vs 0.9%,
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Conclusion These real-world data do not show any signicant difference in the clinical outcome for patients who had bivalirudin or abciximab. There was no advantage seen with the more expensive agent (abciximab) in keeping with previous trial data. Therefore bivalirudin should be considered as a non-inferior alternative to abciximab. This would have considerable economic benets in the present situation. The UFH only group had similar outcomes to both bivalirudin and abciximab, which suggests that this may be a viable alternative in its own right. However, our study is clearly limited by not being randomised and those patients treated with UFH alone may have been a lower risk group.
31
ASSESSMENT OF LEFT VENTRICULAR FUNCTION WITH CARDIAC MRI AFTER PERCUTANEOUS CORONARY INTERVENTION FOR CHRONIC TOTAL OCCLUSION
doi:10.1136/heartjnl-2011-300198.31
1 G A Paul, 2K Connelly, 1A J Dick, 1B H Strauss, 3G A Wright. 1Sunnybrook Health Sciences Centre, Toronto, Ontorio, Canada; 2St Michaels Hospital, Toronto, Ontorio, Canada; 3University of Toronto, Toronto, Ontorio, Canada
Objective To assess the role of CMR in the treatment of true chronic total occlusions (CTO) with percutaneous coronary intervention (PCI) and drug eluting stent implantation.
BCS Abstracts 2011

Introduction Successful PCI for CTO may confer an improved prognosis and a reduction in major adverse cardiac events (MACE). However most trials have included occlusions of short duration (less than 4 weeks). In this study we assessed the impact of PCI on LV function in patients with true CTOs (TIMI ow grade 0 and greater than 12 weeks duration) using serial CMR imaging as well as the predictive value of late gadolinium enhancement when performed prior to revascularisation. Methods Thirty patients referred for PCI to a single vessel CTO underwent CMR examination prior to and 6 months after PCI. Technical success was dened as recanalisation of the occluded vessel and DES implantation with a nal residual diameter stenosis <30%. LV function and infarct size were assessed using a 1.5T GE MRI system. Segmental wall thickening (SWT) was measured within the perfusion territory of the CTO using the 16-segment model and segments were dysfunctional if the SWT was #45%. The transmural extent of infarction (TEI) was calculated by dividing the hyperenhanced area by the total area3100; a score of #25% were considered viable. Results Technical success was achieved in 19 of the 30 patients (63%). CTO duration was greater in patients with failed revascularisation but other baseline demographics were well matched between groups (Abstract 31 table 1). PCI-CTO success resulted in a signicant increase in LVEF when compared to both baseline (50 6 13 vs 54 6 11; p<0.01) and with PCI-CTO failure (11.8 6 19.8 vs -2.3 6 5.1, p<0.01, Abstract 31 gure 1). In dysfunctional but viable segments only PCI success conferred a signicant improvement in SWT compared to baseline (26 6 6 vs 40 6 10; p<0.001, Abstract 31 gure 2). There were no episodes of MACE in either group at 21 months follow-up.
Conclusion PCI-CTO success of true CTOs can improve global LV function. The TEI, assessed with CMR, can be used to help predict improvements in regional wall function. PCI-CTO failure was not associated with increased MACE at medium-term follow-up.
32
Abstract 31 Table 1
Total (n[30) Age/ years Male, n (%) CCS Anginal Class LVEF/ % CTO duration, months Vessel, n (%) RCA LAD LCx Prior MI, n (%) Diabetes Mellitus, n (%) Hypertension 62.2610.2 25 (83) 2.1360.68 53.0611.6 36.9670.8 16 (53) 11 (37) 3 (10) 17 (59) 7 (23) 23 (77) CTO-PCI Success (n[19) 62.469.8 14 (74) 2.2160.63 50.3612.6 12.6626.4 9 (47) 7 (37) 3 (16) 11 (58) 5 (26) 14 (74) CTO-PCI Failure (n[11) 61.8611.4 11 (100) 2.060.77 57.668.1 78.86101.1 7 (64) 4 (36) 0 6 (56) 2 (18) 9 (82) 0.61 0.61 0.61 p value 0.89 0.13 0.42 0.09 0.01 0.35
DOES COMPLETE REVASCULARISATION CONFERS A LONG TERM SURVIVAL BENEFIT IN PATIENTS WITH CHRONICALLY OCCLUDED CORONARY VESSELS?
doi:10.1136/heartjnl-2011-300198.32
N H Shah, M F Khan, T Ungvari, P H Loh, L Buchanan, A Hoye, R M Oliver, S Thackray, J L Caplin, M F Alamgir. Castle Hill Hospital, Kingston upon Hull, UK
Introduction Chronic total occlusion (CTO) of coronary vessels is a relatively common nding on diagnostic angiography. There has been increasing interest in this clinically important area with development of technologies resulting in improved recanalisation rates. However, long term survival data in this cohort is lacking. In this study we looked at survival of patients in whom complete, successful revascularisation was achieved. Methods We identied consecutive patients, found to have CTO of at least one vessel of more than 1-month duration, on angiography performed between January 1999 and August 2000 in a single tertiary centre. We used a dedicated database to record data on variables and used central National Health Service database to obtain survival data. Results were analysed using SPSS statistics version 17. Results We included 331 patients in the analysis. Mean age was 56.8 619.8 years, 76.1% were male and 21.8% (n71) were diabetic. Mean duration of CTO was 29.5625.9 months and was only reliably estimated in 82.5% of cases. Median follow-up duration was 10.0963.3 years. Complete revascularisation was successfully achieved in 53.5% (n177) patients, while 46.5% (n154) were either treated medically from the outset or had failed or incomplete revascularisation. Both groups were age matched. Overall 10-year survival was 66.5%; those with complete revascularisation had signicantly improved survival over those with incomplete revascularisation or medical therapy (75.1% vs 56.5%, p<0.001). Conclusion Complete revascularisation confers a signicant long term survival in patients with CTO and underscores the importance of improved recanalisation rates when performing angioplasty in this patient group. Overall survival was relatively poor and emphasises the importance of optimal medical therapy in this cohort.
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BCS Abstracts 2011

dysfunction. Over a follow-up period of 2.661.1 years there were 42 deaths. All-cause mortality was inversely related to baseline BCIS-1 JS (HR 2.20 (1.34 to 3.62), p0.002) and to post-PCI BCIS-1 JS (HR 3.98 (2.33 to 6.78), p0.0001). Increasing degrees of revascularisation were associated with improved survival (Abstract 33 gure 1); a revascularisation index of $ 0.67 was associated with a survival advantage compared to a RI #0.66 (HR 0.39 (0.24 to 0.54), p0.0001) (Abstract 33 table 2). A multiple regression model, incorporating age, acuity of presentation, LV function and renal failure, demonstrated that RI0.67e1 continued to be an independent predictor of survival (HR 0.51 95% CI 0.35 to 0.81, p0.004) (Abstract 33 gure 1).
33
COMPLETENESS OF REVASCULARISATION PREDICTS MORTALITY FOLLOWING PERCUTANEOUS CORONARY INTERVENTION: UTILITY OF THE BCIS-1 JEOPARDY SCORE
doi:10.1136/heartjnl-2011-300198.33
K De Silva, G Morton, P Sicard, E Chong, A Indermeuhle, B Clapp, M Thomas, S Redwood, D Perera. St. Thomas Hospital, Kings College London, London, UK
Introduction Many coronary-scoring systems are complicated to use on a day-to-day basis, have varying degrees of reproducibility and exclude important subsets of patients such as those with previous coronary artery bypass grafts (CABG) or left main stem (LMS) disease (Abstract 33 table 1). The recently described BCIS-1 Myocardial Jeopardy score (BCIS-1 JS), a modication of the Duke Jeopardy score to include LMS and CABG, is simple to use and overcomes many of these limitations. We assessed the prognostic relevance of the BCIS-1 JS in patients undergoing percutaneous coronary intervention (PCI).
Abstract 33 Figure 1 tion Index (RI). Abstract 33 Table 2

Variables
Cumulative survival according to Revascularisa-
Univariate analysis HR (95% CI) 0.36 (0.24 to 0.54) 1.26 (1.14 to 1.39) 1.35 (1.23 to 1.48) 3.76 (2.53 to 5.58) 1.04 (1.01 to 1.08) 5.82 (2.77 to 12.24) 2.31 (1.24 to 4.30) 14.56 (6.45 to 32.88) 3.35 (1.80 to 6.25)
p value 0.0001 0.0001 0.0001 0.0001 0.01 0.0001 0.008 0.0001 0.0001
Multivariate analysis HR (95% CI) 0.51 (0.33 to 0.81) 1.14 (0.65 to 2.02) 1.78 (0.93 to 3.39) 1.97 (1.21 to 3.20) 1.04 (1.00 to 1.08) 3.74 (1.60 to 7.37) 1.30 (0.63 to 2.66) 2.83 (0.69 to 11.54) 1.83 (0.88 to 3.82)
p value 0.004 0.65 0.08 0.007 0.05 0.002 0.47 0.15 0.10
Abstract 33 Table 1
Left Main Stem Disease classied Duke Jeopardy Score (Original) Syntax Score BCIS-1 JS x O O Patients with CABG classied x x O Ease of use O x O Relevance to contemporary PCI x O O Prognostic validation O O x
Revascularisation Index (0.67e1) BCIS-1 JS pre PCI BCIS-1 JS post PCI LV impairment Age Renal dysfunction Acute coronary syndrome Cardiogenic shock Previous CABG
Methods Consecutive patients undergoing PCI between 2005 and 2009 a single cardiac centre were screened. Patients were eligible if they had undergone assessment of left ventricular function before PCI and the sample was enriched for coronary artery bypass graft (CABG) cases by using the following weightingd1 CABG: 3 nonCABG. Clinicians (who were blinded to clinical or outcome data) scored diagnostic and procedural coronary angiograms. The BCISd1 JS was recorded before and after PCI (range: 0 to 12) and a Revascularisation Index (RI) calculated as RI(JSPREdJSPOST)/JSPRE. RI1.0 indicates full revascularisation and 0 indicates no revascularisation. The primary end-point was all-cause mortality. Mortality data was captured by tracking the database of the UK Ofce of National statistics. Predictors of outcome were assessed by univariate and multivariate analyses. Results 660 patients were included (6869 years). 44% presented as acute coronary syndromes with 41% having left ventricular
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Conclusion The BCIS-1 Jeopardy Score predicts mortality following PCI. Furthermore, it can be used to assess the degree of revascularisation, with more complete revascularisation (RI$0.67) conferring a survival advantage in the medium term.
34
COMPARISON OF PCI VS CABG IN INSULIN TREATED AND NON-INSULIN TREATED DIABETIC PATIENTS IN THE CARDIA TRIAL
doi:10.1136/heartjnl-2011-300198.34
1 6
A Baumbach, S Kesavan, K Beatt, E Cruddas, 4M Flather, 2G Angelini, 5R Hall, A Kapur. 1Bristol Heart Institute, Bristol, UK; 2Bristol Heart Institute, Bristol, UK; Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011

Mayday University Hospital, London, UK; 4Royal Brompton, London, UK; 5Imperial College, London, UK; 6London Chest Hospital, London, UK
3
to 4 years (mean 2.961.6) and stratied according to successful or unsuccessful CTO recanalisation.
Aims The CARDia trial randomised diabetic patients to coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and concluded that PCI is a potentially safe and feasible alternative to CABG in selected patients with diabetes mellitus (DM) and multivessel coronary artery disease. The impact of insulin treatment on clinical outcomes after revascularisation is unclear. The present study is a sub group analysis of the CARDia trial comparing the cardiovascular outcomes at 12 months following revascularisation between the insulin treated (IT) and non-insulin treated (NIT) group. Methods 508 patients with an established diagnosis of DM and de novo coronary artery disease were identied and randomised to CABG or PCI. Of those, 316 patients were treated with oral antidiabetic medication and the rest were treated with additional subcutaneous insulin injections. Demographics, clinical presentation, history, haemodynamic parameters, anti diabetic therapy, concomitant medications, duration of DM and HBA1C were documented. Death, stroke and myocardial infarction were classied as the primary outcome events. The secondary outcome events included death, MI, Stroke, repeat revascularisation and TIMI major bleed. The clinical results of patients in the IT and NIT groups were compared. Results There were 192 patients in the IT group (37.8%). Asian patients constituted one fth of the total population with a slightly higher representation (24.5% vs 21.6%) in the NIT. The clinical severity of dyspnoea, heart rate, systolic and diastolic BP, body mass index, risk factors for coronary artery disease appeared similar in the IT and NIT groups, but more patients in the IT group had a prior MI (30.7% vs 19.6%, p0.004) and duration of diabetes was longer in the IT group (14 vs 6 yrs, p<0.001). For the comparison of CABG vs PCI for the primary outcome events the HR and 95% CI in the IT and NIT groups respectively were 1.66 (0.76 to 3.76) and 1.01 (0.51 to 2.01). For death, MI, stroke, repeat revascularisation they were 2.47 (1.18 to 5.20) in the ITand 1.41 (0.71 to 2.57) in the NIT group. The results suggest that IT patients may have a worse outcome with PCI compared to CABG, whereas no difference was found for NIT patients. Conclusion Our data suggest that insulin treatment is a marker for higher risk for PCI when compared with CABG. Treatment with insulin rather than diabetic status alone should be considered when choosing the mode of revascularisation.
Abstract 35 Table 1
Successful (n[572) Age Male Diabetes Hypertension Hypercholesterolaemia Previous MI Radial access Femoral access Dual site access (bilateral femoral or radial + femoral) 62.460.47 433 (75.7%) 151 (26.9%) 320 (63.8%) 281 (56.0%) 174 (31.7%) 123 (21.5%) 416 (72.7%) 23 (4.0%) Unsuccessful (n[264) 63.760.69 209 (79.2%) 74 (28.6%) 160 (66.6%) 147 (61.2%) 94 (36.4%) 47 (17.8%) 193 (73.1%) 18 (6.8%) p value 0.1 0.3 0.6 0.5 0.2 0.2 0.3 0.6 0.5
Results 572 (68.4%) CTO procedures were successful. Coronary stents were implanted in 96.9% (mean 2.360.1 stents per patient, 70% drug eluting). Prior revascularisation was more frequent among patients with unsuccessful CTO-PCI than successful; prior CABG 16.5% unsuccessful vs 7.4% successful, (p<0.0001), PCI 36.0% vs 21.2%, (p<0.0001). Baseline characteristics were otherwise similar (Abstract 35 table 1). Intra-procedural complications (coronary dissection, perforation, access site (dissection, haematoma) were more frequent in unsuccessful cases (19% (52) vs 4.1% (20) (p<0.0001) but did not have an impact on in-hospital MACE (2% vs 1.8%, p0.6). All cause mortality was 8% (21) in the unsuccessful group and 3% (17) in the successful group out to 4 years, (Abstract 35 gure 1). Mortality following successful CTO-PCI was similar to that of the non-CTO elective PCI group (5.1%, pNS).
35
SUCCESSFUL RECANALISATION OF CHRONIC TOTAL OCCLUSIONS IS ASSOCIATED WITH INCREASED LONG TERM SURVIVAL
doi:10.1136/heartjnl-2011-300198.35
J M Behar, 1D A Jones, 1R Weerackody, 1K Rathod, 1C J Knight, 1A K Kapur, 1A Jain, A Wragg, 2C A Thompson, 1A Mathur, 1E J Smith. 1The London Chest Hospital, Barts and the London NHS Trust, London, UK; 2Department of Cardiology, Yale University, New Haven, Connecticut, USA
1
All cause mortality after PCI for elective patients.
Introduction Chronic total occlusion (CTO) remains a challenging lesion subset. Despite advances in equipment and expertise, many CTO patients may not be offered PCI as physicians perceive procedural success may be lower, and the anatomy is stable. The aim of this study was to investigate the impact of procedural success on mortality following CTO-PCI in a large cohort of patients in the drug eluting stent era. Methods 6122 consecutive patients underwent elective PCI at a single centre (October 2003eMay 2010), 836 (13.7%) for CTO. Demographic and procedural data were collected at the time of intervention (Abstract 35 table 1). In-hospital MACE (myocardial infarction, urgent revascularisation, stroke or death) was documented at discharge. All cause mortality data was obtained from the Ofce of National Statistics via the BCIS/CCAD national audit out
Conclusion A successful angiographic outcome following CTO-PCI is associated with a survival advantage out to 4 years following intervention. These data suggest that the adoption of new techniques and technologies to improve procedural success may improve prognosis.
36
IN-STENT RESTENOSIS PRESENTS AS AN ACUTE CORONARY SYNDROME (ACS) IN 40% OF CASES: NOT SIMPLY A BENIGN CLINICAL ENTITY
doi:10.1136/heartjnl-2011-300198.36
H Abu-Own, E Sammut, K Rathod, L A McGill, D A Jones, A Jain, C Knight, A Mathur, A Wragg. Barts and the London NHS Trust, London, UK
Background In-stent restenosis (ISR) following stent implantation may occur in 20% to 40% of the cases according to patient and lesion complexity. Although in the past ISR used to be seen as a benign
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BCS Abstracts 2011

event, more recent studies suggested that a reasonable amount of patients with ISR many develop ACS as the rst manifestation of this adverse event. The aim of this study was to determine the different clinical presentations of ISR in a large cohort of consecutive, nonselected patients and compare with native coronary disease. Methods 14 445 consecutive patients underwent PCI at a single centre (October 2003eMay 2010), we identied 922 (6.4%) cases presenting with restenosis after previous PCI. All patients with restenosis presented with new or recurrent symptoms. Demographic and procedural data were collected at the time of intervention (Abstract 36 table 1). In-hospital MACE (myocardial infarction, urgent revascularisation, stroke or death) was documented at discharge. All cause mortality data was obtained from the Ofce of National Statistics via the BCIS/CCAD national audit out to 3.2 years (mean 3.161.8 years).
Abstract 36 Table 1
Total Age Ethnicity (cau) Previous MI Previous CABG DM HTN Hchol Card Shock Restenosis n[922 63.09 683 (74.2%) 411 (44.6%) 120 (13.0%) 299 (32.5%) 545 (59.1%) 544 (59.0%) 6 (0.7%) Native disease n[13 523 63.76 9160 (97.8%) 2160 (23.1%) 648 (6.9%) 1986 (21.2%) 4170 (44.5%) 3540 (37.8%) 100 (1.1%) Sig e 0.0868 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 0.2339
Abstract 36 Figure 2 Comparison of mortality between restenosis and no restenosis in ACS.

Conclusions Clinical in-stent restenosis can frequently present as MI and such patients are more likely to have an aggressive angiographic pattern of restenosis. Drug-eluting stents with improved designs or drug elution systems that further decrease the incidence of ISR are needed.
37
Results Restenosis presented in 60.4% as stable angina, 30.6% as unstable angina/Non-ST elevation MI and 9% with ST-elevation Myocardial Infarction. Cardiogenic shock was reported in 6 patients (0.65%). Women had a higher incidence of unstable angina/nonSTEMI compared with men (32.6% vs 29.1%) but a lower incidence of STEMI (5% vs 10.4%). Baseline characteristics are listed in Abstract 36 table 1. Mortality rate was 0.98% at 30 days, 3.9% at 1 year and 8.7% at 5 years in patients with restenosis. Comparing the restenotic group with those undergoing PCI for de novo coronary artery disease, there were similar ages and incidence of cardiogenic shock but the restenotic group had higher rates of baseline risk factors (diabetes, hypertension, hyerpcholesterolaemia) and higher rates of previous CABG and MI. There was also a higher proportion of South Asians in the restenotic group. See Abstract 36 table 1. Comparing outcome measures, there were similar rates of inhospital MACE in the 2 groups and over a 5year follow-up period, there was no difference in all cause mortality. There was no difference in outcome of patients with restenosis vs de novo coronary artery disease regardless of presentation (angina, UA/ NSTEMI/STEMI). See Abstract 36 gures 1 and 2.
DECREASE IN MACE RATES ASSOCIATED WITH DRUG ELUTING STENT USE IN PATIENTS WITH DIABETES UNDERGOING PCI IN LARGE DIAMETER CORONARY ARTERIES
doi:10.1136/heartjnl-2011-300198.37
A Dixit, 2S Nair, 2P Williams, 2A Wiper, 2B Clarke, 2C Deaton, 2M El-Omar, 2D Fraser, R Khattar, 2V Mahadevan, 2L Neyses, 2F Ordoubadi, 2M Mamas. 1University Hospital Manchester MHC, Manchester, UK; 2Manchester Royal Inrmary, Manchester, UK
2
Abstract 36 Figure 1 Comparison of mortality between restenosis and no restenosis in STABLE.

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Introduction Both large multi centre trials and registry studies have demonstrated that PCI with drug eluting stents (DES) is associated with reduced MACE and restenosis rates compared to bare metal stents (BMS) in native coronary vessels, although this benet is less evident in those patients with a larger coronary vessel diameter and MACE rates may actually paradoxically increase in this cohort as observed in the BASKET trial. In diabetic patients, a similar or even greater absolute reduction in MACE rates / restenosis risk is seen associated with DES use, although it is unclear as to whether any benet persists in those with larger diameter native coronary vessels. Previous data derived from diabetic patients in large diameter native coronary vessels has come from registry studies in which numbers were either small (<200 patients) or were from highly selected patient sub groups excluding high-risk individuals (SCAAR registry). Methods We therefore retrospectively studied 1165 consecutive diabetic patients with target vessel diameter $3 mm admitted to our centre for PCI from 2003 to 2009, the largest series of its kind to date. Primary endpoint was dened as total mortality and secondary endpoint was major adverse cardiac event (MACE) dened as composite endpoint of Death, Stroke, MI, Stent Thrombosis and Target Lesion / Vessel Re-Vascularisation. Results Of the 1165 patients studied, 170 had BMS and 995 had DES. Mean follow-up period was 43.3621.8 months (median 41.8 months). 73.5% were male in the BMS cohort vs 73.1% in the DES cohort (p>0.05). Mean age was 62.8611.2 in BMS and 62.36 10.4 years old in DES (p0.55). Other demographic parameters were similar in both groups. There were a total of 23/170 deaths in BMS cohort (13.5%) and 91/995 in DES cohort (9.1%), (HR 1.38; 95% CI 0.83 to 2.27, p0.21). A total of 42/170 (24.7%) and 163/995 (16.3%) MACE events were observed in the BMS and DES cohort respectively (HR 1.49; 1.02 to 2.19, p0.04). Multivariate analysis
BCS Abstracts 2011

illustrated that use of BMS was independently associated with increased risk of MACE (HR 1.54; 95% CI 1.05 to 2.25, p0.03), driven through an increase in revascularisation. Conclusion In conclusion, in one of the largest analyses of its kind, use of DES in patients with diabetes in a real world setting undergoing PCI in large diameter coronary vessels ($3 mm) is safe and is independently associated with a reduction in MACE events. This is in contrast to that of non-diabetic patients where the benets of DES in large diameter coronary vessels are less evident.
39
A RANDOMISED CONTROLLED TRIAL COMPARING CONVENTIONAL CORONARY ARTERY BYPASS GRAFT SURGERY WITH A COMPOSITE ARTERIAL GRAFT TECHNIQUE
doi:10.1136/heartjnl-2011-300198.39
1 A Alahmar, 2R A Perry, 2R H Stables. 1Leicester University Hospital Gleneld, Leicester, UK; 2Liverpool Heart and Chest Hospital, Liverpool, UK
38
FALSE ACTIVATION FOR PRIMARY PERCUTANEOUS CORONARY INTERVENTION IS NOT A BENIGN PHENOMENON
doi:10.1136/heartjnl-2011-300198.38
U Chaudhry, C Mavroudis, R D Rakhit. Cardiology Department, Royal Free Hospital, London, UK
Introduction Primary percutaneous coronary angioplasty (PPCI) is the preferred reperfusion strategy following an acute ST elevation myocardial infarction (STEMI). Since 2005 24/7 primary PCI has been the rst line treatment for an acute STEMI in our centre. 93% of patients are direct access admissions by London Ambulance but a signicant proportion (up to 20%) do not full the diagnostic criteria for STEMI and are termed false activations. Data on the outcome of this cohort of patients is limited. Aim To review the clinical outcome of patients presenting to our heart attack centre with false activation PPCI. Method From January 2008 until October 2010, we identied 209 false PPCI activations dened as patients with incomplete diagnostic criteria for acute STEMI: absence of chest pain and/or typical ECG features (ST elevation or new LBBB). Data was collected via a false activation database together with retrospective review of case records. Results Complete data was available in 165 cases. 71% were male and 29% were female (mean age 67). The mean length of stay was 4 days (range 1e33). 71% presented with chest pains and 29% had no chest pains, but presented with breathlessness, palpitations or syncope. The ECG abnormality was non-specic ST-T changes in 22%, LBBB in 19%, left ventricular hypertrophy in 15%, xed ST elevation or Q waves in 14%, early repolarisation changes in 10%, RBBB in 8% and other ECG abnormalities in 12%. The nal diagnosis was non-ST elevation acute coronary syndrome (NSTEACS) in 19%, sepsis in 19% and congestive heart failure (CHF) in 15%. Stable angina was observed in 8% and syncope in 7%. Musculoskeletal or non-cardiac chest pains were noted in 8% and 7% of the patients respectively. 2% of the patients had pulmonary embolism and in 5%, a gastric cause for presentation was diagnosed. 14% had other cardiac problems, including arrhythmia, dilated cardiomyopathy, hypertension, pericarditis, pericardial effusion and late presentation STEMI. 15% had other diagnoses. The mean follow-up period was 18.7 months, during which 21.5% of false PPCI activation admissions died (n45). 25% (n11) died during the index admission and 33% (n15) died within 30 days of admission. The overall 30-day mortality for false activations was 7.2%, which is higher than the overall PPCI mortality of 6.0% (including cardiogenic shock) (p0.008) and 3.3% (excluding shock) (p<0.0001) in our centre. 49% of deaths were cardiac (NSTEACS and CHF), 29% sepsis and 22% other causes. The mean age for this cohort was 83. Conclusion Patients presenting with false PPCI activation have a high observed mortality. This is probably due to signicant associated comorbidities, including occult cardiac disease. Thus, false PPCI activation is not a benign phenomenon and masks underlying signicant disease. Robust pathways are required to minimise delay in further investigations and a need for risk stratication for a signicant proportion who present with NSTEACS.
Background Composite (Y/T) coronary artery bypass graft surgery (CABG) confers full arterial revascularisation, and hands off aorta compared to conventional bypass graft surgery. However, the composite surgical conguration could lead to preferential blood ow down one arm than the other (left internal mammary artery LIMA or radial artery RA) with its potential impact on graft patency. Aim To investigate the impact of bypass graft conguration on short-term grafts patency and cardiac related quality of life. Methods and Results This is a single centre randomised, controlled trial Between March 2006 and July 2007, 322 patients undergoing isolated bypass graft surgery at our institution were screened and 89 (27%) met the inclusion criteria and were randomised. Patients were allocated to conventional (conv n46) or composite (comp n43). The two primary end points were graft patency dened as (Thrombolysis In Myocardial Infarction) TIMI III ow in distal anastomosis at angiography 12e24 months after surgery, and cardiac-related health status assesses by Seattle angina questionnaire (SAQ). Baseline characteristics were similar between the two groups apart from diabetes where there were more diabetic patients in the composite arm than the conventional one (15(35%) vs 5(11%) p<0.01 respectively). Trial was stopped prematurely following 18 months interim analysis which showed signicant graft failure in the composite arm (40%). Final Analysis was performed on intention to treat basis. Sixty-ve (73%) had follow-up angiography (34 conv, 31 comp), with total of 116 graft in conventional arm and 100 grafts in composite arm. All patients in both groups had LIMA graft to left anterior descending artery (LAD). Graft patency rate was signicantly higher in the conventional compared to composite arm (95(82%) vs 59(59%) p<0.001 respectively). Three main domains of the SAQs there was signicant improvement between before and 6 months after surgery in both groups. There were no signicant differences between the two groups in the percentage of improvement in these four domains (Physical limitation, Angina stability, Angina frequency, Quality of life). Conclusions In our randomised trial, composite bypass graft surgery was associated with higher graft failure rate at 12e24 months after surgery compared to conventional type. This difference may be due to the composite conduit conguration. Further blood ow characteristics study in this conguration can help understand such an important nding and its implication on our clinical practice. Despite the difference in graft patency there were no differences in physical limitation, angina stability, angina frequency, or quality of life between the two groups.
40
PATIENT VS PHYSICIAN REPORTED ANGINA BEFORE AND AFTER REVASCULARISATION OF CORONARY ARTERY DISEASE: EVIDENCE FROM A LARGE RANDOMISED CONTROLLED TRIAL (THE SOS TRIAL)
doi:10.1136/heartjnl-2011-300198.40
C Appleby, I Kemp, R H Stables. Liverpool Heart and Chest Hospital, Liverpool, UK
Introduction The success of revascularisation therapies for coronary artery disease (CAD) must be measured by both an improvement in hard clinical endpointsdmortality, repeat revascularisation procedures and myocardial infarction, the traditional focus of clinical trialsdand, critically for patients, the relief of angina symptoms. Interest in patient reported outcomes (PROMs) has increased, although their use in cardiovascular trials is far from universal. In
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BCS Abstracts 2011

particular the differences between physician and patient reported outcomes has not been analysed. High quality data from the Stent or Surgery (SOS) trial allows such an analysis. Methods The SoS trial was a large RCT (n988) comparing stentassisted percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel CAD. Participation in the SoS trial included an appraisal of angina symptoms by both patient and physician according to the Canadian Cardiovascular Society (CCS) Classication System prior to, and subsequently at 6 and 12 months following coronary intervention. In this study patient and doctor reported outcomes were compared systematically. Results Paired CCS scores at baseline, 6 months and 12 months were available for 919, 886 and 888 cases respectively. At baseline the overall level of agreement was good with >75% paired data sets demonstrating a difference of #61 CCS class. Patterns of discordance change however between baseline and follow-up time points. Abstract 40 gure 1 shows the paired scores at baseline, charting the patient score and, for each CCS grade, the observed differenceddoctor (D) minus patient (P). Doctors are reluctant to record scores of 0 or 4, preferring CCS grades 2 and 3. Thus there is little overall difference in mean CCS score (P 2.2 vs D 2.5, p<0.001). Yet at follow-up, doctors record freedom from angina (CCS0) in a more substantial proportion of the population, considerably more so than patients self-report (p<0.0001) (Abstract 40 gure 2). The published results of the SOS trial used doctor gradings to report freedom from angina at 1 year in 79% of CABG patients vs 66% of PCI patients (p<0.0001). If patient gradings are used instead these gures are reduced to 57% in CABG and 44 % in PCI (p<0.0001), rendering both treatment strategies signicantly less effective at relieving angina from a patients perspective (p<0.0001), Abstract 40 table 1.
Abstract 40 Table 1
PCI (%) Doctor scoring CCS class 0 Patient scoring CCS class 0 66 44 CABG (%) 79 57 p <0.0001 <0.0001
Conclusions This is the rst randomised study to compare the improvement in angina status reported by patients and clinicians following revascularisation therapy for coronary artery disease. The observed trend for doctors to insist that all patients must have some symptoms at baseline, and more importantly, to suggest that a greater proportion of patients have been rendered symptom free at follow-up (than is suggested by self-reported estimates) has important implications and may call into question our current understanding of the impact of revascularisation.
41
REDUCED ARTERIAL WAVE REFLECTION AND ENHANCED LV RELAXATION CONTRIBUTE TO WARM-UP ANGINA
doi:10.1136/heartjnl-2011-300198.41
1 2
T P E Lockie, 2A Guilcher, 3C Rolandi, 1D Perera, 1K De Silva, 1R Williams, 3M Siebes, P Chowienczyk, 1S Redwood, 1M Marber. 1Rayne Institute, St Thomas Hospital, KCL,
Abstract 40 Figure 1 Difference between doctor and patient classication of Angina before revascularisation.
Abstract 40 Figure 2 Difference between doctor and patient classication of Angina at 12 m Fup.
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Abstract 41 Figure 1 (A) shows aortic pressure traces taken at peak exertion with a reduction in pressure augmentation during Ex2; (B) shows WIA with an increase in the backward expansion, or sucking wave originating from the microvasculature.
BCS Abstracts 2011

London, UK; 2Clinical Pharmacology, St Thomas Hospital, KCL, London, UK; 3Department of Bio-Engineering, University of Amsterdam, AMC, Amsterdam, The Netherlands
Background The mechanisms of the clinically observed phenomenon of reduced angina on second exertion, or warm-up angina, are poorly understood. This study compared changes in central haemodynamics, peripheral wave reection and patterns of coronary blood ow during serial exercise that may contribute. Methods and Results 16 patients (15 male, 6164.3 yrs) with a positive exercise stress test and exertional angina completed the protocol. During cardiac catheterisation via radial access they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure (Pd) and ow velocity (V) were recorded in the culprit vessel using a dual sensor coronary guide wire while aortic pressure was recorded using a second wire. Time to 1 mm ST depression was longer in Ex2 (p0.003) and rate pressure product (RPP) was higher (p0.025) conrming warm-up. A 33% decline in aortic wave reection (p<0.0001) in Ex2 (see Abstract 41 gure 1A) coincided with a reduction in both tension time index and diastolic time index (p<0.0001). However, the latter was offset by reduced microvascular resistance (Pd/V), p0.0002, and enhanced left ventricular relaxation during Ex2 as suggested by a larger backwardtravelling suction wave (p0.01) on wave intensity analysis (WIA) of the intra-coronary signals. See Abstract 41 gure 1B. The energy of the forward compression wave and overall coronary blood ow, as measured by the velocity time integral, did not change. Conclusions In patients with warm-up angina, exercise induces changes in the aortic pressure waveform, microvascular function and LV relaxation. These combine to reduce afterload without compromising myocardial diastolic blood ow thereby likely enabling improved performance on second exercise.
Discussion The majority of patients undergoing PCI at the FRH have SYNTAX scores in the lowest tertile. There is no difference in the SYNTAX scores in patients having PCI from referral bases within the centre or from outside. In total almost one quarter of all patients undergoing CABG have a SYNTAX score in the lowest tertile. And this rises to almost one third in those patients referred from district general hospitals. Only a small number of these patients have an additional clear indication for CABG over PCI. Furthermore we found that a signicant proportion of these do not go through MDT planning. These results may indicate that cardiologists are more likely to bring patients to MDT meetings than surgeons and, according to SYNTAX scoring, more patients are inappropriately having CABG than are inappropriately having PCI. Based on this data in our institution discussing all patients at an MDTand the use of SYNTAX scoring at point of referral would be more likely to increase PCI revascularisation rates.
Abstract 42 Table 1
% Patients with Average SYNTAX score SYNTAX in lower third score (0e22) All Referrals for PCI 14.9 Referrals for PCI from within trust Referrals for PCI from outside trust 15.0 14.8 84 84 84 % Patients with SYNTAX score % Patients with in middle third SYNTAX score in (23e32) higher third (>33) 11 12 10 5 4 6
Abstract 42 Table 2
% Patients with Average SYNTAX score SYNTAX in lower third score (0e22) All Referrals for CABG 28.8 Referrals for CABG from within trust Referrals for CABG from outside trust 31.0 25.0 24 19 32 % Patients with SYNTAX score % Patients with in middle third SYNTAX score in (23e32) higher third (>33) 40 34 50 35 47 18
42
RETROSPECTIVE CALCULATION OF SYNTAX SCORE IN 200 PATIENTS UNDERGOING ELECTIVE CORONARY ARTERY BYPASS GRAFTING (CABG) AND PERCUTANEOUS CORONARY INTERVENTION (PCI); ARE WE FOLLOWING BEST PRACTICE?
doi:10.1136/heartjnl-2011-300198.42
L J Mullen, R Edwards, R Taylor, B Nyawo. Freeman Hospital, Newcastle upon Tyne
43
Introduction Cardiologists are generally the gatekeepers of coronary artery disease and have been much criticised for not discussing all patients being considered for revascularisation therapy at an MDT (multi-disciplinary team) meeting or not referring patients with traditional surgical disease for CABG. At the Freeman Hospital (FRH), a large cardiothoracic unit in the North of England, patients are typically referred for PCI or CABG by cardiologists working within the Newcastle upon Tyne Trust or from district general hospitals within the network. Patients are not routinely discussed at MDT but can be brought to the weekly meeting at the discretion of the referrer. The recently reported SYNTAX study allows objective quantication of the degree of coronary disease and facilitates an evidence based decision between CABG and PCI. This gives us the opportunity to examine whether elective revascularisation is being performed appropriately at our institution. Methods We performed a retrospective analysis at the Freeman Hospital. 200 patients who had elective revascularisation between April 2009 and April 2010 were selected. This included 100 cases of CABG and 100 of PCI. Half of each were referrals from other hospitals. Patients SYNTAX scores were calculated using pre-procedure angiograms. MDT meeting records and patients notes were reviewed. Results The average SYNTAX score for patients undergoing elective PCI was 15, compared to 29 for those undergoing CABG. 84% of patients undergoing elective PCI had SYNTAX scores less than 22. 35% of all patients referred for elective CABG had scores greater than 33. The average SYNTAX score for CABG referrals from outside the trust was lower (25) than from within the trust (31).
PROGNOSIS AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR STEMI: CAN THE SYNTAX SCORE HELP?
doi:10.1136/heartjnl-2011-300198.43
A J Brown, L M McCormick, N E J West. Papworth Hospital, Cambridge, UK
Background Factors affecting prognosis after primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) include age at presentation, the presence of diabetes mellitus, left ventricular function and/or cardiogenic shock. Although the debate continues over a strategy of complete revascularisation (immediate or staged) vs culprit-only, little is known about the impact of the extent of coronary disease at presentation on prognosis after PPCI. The SYNTAX score, designed to stratify outcomes in multivessel PCI and CABG, has been validated in unselected populations undergoing elective PCI; to date, no studies have assessed its utility in PPCI. Methods Consecutive patients attending a single UK tertiary centre for PPCI between September 2008 and June 2010 (n695) were included. SYNTAX scoring was performed by a single trained operator blinded to patient details and outcome. Scoring was validated by analysis of 3 separate cohorts by 2 other experienced operators. Patients were split into 3 subgroups as in the SYNTAX trial (score #22 (low, L), 22.5e32 (intermediate, IM) and $32.5 (high, H)), and patient data and outcome measures obtained by interrogation of local and national databases. Results 671 of 695 patients were included in the analysis with 24 being excluded owing to inability to score (previous CABG, images
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BCS Abstracts 2011

unavailable). The ability to allocate a SYNTAX tertile was reproducible between observers (r0.94). Median scores in the 3 groups were: L 14, IM 26, H 36 (Abstract 43 gure 1A). Although there was no correlation between SYNTAX score and patient sex or diabetic status, there was a linear relationship with patient age (r20.03; p<0.0001). 1-year absolute survival (Abstract 43 gure 1B) followed SYNTAX score groups: L 94.7%, IM 88.7%, H 82.1% (p0.0002). Similar results were obtained for freedom from death or unplanned revascularisation (p<0.0001) and death or any revascularisation (p<0.0001). maximum clinically tolerated doses. We examined whether medical therapy is being applied appropriately in patients referred for PPCI. Methods Consecutive patients with STEMI referred for PPCI to a large tertiary centre between 1st March and 1st August 2009 were included (n167). The case records of all patients were reviewed. Myocardial infarction was diagnosed according to standard criteria. Medications and doses on admission, discharge and follow-up were recorded. Contraindications and limits to dose escalation were noted (symptoms, systolic blood pressure <90 mm Hg, heart rate <50 bpm, serum creatinine and potassium). Results Mean age was 62.0611.9 years, 72% were male. On discharge, 100% of patients were prescribed clopidogrel, 95.8% aspirin, 98.8% statin, 88.6% b-blockers, and 91.0% ACEI/ARB. However, the inpatient dose of b-blocker or ACEI/ARB was maximum or clinically limited in only 13% and 15% of patients respectively (Abstract 44 gure 1). Outpatient follow-up at a mean of 5.0 months was equally concerning. The majority of patients (83%) were neither receiving maximum tolerated doses of b-blocker or ACEI/ARB, nor received instructions to escalate the dose (Abstract 44 gure 2).
Inpatient titration of b-blocker and ACEI/ARB.
Conclusions The SYNTAX score, when applied to an unselected population of patients undergoing PPCI for STEMI, provides important prognostic information regarding 1-year survival from death and revascularisation. These ndings may provide supporting evidence towards routine complete revascularisation of obstructive coronary artery disease after PPCI.
Outpatient titration of b-blocker and ACEI/ARB.
44
PRIMARY PERCUTANEOUS INTERVENTION: HAVE WE TAKEN OUR EYE OFF THE MEDICINE BALL?
doi:10.1136/heartjnl-2011-300198.44
Conclusion The national service framework and target driven initiatives such as advancing quality promote tick box medicine. Quantitative prescribing of secondary prevention is excellent. Qualitative follow-up and titration is not. Whether suboptimal doses convey the mortality benets observed in landmark clinical trials is unknown. Frameworks to deliver titration of medical therapy must be explored. Options include nurse or pharmacy led services and expansion of cardiac rehabilitation. Reorientation is needed to focus on both quantity and quality.
45
J D Jones, E Damm, M Nijjar, S Pettit, N M Hawkins, R Perry. University Hospital Aintree NHS Foundation Trust, Liverpool, UK; 2Liverpool Heart and Chest Hospital, Liverpool, UK
SHOULD PRIMARY PERCUTANEOUS CORONARY INTERVENTION BE THE ROUTINE REPERFUSION STRATEGY IN OCTOGENARIANS AND NON-AGENARIANS PRESENTING WITH ST ELEVATION MYOCARDIAL INFARCTION?
doi:10.1136/heartjnl-2011-300198.45
Introduction Primary percutaneous intervention (PPCI) improves survival in patients with ST elevation myocardial infarction (STEMI). Signicant resources have been directed to achieving timely reperfusion throughout the UK. However, intensive medical therapy is of equal importance, with landmark clinical trials demonstrating unequivocal morbidity and mortality benets from b-blockers, angiotensin-converting enzyme inhibitors (ACEI), and angiotensin II receptor blockers (ARB). All trials employed rigorous titration to
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R Showkathali, E Boston-Grifths, J Davies, G Clesham, J Sayer, P Kelly, R Aggarwal. The Essex Cardiothoracic Centre, Basildon, UK
Introduction Primary percutaneous coronary intervention (PPCI) has been established as standard therapy for ST elevation myocardial infarction (STEMI). Very few trials have looked at the outcome of PPCI in elderly patients. Even in trials which claimed to have looked
BCS Abstracts 2011

at PPCI in elderly patients such as SENIOR PAMI (Grines, 2005) and TRIANA (Bueno, 2009) the minimum age for inclusion was 70 yrs and 75 yrs respectively. With an ageing population in the western world, about 20% of patients admitted for suspected STEMI are $80 yrs. We evaluated the outcome of PPCI in patients $80 yrs who were admitted to our unit with STEMI. Methods Our PPCI service was started in September 2009 and we analysed all the patients who were $80 yrs presenting to the PPCI service between September 2009 and September 2010 (13 months). Prospectively entered data were obtained from our dedicated cardiac service database system (Philips CVIS). Mortality data were obtained from the summary care record (SCR) database. Follow-up data were obtained from patients respective district general hospitals and general practitioners medical records. Results Of the 998 patients who were admitted to our unit for primary PCI for suspected STEMI during the study period, 183 (18.3%) were $80 yrs of age. After excluding 51 patients (27.9%) who did not undergo PPCI, we included 132 (70.1%) patients for analysis. Of those who were included in the study (n132, 63 female), the mean age was 8563.95 yrs (range 80e99 yrs, median 85 yrs). There were 20 diabetics (15.2%) and 39 (29.5%) had previous myocardial infarction. Ten patients (7.6%) were in cardiogenic shock on arrival of which 9 (90%) had an Intra aortic balloon pump (IABP). The infarct related vessel was the right coronary in 42.4% and left anterior descending in 37.1%. Drug eluting stents were used in 40.2% of patients. In-hospital and 30-day mortality was 14.4% and 19.7% respectively. There was a signicant difference in the mortality between patients age <80 yrs and those $80 yrs (Abstract 45 gure 1). In patients $80 yrs, mortality and bleeding risk increased markedly with advancing age (Abstract 45 table 1).
46
PROGNOSTIC VALUE OF BASELINE RENAL FUNCTION ON LONG TERM OUTCOME IN PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST-ELEVATION MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.46
O P Guttmann, K Rathod, B Rathod, E Wicks, S Gallagher, D A Jones, A Jain, C Knight, A Mathur, A Kapur, A Wragg. Barts and the London NHS Trust, The London Chest Hospital, London, UK
Background Renal impairment is associated with increased cardiovascular mortality following acute coronary syndromes (ACS), however there is limited data assessing this relationship in the context of primary PCI and whether it exists with other major adverse cardiovascular events. Methods Clinical information was analysed from a prospective data base on 2310 STEMI patients who underwent primary PCI between January 2004 and May 2010 at a London centre. Information was entered at the time of procedure and outcome assessed by all-cause mortality information provided by the Ofce of National Statistics via the BCIS/CCAD national audit. Estimated glomerular ltration rate (eGFR) was calculated using the modied diet in renal disease equation and patients were divided into groups based on eGFR (<40, 40e50, 50e60, >60 ml/min/1.73 m2). 3-year composite of MACE (death, reinfarction, stroke and target vessel revascularisation) were compared between groups. Results The average eGFR in all patients was 73.40623.37 (95% CI 72.25 to 74.56) ml/min/1.73 m2. The prevalence of coexisting risk factors (hypertension, diabetes mellitus, hypercholesterolaemia), previous MI, previous CABG and cardiogenic shock were higher among patients with reduced eGFR. There was a progressive increase in MACE with declining eGFR (OR4.84, 95% CI 2.94 to 7.96, for comparison between the highest and lowest eGFR groups). See Abstract 46 gure 1. After adjustment for baseline characteristics including age, diabetes and cardiogenic shock renal function based on the GFR at admission remained a strong independent predictor of outcome.
Abstract 45 Figure 1 Abstract 45 Table 1

% Inhospital mortality 30-day mortality 30-day MI 30-day CVA Major bleeding requiring blood transfusion 80e84 yrs (N[62) 9.7 14.5 3.2 1.6 1.6 85e89 yrs (N[51) 15.7 23.5 2.0 0 3.9 90 yrs (N[19) 26.3 26.3 0 0 10.5
All MACE after PCI for STEMI.
Conclusion Baseline renal dysfunction in patients undergoing primary PCI is associated with an increased risk for combined death, re-infarction and recurrent angina. This risk increases linearly with declining eGFR.
47
CARDIOVASCULAR EVALUATION OF ENGLISH PREMIERSHIP RUGBY PLAYERS

doi:10.1136/heartjnl-2011-300198.47
Conclusion This study clearly demonstrates a signicant mortality difference between patients aged <80 yrs and those $80 yrs treated with PPCI. Our 30-day mortality outcome in patients $80 yrs (19.7%) was similar to the subgroup analysis of the PPCI arm in similar SENIOR-PAMI patients (19%). In the same analysis, the thrombolytic group had a lower (16%) mortality. Further studies are required to determine whether PPCI should be routinely used in very elderly patients presenting with STEMI.
S Ghani, 1H Raju, 1A Zaidi, 1N Sheikh, 1S Gati, 2J Somauroo, 3S Kemp, 1S Sharma. St Georges University London, London, UK; 2Countess of Chester Hospital; 3Rugby Football Union (RFU)
1
Introduction Recent experience of pre-participation cardiovascular evaluation (PPCE) in Italian athletes demonstrates a signicant
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BCS Abstracts 2011

reduction in mortality from cardiomyopathies and cardiac conduction disorders. Although PPCE is endorsed by large medical and sporting organisations, including the European Society of Sports Cardiology, the International Olympic Committee and FIFA, the state health system in the UK (and many other Western countries) does not support cardiovascular evaluation of athletes. Certain elite sporting organisations in the UK mandate PPCE in all athletes prior to competition. In 2010 the English Premier Rugby league introduced formal PPCE in all competing players. Methods Athletes participating in the English Premiership Rugby underwent PPCE with a structured clinical questionnaire and 12lead ECG. Trans-thoracic echocardiogram (TTE) and additional investigations were performed where indicated. Results A total of 606 players were assessed (mean age 22.9 years; range 15e37). Of these, 45 (7.4%) required TTE (35 (5.7%) due to ECG abnormalities; 5 (0.08%) due to family history of sudden death; 5 (0.08%) due to symptoms). ECG abnormalities warranting TTE included right axis deviation (n4), left axis deviation (n17), right bundle branch block (n3), right ventricular hypertrophy (n1), abnormal T wave inversion (n5) and prolonged QT (n1). Six of the 45 subjects demonstrated mild changes on TTE (markedly dilated LV cavity (n3), mitral regurgitation (n1), pulmonary stenosis (n1), dilated aortic root (n1)), requiring serial surveillance. Five demonstrated abnormalities on TTE and/or ECG that warranted referral for further evaluation including exercise stress test (n5), 24-h ECG (n5) and cardiac MRI (n3). The reasons for these tests included possible arrhythmogenic right ventricular cardiomyopathy (n3), suspicion of hypertrophic cardiomyopathy (n1) and QT prolongation on ECG (n1). None of the players exhibited a cardiac disorder that warranted disqualication from sport. Overall 7.4% of athletes required further investigation following initial ECG, and 1.8% required further tests following TTE. False positive rate was 5.6%. Conclusion Cardiovascular evaluation of British rugby players with a structured questionnaire and ECG resulted in clearance of 92.6% following initial tests, and 5.6% were reassured after TTE. Only 1% players required surveillance echocardiograms and 0.8% were referred for further diagnostic evaluation. False positive rate was 5.6%. The results indicate that PPCE carried out in an expert setting results in a relatively small number of athletes requiring further tests, and a low false positive rate. enhanced by ischaemia; whether they are present in humans is unknown. We examined whether the erythropoietin analogue darbepoetin improves ow mediated dilatation (FMD), a measure of endothelium-derived NO, and whether this is inuenced by preceding ischaemia-reperfusion. Methods 36 patients (50e75 years) with stable coronary artery disease were randomised to receive a single dose of darbepoetin 300 mg or saline placebo. Immunoreactive erythropoietin was measured by an enzyme linked immunospecic assay. FMD was measured at the brachial artery using high resolution ultrasound. CD34+/VEGFR2 +/133+ circulating EPC were enumerated by ow cytometry. Measurements were made immediately before darbepoetin/placebo and at 24 h, 72 h and 7 days. At 24 h FMD was repeated after 20 min ischaemia-reperfusion of the upper limb. A further group of 11 patients were studied according to the same protocol, all receiving darbepoetin, with omission of forearm ischaemia-reperfusion at 24 h. Results Immunoreactive erythropoietin peaked at 24 h in the darbepoetin group (median value of 724 U/l (IQR 576e733 U/l), compared to 12 U/l (IQR 9e21 U/l) in the placebo group) and remained elevated at approximately 500 fold baseline at 72 h. FMD did not differ signicantly between groups at 24 h (before ischaemiareperfusion). At 72 h, (48 h after ischaemia-reperfusion) FMD increased from baseline in the darbepoetin group but not in the placebo group so that FMD (and change in FMD from baseline) was signicantly greater in the darbepoetin group (change from baseline 1.760.3% and 0.660.4% in darbepoetin and placebo groups respectively, p<0.001).The increase in FMD at 72 h after darbepoetin and ischaemia-reperfusion at 24 h was signicantly greater than that without preceding ischaemia-reperfusion (p<0.01). A w20% increase in CD133+/VEGFR2+ cells after darbepoetin was temporally dissociated with the increase in FMD. Conclusions Preceding ischaemia-reperfusion is required for darbepoetin to enhance endothelial function, possibly by increasing expression of the erythropoietin receptor and by a mechanism likely to involve Akt/NO rather than circulating EPC.
48
DARBEPOETIN ENHANCES ENDOTHELIAL-DEPENDENT VASOMOTOR FUNCTION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE ONLY AFTER PRECEDING ISCHAEMIA-REPERFUSION
doi:10.1136/heartjnl-2011-300198.48
1,2 L M Tilling, 1,2J Hunt, 1,2A Donald, 1,2B Clapp, 1,2P Chowienczyk. 1British Heart Foundation Centre, Kings College London, St Thomas, London, UK; 2Department of Clinical Pharmacology, Cardiovascular Division, Kings College London, St Thomas, London, UK
Background Vasoprotective effects of erythropoietin in animal models are mediated by endothelium-derived nitric oxide (NO) and/ or mobilisation of endothelial progenitor cells (EPC) and may be
Abstract 48 Figure 1 Change from baseline in FMD at 72 h, 48 h after ischaemia-reperfusion (+IR), after placebo and darbepoetin (study 1) and after darbepoetin without preceding ischaemia-reperfusion (IR, study 2).
Abstract 48 Table 1
Endothelial function FMD% Progenitor cells CD133+/VEGFR2+ CD34+/VEGFR2+ CD133+/CD34+ Values are means6SE. * p<0.05, ***p<0.001
Endothelial function and EPC

Placebo Baseline 3.560.80 110617.6 4.160.6 17.362.9 Placebo 24 h 3.460.73 117619 3.960.5 17.061.9 Placebo 72 h 2.960.63 101619 3.160.6 17.763.6 Placebo 7d 3.460.75 123621 4.760.8 20.463.2 Darbepoetin Baseline 3.560.92 146613 8.763.07 23.662.4 Darbepoetin 24 h 4.460.97 180613* 11.163.9 29.364* Darbepoetin 72 h 5.260.9*** 180611* 7.161.4 31.664.6* Darbepoetin 7d 3.760.61 182616* 13.364.5 29.964.8*
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BCS Abstracts 2011

49
ETHNIC VARIATION IN QT INTERVAL AMONG HIGHLY TRAINED ATHLETES
doi:10.1136/heartjnl-2011-300198.49 H Raju, 1M Papadakis, 2V Panoulas, 2J Rawlins, 2S Basavarajaiah, 1N Chandra, E R Behr, 1S Sharma. 1St Georges University of London, London, UK; 2University Hospital Lewisham, London, UK
1 1
Background Studies in Caucasian (white) athletes indicate that a signicant proportion exhibit an isolated prolonged corrected QT interval (QTc), raising concerns for potentially false diagnoses and disqualication from competitive sport. The prevalence of prolonged QTc interval in athletes of African/Afro-Caribbean (black) descent is unknown. However, this ethnic group generally exhibits a high proportion of ECG repolarisation changes and increased left ventricular wall thickness, that may impact on QTc. Aim We aimed to assess the impact of ethnicity on QTc in young elite athletes. Methods We assessed 3035 elite athletes, aged 14e35 years, who were participating at national and international level in a variety of sporting disciplines. Athletes were evaluated with ECG and 2D echocardiography. Athletes diagnosed with structural heart disease or hypertension were excluded from analysis. Results Demographic and cardiological results are summarised in Abstract 49 table 1. Black male athletes exhibited shorter QTc than white male athletes, but QTc was similar among black and white female athletes. Bivariate analysis revealed that none of T wave inversions, ST segment elevation, or left ventricular wall thickness were associated with QTc. No ethnic difference was observed in prevalence of QT prolongation, as dened by ESC Sports Consensus criteria (male >440 ms; female >460 ms).
Aim We determined the diagnostic yield of exercise tolerance testing (ETT) in investigation of inherited cardiac conditions following familial premature SCD. Methods Between 2006 and 2010, we evaluated 308 blood relatives of 148 SCD victims, who completed at least 3 min of the Bruce protocol. ETTs were analysed for: QT prolongation; Brugada type 1 pattern; ST depression: blood pressure (BP) response; multiple ventricular ectopics or arrhythmia. Individual pathological phenotypes were determined by a combination of 12-lead ECG, echocardiogram, 24-h holter monitor, with additional MRI, CT coronary angiography and genetic mutation analysis, as appropriate. Results Thirty (9.8%) patients had an abnormality during ETT, details of which are summarised in Abstract 50 gure 1. All ETTs with abnormal QT prolongation and dynamic Brugada pattern were associated with diagnoses of long QT syndrome and Brugada syndrome respectively. An example of dynamic Brugada phenotype is given in Abstract 50 gure 2. Ventricular ectopy was seen in 15 patients, of whom 5 demonstrated phenotypic cardiomyopathy or channelopathy on further investigations. No patients with signicant ST depression had evidence of coronary abnormalities on imaging. No hypotensive BP response was seen, but exertional hypertension was associated with systemic hypertension.
Abstract 49 Table 1
Characteristics of athletes evaluated

Black Male White Male Black Female White Female (n[901) (n[1652) (n[122) (n[360)
Abstract 50 Figure 1 familial evaluation.
ETT abnormalities and associated diagnoses at
Mean Age, years Mean Heart Rate, bpm
2265 61612
1764 56610 96610 9.4*61.2
2165 63610 84610 9.261.2
1864 5969 8869 7.9*62.9 64 (17.8%) 15* (4.2%) 412627 39 (10.9%) 5 (1.4%)
Mean QRS duration, ms 88614 Mean LV wall thickness, mm 10.661.6 ST segment elevation, n (%) T wave inversions, n (%) Mean QTc (Bazetts), ms QTc >440 ms, n (%) QTc >460 ms, n (%)
570 (63.3%) 406 (24.6%) 20 (16.3%) 204 (22.6%) 66* (4.0%) 18 (14.6%) 393626 20 (2.2%) 4 (0.4%) 404*620 49 (3.0%) 7 (0.4%) 407625 13 (10.6%) 1 (0.8%)
Means presented as mean 6 SD. *p<0.001 white vs black athletes.
Conclusion Despite demonstrating a higher prevalence of repolarisation changes and morphological left ventricular hypertrophy, black athletes do not exhibit a longer QTc than white counterparts. Based on ESC Sports Consensus criteria, prevalence of a long QTc in black and white athletes is similar, obviating the need for ethnicity specic criteria for dening a long QTc.
50
DIAGNOSTIC ROLE OF EXERCISE TOLERANCE TESTING IN FAMILIAL PREMATURE SUDDEN CARDIAC DEATH
doi:10.1136/heartjnl-2011-300198.50
H Raju, M Papadakis, R Bastiaenen, A Zaidi, N Chandra, M Muggenthaler, N Spath, S Sharma, E R Behr. St Georges University of London, London, UK
Abstract 50 Figure 2 Exercise tolerance test demonstrating dynamic Brugada ECG pattern. Stage 1 of Bruce protocol exercise (left) and postexercise recovery (right).
Conclusion The ETT is a useful diagnostic adjunct when evaluating relatives of victims of premature SCD. Reliable diagnostic indicators include inappropriate QT prolongation and dynamic Brugada
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Background Investigation of blood relatives for evidence of an inherited cardiac condition is advocated following an unexplained sudden cardiac death (SCD).
BCS Abstracts 2011

pattern. Ventricular ectopy is non-specic, but is associated with both cardiomyopathic and channelopathic processes in a signicant minority. ST segment depression, however, is unhelpful and should be viewed in the context of the patients cardiovascular risk prole. of DPSV/DHR were different in the saline/ischaemia group compared to the three other groups (ie, saline/ischaemia 3.760.6 cm/s/s, NO2-/ischaemia 8.261.0 cm/s/s, saline/control 10.561.1 cm/s/s, NO2-/control 8.460.7 cm/s/s; p<0.01, repeated-measures ANOVA with Bonferroni post-test). No difference was present between the three other groups.
51
LOW-DOSE SODIUM NITRITE RELIEVES MYOCARDIAL ISCHAEMIA IN PATIENTS WITH CORONARY ARTERY DISEASE: A TARGETED NO-DONOR EFFECT
doi:10.1136/heartjnl-2011-300198.51
1 1
T E Ingram, 2R A Bleasdale, 2C Templeton, 2C Williams, 1A Margulescu, 1A G Fraser, P E James. 1Cardiff University, Cardiff, UK; 2Royal Glamorgan Hospital, Llantrisant, UK
Introduction Sodium nitrite (NaNO2) became a popular means of treating angina in the 19th century, as its stable chemical structure allowed for cheap preparation and easy storage. However, the effects were slow and unpredictable and so it fell out of favour as more potent and faster-acting agents became available, (eg, organic nitrates). Recent in vitro evidence shows that nitrite (NO2-) exhibits an enhanced vasodilator effect in hypoxia; an environmental modication which encourages its reduction to nitric oxide (NO). Therefore NaNO2 could potentially be an anti-ischaemic agent at much lower doses than those used historically, and be without the adverse side effects associated with organic nitrates (eg, systemic hypotension and tachyphylaxis). Method A double-blind, placebo-controlled, cross-over study was performed in 10 subjects with proven myocardial ischaemia documented by exercise tolerance testing and coronary angiography. Two dobutamine stress echocardiography (DSE) studies were performed on each subject: one with 0.9% saline and one with NaNO2, 1.5 mmol/min for 20 min. This dose of NaNO2 has previously been shown to be inert in normoxia but to vasodilate hypoxic tissue. Myocardial ischaemia was identied by the peak systolic velocity (PSV) response during DSE in a six basal-wall segment model of the left ventricle. Using placebo study data-set, walls were classied into tertiles: the lowest tertile of responders of PSV to an increase in heart rate (DHR) labelled ischaemia (n18) and the upper tertile control (n18). Data was divided into four groups according to the study-infusion received and the myocardial-wall examined: saline/ ischaemia, NO2-/ischaemia, saline/control and NO2-/control. Results Data from each stage of each DSE was plotted on a scatter plot graph with change in (DHR) on the x-axis and corresponding change in PSV (DPSV) on the y-axis (increase in both values compared to baseline), see Abstract 51 gures 1 and 2. Linear regression analysis of the saline/ischaemia group was lower than the NO2-/ischaemia group, with no overlap in their 95% CI, see Abstract 51 gure 1. In addition, the linear regression gradient of the NO2-/ ischaemia group was similar to the saline/control and the NO2-/control gradient, see Abstract 51 gure 2. The peak-dose dobutamine values
Conclusions Low-dose NaNO2 delivers a therapeutic effect to ischaemic myocardial tissue in the absence of a vasodilator effect on normoxic tissue. This is the rst study in patients to demonstrate a targeted vasodilator effect of NO2- to tissues in need only.
52
BRAIN NATRIURETIC PEPTIDE PREDICTS ALL CAUSE MORTALITY IN PATIENTS WITH TYPE 2 DIABETES AND NORMAL EJECTION FRACTIONS
doi:10.1136/heartjnl-2011-300198.52
B R Szwejkowski, D H J Elder, A Dawson, A D Struthers. 1University of Dundee, Dundee, UK; 2Department of Cardiology, NHS Tayside, Dundee, UK
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Introduction The use of brain naturetic peptide (BNP) to predict outcome in patients with normal ejection fractions (EF) and type 2 diabetes (T2DM) is understudied. Only three previous studies have specically addressed the question as to whether BNP adds prognostic information in T2DM. There appears to be a link between survival and BNP in T2DM, however these studies included small numbers of patients and did not fully exclude left ventricular systolic dysfunction (LVSD). We therefore studied the 5-year survival in a cohort of 500 T2DM patients prospectively phenotyped with echocardiography. Methods 500 patients with T2DM where studied with echocardiography between April 2002 and October 2003. Patients were recruited from the diabetes clinics at Ninewells Hospital, Dundee. Transthoracic echocardiography was performed by one trained operator and left ventricular (LV) assessment was performed using modied biplane Simpsons method over three cycles. We excluded individuals with EF of <55%. Follow-up data was linked via the Health Informatics Centre (HIC), to mortality data, laboratory test data, hospitalisation, and prescribing via the community health index (CHI) number. Cox proportional hazards model was used to examine the effects of BNP (bedside stick measurement) measure on all-cause mortality using age, sex, smoking status, hypertension, IHD, duration of diabetes, and diabetic drug prescription as co-variants. Outcome was all cause mortality. Results In total we followed 316 patients over 8 years. 56 patients died over this time. After adjusting for confounding factors we have shown that for every 10-unit increase in BNP there is a 6% increased risk of death. HR 1.06 (95% CI 1.02 to 1.10) (p<0.01). Conclusions In patients with normal EF, BNP is an independent predictor of death in a cohort of T2DM patients. Although more research is needed, BNP may become an important tool in risk stratifying T2DM patients in the future.
BCS Abstracts 2011

53
B-TYPE NATRIURETIC PEPTIDE PERFORMS BETTER THAN CURRENT CARDIOVASCULAR RISK SCORES IN IDENTIFYING SILENT PANCARDIAC TARGET ORGAN DAMAGE IN ALREADY TREATED PRIMARY PREVENTION PATIENTS
doi:10.1136/heartjnl-2011-300198.53
1 1
A Nadir, 1S Rekhraj, 2J Davidson, 1T M MacDonald, 1C C Lang, 1A D Struthers. University of Dundee, Dundee, UK; 2Ninewells Hospital, Dundee
Background Primary prevention needs to be improved because up to 70% of cardiovascular (CV) events occur outwith those classied as high risk by CV risk scores currently used in clinical practice (eg, Framingham). One possible way to improve primary prevention of CV disease is to identify those patients who may already harbour silent pancardiac target organ damage in the form of left ventricular hypertrophy (LVH), systolic dysfunction (LVSD), diastolic dysfunction (LVDD), left atrial enlargement (LAE) or silent myocardial ischaemia. This could be achieved by reapplying traditional CV risk scores to primary prevention patients after they have been treated or by screening with a simple biomarker like B-type natriuretic peptide (BNP). Methods We prospectively recruited 300 asymptomatic individuals without known cardiovascular disease already on primary prevention therapy. Patients with valvular heart disease, atrial brillation and renal impairment were excluded. We measured BNP and calculated 10year global CV risk scores (based on Framingham, QRISK and ASSIGN) in each participant. Transthoracic echocardiography was used to assess LV mass, LV systolic and diastolic function, and left atrial volume while the presence of inducible ischaemia was assessed by dobutamine stress echocardiography or dipyridamole myocardial perfusion imaging. Patients were divided into low, intermediate and high risk groups based on 10-year global CV risk. The prevalence of various cardiac TOD in each group was compared and ROC curves were constructed for BNP and for 10-year global CV risk scores to assess their ability to detect presence of silent cardiac TOD. Results One hundred and two (34%) patients (Mean age 6466.0 years, 58% males) had evidence of silent cardiac TOD (29.7% LVH, 18% LAE, 17.3% LVDD, 7.3% LVSD and 6.3% Ischaemia). The prevalence of cardiac TOD ranged from 19 to 28% in the low risk, 26%e33% in the intermediate risk and 36%e41% in the high risk groups based on three commonly used CV risk equations. BNP levels were signicantly higher (median (IQR); 21.6 (13.6e40.0) vs 11.4 (6.3e20.0) pg/ml, p<0.0001) in those with cardiac TOD compared to those without. The AUC for BNP to identify any form of cardiac TOD was 0.77 (p<0.0001) overall and 0.83 (p<0.0001) in males. However, discrimination power of CV risk scores was poor with area under curve of only 0.58 (p0.02) for QRISK, 0.62 (p0.001) for Framingham and 0.62 (p0.001) for ASSIGN to detect presence of any form of TOD. Conclusion Silent cardiac TOD is highly prevalent (34%) in already treated primary prevention population but current CV risk estimation alone performs poorly in the detection of these silent cardiac abnormalities. However, a raised BNP is able to identify existing silent cardiac TOD of various subtypes particularly in males. Using BNP to identify silent cardiac TOD could, in the future, become a new way to improve the primary prevention of CV events.
tion. We sought to investigate whether micoalbuminuria identied the presence of silent pancardiac target organ damage (TOD) ie, left ventricular hypertrophy (LVH), systolic dysfunction (LVSD), diastolic dysfunction (LVDD), left atrial enlargement (LAE) or silent myocardial ischaemia in a non-diabetic primary prevention population. Methods Two hundred and sixty-three asymptomatic individuals without diabetes or previous cardiovascular disease on primary preventive therapy were prospectively recruited. Each participant underwent a comprehensive echocardiographic examination for the assessment of LV mass, LV systolic and diastolic function, and left atrial volume while the presence of inducible ischaemia was assessed by dobutamine stress echocardiography or dipyridamole myocardial perfusion imaging. A spot urine sample was analysed for microalbuminuria and urinary creatinine by a trained laboratory technician blinded to clinical or echocardiographic data. Microalbuminuria was dened as urinary albumin to creatinine ratio of $2.5 mg/mmol in males and $3.5 mg/mmol in females. Results Out of 263 participants (Mean age 6466.3 years, 57% males) 89 (33.8%) had evidence of silent cardiac TOD (29.7% LVH, 16.7% LAE, 17.1% LVDD, 6.8% LVSD and 6.1% Ischaemia). The prevalence of cardiac TOD was signicantly higher (53% vs 29%, p0.002) among those with microalbuminuria than those without. In multivariate analysis adjusted for age, gender, hypertension and dyslipidemia, presence of microalbuminuria was an independent predictor of cardiac TOD with an adjusted HR of 2.54 (95% CI, 1.2 to 4.4, p0.005). The utility of UACR in discriminating between those with or without cardiac TOD was assessed by receiver operating characteristic analysis but the area under curve was only 0.6160.04, p0.003. Conclusion Microalbuminuria is an independent predictor of silent pancardiac target organ damage in a non-diabetic primary prevention population. Presence of microalbuminuria may help to identify those primary prevention patients who are at a particularly higher risk.
55
GENE-GENE INTERACTIONS IN CORONARY ARTERY DISEASE

doi:10.1136/heartjnl-2011-300198.55
M D Musameh, W Y S Wang, A J Balmforth, S G Ball, 5A S Hall, 1M Tomaszewski, N J Samani. 1Department of Cardiovascular Sciences, University of Leicester, Gleneld Hospital; Leicester BRU, Leicester, UK; 2School of Medical Sciences and Institute for Biomedical Research, University of Sydney, Sydney, Australia; 3Division of Cardiovascular and Diabetes Research, University of Leeds, Leeds, UK; 4LIGHT Research Institute, Faculty of Medicine and Health, University of Leeds, Leeds, UK; 5Division of Cardiovascular and Neuronal Remodelling, University of Leeds, Leeds, UK
1
54
CAN MICROALBUMINURIA IDENTIFY SILENT PANCARDIAC TARGET ORGAN DAMAGE IN A NON-DIABETIC PRIMARY PREVENTION POPULATION?
doi:10.1136/heartjnl-2011-300198.54
1 1
A Nadir, 1S Rekhraj, 2J Davidson, 1T M MacDonald, 1C C Lang, 1A D Struthers. University of Dundee, Dundee, UK; 2Ninewells Hospital, Dundee, UK
Background Microalbuminuria is associated with increased cardiovascular mortality and is a marker of generalised vascular dysfuncHeart June 2011 Vol 97 Suppl 1
Background Only a small fraction of the heritability of coronary artery disease (CAD) has been explained by common variants identied by genome-wide association studies. Among the stones to be turned in the hunt for the missing heritability of CAD are genegene interactions. We investigated whether interactions between common alleles in genes and pathways of known importance to cardiovascular regulation may contribute to the heritability of CAD. Methods 2101 CAD cases and 2426 controls of Caucasian origin recruited into Wellcome Trust Case Control Consortium were genotyped using 50 K IBC gene-centric array containing 45 707 single nucleotide polymorphisms (SNPs) of the highest biological relevance to cardiovascular system. After applying appropriate quality control lters, 11 332 common (minor allele frequency >10%), independent (r2 linkage disequilibrium coefcient of #0.5) were included in pair-wise SNP-SNP interaction analysis using two complementary statistical approaches: logistic regression (PLINK and INTERSNP software packages) and Bayesian model (BEAM software). Results None of the analysed SNP-SNP interactions was statistically signicant after correction for multiple testing (p7.8310-10). The most signicant interaction identied in this analysis was
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between rs727139 (KCNH8) on chromosome 3 and rs11167496 (PDGFRB) on chromosome 5 (p2.453108). Analysis of subsets of SNPs pre-selected based on their nominal association with CAD (p<0.05) or molecular functionality (non-synonymous SNPs) did not contribute more signicant ndings than investigation of random set of SNPs. Conclusion Our analysis suggests that common SNP-SNP interactions are unlikely to account for a large proportion of the missing heritability of CAD.
56
CLINICAL AND FINANCIAL REPERCUSSIONS OF THE MARCH 2010 NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE (NICE) GUIDELINE CHEST PAIN OF RECENT ONSET ON THE RAPID ACCESS CHEST PAIN CLINIC (RACPC)
doi:10.1136/heartjnl-2011-300198.56 T Rogers, S Claridge, K Al Fakih. University Hospital Lewisham, London, UK
Abstract 56 Table 1
All Numbers (%) Age (mean 6 SD) Diabetes (%) Hypertension (%) Hypercholesterolaemia (%) Family history (%) Smoking (%) Systolic BP (mean 6 SD) / Diastolic BP (mean 6 SD) Fasting glucose (mean 6 SD) Total cholesterol (mean 6 SD) LDL (mean 6 SD) / HDL (mean 6 SD) BMI (mean 6 SD) 167 56.0612.6 29 (17.4) 72 (43.1) 100 (59.9) 58 (34.7) 87 (52.1) 134621 / 79611 5.261.0 5.1761.04 3.1960.90 / 1.3060.43 30.166.0 Men 86 (51.5) 55.2613.3 15 (17.4) 40 (46.5) 53 (61.6) 28 (32.6) 54 (62.8) 131618 / 80611 5.761.0 5.0661.06 3.1460.90 / 1.2360.46 29.464.9 Women 51 (48.5) 57.0611.8 14 (17.3) 32 (39.5) 47 (58.0) 30 (37.0) 33 (40.7) 137623 / 78610 5.361.1 5.2961.01 3.3360.86 / 1.3860.38 30.966.9
Background The RACPC is a well-established one-stop service, with goal to identify patients with stable chest pain due to coronary artery disease (CAD) and quickly reassure those with non-cardiac pain. In March 2010, NICE published a new guideline, which advocates assessing likelihood of CAD based on age, gender, history and risk factors (RF). If estimated likelihood is >60%, invasive coronary angiography (ICA) is recommended as the rst-line diagnostic investigation. If estimated likelihood is 30%e60%, functional imaging is recommended. If estimated likelihood is <30%, CT calcium scoring CT coronary angiography (CTCA) is recommended. Signicantly, the guideline discourages the use of ETT to diagnose or exclude stable angina in patients without known CAD. Methods 167 consecutive patients referred to RACPC between October 2009 and March 2010 were retrospectively assessed for likelihood of CAD according to the new NICE guideline. Choice of investigations and eventual outcome (conrmed CAD vs no evidence of CAD) were compared between subgroups dened by estimated likelihood of CAD. An economic analysis of cost of investigation per patient was undertaken using current Payment by Results national tariffs. Results Our patient population had a high prevalence of RF with 38.1% having a total of three or more RF. Consequently 23.2% of patients had an estimated likelihood of CAD of <30%. 27.4% had an estimated likelihood of 30%e60%. 49.4% had an estimated likelihood of >60%. 7.2% of patients were lost to follow-up. 14.4% of patients were ultimately conrmed to have CAD on ICA, which correlated with pre-test estimated likelihood. 6% of patients with likelihood <30%, 8.7% of those with likelihood 30%e60% and 23.2% of those with likelihood >60% were conrmed to have CAD. Average cost of investigation per patient was 528. A negative ETT resulted in average cost per patient of 347. An inconclusive ETT resulted in higher cost (728) as did inability to exercise (435) due to the need for further investigations. A positive ETT resulted in average cost of 1174 due to the high cost of ICA. Were the NICE guideline strictly applied to our patient population, average cost per patient would have been substantially higher at 838 (362 per patient if likelihood <30%, 566 if likelihood 30%e60% and 1218 if likelihood >60%). Overall this corresponds to a 60% increase in cost. Conclusion The 2010 NICE guideline appears to signicantly overestimate the true risk in our patient population. Were the guideline strictly applied, almost half of our patients would proceed to ICA as a rst-line investigation, but many of them would be found to have unobstructed coronary arteries. As ICA is an expensive investigation, this would inevitably result in a signicant increase in average cost per patient. Relatively few patients would be eligible for CTCA, which is an excellent non-invasive rule-out test for CAD and relatively inexpensive compared with other investigations.
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Abstract 56 Table 2
Average cost per patient prior to NICE guideline implementation Predicted likelihood <30% Predicted likelihood 30%e60% Predicted likelihood >60% OVERALL AVERAGE COST PER PATIENT 324 467 661 528 Average cost per patient were NICE guideline strictly implemented 362 566 1218 838
57
THE IMPACT OF PREOPERATIVE RENAL DYSFUNCTION AND THERAPY TYPE IN PATIENTS WITH TYPE 2 DIABETES UNDERGOING CORONARY ARTERY BYPASS SURGERY
doi:10.1136/heartjnl-2011-300198.57
A Menon, J Hodson, D Pagano, J Mascaro, I C Wilson, S J Rooney, T R Graham, R S Bonser. University Hospital Birmingham, Birmingham, UK
Introduction There is limited data addressing the impact of preoperative renal dysfunction in type 2 diabetics (T2DM) undergoing rsttime coronary artery bypass surgery (CABG); specically exploring the inuence of diabetic management (oral hypoglycaemic (OH) and insulin therapy (IN)). We assessed the impact of preoperative renal status and diabetic management on the post operative renal status, morbidity, 30-day and long-term survival in T2DM-CABG. Methods We reviewed prospectively accrued data from 1/1/1999 to 31/12/2009. Pre and 4 to 5-day postoperative creatinine clearance
BCS Abstracts 2011

(CrCl) was calculated using Cockcroft-Gault formula. Patients were subgrouped into 5 grades based on preoperative CrCl; Group I CrCl$90 ml/min; II 60e89; III 30e59; IV 15e29; V <15 or haemodialysis. Late KaplaneMeier survival data (compared by log rank method), censored at 1/10/2009 were obtained from the UK CCAD. Surgical morbidity outcomes included re-exploration for bleeding, stroke (type 1 decit) and low cardiac output state (LCOS) requiring inotropes 6 intra-aortic balloon counterpulsation were compared using Fishers Exact tests. Results 1215 patients (921 males) with a mean age of 64 years (31e89 years) underwent CABG; 742 on OH and 472 on IN. Preoperative renal status in the groups were Group I -209(17%), II-584 (48%), III-387(32%), IV-26(2%) and V (8(1%). Similar percentages in each group had $1 grade deterioration of renal function postoperatively 19%, 18%, 16% and 23% (grades IeIV respectively; p0.470). When examined as a continuous variable, higher preoperative CrCl correlated with a better postoperative improvement in CrCl (r0.073, p0.012 Spearman Rank). Overall 30-day mortality was 3.33% (CI 2.32 to 4.34%) and was not different by group I-3.37% (CI 0.92 to 5.82), II-2.09% (CI 0.92 to 3.26%), III 4.92% (CI 2.76 to 7.08%), IV 8% (CI 0 to 18.6%) and Stage V 0% (CI 0 to 0.4%; p0.101) or by therapy type; (p0.411). IN patients had similar preoperative renal function (median CrCl 66.8 vs 68.6; p0.828) but a higher rate of postoperative renal deterioration (53.3 vs 46.7%, p<0.001). Stroke (p1.000), bleeding (p0.755) and LCOS (p0.335) incidence were not different between therapy type. Overall mean survival was 9 years (CI 8.7 to 9.2 years) and was not different by renal function grade (p0.612). However, IN patients had shorter mean survival 8.7 (8.3 to 9.0) vs OH 9.1(8.8 to 9.4) years; p0.03. Conclusions In T2DM-CABG, 36% of patients have CrCl <60 ml/min. Higher CrCl protects against postoperative renal deterioration. Renal dysfunction does not appear to affect hospital outcome or survival. However, preoperative IN requirement increases the risk of renal dysfunction and is associated with worse longer-term survival. EMMACE risk score, revascularisation, reperfusion, ACE-inhibitor, ablocker, statins, anti-platelet agent, admitting cardiologist) was used to compare the temporal long-term survival estimates (all cause mortality) by CR referral. Results 4341 had AMI. CR referral was 44% in 1995 and 59 % in 2003 (p<0.001). CR referral was associated with reduced mortality in 2003 (RRR, 95%CI: 0.54; 0.50 to 0.60), but was not in 1995 (1.02; 0.96 to 1.09). Unadjusted survival for patients not referral for CR in 1995 was similar to that for patients referred for CR in 1995; (Abstract 58 gure.1). For those referred for CR, the mean mini-GRACE score for CR referrals was lower in 2003 than 1995; 0.53 and 0.72, p<0.001. After adjustment using the min-GRACE score (Model 1), the impact (HR, 95% CI) of CR referral was 0.63, 0.55 to 0.73 in 2003 and 1.07, 0.92 to 1.3 in 1995. After adjustment using Model 2, the impact (HR, 95% CI) of CR referral was 0.57, 0.48 to 0.66 in 2003 and 1.31, 1.04 to 1.60 in 1995. Conclusion Between 1995 and 2003, referral for CR increased and became a signicantly important factor contributing to reduced mortality rates post-AMI. This is despite the differences in patient and treatment factors between the 2 studies periods. Even so, rate of referral for CR remain sub-optimal.
58
TEMPORAL EVALUATION OF REFERRAL FOR AND LONGTERM SURVIVAL FROM CARDIAC REHABILITATION FOR ACUTE MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.58
KaplaneMeier survival estimates.
C L Lewinter, M B Bland, P D Doherty, B L Lewin, A S H Hall, C P G Gale. University of York, York, UK; 2York St John University, York, UK; 3Yorkshire Heart Centre, Leeds, UK; 4University of Leeds, Leeds, UK
1
59
Background Cardiac rehabilitation (CR) is a cost-effective, evidencebased approach to managing heart disease. Rates of uptake have and continue to vary despite recommendations from the NSF for CHD and NICE. The Evaluation of the Management and Methods of Acute Coronary Events (EMMACE) 1 and 2 studies are 2 large prospective multi-centre registries of care of acute coronary syndromes (ACS) in Yorkshire undertaken in 1995 and 2003 in respectively. We studied the temporal changes in referral for and long-term survival from CR in patients who were admitted to hospital with an acute myocardial infarction (AMI). Methods Baseline characteristics were described as numbers (%) or as means with IQRs. For Continuous variables, the Kruskal Wallis test was used for comparisons. Discrete variables were assessed by the c2 test. Unadjusted relative risk ratios (RRR) were calculated to assess mortality after referral for CR. KaplaneMeier (KM) curves compared unadjusted survival stratied by CR referral and EMMACE study. Log rank tests compared the survival estimates. Sex, age, STEMI, heart failure, diabetes, COPD and mini-GRACE score, revascularisation, reperfusion, ACE-inhibitors, a-blockers, statins, anti-platelet agents and admitting cardiologist were regressed (backward logistic, p<0.10 and goodness of t with a group of 10) on CR referral and represented as 95% CI OR. A Cox proportional model (Model 1: mini-GRACE score, Model 2: sex, age, STEMI, heart failure, diabetes, COPD,
SHORT TERM ELEVATION OF CHOLESTEROL LEVEL IN NEONATAL LIFE AND LONG TERM CHANGES IN AORTIC STIFFNESS: INSIGHTS FROM USE OF INTRAVENOUS LIPIDS
doi:10.1136/heartjnl-2011-300198.59
A J Lewandowski, 1M Lazdam, 1E Davis, 1R Poole, 1J Diesch, 1J Francis, S Neubauer, 2A Lucas, 2A Singhal, 1B Kelly, 1P Leeson. 1Cardiovascular Medicine, University of Oxford, Oxford, UK; 2Institute of Child Health, University College London, London, UK
1
Introduction Offspring born to hypercholesterolaemic mothers have increased fatty streak formation in the fetal aorta, which persists into adolescence. To understand whether exposure to elevated cholesterol in early life, independent of a maternal history of hypercholesterolaemia, also has a long-term impact on the cardiovascular system we studied the vascular phenotype of adults in whom cholesterol levels were articially elevated for a short period postnatally. Methods We prospectively followed-up 102 subjects born premature now aged 23 to 28 years. Individuals exposed to maternal hypercholesterolaemia were excluded. 18 received intravenous (IV) lipids during the rst nine weeks of life and were matched 2:1 for pregnancy and early life complications, age, sex, birthweight and gestational age with controls that did not receive IV lipids. Aortic pulse wave velocity (aPWV), regional aortic distensibility, left ventricular mass and ejection fraction were determined by cardiovascular
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magnetic resonance. Detailed lifestyle information and anthropometric measurements were collected during childhood and adolescence. Metabolic parameters were measured multiple times per week for the rst 9 weeks of life and again at follow-up visits. Results Individuals that received IV lipids achieved signicantly higher maximum cholesterol levels during the rst 9 weeks of life than those that did not (mean6SD4.3861.65 vs 3.1260.78 mmol/ l, p0.006). Dose given and number of days on IV lipids also associated with maximum cholesterol level during this period (r0.557, p<0.001 and r0.567, p<0.001, respectively). There was a graded relation between the maximum elevation in circulating cholesterol postnatally and aortic stiffness (aPWV) in young adulthood (r0.596, p<0.001). The greatest increase in stiffness was seen in the abdominal aorta, where distensibility was signicantly reduced in the group that received IV lipids (mean6SD9.7464.27 vs 12.9164.11/mm Hg3103, p0.012). There were no differences between the groups in other vascular or left ventricular measures. In a stepwise regression model, maximum cholesterol level achieved in the rst few weeks of life was an independent predictor of aPWV in young adulthood (b0.596, p<0.001) and accounted for 30.9% of the variance in hierarchical multiple regression (b0.584, p<0.001). Conclusions Brief articial elevation of cholesterol level in immediate postnatal life is associated with long term changes in aortic function independent of later cholesterol levels. The association is graded depending on the degree of elevation of circulating cholesterol. High cholesterol exposure during sensitive periods of early postnatal life may have long term impacts on the cardiovascular system. elite level, since extrapolation of ECG and echocardiographic criteria, solely derived from Caucasian cohorts, would result in 25.6% of BA requiring further investigations for cardiac pathology.
Abstract 60 Figure 1 Bar chart depicting the distribution of left ventricular wall thickness in black and white adolescent athletes.
61
FIVE-MIN HEART RATE VARIABILITY CAN PREDICT OBSTRUCTIVE ANGIOGRAPHIC CORONARY DISEASE
doi:10.1136/heartjnl-2011-300198.61
60
ETHNIC DIFFERENCES IN REPOLARISATION PATTERNS AND LEFT VENTRICULAR REMODELLING IN HIGHLY TRAINED MALE ADOLESCENT (14e18 YEARS) ATHLETES
doi:10.1136/heartjnl-2011-300198.60
1 D Kotecha, 2G New, 1M Flather, 3D Eccleston, 3H Krum. 1Royal Brompton Hospital, London, UK; 2Box Hill Hospital, Melbourne, UK; 3Monash University, Melbourne, UK
N Sheikh, 1M Papadakis, 2F Carre, 2G Kervio, 1J Rawlins, 3V Panoulas, 1N Chandra, H Raju, 1R Bastiaenen, 1E Behr, 1S Sharma. 1St. Georges University of London, London, UK; 2French Institute of Health and Medical Research, University of Rennes, Rennes, France; 3University Hospital Lewisham, London, UK
1
Purpose Studies in adult, black athletes (BA) demonstrate a high prevalence of ECG repolarisation changes and echocardiographic left ventricular hypertrophy (LVH) that may overlap with hypertrophic cardiomyopathy (HCM). The prevalence of ECG repolarisation changes and echocardiographic LVH in adolescent BA, the group most vulnerable to exercise-related sudden death from HCM, is unknown. Methods This study evaluated 219 male adolescent BA (14e18 years, inclusive) with 12-lead ECG and 2-D echocardiography. Results were compared with 1440 male adolescent WA. Athletes with T wave inversions and morphological LVH were invited for further investigation with exercise stress test, 24 h Holter and CMR. Results ST segment elevation was common in both groups but more frequent in BA (63.5% vs 14.9%, p<0.001), while ST segment depression was exceedingly rare. Both T wave inversions (21.5% vs 2.9%, p<0.001) and deep T wave inversions (11% vs 0.3%, p<0.001) were commoner in BA. Black athletes demonstrated greater left ventricular wall thickness (10.461.6 vs 9.461.2 mm, p<0.001) compared to WA. Twenty-three (10.5%) BA exhibited a left ventricular wall thickness >12 mm vs only 6 (0.4%) WA (p<0.001). None of the athletes exhibited the broader phenotype of HCM on further investigation. In multivariable analysis black ethnicity was the strongest independent predictor for the presence of T wave inversions (OR 3.56, 95% CI 1.56 to 8.13, p0.003) and LVH (OR 3.17, 95% CI 1.77 to 5.71, p<0.001). Conclusions As with adult athletes, Twave inversions and LVH were more prevalent in adolescent BA compared to WA. These ndings have important implications in the pre-participation screening era, particularly in countries with a high proportion of BA competing at
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Background Obstructive coronary artery disease (CAD) is evident in only half of patients referred for diagnostic coronary angiography. Five-minute heart rate variability (HRV) is a marker for autonomic control of the vasculature, which we hypothesised could be used to risk-stratify cardiac patients (the Alternative Risk Markers in Coronary Artery Disease (ARM-CAD) study. Methods Resting HRV prior to elective coronary angiography was analysed in 470 participants with predominantly normal cardiac rhythm, regardless of comorbidity. The presence of obstructive CAD ($50% stenosis) was regressed in a multivariate model including risk factors, ECG variables and medications. Results Mean age was 65 years (SD 11), 67% were male, 21% had diabetes, mean blood pressure was 144/79 mm Hg (SD 21/10) and 16% had impaired left-ventricular function. Patients with obstructive CAD had signicantly reduced HRV, particularly in the low frequency (LF) range (median 180 vs 267 ms2 without CAD; p<0.001). There was a linear trend according to the severity of CAD; the median LF power (IQR) in patients with normal coronaries was 275 (612), with minor coronary irregularities 255 (400),
BCS Abstracts 2011

single-vessel CAD 212 (396) and more severe disease 170 (327) ms2; p-value for trend0.003. There was a similar reduction in LF power regardless of the anatomical location of coronary stenoses (see Abstract 61 gure 1). Comparing patients with LF<250 and $250 ms2, the OR for obstructive CAD was 2.42, 95% CI 1.33 to 4.38 (p0.004) after adjusting for risk factors, medications and heart rate. No interactions were noted in sub-group analysis of age, gender, diabetes, prior cardiovascular disease or high-sensitivity CRP. In addition, HRV added to risk prediction irrespective of baseline Framingham risk (p<0.0001). Conclusion Low HRV is strongly predictive of angiographic coronary disease regardless of other comorbidities and is clinically useful as a risk predictor in patients with sinus rhythm.
Comparison CHADS2 & CHA2DS2-VASc scores.
62
WILL THE NEW EUROPEAN AF GUIDELINES LEAD TO MORE PATIENTS RECEIVING ORAL ANTICOAGULATION THERAPY?
doi:10.1136/heartjnl-2011-300198.62
T Kaier, R Williams, S Khan. West Middlesex University Hospital, London, UK
63
Atrial brillation (AF) confers a 5-fold risk of stroke and the risk of death from AF-related stroke is doubled; it is the most common sustained cardiac arrhythmia, occurring in 1%e2% of the general population. Meta-analysis of anti-platelet therapy demonstrate a non-signicant 19% reduction in the incidence of stroke, proving oral anticoagulation (OAC; such as warfarin) to be far superior (64% relative risk reduction) in stroke prevention. Recent guidelines have been published by the European Society of Cardiology (ESC) which focus on the most effective antithrombotic therapy in AF and propose a new risk scoring system, the CHA2DS2-VASc score. In our institution the prescription and documentation of antithrombotic therapy in AF has been the focus of a previous audit that demonstrated poor compliance with the guidelines and documentation of decision making. The focus of this audit was twofold: rst to determine whether compliance with the guidelines and documentation had improved and second determine the effect of the new risk scoring system on prescription of OAC. A random 10% of cases of patients discharged with a coding diagnosis of AF were selected (125 cases). They were risk assessed using the NICE 2006 stroke risk stratication, CHADS2 and CHA2DS2-VASc score. In all cases the agent used for thromboprophylaxis was reviewed as to whether NICE recommendations had been met. The scoring systems were compared to identify patients in whom the ESC guidelines would change treatmentie, OAC instead of Aspirin or as rst line antithrombotic therapy. Of the 125 selected case notes 114 arrived in time for analysis; out of these 8 were excluded due to erroneous coding as AF. 106 patients were risk stratied, of whom 68.22% (73) were high risk, 28.04% (30) moderate and 2.80% (3) low risk according to NICE guidelines. 74.77% (80) scored 2 or more points on the CHADS2 risk assessmentthis number increased to 93.46% (100) if CHA2DS2-VASc was applied, for whom OAC would be the recommended antithrombotic therapy (see Abstract 62 gure 1). Only 57.50% or 61 patients were on the appropriate choice of thromboprophylaxis if the NICE guideline was used as risk assessment. 73.77% (45) of patients had no formal documentation why NICE guideline had not been followed; this mostly comprised patients who were on Aspirin but, correctly risk assessed, were candidates for OAC. We extrapolate our ndings to suggest that in an average sized DGH, 200 patients more per year would be considered high thromboembolic risk and hence appropriate for OAC. This audit shows that the rate of appropriate anti-coagulation among patients with AF is still low and could be improved further. The new ESC guidelines add to this challenge as signicantly more patients will be considered for OAC therapy.
IMPLICATIONS OF A LIKELIHOOD BASED APPROACH TO DIAGNOSTIC TESTING IN CORONARY ARTERY DISEASE: IMPACT OF THE NEW NICE GUIDELINES
doi:10.1136/heartjnl-2011-300198.63
I U Haq, J S Skinner, P C Adams. Royal Victoria Inrmary, Newcastle upon Tyne, UK
Background The NICE clinical guideline for chest pain of recent onset (NCG 95) published in March 2010 recommends diagnosing angina based on clinical assessment and likelihood of coronary artery disease (CAD). If the estimated likelihood of CAD is 61%e 90%, coronary angiography should be offered. If 30%e60%, functional imaging should be offered, and if 10%e29%, CT calcium scoring should be offered. We determined the number and types of different investigations to diagnose coronary artery disease in patients referred with suspected cardiac pain before the publication of NCG 95 and compared this with the predicted investigations after the application of the guidelines. Methods Data was collected prospectively in a bespoke database for patients referred to the Rapid Access Chest Pain Clinic, Newcastle upon Tyne, UK. Patients with chest pain of suspected cardiac origin were referred from primary care between February 2002 and March 2010. Patients with previous MI, PCI or CABG were excluded. The analysis comprised 5598 men and women with no past history of coronary disease. Likelihood of CAD was calculated by the Pryor equation using the variables age, sex, type of chest pain (typical or atypical), ECG Q waves, smoking, hyperlipidaemia, diabetes and ST/T changes on ECG. The main outcome measures were actual and predicted future frequency of exercise tests, CT coronary angiograms, functional imaging tests and invasive coronary angiograms by pretest likelihood of coronary artery disease. Results The proportion of the study population before and after the guidelines undergoing exercise testing was 50.1% vs 0.0%; for calcium score/CT coronary angiography 0.0% vs 14.7%; for functional imaging 25.6% vs 13.4%; and for invasive coronary angiography 15.3% vs 25.8%. The proportion not requiring further testing was unchanged (30.0% vs 31.0%). Conclusions Application of NICE CG95 will change the investigation of patients with chest pain substantially. A signicant reallocation of resources will be required. Exercise testing will be replaced by anatomic or functional imaging. CT coronary angiography will play an important role and replace functional imaging in some patients. Invasive angiography will take on a more important role in the diagnosis of coronary artery disease. It will, however, empower us to reassure almost a third of referrals that they do not have angina on clinical assessment alone.
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64
DIAGNOSTIC ACCURACY OF EXERCISE STRESS TESTING IN INDIVIDUALS WITHOUT KNOWN CORONARY ARTERY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
doi:10.1136/heartjnl-2011-300198.64 A Banerjee, D Newman, A Van den Bruel, C Heneghan. 1West Midlands Deanery, Birmingham, UK; 2Department of Primary Care, University of Oxford, Oxford, UK
1 2 2 2
Background Exercise stress testing offers a non-invasive, less expensive way of risk stratication prior to coronary angiography, and a negative stress test may actually avoid angiography. However, previous meta-analyses have not included all exercise test modalities, or patients without known coronary artery disease. Objectives To systematically review the literature to determine the diagnostic accuracy of exercise stress testing for coronary artery disease on angiography. Search methods MEDLINE (January 1966eNovember 2009) and EMBASE (1980e2009) databases were searched for articles on diagnostic accuracy of exercise stress testing. Selection criteria We included prospective studies comparing exercise stress testing with a reference standard of coronary angiography in patients without known coronary artery disease. Results From 6055 records, we included 34 studies with 3352 participants. Overall, we found published studies regarding ve different exercise testing modalities: treadmill ECG, treadmill echo, bicycle ECG, bicycle echo and myocardial perfusion imaging. The prevalence of CAD ranged from 12% to 83%. Positive and negative likelihood ratios of stress testing increased in low prevalence settings. Treadmill echo testing (LR+ 7.94) performed better than treadmill ECG testing (LR+ 3.57) for ruling in CAD and ruling out CAD (echo LR 0.19 vs ECG LR 0.38). Bicycle echo testing (LR+ 11.34) performed better than treadmill echo testing (LR+ 7.94), which outperformed both treadmill ECG and bicycle ECG. A positive exercise test is more helpful in younger patients (LR+ 4.74) than in older patients (LR+ 2.8). Conclusions The diagnostic accuracy of exercise testing varies, depending upon the age, sex and clinical characteristics of the patient, prevalence of CAD, and modality of test used. Exercise testing, whether by echocardiography or ECG, is more useful at excluding CAD than conrming it. Clinicians have concentrated on individualising the treatment of CAD, but there is great scope for individualising the diagnosis of CAD using exercise testing.
Probability of coronary artery disease.
65
OUTCOMES AFTER CARDIAC SURGERY: ARE WOMEN OF SOUTH ASIAN ORIGIN AT INCREASED RISK?
doi:10.1136/heartjnl-2011-300198.65
D A George, D Morrice, A M Nevill, M Bhabra. 1New Cross Hospital, Wolverhampton, UK; 2University of Wolverhampton, Wolverhampton, UK
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Objectives The population served by our centre has a relatively high proportion of people originating from the Indian subcontinent (South Asians) compared to the national average (14.3% vs 4.6%). We observed that the mortality rate in South Asian women undergoing cardiac surgery in our unit appeared to be relatively high. We investigated this observation further to determine whether ethnic origin was an independent risk factor for postoperative death in females. Methods Data for all patients undergoing cardiac surgery were collected prospectively in a registry. Retrospective analysis was carried using SPSS on data for 4901 patients operated on in the 6year period April 2004 to March 2010. Categorical data associated with mortality were analysed using c2 tests. Risk factors for inhospital mortality were subjected to univariate analysis, and those found to be signicant were tested for independence using multivariate logistic regression. Results During the study period, 1160 female patients underwent surgery with a mortality rate of 4.7%. Mortality in 113 South Asians was 8.9% vs 4.3% in non-Asians (p0.03). Of 20 risk factors tested with univariate analysis, 16 were signicantly associated with mortality. Logistic regression showed the following to be independent predictors of postoperative mortality: urgency of operation (OR 32.0; p<0.001), older age (OR 24.2; p<0.001), preoperative renal dysfunction (OR 15.8; p<0.001), diabetes (OR 7.8; p0.005), South Asian ethnicity (OR 7.3; p0.007), extra-cardiac arteriopathy (OR 4.8; p0.028), and an operation other than isolated CABG (OR 5.8; p0.016). Conclusions In our population, South Asian ethnicity appears to be an independent risk factor for mortality in females undergoing cardiac surgery. Studies in larger populations are warranted.
BCS Abstracts 2011

66
ETHNIC DIFFERENCES IN CAROTID INTIMAL MEDIAL THICKNESS AND CAROTID-FEMORAL PULSE WAVE VELOCITY ARE PRESENT IN UK CHILDREN
doi:10.1136/heartjnl-2011-300198.66
1 2
P H Whincup, C M Nightingale, A Rapala, D Joysurry, 2M Prescott, 2A E Donald, E Ellins, 1A Donin, 2S Masi, 1C G Owen, 1A R Rudnicka, 1D G Cook, 2J E Deaneld. 1 Division of Population Health Sciences, St Georges, University of London, London, UK; 2 Vascular Physiology Unit, Institute of Child Health, UCL, London, UK
Introduction There are marked ethnic differences in cardiovascular disease risks in UK adults; South Asians have high risks of coronary heart disease and stroke while black African-Caribbeans have high risks of stroke and slightly low risks of coronary heart disease when compared with white Europeans. Ethnic differences in cardiovascular risk factors are apparent in childhood, but little is known abut ethnic differences in vascular structure and function during childhood. We set out to measure two vascular markers of cardiovascular risk, common carotid intimal-medial thickness (cIMT) and carotidfemoral pulse wave velocity (PWV) in UK children from different ethnic groups. Methods We conducted a school-based study examining the cardiovascular risk proles of 9e10 year-old UK children, including similar numbers of South Asian, black African-Caribbean and white European participants. Following a baseline cardiovascular risk survey with measurements of body build, blood pressure, fasting blood lipids, insulin and HbA1c, 1400 children were invited to have measurements of cIMT (bilateral measurements were made with a Zonare ultrasound scanner). A subgroup of these children (n900) was also invited for PWV measurements, made with a Vicorder device. All analyses were adjusted for age, gender and allowed for clustering at school level. Results In all, 939 children (67% response) had measurements of cIMT and 631 children (70% response) had measurements of PWV. Mean cIMT was 0.475 mm (SD 0.035 mm); mean PWV was 5.2 m/s (SD 0.7 m/s). Compared with white European children, black African-Caribbeans had higher cIMT (mean difference 0.014 mm, 95%CI 0.008 to 0.021 mm) and PWV (% difference 3.3, 95%CI 0.4 to 6.2); South Asian children had similar cIMT to white Europeans but slightly higher PWV (% difference 2.7, 95%CI 0.1 to 5.5%). cIMT was positively associated with systolic and diastolic blood pressure but not with other cardiovascular risk markers. In contrast, PWV was positively associated with adiposity, diastolic blood pressure and insulin resistance. Black African-Caribbean children had lower LDL-cholesterol levels and higher insulin and HbA1c levels than white Europeans; South Asian children had higher insulin, HbA1c and triglyceride levels. However, adjustment for these risk factors had little effect on the ethnic differences in cIMT and PWV observed. Conclusions Ethnic differences in cIMT and PWV, markers of longterm cardiovascular risk, are apparent in childhood. These differences are not fully explained by the ethnic differences in established cardiovascular risk markers observed. The results suggest that there may be important opportunities for prevention of cardiovascular disease before adult life, particularly in high-risk ethnic minority groups.
reported at around 30% in many pivotal heart failure studies. DM is an independent predictor of mortality in patients with HF, however molecular mechanisms that contribute to HF development in the diabetic population are poorly understood. Using a novel human relevant mouse model of DM (GENA348), identied through the MRC mouse mutagenesis programme with a point mutation in the pancreatic glucokinase (GLK) gene we investigate the molecular mechanisms that contribute to the HF phenotype in DM. GLK is the glucose sensor which regulates insulin secretion and GLK activity is reduced by 90% by the GENA348 point mutation resulting in severe hyperglycaemia. Similar mutations underlie Maturity Onset Diabetes of the Young Type 2 (MODY 2) in humans. Mean random blood glucose was found to be increased in the GENA348 mutant (HO) mice compared to wild type (WT) littermates (WT 6.960.3 mmol/l vs HO 20.660.8 mmol/l, p<0.001). Serial echocardiography was performed, at 3, 6 and 12 months. No signicant changes in echocardiographic parameters were observed at 3 months, although by 6 months development of signicant cardiac hypertrophy in HO mice was observed. At 12 months of age left ventricular dilatation was evident, characterised by an 8% increase in diastolic diameter (WT 4.0860.10 vs HO 4.4160.12, p<0.05). Systolic function was preserved although signicant diastolic dysfunction was evident at 6 and 12 months with a 31% reduction in the E:A ratio. Histological staining illustrated signicant cellular hypertrophy with real time PCR data demonstrating a relative 150% increase in the hypertrophic marker BNP. Hypertrophic pathways were examined through western blot analysis revealing an age dependant increase in Akt phosphorylation (3 months- no increase, 6 months-140%, 12 months-460%). Serum levels of advanced glycation end products (AGE) were also elevated by 86% (WT 2163.5 ng/ml vs HO 3968.3 ng/ml, p<0.05) as was the protein expression level of the receptor for AGEs (RAGE). In vitro cellular experiments also revealed AGEs directly activate Akt through phosphorylation and increase levels of the receptor RAGE. AGE induced phosphorylation of Akt is inhibited in the presence of wortmannin, suggesting a PI3K dependent signalling mechanism. This was further conrmed in vivo where a bolus injection of wortmannin in 6-month old mutant mice returned Akt phosphorylation levels to those seen in WT mice. In conclusion, using the rst human relevant mouse model of diabetes, GENA348 we demonstrate the development of a progressive cardiac phenotype including cardiac hypertrophy, LV dilatation and diastolic dysfunction similar to the clinical manifestations of diabetic cardiomyopathy. We propose that the RAGE/PI3K/Akt pathway contributes to the molecular mechanisms associated with the cardiac phenotype.
68
RARE ALLELES IN GENETIC PREDISPOSITION TO CORONARY ARTERY DISEASE: INSIGHTS FROM THE NOVEL ANALYSIS OF GENE-CENTRIC ARRAY
doi:10.1136/heartjnl-2011-300198.68
P Christodou, 1R Debiec, 1C P Nelson, 1P S Braund, 1L D S Bloomer, 2S G Ball, A J Balmforth, 2A S Hall, 1M Tomaszewski, 1N J Samani. 1University of Leicester, Leicester, UK; 2University of Leeds, Leeds, UK
2
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SPONTANEOUS CARDIAC HYPERTROPHY AND ADVERSE LV REMODELLING IN A NOVEL HUMAN RELEVANT MOUSE MODEL OF DIABETES; A MECHANISTIC INSIGHT
doi:10.1136/heartjnl-2011-300198.67
1 1
S M Gibbons, 1Z Hegab, 1M Zi, 1S Prehar, 1T M A Mohammed, 2R D Cox, E J Cartwright, 1L Neyses, 1M A Mamas. 1University of Manchester, Manchester, UK; 2 MRC mammalian genetics unit, oxford, UK
Heart failure (HF) is one of the commonest cardiovascular complications of Diabetes Mellitus (DM) with the prevalence of DM
Background Genome-wide association studies have been successful in identifying association between several common variants and coronary artery disease (CAD). However, collectively these variants explain only a small proportion of CAD heritability. It is becoming increasingly clear that the remainder of the missing CAD heritability could be explained by low frequency/rare alleles. Because of the small number of observations for any given rare allele, the power to detect its association with a phenotype is a major limiting factor in genetic analysis. In this study we have undertaken a novel statistical approach that combines information from all low frequency
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(MAF<5%) SNPs at one locus in gene-centric analysis of CAD. We hypothesised that patients with CAD will show over-representation of rare alleles compared to controls. Methods To examine associations between rare alleles and CAD, we have used data from 2119 CAD cases and 2440 healthy controls recruited to the Welcome Trust Case-Control Consortium (WTCCC) Study. DNA from each subject was genotyped for approximately 45 000 SNPs in more than 2000 genes/loci using 50K IBC array (version 1). Association analysis was based on the CCRaVAT (Case-Control Rare Variant Analysis Tool) algorithm that maximises statistical power by combining all rare alleles within dened regions into a single super locus. Differences in the proportion of cases and controls carrying rare super loci were tested by Pearsons or Fishers exact test. Empirical p values were generated by permuting case-control status a predened number of times and repeating the analysis for each replicate. Results 5 candidate regions (MMP23B, VEGFA, DVL1, RIPK1, LPAL2) showed an over-accumulation of rare alleles in patients with CAD when compared to controls (FDR<50%). The number of analysed rare alleles at each of these loci ranged from 4 to 42. The most signicant over-representation of rare variants were identied at MMP23B (matrix metallopeptidase 23B gene; p1.3/104), a gene previously unsuspected to play a major role in CAD and VEGFA (vascular endothelial growth factor A; p2.63104). Only one of the identied genes (LPAL2; p1.73103) lies within the locus that was previously shown to harbour rare variants associated with susceptibility to CAD. Conclusions Rare alleles are associated with predisposition to CAD and this gene-centric analysis combining information from lowfrequency variants of the same locus has a potential to uncover, at least a proportion of, the missing heritability of CAD. tional importance of differences in methylation level in cases and controls for individual genes, we examined the relationship of methylation level to transcript level in monocytes and macrophages on a gene by gene basis and identied several genes including GNAS and PCMT1 that showed signicant correlations between gene expression and methylation. Pathway enrichment analysis of the differentially methylated genes using the DAVID bioinformatics resource identied a number of pathways that showed signicant enrichment including the calcium signalling pathway (p3.853107). Conclusions This pilot study has shown several signicant differences in gene methylation patterns between CAD cases and controls. We also found a correlation between methylation level and gene expression for a number of these genes. Genes differentially methylated in CAD are signicantly enriched for a number of pathways including the calcium signalling pathway. While these ndings require further validation they suggest that epigenetic changes may play an important role in the pathogenesis of CAD.
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1 1
GENE EXPRESSION AT THE 9p21 LOCUS AND CAD RISK

doi:10.1136/heartjnl-2011-300198.70
C P Nelson, P Lundmark, V Codd, A H Goodall, 2A C Syvanen, 1N J Samani. Department of Cardiovascular Sciences, University of Leicester, Gleneld Hospital, Leicester, UK; 2Department of Medical Sciences, Molecular Medicine, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
69
GENOME WIDE METHYLATION ANALYSIS IN CORONARY ARTERY DISEASE

doi:10.1136/heartjnl-2011-300198.69
K J Dick, C P Nelson, P S Braund, A H Goodall, N J Samani. University of Leicester, Leicester, UK
Background Using genome-wide association studies several genes have been identied that affect the risk of CAD. However, these genes only explain part of the heritability. There is increasing evidence of the role of epigenetic regulation in complex diseases that may explain part of the missing heritability. DNA methylation is an important epigenetic change that regulates gene expression. Any role of methylation in CAD is poorly understood. Therefore we undertook an exploratory genome-wide screen to identify genes differentially methylated in CAD cases and controls. Methods We characterised DNA methylation in 24 CAD patients with a documented history of MI and 24 matched controls from the Cardiogenics case-control cohort. All subjects were male, ranging in age from 40 to 57 years. For each subject, genomic DNA, isolated from whole blood, was bisulphite converted and run on Illumina HumanMethylation27 bead chips. The HumanMethylation27 chips interrogate 27 578 CpG sites spanning 14 495 genes with an average of 2 CpG sites per gene. Results Global DNA methylation level was signicantly higher in cases compared to controls (p9.03104). Furthermore, 686 individual CpG sites, spanning 633 genes showed statistically signicant differences in methylation levels between cases and controls. Signicant signals after Bonferroni correction for multiple comparisons included GNAS (p7.943105), which is involved in receptormediated signal transduction, PCMT1 (p7.943105), ACD (p3.483104 part of the telosome/shelterin complex), ATXN2 and APOA1 (p5.63103 and p0.01). To explore the potential funcA42
Background Human chromosome 9p21 harbours a locus that affects risk of coronary artery disease (CAD) through an unknown mechanism. The variants at the locus most strongly associated with CAD lie in non-coding regions suggesting that the affect on CAD risk may be mediated through regulation of gene expression. We investigated the association of single nucleotide polymorphisms (SNPs) across the locus with expression of genes in the locus and compared this with association of the same SNPs with CAD risk. Methods We quantied transcript levels for CDKN2A, CDKN2B, ARF and MTAP in circulating monocytes from 422 healthy blood donors and 386 CAD cases and obtained genotypes for SNPs in the 9p21 region in the same subjects using genome-wide platforms. We also quantied allelic expression (AE) for these genes and for ANRIL in 186 of the healthy blood donors. We compared expression quantitative trait loci (eQTL) associations for the genes with association ndings for the same SNPs for CAD in the Wellcome Trust Case Control Consortium study. Results In the global gene expression analysis, we found strong cis eQTLs for both CDKN2B (p1.331038) and MTAP (p6.631023), explaining 17.0% and 8.0% of the expression of these genes. AE analysis conrmed these ndings (CDKN2B, p6.031064; MTAP, p1.431038) and also showed a signicant cis-eQTL effect on ANRIL expression (p3.531028). Interestingly, the SNPs associated with CDKN2B and ANRIL expression were the same. However, the SNPs showing e-QTL effects were distinct from SNPs that showed an association with CAD risk (p2.231012). Even in the region with a physical overlap of variants affecting expression of CDKN2B/ANRIL and CAD risk, the effects of the respective variants were independent of each other. Expression of CDKN2A and ARF was low but did not show any obvious eQTL effect, or differences according to genotype at CAD-associated SNPs. Conclusions Our ndings in monocytes do not support the hypothesis that the chromosome 9p21 locus mediates CAD risk by affecting expression of the genes at the locus. The mechanism by which the chromosome 9p21 locus affects CAD risk requires further elucidation.
BCS Abstracts 2011

71
A GENOME-WIDE ASSOCIATION STUDY IN INDIAN ASIANS IDENTIFIES FOUR SUSCEPTIBILITY LOCI FOR TYPE-2 DIABETES
doi:10.1136/heartjnl-2011-300198.71 J Sehmi, D Salaheen, Y Yeo, W Zhang, 1,2D Das, 6M I McCarthy, 4E S Tai, J Danesh, 1,2J Kooner, 2,7J Chambers. 1National Heart and Lung Institute, Imperial College, London, UK; 2Ealing Hospital NHS Trust, London, UK; 3Department of Public Health and Primary care, Cambridge University, Cambridge, UK; 4Department of Medicine, National University of Singapore, Singapore; 5Department of Epidemiology and biostatistics, Imperial College London, London, UK; 6Wellcome Trust for human Genetics, Oxford University, Oxford, UK; 7Department of Epidemiology and biostatistics, Imperial College London, London, UK
3 1,2 3 4 5
Background Type-2 diabetes (T2D) is a major risk factor for cardiovascular disease, and a leading causing of mortality worldwide. T2D is 2e4 fold more common among Indian Asians than Europeans, and contributes to higher cardiovascular disease mortality in Asians. Little is known of the genetic basis of T2D in Indian Asians. Methods We carried out a genome-wide association (GWA) study of T2D in 5561 Indian Asian cases and 14 458 controls from LOLIPOP, PROMIS and SINDI cohorts. Whole genome scans were performed using the Illumina 317 k or 610 k arrays. Further testing of suggestive SNPs was carried out in independent cohorts of Indian Asian (12 K T2D cases and 25 K controls) and European ancestry (DIAGRAM+, 8 K T2D cases and 39 K controls). Results There were two novel loci associated with T2D at p<106, and an additional 57 loci associated with T2D at p<104 in the GWA study. We used results from DIAGRAM+ to prioritise 19 loci for further testing in Indian Asians. In combined analysis of results from GWA and further testing, four loci now reached genome-wide signicance (p<53108) among Indian Asians. Coding variant and eQTL studies at these loci identify genes closely involved in insulin secretion and signalling. Conclusion We identify four novel genetic loci associated with T2D in Indian Asians. Our observations provide new insights into the biological mechanisms underlying T2D, a major risk factor for cardiovascular disease.
sodium nitroprusside (NO donor) (100mM) from 24-h post fertilisation (hpf) until imaging at 4dpf. Results Imaging of the developing trunk vasculature revealed that vhl mutant embryos display excessive and aberrant angiogenesis from 3dpf (Abstract 72 gure 1A, B). Cardiac troponin T2 knockdown prevented any cardiac contraction, but embryos develop normally due to passive oxygen diffusion. Loss of blood ow did not alter normal intersegmental vessel patterning in either controls (Abstract 72 gure 1C) or vhl mutants (Abstract 72 gure 1D). However, loss of blood ow completely prevented excessive angiogenesis in vhl mutants (Abstract 72 gures 1D and 2), implying that both blood ow and hypoxic signalling are required for pathological angiogenesis but not developmental angiogenesis (vasculogenesis). NO synthase inhibition with L-NAME had no effect, suggesting that the contribution of ow to excessive angiogenesis in response to upregulated hypoxic signalling is NO independent.
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ANGIOGENESIS IN RESPONSE TO UPREGULATED HYPOXIC SIGNALLING IS DEPENDENT ON HAEMODYNAMIC FLOW

doi:10.1136/heartjnl-2011-300198.72
O J Watson, F J van Eeden, C Gray, T J A Chico. 1MRC Centre for Developmental Biology and Genetics, University of Shefeld, Shefeld, UK; 2NIHR Cardiovascular Biomedical Research Unit, Shefeld Teaching Hospitals NHS Foundation Trust, Shefeld, UK
Introduction Hypoxia drives angiogenesis in a range of pathologies. Mutations in von hippel lindau protein (vhl) lead to excessive angiogenesis via upregulation of hypoxic signalling, due to impaired HIF-1a degradation. Physical forces exerted by blood ow have been shown to contribute to vascular remodelling. We therefore used vhl mutant zebrash to observe the interplay between hypoxic signalling, haemodynamic ow and vascular development. Since NO has been shown to be both pro-angiogenic and released in response to haemodynamic force, we assessed whether NO contributed to angiogenesis in this model. Methods Vhl mutant zebrash were crossed with a i1; GFP transgenic that expresses Green Fluorescent Protein (GFP) in the endothelium. Embryonic vascular development was observed in mutants and wild type siblings by confocal microscopy. To determine the role of blood ow in the angiogenic response, cardiac troponin t2 was knocked down by morpholino antisense injection. To assess the contribution of nitric oxide, embryos were treated with either L-NAME (nitric oxide synthase inhibitor) (1mM) or
Abstract 72 Figure 2 length.
Effect of troponin T knockdown on total vessel
Conclusion Angiogenesis in response to hypoxic signalling is critically dependent upon haemodynamic force, compared with developmental vasculogenesis that can proceed in the absence of any blood ow. This indicates a different mechanism of development for hypoxia driven angiogenesis and vasculogenesis which may have important therapeutic implications.
73
HERITABILITY OF CORONARY FLOW RESERVE

doi:10.1136/heartjnl-2011-300198.73
R Ahmed, P Muckett, S Cook. Clinical Sciences Centre, Imperial College, London, UK
Introduction Coronary ow reserve (CRF) is the ratio of peak coronary ow during maximal coronary artery dilatation to basal
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BCS Abstracts 2011

coronary ow and is an important predictor of coronary microvascular function. A variety of environmental stimuli have been shown to affect CFR but little is known about the genetic component of CFR. To characterise the genetics of CFR we initially measured in vivo blood pressure (BP) and ex vivo cardiac phenotypes including CFR in two inbred rat strains, Brown Norway (BN) and Spontaneously Hypertensive Rat (SHR) which is a genetic model for hypertension and microvascular dysfunction. We then studied BP and coronary ow (CF) phenotypes in F1 and F2 crosses derived from BN and SHR to estimate the heritability of CFR and its relationship with BP. Methods Animals were anaesthetized using a mixture of Oxygen and Isourane. BP was measured invasively by cannulation of carotid artery. Following BP measurement hearts were excised and rapidly transferred to the ex vivo perfusion apparatus where retrograde perfusion was established using the Langendorff technique. Hearts were perfused with Carbogen buffered Kreb9 s solution and paced constantly at 360 bpm. A uid lled balloon was placed in the left ventricular (LV) cavity to measure the pressure indices. CF, LV developed pressure, myocardial contractility (LV dP/dtmax) and myocardial relaxation (LV dP/dtmin) were recorded at baseline, during peak hyperaemia, regional ischaemia (induced by ligation of the proximal left anterior descending artery) and reperfusion. Results 1) CFR differs signicantly between the two inbred parental rat strains. (BN2.1 6 0.32, SHR1.5 6 0.18, p2.63107, n16 each). 2) Heritability of CFR: Broad sense heritability (the proportion of total phenotypic variance attributable to total genetic variance) for CFR is 62% indicating a large and previously unrecognised genetic component of CFR. 3) Relationship between CFR and BP: We did not nd statistically signicant correlation between CFR and BP in the F2 intercross (r0.11, p0.11, n176). 4) Relationship between CF and myocardial relaxation (LV dP/dtmin): LV dP/dtmin correlated strongly with CF during all stages of the experiment (baseline CF, r0.36, p<0.0001, reperfusion CF, r0.40, p<0.0001). Conclusions Our results demonstrate that CFR has a signicant genetic component and is largely independent of BP effects. Furthermore we demonstrate a very signicant relationship between CF and LV dP/dtmin indicating a link between LV diastolic dysfunction and impaired CF. Using 768 SNP genotyping assay for linkage mapping and gene expression analysis with Affymetrix rat gene chip, we will determine the quantitative trait loci and transcripts associated with CFR to improve our understanding of the genomic architecture of CFR.
Correlation between BP and CFR.
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MECHANISTIC STUDY FOR THE ROLE OF ADVANCED GLYCATION END PRODUCTS IN THE DEVELOPMENT OF DIABETIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.74
Z Hegab, T M A Mohammed, L Neyses, M Mamas. Manchester University, Manchester, UK
Coronary ow reserve.
Advanced glycation end products (AGEs) are thought to play a crucial role in the development of diabetic complications including heart failure, a leading cause of morbidity and mortality in diabetic patients. However, the molecular mechanisms that underlie the pathophysiological contribution of AGEs to heart failure development are not yet fully understood. We therefore investigated the effects and mechanisms of action of AGEs on isolated neonatal rat cardiomyocytes (NRCM). Standard molecular techniques were applied. Western blot showed that RAGE receptor is expressed in NRCM and adult mouse cardiomyocytes. Incubation of NRCM for 24 h with AGEs showed a dose dependant reduction of calcium transient amplitude with a maximum of 52% at 1 g/l (p<0.01) accompanied with 32% reduction in SR calcium content with no signicant changes in the protein expression of calcium handling proteins. We demonstrated a 24% increase (p<0.01) in the production of reactive oxygen species ROS in AGE treated cardiomyocytes mediated through increased NADPH oxidase activity (p<0.05). Subsequent translocation of NF-KB, a transcriptional factor from the cytoplasm to the nucleus together with increased NF-KB activity resulted in a 56% increase in iNOS gene protein expression (p<0.01), a downstream target of NF-KB. The latter was associated with 10% increase in NO production (p<0.05) with subsequent nitrosylation of the Ryanodine receptor shown through immunouoresence. Changes in calcium transient were completely inhibited when we incubated the cardiomyocytes with inhibitors of NADPH oxidase, NOS or NF-KB prior to their incubation with AGEs. In conclusion, AGEs directly decline cardiomyocytes function through binding to their RAGE receptor leading to calcium handling impairment through increased ROS production inducing activation and translocation of NF-KB to the nucleus. The latter increased transcription of iNOS with increased NO production. Coexistence
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BCS Abstracts 2011

of ROS and NO favours the production of peroxynitrite that is capable of nitrosylation of key cellular proteins such as the Ryanodine receptor that has a crucial role in cardiac excitationcontraction coupling. This study provides novel insights into the mechanisms of cardiac damage in diabetes that occur independent of vascular disease through AGEs. patients attended the pre and post CRT nurse clinic to optimise medical therapies and provide adjunctive HF support. Abstract 75 table 1 describes the frequency of use and daily dose equivalent of each class of medication used in the patients prior to and 6 months after device implantation. The frequency of bB and digoxin use increased by 10% and 5% respectively. In addition, the dose of bB, ACE-I/ARB, and digoxin signicantly increased, while the dose of loop diuretics signicantly reduced in the 6 months after CRT implantation. Conclusions The benecial haemodynamic and pacing proles provided by CRT offer important opportunities to further optimise heart failure medications after device implantation. In a dedicated nurse-led CRT follow-up clinic, we successfully initiated b blockers and digoxin in previously naive patients, and signicantly uptitrated the doses of b blockers, ACE-I/ARB, and digoxin, while signicantly reducing loop diuretic use in the 6 months after device implantation.
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OPTIMISATION OF MEDICAL THERAPY AFTER CARDIAC RESYNCHRONISATION: A NURSING OPPORTUNITY NOT TO BE MISSED
doi:10.1136/heartjnl-2011-300198.75
1 S J Russell, 2J Bell, 3L Edmunds, 4J Davies, 3H Rose, 3Z R Yousef. 1Wales Heart Research Institute, Cardiff, UK; 2Cardiff University, Cardiff, UK; 3University Hospital of Wales, Cardiff, UK; 4University Hospital Llandough, Cardiff, UK
Introduction Cardiac resynchronisation therapy (CRT) is indicated in patients with left ventricular dysfunction (EF#35%), electromechanical dyssynchrony, and limiting heart failure (HF) symptoms despite optimal medical therapy. In many cases target doses of HF medications prior to CRT are not achieved due to bradycardia and/or limiting hypotension. CRT however provides bradycardia backup and improved haemodynamics, thus providing an opportunity to further optimise HF medical therapies known to confer substantial morbidity and mortality benets. We conducted the present study to evaluate the potential to further optimise medical treatments in patients receiving CRT within the framework of nurse-led pre and post CRT clinics. Methods Our unit operates an integrated CRT service with preassessment, implantation, and follow-up components. Pre-assessment and follow-up incorporate dedicated HF nurse clinics to support protocol-driven optimisation of medical therapies. We therefore conducted a retrospective analysis of our CRT database over a 9-month period to quantify the frequency of use, and dose of HF medications (bblockers; bB, angiotensin converting enzyme inhibitors: ACE-I or angiotensin receptor blockers: ARB, aldosterone antagonists, digoxin, and loop diuretics) before and 6 months after CRT. Total daily dose equivalences within each class of medication (bisoprolol for bB, lisinopril for ACE-I/ARB, spironolactone for aldosterone antagonists, and frusemide for loop diuretics) and titration protocols were based on National Institute of Clinical Excellence guidelines for HF (guideline 5). Results Between October 2009 and Jun 2010, 74 patients (age: 67611 yrs, 86% male) underwent implantation of a CRT device. All
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EXPANDING THE ROLE OF CARDIAC CARE UNIT NURSES TO REDUCE TIME TO TREATMENT FOR PATIENTS REQUIRING PRIMARY ANGIOPLASTY
doi:10.1136/heartjnl-2011-300198.76
S Young, G Pretsell, A Gibbins, G Dixon, A de Belder. Royal Sussex County Hospital, Brighton, UK
Introduction In Brighton, UK, 24-h Primary Angioplasty has been used for the treatment of ST segment elevation myocardial infarction (STEMI) since October 2008, with local patients being admitted via the Accident and Emergency (A&E) department. With the publication of the National Infarct Angioplasty project report (DH 2008) it was evident that direct admission into the cardiac catheter lab from the ambulance could further reduce time to treatment. Call to Balloon time (CTBT) <150 mins is a nationally recognised indicator measuring the time the patient rst calls for professional help (usually the ambulance) to the opening of the coronary artery on the catheter lab Abstract 76 table 1.
Abstract 76 Table 1
% CTBT 150 mins Financial Year 2009e2010 Quarter 1 (AprileJune 2010) Quarter 2 (JulyeSeptember 2010) *p0.0013. 59/78 76%* 32/36 89% 44/45 98%* Median CTBT 125 mins 111 mins 99 mins
Abstract 75 Table 1 Heart Failure nurse supervised use of medications before and 6 months After CRT
Pre-CRT Post-CRT p Value <0.01
b-Blocker: exemplar bisoprolol

Frequency of use 78% 88% 6.963.2 mg/day 93% 12.463.8 mg/day 28% 15.567.3 mg/day 48% 96.1613.6 mg/day 100% 48.168.4 mg/day <0.01 <0.01 0.02 Daily dose equivalent 5.363.1 mg/day ACE-I/ARB: exemplar lisinopril Frequency of use Daily dose equivalent 93% 11.864.5 mg/day
Aldosterone Antagonist: exemplar spironolactone Frequency of use 32% Daily dose equivalent 16.666.2 mg/day Cardiac Glycoside: exemplar digoxin Frequency of use 43% Daily dose equivalent 83.8611.4 mg/day Loop Diuretic: exemplar frusemide Frequency of use Daily dose equivalent 100% 63.065.8 mg/day
0.32
Methods The on-call cardiology team are non-resident out of hours. It was therefore agreed the point of contact and immediate decision making would lie with the Cardiac Care Unit (CCU) nurses. A pathway was developed following consultation with the multidisciplinary team at an educational and mapping day, and risks were addressed. It was agreed that the ambulance crew would telephone the CCU nurse who would review the clinical history and the telemetry ECG. They would then make the decision to activate the catheter lab team. Patient Group Directions for the administration of GTN, diamorphine, metoclopramide and clopidogrel were developed so that immediate treatment could be delivered by the CCU nurse without medical prescription before the cardiac catheter lab team arrived, if required. The nurses were trained in their use and assessed as competent. Nurses were already competent in ECG interpretation, debrillation, cannulation and venepuncture. Nursing documentation was developed to prioritise the patient9 s emergency care. CTBT were monitored.
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Results Following the implementation of the direct entry pathway in May 2010 the CTBT for all patients admitted direct to our hospital have reduced. This is statistically signicant when looking at Quarter 2 results from baseline. Patient safety has not been compromised. Patients who were admitted directly have been asked about their experience and if anything could be done differently from their perspective. They have said:
Abstract 77 Table 1 Screening outcomes of 221 at risk subjects identied from 64 index cases of hypertrophic cardiomyopathy
Number of Patients New screening initiated (local heart muscle clinic) New screening initiated (local paediatric clinic) New screening initiated (out of area service) Pre-existing screening in place Personal preference (declined screening) Awaiting response from subject (literature delivered) Complex family relationships (unable to deliver literature) Geographical/Logistical constraints Subject deceased (non-hypertrophic cardiomyopathy) Subject deceased (hypertrophic cardiomyopathy) 52 19 6 63 28 19 14 10 3 7
< < < <
The process is quick which is good from their perspective They are fully informed The ambulance crews deal with them competently The lab staff are waiting for their arrival.
Conclusions The CCU nurses have embraced this development and expansion of their nursing practice, allowing major changes to be made to the Primary Angioplasty pathway within the existing infrastructure, despite the challenges of working within the complex nature of traditional geographical referral patterns. Along with the work of all members of the multi disciplinary team this has signicantly reduced times to treatment for patients.
Conclusions Proactive screening for HCM can be effectively facilitated by cardio-genetic nurse services. Each new index case generates 3e4 at risk relatives who require long-term surveillance. Of 71 asymptomatic at risk subjects screened in our unit, we diagnosed 15 new cases of HCM, and 3 patients at high risk of sudden cardiac death who subsequently received primary prevention debrillator implantation.
77
SCREENING FIRST DEGREE RELATIVES FOR HYPERTROPHIC CARDIOMYOPATHY: 12-MONTH EXPERIENCE OF A CARDIOGENETICS NURSE SERVICE
doi:10.1136/heartjnl-2011-300198.77
1 2
S Finch, S Russell, D Kumar, Z R Yousef. University Hospital of Wales, Cardiff, UK; Wales Heart Research Institute, Cardiff, UK
Introduction Hypertrophic cardiomyopathy (HCM) is an autosomally transmitted cardiomyopathy with an estimated gene prevalence of 1:500, and an important cause of sudden cardiac death. Screening to identify at risk rst degree relatives is therefore recommended. The British Heart Foundation (BHF) recently funded nine Nationwide cardio-genetic nurses to support local initiatives. Our application for a nurse was successful and we present our 12-month experience of HCM screening. Methods We mapped the course of patients with suspected HCM referred to our tertiary heart muscle clinic which serves a population of 1.4million. Following phenotype conrmation, a family tree and contact details from the index case were recorded by the cardiogenetic nurse. The index case was given literature to pass onto at risk relatives. The information pack included an open invitation (referral via primary care) to attend for screening. For relatives residing outside our catchment area screening was arranged via links with the BHF cardio-genetic network and other health care providers. Relatives domiciled outside UK were given our details with offers to support screening. Throughout, strict adherence to patient condentiality was maintained. Results Over 12 months, 64 index HCM cases presented to our heart muscle clinic. Pedigree analysis identied 221 rst degree relatives at risk of carrying the HCM gene; mean index-to-at RR: 1-to-3.4 (range 0e14 subjects). Of the 221 at risk subjects, 71 (19 through paediatrics) have undergone screening through clinical assessment at our unit with plans for long-term 2e5 yearly follow-up in view of variable gene penetrance. Of the 71 screened subjects, 15 were newly diagnosed with HCM. Newly diagnosed HCM patients underwent further risk stratication for sudden cardiac death; where we identied 3 patients at high risk ($2 conventional high sudden death risk factors). After appropriate counselling, these 3 patients have received primary prevention debrillators. Despite our approach, 52 subjects remain unscreened (Abstract 77 table 1), either due to complex family relationships (n14), personal preference (n28) and/or geographical/logistical reasons (n10).
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78
FIRST YEAR EXPERIENCE OF A DEDICATED RADIAL LOUNGE FOR PATIENTS UNDERGOING ELECTIVE PERCUTANEOUS CORONARY PROCEDURES
doi:10.1136/heartjnl-2011-300198.78
S Brewster, R Weerackody, K Khimdas, A Little, N Cleary, A Penswick, M Rothman, A Archbold. London Chest Hospital, London, UK
Introduction The potential to achieve safe early mobilisation and same day discharge on a consistent basis after radial artery access has provided us with the opportunity to make a step change in the way we deliver elective care to patients undergoing percutaneous coronary procedures. We designed a dedicated radial lounge to accommodate patients before and after their procedure with the aim of minimising the feeling of hospitalisation that accompanies most encounters with health services. The lounge is a day case unit that has no beds, only chairs, and televisions but no cardiac monitors. Patients remain in their clothes throughout their hospital visit. Here we report our rst year9 s experience of this facility. Methods: The study population comprised all patients who attended the radial lounge between July 2009eJune 2010 for coronary angiography or percutaneous coronary intervention (PCI). Patients were suitable for the radial lounge if they were elective cases who had a satisfactory radial pulse and no pre-procedure contraindication to
BCS Abstracts 2011

same day discharge. Patients were excluded if they had any of the following: an unsuitable radial pulse, planned femoral access, prior coronary artery bypass surgery, or the requirement for an overnight hospital stay for planned complex/high risk PCI, renal impairment, or social reasons. The nal decision regarding route of arterial access was left to the operator. Results In the one year study period, 1548 patients were managed in the radial lounge. 1109 patients underwent coronary angiography, 114 (10.2%) of whom also had a pressure wire or intravascular ultrasound, and 439 underwent PCI. This represented approximately 88% of our unit9 s elective angiograms and 60% of our elective PCIs. Among the patients who underwent angiography, 938 (84.5%) were performed radially and 1076 (97.0%) were discharged from the radial lounge on the same day as their procedure. Among the PCI patients, 359 (81.8%) were performed radially and 372 (84.7%) were discharged the same day. The PCI group included 326 (74.3%) patients who had a single vessel treated, 105 (23.9%) who had two vessels or a bifurcation with a signicant side branch treated, and 8 (1.8%) patients who had three vessels treated. There were no deaths or arrhythmias in the radial lounge. Requirement for overnight admission was signicantly more common after femoral access compared with radial access for both angiography (4.1% vs 2.8%; p<0.05) and PCI (21.3% vs 14.2%; p<0.01). Conclusions A dedicated radial lounge free of cardiac monitors is a safe environment in which to manage most patients before and after elective coronary angiography and PCI. The lack of monitoring necessitates patient selection but this does not prevent the lounge being suitable for the majority of elective patients. Femoral access is associated with a signicantly greater requirement for overnight admission. these 12 patients 92% (11/12) stated that not having to undress was a good idea while an identical number felt much more relaxed than their previous DCA experience. Of the 45 patients that had not had a previous DCA, 96% (43/45) stated that not having to undress was a good idea while 96% (43/45) felt that this had made them feel very relaxed during their pathway. The other two patients felt that it made no difference. No patients required cross-over to femoral access and there were no blood or iodine stains on any clothes. Having patients remain dressed did not reduce uoroscopic image quality and there were no issues with infection. Conclusion Offering patients the option of having their radial DCA done without undressing is safe and helps to improve the patient journey through the cardiac catheter laboratory by making them feel more relaxed and less hospitalised. This is now standard at our Institution.
80
PPCI: IS THERE A ROLE FOR THE ACS ANP?

doi:10.1136/heartjnl-2011-300198.80
V Oriolo, J Tagney. Bristol Heart Institute University Hospital Bristol NHS FT, Bristol, UK
79
REMAINING CLOTHED FOR RADIAL DIAGNOSTIC CORONARY ANGIOGRAPHY: AN IMPROVEMENT IN THE PATIENT JOURNEY
doi:10.1136/heartjnl-2011-300198.79
S Eve, M Sinha, T A Wells. Salisbury District Hospital, Salisbury, UK
Background Patients undergoing invasive diagnostic coronary angiography (DCA) for the rst time often display high levels of anxiety at the time of their procedure as they are unfamiliar with the cardiac catheter laboratory set up. It is therefore part of the cardiac catheter laboratory staff9 s role to reduce patient fears and hence improve their journey through the cardiac catheter laboratory. Several Cardiac centres have recently introduced radial lounges whereby patients feel less hospitalised by not needing to undress for their procedure. Methods Following infection control approval, between mid-August 2010 and the end of October 2010, patients undergoing radial DCA at Salisbury District Hospital were offered the option of remaining clothed for their procedure. Each patient was given an information leaet included in which was explained possible downsides to being dressed including if CPR were needed then clothes would be cut, failure of radial access and the subsequent need for femoral access, and the possibility of soiling the clothes with either blood or iodine. The only caveat stated was that female patients were not allowed to wear an underwire bra. Following their DCA, patients were then asked to ll in an anonymous questionnaire in which they were asked about their experience and whether not having to undress made them feel more relaxed. Results 57 consecutive patients underwent (DCA) during this time period (100% uptake) with an average age of 68.1 6 9.6 years. 71% were male and 21% (12/57) had undergone a DCA previously. Of
Introduction Primary Percutaneous Coronary Intervention (PPCI) is now considered the treatment of choice for patients experiencing ST Elevation Myocardial Infarction (STEMI) (European Society of Cardiology/European Association for Cardio-Thoracic Surgery 2010). One of the many benets claimed is reduced length of stay due to decreased morbidity (Zahn et al 2000, Kalla et al 2006). To assess performance of one English PPCI 24/7 provider organisation against the national average length of stay (LOS) for patients post PPCI, a retrospective baseline audit was conducted. This demonstrated an average LOS of 4.4 days which is above the National Infarct Angioplasty Project 2008 average LOS of 3 days. A 48 h nurse led discharge (NLD) protocol was therefore developed and introduced by the acute coronary syndromes advanced nurse practitioner to streamline the patient journey. This instructed the nurse and/or physician to ensure appropriate investigation and documentation was carried out in a timely manner to avoid unnecessary delays in patient discharge. Method Suitability criteria for the 48-h NLD protocol were established, which included: absence of acute complications (eg,: bleeding, haemodynamic instability, ongoing chest pain, ejection fraction <40%, respiratory compromise); appropriate support at discharge. Following the baseline audit, data were electronically collected prospectively for 5 months, measuring date of admission to date of discharge to the usual place of residence. After 5 months the audit was repeated to assess the average length of stay for patients presenting with STEMI. Result Between 1st April 2010 and 31st August 2010, a total of 274 patients were admitted with STEMI. Of these, 122 (45%) met the NLD criteria and were discharged by the ACS ANP. The remaining 152 (55%) were discharged by the medical physicians. It was noted that introduction of the protocol also facilitated a structured approach to discharge for the medical team. The average LOS for all PPCI patients (n274) decreased from 4.4 days to 3 days (30%). For patients that were seen and discharged solely by the advanced nurse practitioner (n122), the average LOS decreased from 4.4 days to 2.0 days (55%). Conclusions/Implications In the current nancial climate, a decrease in LOS can have a signicant impact on any organisational resources thus increasing efciency saving and patient throughput. This demonstrates part of the added value the advanced nurse practitioner brings to patient care and to tertiary centres that provide a 24/7 PPCI service.
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PPCI NURSE LED DISCHARGE PROTOCOL PPCI -REPERFUSION TIME 0 CCU 12HRS PATIENT STABLE* (SYSTOLIC BP> 100 mmHg - NO NEW ECG CHANGES - PAIN FREE - SaO2>93%)
REG/SENIOR NURSE TO BOOK ECHO & TRANSFER TO WARD (IF APPLICABLE)
Results As previously described apical rotation was reduced at rest and on exercise Basal rotation was comparable at rest but signicantly reduced on exercise in patients. The SD for four different systolic peak motions (basal and apical rotation, longitudinal and radial displacement) was comparable at rest but on exercise controls showed a signicantly reduced SD compared to patients showing a greater ability to synchronise motions. Furthermore a ratio of untwist during IVRT and longitudinal extension (Ratio Untwist /Extension in IVRT) showed a signicant deeper slope on exercise for patients indicating a loss of synchrony in diastole, too. All results are presented in Abstract 81 table 1.
24 HRS PATIENT STABLE * (AS ABOVE)
Abstract 81 Table 1
DEMONITOR + ECHOCARDIOGRAM+ REHAB REFERRAL ECHO PERFORMED?
Patients Rest Apical Rotation (8) Basal Rotation (8) Twist (8) 9.964.4
Controls Rest
Patients p value Exercise
Controls Exercise
p value
EF 39%
36 HRS PATIENT STABLE* (AS ABOVE) EF 40% & KILLIP I
N ARRANGE ASAP
13.464.0 <0.001 12.564.7 16.663.9 <0.001 7.763.2 9.763.0 0.011 19.565.9 25.966.0 <0.001 40.1627.1 25.9615.5 9.6614.7 3.363.8 0.01 0.034
DR R/V SCREEN FOR ICD
8.363.3 8.063.4 0.676 18.065.7 21.064.9 0.01
TTAS, D/C LETTER, MINAP, REHAB TO SEE 48 HRS PATIENT STABLE* (AS ABOVE) BLOODS, ECG, COPY OF PROCEDURE, VENFLON OUT, MINAP TO BE SEEN BY ACS NURSE/DR HOME
SD Systolic Motions (ms) 48.6632.9 43.1625.3 0.38 Ratio Untwist/Extension 25.3651.4 7.1610.7 0.059 in IVRT (8/mm)
Conclusion Patients with HFNEF show a deterioration of basal rotation and a systolic and diastolic three plane dyssynchrony particularly on exercise. This might further contribute to the deterioration of early diastolic suction and therefore decrease stroke volume on exercise. This might be a major contribution to their symptoms.
IF PATIENT UNSTABLE AT ANY STAGE PLEASE D/W DR/ACS NURSE
82
Abstract 80 Figure 1 PPCI nurse LED discharge protocol.
MANAGEMENT OF ADVANCED HEART FAILURE IN THE UK: TRENDS IN HEART TRANSPLANTATION AND MECHANICAL CIRCULATORY SUPPORT
doi:10.1136/heartjnl-2011-300198.82
81
DYSSYNCHRONOUS THREE PLANE MOTION AND IMPAIRED LEFT VENTRICULAR TWIST IN PATIENTS WITH HEART FAILURE AND NORMAL EJECTION FRACTION
doi:10.1136/heartjnl-2011-300198.81
Y T Tan, F W G Wenzelburger, F Leyva, J E Sanderson. 1Department of Cardiovascular Medicine, Birmingham, UK; 2Institute for Science and Technology in Medicine, Keele University, Stoke on Trent, Keele, UK; 3Department of Cardiovascular Medicine, University of Birmingham, Birmingham, UK
Background The pathophysiology of heart failure with normal ejection fraction (HFNEF) is complex and not fully understood. Recent publications showed a loss of apical rotation and longitudinal function particularly on exercise in these patients. Whether a deterioration of basal rotation and a dyssynchrony of different three plane motions on exercise might contribute to symptoms in these patients is not known. Method 72 Patients (age 7367 years, 48 female) with breathlessness on exertion and normal EF (6067%) underwent cardiopulmonary exercise test to rule out alternative clinical reasons (VO2max 18.464.9 ml/min/kg). Data were compared to 38 age-matched control subjects (age 7167 years, 29 female, EF 6367%) with a normal exercise tolerance (VO2max 28.665.1 ml/min/kg). All underwent full Doppler 2D-echocardiography at rest and on supine exercise. Echo images were analysed off-line. Apical and basal rotation, longitudinal and radial displacement were measured by speckle tracking. Speckle tracking pictures and colour TDI curves were loaded into custom made software. The software interpolated all curves and calculated twist as the difference of rotation at apex and at base. The software offered timing information to calculate SD and time delays for different motions.
A Emin, 2C A Rogers, 3H L Thomas, 4S Tsui, 5S Schueler, 5G MacGowan, 6A Simon, R S Bonser, 4J Parameshwar, 8N R Banner. 1Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, UK; 2Clinical Trials and Evaluation Unit, University of Bristol, Bristol, UK; 3NHS Blood and Transplant, Bristol, UK; 4Cardiopulmonary Transplantation, Papworth Hospital NHS Foundation Trust, Cambridge, UK; 5 Cardiopulmonary Transplantation, Freeman Hospital, Newcastle, UK; 6Heart and Lung Transplantation, Royal Brompton and Hareeld NHS Trust, Middlesex, UK; 7Cardiopulmonary Transplantation, Queen Elizabeth Hospital, University of Birmingham, Birmingham, UK; 8Royal Brompton and Hareeld NHS Trust - on behalf of the UK VAD Forum and UKCTA Steering Group, Middlesex, UK
7
Introduction Patients with advanced heart failure due to systolic ventricular dysfunction require pump replacement therapy. Previously, heart transplantation (HTx) met this need but waiting times have increased due to shortage of donor hearts. Consequently, more patients require a ventricular assist device (VAD) as a bridge to transplant (BTT). We report UK activity, trends and outcome for HTx and BTT VAD. Methods Data were acquired from a comprehensive national database using 3 eras for analysis: E1: 5/2002e12/2004, E2: 1/2005e12/ 2007 & E3: 1/2008e6/2010. Paediatric and multi-organ transplants were excluded from the transplant cohort. Patients who received prior short-term support (bridge to bridge) were excluded from the VAD group. Results 1278 patients were listed for HTx over the 3 eras: E1 155 per year, E2 165 per year, E3 148 per year. The number of adult HTx fell from 132 per year in E1 to 94 per year in E3. The median waiting time for non-urgent HTx increased from 87 days in E1 (95%CI 55 to 119) to 321 days in E3 (95%CI 203 to 439) (p<0.001). 239 patients needed left VAD support as BTT; 75 (31%) also received a right VAD. Activity rose from 26 per year in E1 to 41 per year in E3. Device
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BCS Abstracts 2011

choice has changed in favour of rotary pumps; 19%, 69% and 96% for E1, E2 and E3 respectively. Median duration of VAD support increased from 84 days (IQR 20e209) in E1 to 280 days (IQR 86e661) in E3 (p<0.01). Overall survival to 1 year after VAD implant rose from 52.9% (95%CI 40 to 64) in E1 to 65.6% (95%CI 54 to 75) in E3 (p0.10). Of the 239 patients implanted, 83 (35%) have undergone HTx, 52 (22%) are alive on VAD support & 84 (35%) died on support. Twenty were explanted following myocardial recovery; 18 of these remain alive & 2 died. Survival after HTx for patients with or without a pre-HTx VAD was 81.4% (95%CI 71 to 88) & 90.3% (95%CI 88 to 92) respectively at 30-days (p<0.01) and 80.0% (95%CI 63 to 82) & 84.3% (95%CI 82 to 87) respectively at 1-year (p<0.01). 1-year survival conditional on 30-day survival was similar with & without a pre-HTx VAD (93% vs 91%, p0.48). Conclusion Heart transplant activity has declined and waiting times have become prolonged leading to an increased need for bridging to transplantation. There has been a shift from volume displacement VADs to rotary blood pumps and the duration of support has increased. Post VAD survival has improved. While bridging appears to increase mortality early after HTx, longer term survival is unaffected.
84
TREATMENT OF REFRACTORY RIGHT HEART FAILURE AFTER IMPLANTATION OF A LEFT VENTRICULAR ASSIST DEVICE. IS THE LEVITRONIX CENTRIMAG RIGHT HEART SUPPORT A SOLUTION?
doi:10.1136/heartjnl-2011-300198.84
B Zych, A F Popov, A Barsan, M Hedger, R Hards, N R Banner, A R Simon. Royal Brompton&Hareeld NHS Foundation Trust, Hareeld Hospital, Hareeld, UK
83
CLINICAL AND HAEMODYNAMIC STATUS BEYOND 3 MONTHS OF MECHANICAL SUPPORT WITH THE HEARTWARE VENTRICULAR ASSIST DEVICE
doi:10.1136/heartjnl-2011-300198.83
B Gordon, A McDiarmid, N Robinson, N Wrightson, G Parry, S Schueler, G MacGowan. Freeman hospital, Newcastle upon Tyne, UK
Introduction Limited data exist on the longer term clinical and haemodynamic impact of the HeartWare left ventricular assist device (HVAD) when used as a bridge to heart transplantation. Patients who had a device longer than 3 months were reviewed. Methods 26 patients had a HVAD implanted from 07/2009 to 07/ 2010 (mean age 46.8 years, 18 male, 5174 total days of support). Baseline and follow-up NYHA functional class, peak VO2 (bicycle exercise), right heart haemodynamics, biochemistry and mortality outcome were compared using paired t test. Results: 22/26 (85%) patients survived beyond 3 months. 4 patients died before (mean survival 40 days, 2 stroke and 2 multi-organ failure) and 2 died after (mean survival 173 days, 1 stroke, 1 right heart failure) discharge from hospital. 2 patients were transplanted (at 3 and 241 days after implant) and 1 had recovery of LV function. Follow-up data is available for 14/20 survivors (mean 197 days from implant). Signicant results are shown in the Abstract 83 table 1. There was no signicant change in peak VO2 (9.961.8 to 12.963.8, p0.08), haemoglobin (12.761.7 to 12.161.2, p0.3) or creatinine (122641 to 105638, p0.19).
Introduction Right heart failure after left Ventricular Assist Device (LVAD) implantation is a severe complication, in extreme cases necessitating additional mechanical assist. We present our institutional experience with the Levitronix CentriMag used for right ventricular support commencing LVAD implantation with refractory right ventricular failure. Material and Methods Between March 2001 and November 2010 109 patients underwent implantation of long term, total implantable, continuous ow LVADs: 60 HeartMate II, 25 Jarvik 2000 and 24 HeartWare. All patients requiring right ventricular support were included (n24), for which the Levitronix CentriMag continuous ow, paracorporeal device was used. The analysis included patient demographics as well as overall duration of support and outcome parameters, including survival at 30, 90 days and 1 year. Results 24 pts. underwent implantation, age 37.9613.7 years, gender: M/F-15/9, underlying disease: dilated cardiomyopathy 22 (92%), peripartum cardiomyopathy 1(4%), viral myocarditis 1(4%). Median duration of support: 28 days (5e146). 3(12.5%) pts. underwent heart transplantation (HTx) on RV support, 14(58.5%) underwent RVAD explantation. Of these, 3 underwent successful HTx, 4 recovered LV function and underwent successful LVAD explantation, 3 remain on continuing LVAD support, 4 patients died after RVAD explantation (post explantation day 1, months 3 and 4 and at 2 years), 7(29%) patients died during RV support. Median ITU/hospital stay: 19.5 days (6e145)/78.5 days (10e219). 30-day/ 90-day/1-year survival: 79%/71%/60%. 15(62.5%) patients were discharged from hospital after treatment. Median survival after procedure: 473.5 days (10e1917). Conclusion Levitronix CentriMag right ventricular support is an excellent option for post LVAD implantation treatment of refractory RV failure. It allows either bridging to transplantation or RV function improvement and provides an acceptable rate of survival.
85
PREDICTION OF RESPONSE TO BIVENTRICULAR PACING FROM DYSSYNCHRONY INDICES: THE ABSOLUTE LIMIT ON PREDICTABILITY, AND ITS CLINICAL IMPLICATIONS
doi:10.1136/heartjnl-2011-300198.85
Abstract 83 Table 1
Parameter NYHA functional class Mean PA pressure (mm Hg) Mean PW pressure (mm Hg) Transpulmonary gradient (mm Hg) Right atrial pressure (mm Hg) PA oxygen saturation (%) Cardiac Output (l/min) Sodium (mmol/l) Baseline 3.660.4 3869 2565 1265 1166 5168 2.960.8 13464 Follow-up 2.160.6 2168 1065 963 564 6667 4.360.9 13963 p Value <0.001 <0.001 <0.001 0.02 0.006 0.003 <0.001 0.002
S S Nijjer, 2P Pabari, 3B Stegemann, 4V Palmieri, 5N Freemantle, 2A Hughes, 2D P Francis. Imperial College Healthcare NHS Trust, London, UK; 2Imperial College London, London, UK; 3Medtronic Bakken Research Center, Maastricht, The Netherlands; 4Ospedale dei Pellegrini, Naples, Italy; 5University of Birmingham, Birmingham, UK
1
Conclusions The HVAD results in signicant improvement in functional class, right heart haemodynamics, cardiac output and sodium levels beyond 3 months of therapy. Ongoing randomised clinical trials will establish the long-term outcome of this device.
Background It may be incorrect to believe that, with a good echocardiographic marker of mechanical dyssynchrony, response to biventricular pacing (BVP) should be predictable with a high r2 value. Variability between repeat echocardiographic measurements, and between successive dyssynchrony measurements, may reduce r2. Both will mandatorily limit the achievable r2; we determine this contraction factor. Method and Results We compared correlation coefcients of dyssynchrony indices with response markers, in externally monitored randomised controlled trials (EMRCTs) and highly skilled single centre studies (HSSCSs). DLVEF in CRT recipients comprises true CRT effect plus unpredictable spontaneous variability present in control patients (Abstract 85 gure 1, upper panel). The resultant depression in r2 is calculated. HSSCSs overstate r2 between
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BCS Abstracts 2011

dyssynchrony and remodelling response in contrast to EMRCTs (p<0.0000000001), whether response is LVEF (0.40 vs 0.01), ESV (0.26 vs 0.01); EDV (0.53 v 0.01). An averaged reported r2 between differing dyssynchrony markers to commonly used echocardiographic response markers is shown in Abstract 85 gure 1, lower panel. right ventricular (VV) delays) may be undertaken to improve the chance of response to CRT. However, data to support this approach as standard management are lacking and many institutions programme CRT devices to deliver out-of-the-box intervals, only undertaking optimisation when clinical response is lacking. We sought to determine how often the out-of-the-box settings are optimal or acceptable and how often CRT optimisation results in signicant alteration of the pre-programmed pacing intervals. Methods Data were collected from 180 consecutive patients who underwent CRT followed by optimisation within 24 h. Optimisation was performed with serial adjustment of AV and VV intervals. Haemodynamic assessment was undertaken using either echocardiography or Non-Invasive Cardiac Output Measurement. The optimal pacing intervals were considered to be those which resulted in greatest acute augmentation of cardiac output and the device was programmed accordingly. The nal settings were compared with the pre-programmed settings for that device and the difference (AV or VV Adjustment) derived, taking into account the preset paced or sensed AV delay. An AV or VV Adjustment of more than 40 ms was considered to be clinically signicant. Data are presented as mean (SD). Results Optimal AV delay ranged from 60 to 200 ms (mean 124 ms (30)), VV delay ranged from 0 to 100 ms (mean 23 ms (19)). With the pre-set pacing parameters, cardiac output was acutely augmented by 13.1 (34)%. Optimised CRT produced further improvement of cardiac output, to 24.9 (32)% augmentation. Outof-the-box settings were found to be optimal in 11 (6.1%), or requiring only minor alteration in 120 (66.7%). A clinically signicant alteration in AV delay was made in 40 (22.2%), in VV delay in 12 (6.7%) or in either parameter in 49 (27.2%). Conclusions Signicant adjustment of AV or VV delay is required in over a quarter of patients receiving CRT. Optimisation of pacing intervals provides augmentation of cardiac output over and above the out-of-the-box settings. The ndings suggest that optimisation is an important component of resynchronisation therapy.
DLVEF is 0.57 (DESV, 0.54; DEDV, 0.50). Dyssynchrony indices own

2
EMRCT data shows maximal r2 between dyssynchrony and
variability further contracts observable r values (by x0.68). The overall ceiling to r2 is between dyssynchrony and DLVEF is 0.39 (DESV, 0.37; DEDV, 0.34). All EMRCT r2 values obey these statistical limits; 29% of HSSCSs results do not. Conclusions HSSCSs suggest dyssynchrony markers strongly predict response to BVP but EMRCTs cannot conrm this. Natural variability forces observed correlation coefcients between dyssynchrony and response to be low. EMRCTs, being less susceptible to publication bias, reect this reliably. Frequent citation (without verication in independent cohorts) of the most exuberant values, from HSSCSs creates mathematically unviable, unrealistic, expectations. Simply searching for progressively more extreme correlations is therefore misguided. Rationally, we should concentrate on improving testretest reproducibility of markers of dyssynchrony and of response.
Abstract 86 Table 1 optimisation of CRT

0
Adjustment of pacing intervals following
1e20 mS 21e40 mS 41e60 mS 61e80 mS 81e100 mS 22 (12.2) 53 (29.3) 32 (17.8) 11 (6.1) 7 (3.9) 0 1 (0.6) 1 (0.6)
AV Adjustment 29 (16.1) 89 (49.4) VV Adjustment 50 (27.6) 65 (35.9) Data as N (%).
87
OPTIMISATION OF VV DELAY OF CRT IS MORE REPRODUCIBLE USING PEAK VELOCITIES THAN USING VELOCITY TIME INTEGRAL, AS WELL AS BEING QUICKER
doi:10.1136/heartjnl-2011-300198.87
P A Pabari, A Kyriacou, M Moraldo, C Manisty, A D Hughes, J Mayet, D P Francis. Imperial College London, London, UK
86
HOW OFTEN IS IMPORTANT ADJUSTMENT OF PACING INTERVALS REQUIRED FOR OPTIMAL RESPONSE FOLLOWING CRT?
doi:10.1136/heartjnl-2011-300198.86
V Nayar, F Z Khan, A Rawling, L Ayers, M S Virdee, 2D Begley, 1D P Dutka, P J Pugh. 1Addenbrookes Hospital, Cambridge, UK; 2Papworth Hospital, Cambridge, UK
1
Introduction A signicant minority of patients do not experience clinical benet following cardiac resynchronisation therapy (CRT). Haemodynamically-guided adjustment of the intervals between chambers paced (optimisation of atrio-ventricular (AV) and leftA50
Background It is not obvious which is a better echocardiographic marker for optimisation of AV or VV delay: stroke distance (VTI) or peak velocity. The biggest problem is genuine physiological variability between beats. Because optimisation of VV delay requires detection of persistent changes in cardiac function (signal), which may be small in relation to beat-to-beat variability (noise), we should choose measurements with the best signal-to-noise ratio and reproducibility. The standard echocardiographic method of choice for VV delay optimisation is to maximise left ventricular outow tract velocity time integral (LVOT VTI). An alternative is peak velocity instead of VTI as the parameter to be measured. But surely VTI, which is encompassing and cumulating more data, is more immune to disruption by spontaneous variability between beats,
BCS Abstracts 2011

and therefore simply using peak velocity might give a less reliable optimum? Surely the time saved by using peak would have a price to pay in poorer reproducibility of the optimum? In this study, we evaluate whether peak velocity is a suitable alternative to VTI, having regard to both time consumed and reproducibility. We also examine whether averaging multiple replicate measurements improves optimisation. Methods & Results VV optimisation was performed on 40 subjects with biventricular pacemakers using LVOT velocity (VTI or peak) as the echocardiographic marker being maximised. Importantly, 6 successive replicate optimisations were performed per patient at a single session. Scatter of apparent VV optimum between repeat optimisations was threefold smaller for peak than VTI (p<0.03), with a single measurement for each. Peak velocity had a higher intraclass correlation coefcient (ICC) than VTI (0.66 vs 0.53, p0.003). Scatter between replicate optimisations is reduced if, instead of single measurements, we use pairs, or triplicates (ANOVA p<0.0001). This benet occurs with both peak and VTI (p<0.001 among each). Time taken for acquisition and analysis of a single optimisation (6 settings) was 17.5 s for peak and 57.5 s for VTI (p<0.0001). Conclusions Doppler optimisation of VV delay using peak velocity rather than VTI is (as expected) quicker but (surprisingly) more accurate. Making replicate measurements further improves reproducibility. Perhaps guidelines should favour peak over VTI and mandate multi-replicate averaging? These data suggest a rare opportunity to reduce labour while increasing reliability of optimisation. Indeed, triplicate peak velocity assessment takes the same amount of time as a single VTI, and identies the VV optimum 3 times more condently. While VTI measurement remains essential for assessing stroke volume and cardiac output, for optimisation purposes it comparison of peak velocity between different settings is both faster and more reliable. ments of left ventricular (LV) pulse pressure (systolic minus diastolic), aortic ow velocity and myocardial oxygen consumption (MVO2) at four settings: 3 AV delays during biventricular (BiV) pacing (reference BiV-AV120 ms; BiV-AV40 ms; individualised haemodynamic BiVAVoptimum), and at intrinsic ventricular conduction (LBBB). Atrial pacing at 100 bpm ensured a xed heart rate. Results LV pulse pressure rose from LBBB to BiV-AV120 ms by 1062% (p<0.001) and 261% more (p<0.05) at the haemodynamic BiV-AVoptimum. At BiV-AV40 ms, pressure was 1062% worse than BiV-AV120 ms (p<0.001), no different to LBBB (D0.860.4%, pns). Invasive aortic ow velocity, measured at a xed position throughout each individuals study (ie, cardiac output index), rose by 962% (p<0.01) from LBBB to BiV-AV120 ms, rising a further 361% (p<0.01) at BiV-AVoptimum. At BiV-AV40 ms, aortic ow was, no different to LBBB (pNS). MVO2 increased from LBBB to BiV-AV120 ms by 964% (p0.035) and to BiV-AVoptimum by 1263% (p0.002). MVO2 at At BiV-AV40 ms and LBBB was not signicantly different (D463%, pns), The 4 pacing states lay on a straight line: for Dpressure against Dow, r0.99 (p<0.01), Abstract 88 gure 1. Dexternal work (Dpressure 3Dow) correlated with D MVO2, r0.99 (p<0.01), with slope 1.6160.17, signicantly greater than 1.00 (p<0.05), Abstract 88 gure 2.
Abstract 88 Figure 1 The correlation of LV pulse pressure and aortic ow velocity during acute biventricular pacing, (at three AV delays) and during LBBB, at a xed heart rate.
88
EVALUATION OF THE IMPACT OF AV DELAY VARIATION ON THE ACUTE MECHANOENERGETIC EFFICIENCY OF CARDIAC RESYNCHRONISATION THERAPY AND ASSESSMENT OF PERFORMANCE OF NON-INVASIVE VS INVASIVE HAEMODYNAMIC OPTIMISATION
doi:10.1136/heartjnl-2011-300198.88
A Kyriacou, P Pabari, K Willson, R Baruah, S Sayan, D W Davies, J Mayet, N S Peters, P Kanagaratnam, Z Whinnett, D P Francis. International Centre for Circulatory Health, London, UK
Background The impact of varying AV delay on the acute mechanoenergetic efciency of cardiac resynchronisation therapy (CRT) is not known; nor is known if non-invasive haemodynamic optimisation by blood pressure agrees with invasive haemodynamic measures during optimisation. We studied these invasively, in contemporary patients. Methods Eleven patients with heart failure (EF 2968%) and left bundle branch block (LBBB, QRS 154626 ms) underwent measureHeart June 2011 Vol 97 Suppl 1
Abstract 88 Figure 2 The correlation of cardiac work and myocardial oxygen consumption during acute biventricular pacing, (at three AV delays) and during LBBB, at a xed heart rate.
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BCS Abstracts 2011

The correlations of optimal AV delays by non-invasive (Finometer) systolic blood pressure (SBP) vs invasive measures were as follows; aortic SBP, r20.96, p<0.01; aortic ow velocity, r20.81, p<0.01; LV dP/dtmax, r20.68, p<0.01. Conclusions During acute biventricular pacing, at a xed heart rate, changing the AV delay affects the cardiac mechanoenergetics. When an AV delay improves external cardiac work, compared to LBBB or a physiologically too short AV delay (eg, AV 40 ms), it also increases the myocardial oxygen consumption. However, only 1% more energy is consumed per 1.6% more external work (pressure3ow) done; as a result cardiac efciency improves. Haemodynamic optimisation of AV delay can be achieved with high precision using non invasive beat-to-beat pressure measurements. This should enable routine haemodynamic optimisation (easily automated) of CRT devices in clinical practice.
89
ELECTROMECHANICAL INTERACTION IN PATIENTS UNDERGOING CARDIAC RESYNCHRONISATION THERAPY: COMPARISON OF INTRACARDIAC ACTIVATION MAPS AND EARLY SEPTAL CONTRACTION IN LEFT BUNDLE BRANCH BLOCK
doi:10.1136/heartjnl-2011-300198.89
S G Duckett, 2O Camara, 1M Ginks, 3J Bostock, 1P Chinchapatnam, 1M Sermesant, A Pashaei, 3J S Gill, 3G Carr-White, 2A F Frangi, 1R S Razavi, 2B H Bijnens, 3 C A Rinaldi. 1Kings College London, London, UK; 2UPF, Barcelona, Spain; 3Guys and St Thomas Hospital, London, UK
2
Introduction Early inward motion and thickening/thinning of the ventricular septum associated with left bundle branch block (LBBB) is known as the septal ash (SF). Correction of SF corresponds with CRT response. We hypothesise that electromechanical interactions induced by SF are associated with functional changes in conductivity and a U-shaped activation pattern. Characterising the spatio-temporal relationship between electrical and mechanical events may explain why patients with a SF respond to CRT. Methods 13 patients (63610 years, 10 men) with severe heart failure (EF 22.865.8%) undergoing CRT underwent echocardiography and non-contact mapping (NCM) pre-implant. Presence and extent of a SF was dened visually and with M-mode and fused with NCM bull9 s eye plots of endocardial activation patterns. LV dP/dtmax was measured during different pacing modes. Results Five patients had a large SF, four small SF and four no SF. Patients with large SF had areas of conduction block in noninfarcted regions whereas those with small or no SF did not (Abstract 89 gure 1). Patients with large SF had greater acute response to left ventricular (LV) and biventricular (BIV) pacing vs those with small/no SF (% increase dP/dt 28614% vs 11619% for LV pacing and 42628% vs 22621% for BIV pacing). The lines of conduction block disappeared after LV and BIV pacing, while remaining present with RV pacing (Abstract 89 gure 2). Abstract 89 gure 1 Patient with a large SF. Unipolar isochronal map with NCM electrograms showing fragmented signals (development of split potentials) indicating a reduction of conduction and inability to cross throughout the inferior region. The NCM mapping electrograms show the criteria used by Auricchio et al to dene block, with the emergence of R-wave, smallest and earliest at the superior part of the block (where area of block begins) with largest negative peak. Bold white arrows on the electrogram indicate how the electrical activation spreads superiorly in a U-shape pattern leading to the development of split potentials. Abstract 89 gure 2 Activation maps of patient with a large SF. Row A, baseline with area of block and late anterior breakthrough. Row B, RV pacing showing the area of anterior block remains. Row C, BIV pacing. Functional conduction block has disappeared.
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Conclusion A strong interaction exists between electrical activation and mechanical deformation of the septum. Correction of both mechanical synchrony and the functional conduction block by CRT may explain the large positive response in patients with a SF.
90
INVASIVE ACUTE HAEMODYNAMIC RESPONSE TO GUIDE LV LEAD IMPLANTATION PREDICTS CHRONIC REMODELLING IN PATIENTS UNDERGOING CARDIAC RESYNCHRONISATION THERAPY
doi:10.1136/heartjnl-2011-300198.90
S G Duckett, 1M Ginks, 1A Shetty, 2J Bostock, 2J S Gill, 2S G Hamid, 2S Kapetanakis, E Cunliffe, 1R S Razavi, 2G Carr-White, 2C A Rinaldi. 1Kings College London, London, UK; 2Guys and St Thomas Hospital, London, UK
2
Introduction Cardiac resynchronisation therapy (CRT) reduces mortality and morbidity in heart failure patients, however up to 30% of patients do not derive symptomatic benet. Higher proportions do not remodel. Multi-centre trials have shown echocardiographic techniques are poor at improving response rates. We hypothesised that the degree of acute haemodynamic response (AHR) at implant can predict which patients remodel. We evaluated the relationship between AHR and reverse remodelling (RR) in CRT. Methods 33 patients undergoing CRT (21 dilated & 12 ischaemic cardiomyopathy) were studied. Left ventricular (LV) volumes were assessed pre and post CRT. AHR (LV-dP/dtmax) was assessed at implant using a pressure wire in the LV cavity. The LV lead was placed in potential target veins and the largest percentage rise in LV-dP/dtmax from baseline (AAI or RV pacing with atrial brillation) to DDDLV was used to determine optimal LV lead position. RR was dened as reduction in LV end systolic volume (ESV) $15% at 6 months. Results LV-dP/dtmax increased signicantly from baseline (8016194 mm Hg/s to 9246203 mm Hg/s (p<0.001)) with DDDLV pacing for the optimal LV lead position. There was a signicant difference in the percentage rise in LV-dP/dtmax between the best and worst LV lead position (Abstract 90 gure 1). LVESV
BCS Abstracts 2011

decreased from 186668 ml to 157668 ml (p<0.001). 18 (56%) patients exhibited RR. There was a signicant relationship between percentage rise in LV-dP/dtmax and RR for DDDLV pacing (p<0.001) (Abstract 90 gure 2). A similar relationship for AHR and RR in DCM and ICM (p0.01 & p0.006) was seen. CRT has not been investigated. Cardiovascular magnetic resonance (CMR) is an important tool in the assessment of HF and is considered the gold-standard in estimating RV function. We used this technique to assess the impact of RV dysfunction on clinical outcomes following CRT implantation. Methods We evaluated 48 consecutive patients attending a heart failure pacing clinic who had a CMR study within 6 months prior to CRT implantation. Clinical, biochemical, ECG and imaging data were collected. Biventricular function and myocardial scar were assessed by CMR including gadolinium enhancement. The primary end-point was a composite of all cause mortality (ACM) or unplanned cardiovascular hospitalisation. Results The mean age was 64.5612.7 years. HF was ischaemic in 42% of patients, and 85% were in NYHA class III/IV at the time of implantation. Atrial brillation/utter was found in 27% of patients. The mean LVEF estimated by CMR was 2768%, while the median RVEF was 52% (IQR 35%e63%). The mean tricuspid annular plane systolic excursion (TAPSE) was 14.066.0 mm, and the mean pulmonary artery pressure (on echocardiography) was 37 610 mm Hg. Ten patients (21%) met the primary end-point over a mean follow-up of 28.6 months. On time-to-event analysis, only atrial brillation (HR 4.8, p0.02) and RV dysfunction, ie, reduced RVEF (HR 0.96 per 1% EF, p0.01) or TAPSE (HR 0.80 per mm, p<0.01) were independent predictors of the primary end-point. Atrial brillation and low RVEF were the only independent predictors of mortality (p0.03 and 0.04, respectively). Conclusions RV dysfunction is an independent predictor of adverse clinical outcomes following CRT. The assessment of RV function may be considered in patient selection for CRT implantation.
92
IDENTIFYING PATIENTS WITH CHRONIC HEART FAILURE: A COMPARISON OF THE GOLD STANDARDS FRAMEWORK WITH A CLINICAL PROGNOSTIC MODEL
doi:10.1136/heartjnl-2011-300198.92
Conclusions Acute haemodynamic response to LV pacing is useful for predicting which patients are likely to remodel in response to CRT both for DCM and ICM. There is much variation in the rise in LV-dP/dtmax depending on LV lead position. Using acute haemodynamic response measured with a pressure wire during CRT implant has the potential to guide LV lead positioning and improve response rates in the future.
K K Haga, 2S A Murray, 3J Reid, 3A Ness, 3M ODonnell, 4D Yellowlees, 5M A Denvir. University of Edinburgh, School of Medicine and Veterinary Medicine, Edinburgh, UK; 2 Primary Palliative Care Research Group, University of Edinburgh, Edinburgh, UK; 3 Heart Failure Nursing Service, NHS Lothian, Edinburgh, UK; 4University of Edinburgh, Edinburgh, UK; 5Department of Cardiology, University of Edinburgh, School of Medicine and Veterinary Medicine, Edinburgh, UK
1
91
RIGHT VENTRICULAR DYSFUNCTION IDENTIFIES CLINICAL OUTCOMES FOLLOWING CARDIAC RESYNCHRONISATION THERAPY
doi:10.1136/heartjnl-2011-300198.91
1 K Guha, 2F Alpendurada, 2S Prasad, 2T McDonagh, 1M R Cowie, 2R Sharma. 1Royal Brompton Hospital, Imperial College, London, UK; 2Royal Brompton Hospital, London, UK
Background Cardiac resynchronisation therapy (CRT) is an established treatment for patients with advanced heart failure (HF). However, a proportion of patients do not derive benet post implantation of CRT. Despite an established predictive role in HF, the signicance of RV dysfunction in gauging clinical benet from
Introduction Heart failure has a worse survival rate than many common cancers, yet few patients receive any palliative care input during the course of their illness. One of the main difculties in providing palliative care for heart failure patients is the uncertainty around the course of the disease and the patient9 s life expectancy. The aim of this study was to compare the Gold Standards Framework (GSF) criteria, which were developed to determine the need for palliative care in non-cancer patients, with the Seattle Heart Failure (SHF) Model, which provides a method of calculating a patient9 s predicted mean life expectancy using physiological variables. Methods Chronic heart failure patients, in NYHA class III or IV, who were being managed in the specialist, heart failure nursing service, were identied from a clinical heart failure database. GSF criteria were assessed by interviewing the specialist nurse responsible for each patient9 s care. Clinical data required for the SHF model were obtained from two, online databases and were used to estimate mean life expectancy and predicted mortality at 1 year. Patients were then followed up, at 1 year, to evaluate; 1) all cause mortality, 2) place of death, and 3) the sensitivity and specicity of the GSF and SHF to predict death at 1 year. Results 138 NYHA III-IV patients were identied from a total of 368 patients currently managed within the specialist nurse service; 66% were male, and the mean age was 77 years. GSF criteria,
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BCS Abstracts 2011

identied 119/138 (86%) patients that met the minimum requirement for palliative care input. However, the SHF model predicted that only 6/138 patients (4.3%) had a predicted life expectancy of less than 1 year. Patients who met GSF criteria for palliative care had signicantly more hospital admissions (p0.001) and had signicantly lower predicted survival rates at 1 year (p0.038) than those patients that did not meet GSF criteria. At follow-up, 43/138 patients had died (31%). Of these, 58% (25/43) died in hospital, following an acute admission. The sensitivity and specicity for the GSF and SHF model were 22%/83% and 98%/12% respectively. Overall, the patients renal function (eGFR<35 ml/min) was the best predictor of mortality, (sensitivity/specicity82%/56%). Discussion Neither the GSF nor the SHF were very accurate in predicting which patients were in the last year of life, in this selected sample. Despite the increasing drive towards palliation in heart failure, clinicians are still faced with a substantial prognostic barrier. Therefore, the progress of palliative care in heart failure patients may require a shift away from the traditional end of life model developed in cancer treatment, and focus instead on a patient9 s increasing needs coupled with an understanding that death, itself, may remain unpredictable. tolerated in 92%, 30%, and 18% of patients respectively (Abstract 93 table 1). Resting heart rate and blood pressure before and after optimisation of medical therapy are shown in Abstract 93 table 2.
93
OPTIMAL MEDICAL THERAPY IN HEART FAILURE: IS THERE SPACE FOR ADDITIONAL HEART RATE CONTROL?
doi:10.1136/heartjnl-2011-300198.93
Abstract 93 Figure 1 Heart Failure Patients Potentially Suitable for Additional Heart Rate Reduction After Optimisation of Standard Medical Therapy. Abstract 93 Table 1
NYHA Class (%) I II III IV HF aetiology (%) Ischaemic Non-ischaemic LV function (%) Ejection Fraction #35% Ejection Fraction >35% Cardiac rhythm (%) Sinus Atrial Fibrillation Medication use (%) b-blockers ACE-I/ARBs Aldosterone antagonists Digoxin 58.7 41.3 83 92 30 18 10.5 62.2 26.2 1.1 57 43 92.4 7.6
Patient Characteristics (n172)
S Russell, M Oliver, H Rose, J Davies, H Llewellyn-Grifths, 4A Raybould, 2V Sim, 3 Z R Yousef. 1Wales Heart Research Institute, Cardiff, UK; 2University Hospital Llandough, Cardiff, UK; 3University Hospital of Wales, Cardiff, UK; 4Hywel Dda Health Board, Camarthen, UK
Introduction Current evidence suggests that heart rate (HR) may serve both as a modiable risk factor, and as a disease modifying variable in patients with impaired left ventricular (LV) systolic function. The systolic heart failure (HF) treatment with If inhibitor ivabradine trial (SHIFT) for example recently demonstrated signicantly improved outcomes in otherwise optimally treated HF patients following additional HR reduction with ivabradine. We therefore estimated the number of patients who after optimisation of conventional HF medications may be suitable for additional HR reduction. Methods We performed a retrospective analysis from two HF clinics where patients are referred for nurse lead, protocol-guided optimisation of conventional HF therapies. Data on patient demographics and classication of HF including; severity (ejection fraction>35% vs ejection fraction#35%), functional limitation (New York Heart Association; NYHA class), and cause (ischaemic vs non-ischaemic) were recorded. In addition, we collected data on patients resting pulse (absolute value and rhythm: sinus vs atrial brillation), and blood pressure at the rst and last clinic visits. Between the two clinic visits, patients underwent protocol-guided forced up-titration of standard neurohormonal HF therapies. We also collected data on the maximal tolerated doses of beta blocker (bB), ACE inhibitor (ACE-I) or angiotensin receptor blocker (ARB), and the reasons for the inability to achieve target doses of bB. Results Of 172 consecutive patients referred for optimisation of HF therapies (age 71613 yrs, 67% male), 71 (41%) were in atrial brillation. Of the patients in sinus rhythm, 78% had severe LV systolic dysfunction (Abstract 93 gure 1). Overall, 145 of 172 patients (83%) tolerated bB therapy; of these, 39% achieved the target maximal dose, 57% at least half target dose, and 4% less than half of the target dose of bB. Reasons for failure to initiate bB (n27, 17%) included; severe and limiting hypotension (48%), intractable lethargy (26%), and hospitalisation with worsening airways disease (26%). ACE-I/ARB, aldosterone antagonists, and digoxin were
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Abstract 93 Table 2 Haemodynamic proles before and after optimisation of medication

First Clinic Visit (pre-optimisation) Resting Heart Rate (beats/min) Systolic Blood Pressure (mm Hg) Diastolic Blood Pressure (mm Hg) 73.8614.8 120619.6 71.7611.6 Final Clinic Visit (post-optimisation) 67.369.5 115.1618.0 67.2610.4 p value <0.001 <0.001 <0.001
Conclusions Of 172 unselected patients attending HF clinics for optimisation of medical therapy, w50% are in sinus rhythm with an ejection fraction #35%. Despite forced optimisation of medical therapy, half of these patients have a resting heart rate $70 beats/ minute. Overall, w1 in every 3 patients attending a heart failure clinic may be suitable for additional heart rate control.
BCS Abstracts 2011

94
A COMPARISON OF FUNCTIONAL AND ECHOCARDIOGRAPHIC OUTCOMES IN NICE COMPLIANT AND NON-COMPLIANT PATIENTS UNDERGOING CRT IN THE REAL WORLD
doi:10.1136/heartjnl-2011-300198.94
1 S J Russell, 1I Rees, 2P OCallaghan, 2Z R Yousef. 1Wales Heart Research Institute, Cardiff, UK; 2University Hospital of Wales, Cardiff, UK
Introduction The National Institute for Clinical Excellence (NICE) dene a population of patients that are most likely to respond to cardiac resynchronisation therapy (CRT) and have a favourable health economic prole. Current NICE criteria (technology appraisal; TA120) for CRT include: NYHA class III or IV symptoms despite optimal medical therapy, sinus rhythm, ejection fraction #35%, and either QRS duration >150 mS alone or 120e149 mS together with echocardiographic (echo) evidence of mechanical dyssynchrony. Several randomised clinical trials however have consistently reported benecial effects of CRT in patients outside current NICE guidelines. In our centre, potential CRT patients are discussed at a multi-disciplinary team (MDT) meeting attended by a heart failure specialist, electrophysiologist, interventional cardiologist, cardiac surgeon and hospital manager. CRT is offered where there is consensus agreement that the individual patient is likely to benet. This individualised and evidence based approach provides for a comparison of outcomes in NICE compliant (NICE:+ve) and NICE: ve patients (patients with a clinical need and evidence base supporting CRT, but who do not meet NICE criteria). Methods Our unit operates an integrated CRT service with preassessment, implantation, and follow-up components. Pre-assessment includes clinical evaluation and baseline echo (EF: ejection fraction, and ESV: left ventricular end-systolic volume) and func-
tional characterisation: a) Minnesota quality of life score (QoL), b) 6 min walk test (6MWT), and c) peak oxygen consumption on cardiopulmonary exercise test (VO2). Follow-up at 3 and 6 months post CRT includes clinical evaluation, device/medical optimisation, and reassessment of echo and functional outcomes. This study involves a retrospective analysis of our CRT database and compares outcomes in NICE:+ve and NICE: ve patients. Results Between January 2007 and December 2009, 253 patients received CRT. Complete paired data comparing baseline and 6 month functional and echo data are available for 139 patients; 89 NICE:+ve and 50 NICE: ve (Abstract 94 table 1). Exclusions for the NICE: ve patients included: atrial brillation (n19), QRS 120e149 mS without mechanical dyssynchrony (n12); QRS <120 mS (n5); pacemaker upgrades (n9). An additional 5 patients with right bundle branch block and otherwise NICE CRT compliance are analysed as NICE: ve in this study. Compared to baseline, 6-month outcomes were similar and signicantly improved in both NICE:+ve and NICE: ve groups (Abstract 94 table 2). Conclusions We observed signicantly favourable and similar functional and echocardiographic responses to CRT in patients meeting and not meeting current NICE criteria for CRT. Guidelines should guide therapy but ultimately each therapy should be individualised and evidence based.
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IMPAIRED CARDIAC ENERGETICS IN DILATED CARDIOMYOPATHY: MAGNETIC RESONANCE SPECTROSCOPY AT 3T

doi:10.1136/heartjnl-2011-300198.95
Abstract 94 Table 1 compliant patients
Characteristics of NICE compliant and nonNICE:+ve NICE:Lve 66 (11) 90 24 (7.2) 158 (37) 46
R M Beadle, L K Williams, M Kuehl, S Bowater, 2K Abozguia, 2F Leyva Leon, M P Frenneaux. 1University of Aberdeen, Aberdeen, UK; 2University of Birmingham, Birmingham, UK
1
Age: years (SD) Male: % Ejection fraction: % (SD) QRS duration: mS (SD) CRT-Debrillator: %
65 (11) 83 22 (7.1) 164 (26) 57
Abstract 94 Table 2 patients
Outcomes in NICE compliant and noncompliant

p value (baseline v NICE:Lve 6 months) (n[50) 63.5 (31.7) 38.9 (25.6) <0.001 208.5 (131.8) 291.5 (127.5) <0.01 12.3 (4.0) 12.8 (4.2) 24.3 (7.2) 31.4 (6.6) 177.2 (67.2) 135.2 (57.2) 0.64 <0.001 p value (baseline v 6 months)
NICE:+ve (n[89) QOL (score): baseline (SD) QOL (score): 6 months (SD) 6MWT (m): baseline (SD) 6MWT (m): 6 months (SD) V02 (ml/kg/min): baseline (SD) V02 (ml/kg/min): 6 months (SD) Ejection fraction- baseline (SD) Ejection fraction- 6 months (SD) End-systolic volumebaseline /ml (SD) End-systolic volume6 months /ml (SD) 58.2 (23.6)
40.1 (25.0) <0.001 216.4 (118.3) 324.5 (131.2) <0.001 13.2 (5.6) 14.4 (3.3) 21.5 (7.1) 30.7 (10.4) 185.1 (79.3) 144.6 (73.5) 0.24 <0.001
0.02
0.01
Introduction The aim was to measure the cardiac phosphocreatine to ATP (PCr/ATP) ratio non-invasively in patients with dilated cardiomyopathy and normal controls, and to correlate the patients results to symptom status, ejection fraction (EF) and quality of life scores. Dilated cardiomyopathy is known to be associated with cardiac energy deciency. Magnetic resonance spectroscopy (MRS) has been proposed as a non-invasive method of assessing cardiac energetics and as a method of measuring response to therapy. Interrogation at high eld strength improves signal to noise ratio. Methods 32 patients and 22 control subjects were studied using phosphorus-31 (31P) MRS and patients were classied to NYHA symptom class. In vivo energetics were measured using a commercially available Philips Achieva 3 Tesla scanner and dedicated 31P coil with ISIS volume selection. Java Magnetic Resonance User Interface (jMRUI) was used for analysis. Furthermore, all patients completed a Minnesota Living with Heart Failure (MLWHF) score and underwent echocardiography. LVEF was measured using biplane Simpsons method. Results The PCr/ATP ratio was signicantly reduced in patients (1.3560.31) compared with control subjects (1.9060.40; p<0.005). The PCr/ATP ratio was correlated with NHYA class (r0.68, n32, p<0.0005). No correlation was found with LVEF or MLWHF score. Conclusions This study conrms the presence of energy deciency in dilated cardiomyopathy as measured by MRS at 3T. The energy status correlates strongly with symptom status but not with ejection fraction nor quality of life score. Cardiac energetic status is directly proportional to symptoms status and therefore any treatments targeted to improve cardiac energetics may improve patient symptoms in dilated cardiomyopathy.
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(1.1260.06). The single-visit RISE95 test incorporating incrementaland step- exercise phases, each to the volitional limit, was well tolerated by CHF patients: The SE phase was contraindicated in only 3 of the 47 tests. The RISE95 detected VO2max in 14 of 21 patients with a sensitivity of w10% (ie, similar to healthy subjects), and without the need for secondary criteria or incidence of false-positive. In contrast, the end-exercise RER was sensitive to both modality and ramp rate and provided a false-positive for VO2max attainment in every incidence. Therefore, the RISE95 protocol provides a robust measure of VO2max in CHF patients, to within an individuallydened CI without dependence on secondary criteria.
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INCREASING SKELETAL MUSCLE OXYGENATION BY PRIOR MODERATE-INTENSITY EXERCISE INCREASES AEROBIC ENERGY PROVISION IN CHRONIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.97
T S Bowen, D T Cannon, S R Murgatroyd, K K Witte, H B Rossiter. University of Leeds, Leeds, UK
96
A TEST TO CONFIRM MAXIMAL OXYGEN UPTAKE IN CHRONIC HEART FAILURE PATIENTS WITHOUT THE NEED FOR SECONDARY CRITERIA
doi:10.1136/heartjnl-2011-300198.96
T S Bowen, D T Cannon, G Begg, V Baliga, K K Witte, H B Rossiter. University of Leeds, Leeds, UK
Cardiopulmonary exercise testing for peak oxygen uptake (VO2peak) is widely used to evaluate severity, pathophysiology and prognosis in patients with chronic heart failure (CHF). A VO2peak #14 (or 12 with b-blocker) ml/kg/min is associated with increased mortality and is a key criterion for cardiac transplant listing. A symptom-limited exercise test, however, may elicit a VO2peak lower than the maximum physiological limit (VO2max); the latter commonly conrmed using the secondary criterion of respiratory exchange ratio (RER) >1.05. RER, however, is sensitive to the test format. We, therefore, determined if a ramp-incremental (RI) step-exercise (SE) (or RISE) test could determine VO2max in CHF patients without using RER, by satisfying the criterion that two different work rates are terminated at the same VO2peak. Twenty-one male CHF patients (NYHA class I: n3, II: n16, and III: n1) initially performed a modied Bruce treadmill test. Patients then completed a symptom-limited RISE95 cycle ergometer test in the format: RI (4e18 W/min; w10 min); 5-min recovery (10 W); SE (95% of peak RI work rate). Thirteen of these patients also performed RISE95 tests using slow (RI 3e8 W/ min; w15 min) and fast (RI 10e30 W/min; w6 min) ramp rates. VO2 and RER were measured breath-by-breath by a mass spectrometer and turbine (MSX, NSpire, UK). Peak VO2 and RER were compared within-subjects, between RI and SE, by unpaired t test of the nal 12 breaths of exercise. This approach allowed VO2max and its associated 95% condence limits to be estimated. VO2peak was similar (p>0.05) in treadmill and cycle exercise (mean6SD: 16.262.7 vs 15.063.2 ml/kg/min, n20, respectively), despite RER being greater in cycling (1.0860.12 vs 1.1560.09; p<0.05). As a group, VO2peak was similar (p>0.05) between RI and SE (mean6SD: 14.663.2 vs 14.963.2 ml/kg/min, n21). A within-subject comparison, however, revealed that the VO2max criterion was met in 14 of 21 patients (measurement sensitivity range 0.6e3.8 ml/kg/min), despite RER being >1.05 in the remaining 7 (1.1660.09). There was no effect of ramp rate on VO2peak (p>0.05), however RER was greater (p<0.05) in the fast ramp (1.2460.09) compared to the slow
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Rapid adaptation of pulmonary oxygen uptake (VO2) at exercise onset reduces the reliance on limited anaerobic energy stores and is associated with increased exercise tolerance. These VO2 kinetics, however, are slow in patients with chronic heart failure (CHF). This could be due to limitations in the control of muscle O2 consumption and/or O2 delivery. Recent evidence in CHF of a transient overshoot in microvascular deoxygenation at exercise onset supports the latter. As prior exercise is known to increase muscle blood ow in healthy individuals, we examined whether it could attenuate the fall in microvascular deoxygenation and speed VO2 kinetics on transition to moderate exercise in CHF patients. Thirteen CHF patients (NYHA class I: n3, II: n9, and III: n1) performed a ramp test on a cycle ergometer for estimation of lactate threshold (LT) and VO2max. Patients subsequently repeated two 6-min moderate-intensity exercise transitions (bout 1, bout 2) from rest to 90%LT, separated by 6-min of rest. Measurements included breath-by-breath VO2 using a turbine and mass spectrometer (MSX, NSpire, UK), and tissue oxygenation index (TOI) of the vastus lateralis by spatially resolved near-infrared spectroscopy (NIRO200, Hamamatsu, Japan). The exponential timeconstant (s) for TOI and phase II VO2 were estimated using nonlinear least-squares regression. The sVO2/sTOI, or kinetic index, was taken to reect the relative matching of muscle oxygenation to its instantaneous requirement. LT and VO2max were 9.961.7 (mean6SD) and 15.063.2 ml/kg/min, respectively. Prior exercise increased resting TOI by 1063% (p<0.05), attenuated the transient overshoot in muscle deoxygenation by w50% (p<0.05) and slowed the rate of deoxygenation in the transient (sTOI: 1061 vs 21613 s; p<0.05). Both sVO2 (46620 vs 39618 s; p<0.05) and the kinetic index (4.561.8 vs 2.260.9; p<0.05) were reduced following prior exercise. sVO2 was well correlated to the kinetic index (R20.92) in bout 1. However, although a lower sVO2 was typically reected in a reduced kinetic index in bout 2, VO2 kinetics remained slowed in 4 patients. These patients had a higher NYHA class (2.360.5 vs 1.660.5; p0.06) and greater initial sVO2 (62617 vs 3369 s; p<0.05) than the others. In CHF prior moderate-intensity exercise improved the dynamic matching of muscle oxygenation to its instantaneous requirement and speeded VO2 kinetics in all patients. This suggests that slow VO2 kinetics in CHF are due, at least in part, to a dynamic limitation in O2 delivery. However, this approach revealed an apparent limitation in the control of muscle O2 consumption in the most severe patients, which was only partly ameliorated by improving O2 delivery. Nevertheless, these ndings suggest that an acute intervention to improve muscle oxygenation can increase aerobic energy provision on transition to exercise in CHF patients.
BCS Abstracts 2011

98
HIGH PREVALENCE OF UNDIAGNOSED CARDIAC DYSFUNCTION IN THE OLDEST OLD: FINDINGS FROM THE NEWCASTLE 85+ STUDY
doi:10.1136/heartjnl-2011-300198.98 F Yousaf, J Collerton, A Kenny, T Kirkwood, 1C Jagger, 1A Kingston, 3B Keavney. Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK; 2 Freeman Hospital, Newcastle upon Tyne, UK; 3Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK
1 1 1 2 1
Background Heart failure prevalence increases sharply at older ages. The section of the population aged 85 and over represents the most rapidly increasing demographic worldwide. Previous epidemiological studies of ventricular dysfunction and heart failure have included only small numbers of the oldest old, and have generally been conducted in hospital-based settings, potentially introducing ascertainment biases. We conducted a community-based study of the oldest old using domiciliary echocardiography to estimate the prevalence of cardiac dysfunction and heart failure. Since in elderly people with multiple comorbidities, heart failure may more frequently be incorrectly diagnosed, we cross-referenced our ndings to preceding diagnoses present in general practice records. Methods Four hundred and twenty-seven individuals aged 86e89 years (mean age 87.9 years; 39.1% (n167) men, 60.9% (n260) women) were visited in their usual place of residence. A full cardiovascular and medical history, including current medication, was taken; symptoms were graded using the NYHA classication. Previous diagnoses of heart failure (HF) were abstracted from the GP record. Participants underwent 2-D and Doppler echocardiography, including tissue Doppler measurements of LV long axis velocities, using a portable instrument (Vivid-I, GE Healthcare). LV systolic and diastolic dysfunction were graded according to American Society of Echocardiography guidelines. Results LV systolic function could be quantied in 93.2% (n398) participants and diastolic function (classied as normal, mild, moderate or severe dysfunction) in 88.1% (n376). 37.2% of participants (n140/376) had normal cardiac function or isolated mild diastolic dysfunction; 19.6% (n78/398) had moderate or severe LV systolic dysfunction, which was commoner in men (27.4%) than women (14.5%); and 14.4% (n54/376) had isolated moderate or severe diastolic dysfunction. 65.1% (278/427) of participants had valid data on previous diagnosis of HF, NYHA class and echocardiographic assessment of cardiac dysfunction. Of these, 37.4% (104/278) had clinical evidence of HF, which was dened as NYHA class II, III, or IV symptoms with underlying systolic dysfunction (29.5% (82/278)) or isolated moderate or severe diastolic dysfunction (7.9% (22/278)) on echo. Only 7.6% (21/278) had a previous diagnosis of HF. 33.1% (n92/278) had no previous diagnosis of HF but had clinical evidence of HF and an additional 21.6% (n60/278) had no previous diagnosis but evidence of pre-clinical HF (NYHA class I with systolic or moderate/severe diastolic dysfunction). Of those with a previous diagnosis of HF, 23.5% (n5/21) had no echocardiographic evidence of cardiac dysfunction. Conclusions Systolic and diastolic dysfunction and HF were commoner in our population than previous studies in the younger old have suggested. There are signicant levels of both undiagnosed and misdiagnosed HF in this age group.
warranting consideration for transplantation (Circulation 2010; 122:173). We examined whether this variable is a good indicator of cardiac function in overweight heart failure (HF) patients. Methods We compared the cardiopulmonary exercise performance and non-invasive haemodynamics of overweight (BMI >34 kg/m2) and non-overweight (BMI #30) male heart failure patients in NYHA Classes II and III, with those of healthy male volunteers with no known cardiovascular diseases (n101, age 43.2618.1 (SD) years, BMI 26.063.1) as controls. Their physical and cardiac functional reserves were measured during treadmill exercise testing with standard respiratory gas analyses and rebreathing method of non-invasively measuring cardiac outputs during peak exercise. Results Consecutive overweight HF were screened and 24 patients (age 4968(SD) years, BMI 44.966.8, NYHA 2.5060.50) managed to exercise to acceptable cardiopulmonary limits (peak RER1.0160.12), and achieved Vo2max of 16.864.6 mls/kg/min which was signicantly lower than controls (37.0610.7 mls/kg/min, p<106) and also lower than those of 30 non-overweight HF counterparts (20.063.7 mls/kg/ min, p0.0019, age 49615 years, BMI 25.062.9, NYHA 2.4860.51). As shown in Abstract 99 gure 1, the overweight HF patients had Vo2max values which distributed around the 14 mls/kg/min cut-off value, and 9 of whom were indeed below this cut-off value. However, the uncorrected Vo2max were higher than those of non-overweight counterparts (Overweight: 25756748 vs 15946325 mls/min, p<106), and its range of 1485e4210 mls/min overlapped with the range of 1244e5774 mls/min in controls. The peak cardiac power output (CPOmax, 4.561.6 W, minimum 2.7 W) of overweight HF patients were clearly above those of non-overweight (2.460.6 W, p<106, Abstract 99 gure 2) and all above the transplant cut-off value of 1.5 W.
99
IS VO2MAX/KG A RELIABLE INDICATOR OF CARDIAC DYSFUNCTION IN OVERWEIGHT HEART FAILURE PATIENTS?

doi:10.1136/heartjnl-2011-300198.99
S Chinnappa, N Lewis, D Barker, L B Tan. Leeds Teaching Hospitals NHS Trust, Leeds, UK
Background Peak O2 consumption (Vo2max) of #14 ml/kg/min has been widely accepted as being indicative of poor cardiac function
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Conclusion These results indicate that in principle Vo2max in ml/kg/min as an indirect indicator of cardiac function or for cardiac transplantation selection is unreliable when applied to overweight heart failure patients. Extending this concept to the entire spectrum of body weights, the practice of correcting Vo2max by body weight in cardiological practice would also require urgent reconsideration. optimisation. However, the immediate increment in blood pressure seems to diminish somewhat in the initial minute: it is unclear whether this is due to an (undesirable) fall in stroke volume or a (desirable) compensatory reduction in peripheral resistance. Methods and Results We studied this question by measuring beat-bybeat stroke volume (ow) using Doppler echocardiography, and blood pressure using continuous nger photoplethysmography, during and after atrioventricular delay adjustment from 40 to 120 ms in 19 subjects with cardiac pacemakers. Quintuplicate experimental runs were performed. Blood pressure and stroke volume (ow) both increased immediately (p<0.00001 within one heartbeat). The immediate pressure increment correlated strongly with the immediate ow increment (r0.74, p0.0001). Pressure showed a partial decline a few seconds later (average rate 0.65 mm Hg/beat, re0.98, p<0.0001), in contrast, ow did not decline (pNS), Abstract 100 gure 1. Signal-to-noise ratio was signicantly better for pressure than ow (6.363.6 vs 2.161.4, p<0.0001), Abstract 100 gure 2. Conclusions Improving atrioventricular delay immediately increases blood pressure; however this effect decays slightly over the subsequent minute. This is due to compensatory vasodilatation rather than a reduction in cardiac function. Pressure changes are simpler to measure and easier to distinguish from random variation than Doppler measurements of ow, but are best measured immediately, before the vascular compensation.
100
PRESSURE VS FLOW AS A GUIDE FOR PACEMAKER OPTIMISATION? THE ACUTE HAEMODYNAMIC EFFECTS OF CHANGES TO ATRIOVENTRICULAR DELAY
doi:10.1136/heartjnl-2011-300198.100
C H Manisty, B Unsworth, R Baruah, P Pabari, Z I Whinnett, J Mayet, D P Francis. Imperial College, St. Marys Hospital, London, UK
Background Non-invasive blood pressure monitoring by continuous nger photoplethysmography (Finometer) may have value in pacemaker
101
WHAT DEGREE OF PULMONARY HYPERTENSION PREDICTS POOR OUTCOME IN PATIENTS WITH LEFT VENTRICULAR SYSTOLIC DYSFUNCTION? A 10-YEAR FOLLOW-UP STUDY
doi:10.1136/heartjnl-2011-300198.101
1 1
B R Szwejkowski, 1D H J Elder, 1A M J Choy, 2S D Pringle, 1A D Struthers, 1C C Lang. University of Dundee, Dundee, UK; 2Department of Cardiology, NHS Tayside, Dundee

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Introduction The presence of pulmonary hypertension in left ventricular systolic dysfunction (LVSD) is an ominous sign. It remains unclear the level at which pulmonary hypertension conveys a mortality risk in patients with LVSD. Methods We performed a record-linkage study in Tayside, UK (population approximately 400 000) utilising the Tayside echocardiogram database (>100 000 echos) maintained by the Health Informatics Centre (HIC). Datasets from HIC include mortality data and other health care activities linked anonymously by the community health index (CHI) number. Patients were included in the analysis if they had LVSD and had a right ventricular systolic pressure (RVSP) measurement. Cox proportional hazards regression analysis was used to examine the effects of different ranges of RVSP measures on all cause mortality. Results 2910 patients (mean age, 74.5611.4 years; 43 % male) met entry criteria. Mean RVSP was 43.3 6 12.7 mm Hg and median follow was 362 days (IQR 129e850 days). There was a signicant correlation between RVSP and survival (p<0.0001). In quartiles of RVSP, the HR after adjustment for confounding factors including LVSD and the presence of chronic obstructive pulmonary disease (COPD) were: RVSP 35e41 mm Hg, HR 1.12 (95% CI 0.95 to 1.32, p0.175), RVSP 42e50 mm Hg, 1.27 (1.07 to 1.49, p<0.001) and RVSP 51e106 mm Hg 1.62 (1.38 to 1.1, p<0.001). For each 5 mm Hg stepwise increase in RVSP the HR for all cause mortality was 1.07 (1.04 to 1.09, p<0.001). Abstract 101 gure 1 shows the Kaplan-Meier survival curves for all cause mortality for all patients expressed as different RVSP quartiles.
BCS Abstracts 2011

glyceryltrinitrate- and sodium nitroprusside-mediated (endothelialindependent) response was observed between study groups. In south Asian subjects, parameters of pulse wave velocity and augmentation index did not differ between those with HF and those in control groups. No ethnic differences were detected in pulse wave velocity. Conclusion: South Asian patients with HF have impaired micro- and macro-vascular endothelial function, but preserved arterial elastic properties. Signicant ethnic differences in endothelial function are present in patients with HF.
103
SENILE SYSTEMIC AMYLOIDOSIS: A COMMON CAUSE OF HEART FAILURE IN THE ELDERLY?

doi:10.1136/heartjnl-2011-300198.103
Survival of RVSP quartile.
Conclusion An RVSP of greater than 42 mm Hg is predictive of increased mortality in heart failure. This is nding is independent of LVSD and COPD.
102
ETHNIC DIFFERENCES IN ENDOTHELIAL FUNCTION IN CHRONIC HEART FAILURE

doi:10.1136/heartjnl-2011-300198.102
J H Pinney, 2H J Lachmann, 2J D Gillmore, 2A Wechalekar, 3S D J Gibbs, P Sattianayagam, 4,5S M Banypersad, 6,7J Dungu, 3N Wassef, 3C A McCarthy, 3 P N Hawkins, 3C J Whelan. 1National Amyloidosis Centre and UCL Centre for Nephrology, UCL Division of Medicine, Royal Free Hospital, London, UK; 2National Amyloidosis Centre, UCL Division of Medicine, Royal Free Hospital, London, UK; 3 National Amyloidosis Centre, UCL Medical School, Royal Free Hospital, London, UK; 4 National Amyloidosis Centre, London, UK; 5The Heart Hospital, UCL Medical School, London, UK; 6National Amyloidosis Centre, UCL Medical School, University of London, London, UK; 7St Georges Hospital, University of London, London, UK
3
E Shantsila, 2P S Gill, 3G Y H Lip. 1University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK; 2University of Birmingham, Primary Care and Populational Sciences, Birmingham, UK; 3University of Birmingham Centre for Cardiovascular Science, Birmingham, UK
Background Endothelial dysfunction is characteristic of patients with heart failure (HF) and is associated with an increased risk of future cardiovascular events. However, data on ethnic differences in endothelial function in HF are scarce. In this study we aimed to compare parameters of macro- and micro-vascular endothelial function and arterial elasticity in HF age- and sex-matched patients of different ethnic origin: (i) white European, (ii) south Asian and (iii) African-Caribbean. Additionally, SA patients with systolic HF were compared to two matched control groups: (i) south Asian patients with coronary artery disease without HF(disease controls) and (ii) south Asian healthy controls. Methods We recruited 186 age/sex-matched patients with HF (ejection fraction <40%) of SA (n43, age 66.5611.1 years), white (n44, age 68.469.4 years) and African-Caribbean (n21, age 69.2610.3 years) origin; as well as 36 disease controls (age 64.0610.6 years) and 40 healthy controls (n40, age 63.369.24 years). Macrovascular endothelial function was assessed as brachial artery ow mediated dilation in response to hyperaemia (FMD) and glyceryltrinitrate were assessed by vascular ultrasonography (iE33, Philips, USA). Microvascular endothelial function was evaluated by laser Doppler owmetry of forearm skin (DRT4, Moor Instruments, UK) after iontophoresis of acetylcholine and sodium nitroprusside. Arterial stiffness was quantied by pulse wave velocity and augmentation index using (Sphygmocor, Australia). Results Compared to disease controls and healthy controls south Asian patients with HF had impaired microvascular response to acetylcholine (3906302%, 5496264%, and 123695.5%, respectively, p<0.05) and reduced FMD (7.1263.64%, 11.864.66%, and 4.8664.88%, respectively). HF patients of south Asian origin had impaired microvascular endothelial function (response to acetylcholine123695.5%) compared to white (258615.6%) and African-Caribbean (286617.3%) groups (p>0.05). HF patients of white origin had higher FMD than south Asian (4.8664.88%) and African-Caribbean (5.3663.24%) patients (p<0.05). No difference in
Senile systemic amyloidosis (SSA) is a rare cause of heart failure due to the deposition of wildtype transthyretin. The clinical features and outcome are ill dened; our aim was to evaluate the natural history of the disease in the UK in a group of thoroughly characterised patients. The series included all cases of biopsy proven transthyretin (TTR) amyloidosis with wildtype TTR gene sequencing who were prospectively followed up between January 2001 and May 2010. Clinical, biochemical, ECG and echocardiographic evaluation were performed at presentation to our centre. Patient survival was estimated using KaplaneMeier analysis. 55 patients with histologically proven SSA; 36 (65.5%) from cardiac, 14 (25.4%) from GI tract, 3 (5.5%) from bladder, 1 (1.8%) from fat and 1 (1.8%) from carpal tunnel tissue were identied. 49 (89%) were male. The median age at diagnosis and death were 74 (range 66e89) and 79 (range 69e84) years respectively. Survival from symptom onset and diagnosis was 7.04 (range 0.54e8.41) and 4.58 (range 0.07e5.41) years respectively. In recent years more patients have been diagnosed with 2 (3.6%), 14 (25.5%) and 39 (70.9%) patients between 2001e2003, 2004e2006 and 2007e2009 respectively. The most common presentation was with breathlessness in 28 patients (51%). Twenty-four patients (43.6%) had prior carpal tunnel operations. Twelve (21.8%) patients had a history of ischaemic heart disease. Fifteen had had a coronary angiogram; 8 were reportedly normal and 7 required intervention. Arrhythmias were common, 20 patients (36.3%) had a history of atrial brillation and 6 (10.9) had pacemakers in situ. ECG ndings were; 24 (43.6%) in AF, 6 (10.9%) rst degree block, 10 (18.2%) left bundle and 6 (10.9%) right bundle branch block, 27 (49%) Twave changes, 11 (20%) <5 mm complexes in all inferior leads. Echocardiographic ndings revealed the median IVSd was 1.7 (range 1.1e2.5) cm, median E/A ratio was 2.7 (range 0.79e5.4), E/E9 15.81 (range 7.5e41.1) and ejection fraction was 45.5 (range 13e83)%. Blood results showed; the median baseline NT-proBNP was 356.1 (range 5e2611) and troponin T 0.03 (range 0.01e0.28). Twenty-ve patients had a troponin T >0.03 (45%). Ten patients (18%) had a detectable paraprotein and 2 (3.6%) had bence jones proteins. SSA is present in >25% of the very elderly at post mortem but was rarely diagnosed during life. It is becoming more frequently recognised perhaps due to widespread use of cardiac MRI. Most patients are male but women can be affected. A history of carpal tunnel syndrome is common. The diagnosis is often made after the onset of breathlessness. Systolic and diastolic dysfunction
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BCS Abstracts 2011

can be seen on echocardiogram. A positive troponin is a common nding with a subsequent normal coronary angiogram. Incidental paraproteins are prevalent in up to 8% of this population and it is important to obtain a tissue diagnosis to rule out AL amyloidosis. With supportive management medium term outcomes are good.
Department of Respiratory Medicine, York Hospitals NHS Foundation Trust, York, UK; Department of Echocardiography, York Hospitals NHS Foundation Trust, York, UK; 4 Department of Biochemistry, York Hospitals NHS Foundation Trust, York, UK; 5Leeds Teaching Hospitals, Leeds, UK; 6Department of Cardiology, York Hospitals NHS Foundation Trust, York, UK
3 2
104
PROGNOSTIC UTILITY OF CALCULATED PLASMA VOLUME STATUS IN CHRONIC HEART FAILURE

doi:10.1136/heartjnl-2011-300198.104
H Z Ling, 1N Aung, 1,2J Flint, 1,2S Aggarwal, 1,2S Weissert, 1,2A Cheng, 3D P Francis, J Mayet, 1,2M Thomas, 1,2S Woldman, 1,2,4D O Okonko. 1University College London Hospital, London, UK; 2The Heart Hospital, London, UK; 3International Center for Circulatory Health, NHLI, Imperial College London, London, UK; 4NHLI Imperial College London, London, UK
3
Background Plasma volume (PV) expansion is a hallmark feature of worsening heart failure that is notoriously underestimated by clinical examination. While radioisotope assays optimally quantify PV status, numerous haemodialysis-based equations also exist for its estimation. The prognostic utility of such formulas in chronic heart failure (CHF) is unknown. Methods We analysed the relation between estimated PV status and mortality in 246 outpatients with CHF (mean (6SD) age 67613 years, NYHA class 261, LVEF 2868%). PV status was calculated (Hakim RM, et al) by subtracting the patients actual PV ((1-haematocrit) 3 (a + (b 3 weight)); a and b are gender-specic constants) from their ideal PV ((c 3 weight); cgender-specic constant). Results Median (6IQR) PV status wasd2616550 ml with 78% and 21% of patients having PV contraction and expansion, respectively. Patients with PV excess had signicantly higher creatinine and lower albumin levels. Over a median follow-up of 13616 months, 36 (15%) patients died. PV status predicted mortality (HR 1.001, 95% CI 1.001 to 1.002, p0.001) in a graded fashion (Abstract 104 gure 1A) and did so independently of NYHA class, LVEF, weight, haematocrit and creatinine. A PV status #178 ml optimally predicted survival (ROC AUC 0.68, p0.0007) and conferred a 75% reduced hazard for death (HR 0.16, 95% CI 0.07 to 0.37, p<0.0001, Abstract 104 gure 1B).
Background Brain natriuretic peptides have been shown to be reliable indicators of left ventricular failure and markers of risk in cardiac disease. However, patients with chronic obstructive pulmonary disease (COPD) are also known to have elevated concentrations of brain natriuretic peptides in the absence of overt cardiac disease, likely due to right ventricular strain. This has been shown to have prognostic value and has a potential role in the management of the condition; for example, it has been suggested that it could be used to guide the initiation of non-invasive ventilation. The aim of this study was to identify clinical and echocardiographic determinants of the polypeptide N-terminal proBrain Natriuretic Peptide (NT pro-BNP) in patients with stable COPD. Method Arterial blood gases, plasma NT pro-BNP and transthoracic echocardiographic parameters were studied in 140 patients with stable COPD attending a respiratory outpatient clinic. Results Of the 140 patients, 65 (46%) were male, 26 (19%) received home oxygen therapy, 115 (82%) were current smokers, 38 (27%) were prescribed diuretics and 15 (11%) had a left ventricular ejection fraction <45%. Patients with cor pulmonale (n6) were more likely to have left ventricular systolic dysfunction (p<0.001), reduced tricuspid annular plane systolic excursion (p0.017) and higher pulmonary artery systolic pressures (p0.01). The median (IQR) NT pro-BNP concentration was 16.2 (25.4) pmol/l. Concentrations were signicantly higher in those with a dilated left atrium, aortic stenosis, left ventricular systolic dysfunction, right ventricular impairment, atrial brillation and those prescribed diuretics and ACE inhibitors. Signicant predictors of NT pro-BNP were a dilated left atrium, aortic stenosis and left ventricular systolic dysfunction. NT Pro-BNP was an excellent discriminator of RV impairment (C statistic0.90). Conclusions NT pro-BNP readily identies patients with stable COPD who have right ventricular dysfunction. However, several other clinical variables also associated with increased NT pro-BNP concentrations are prevalent in this population. This is likely to confound clinical decision making.
106
CHF PATIENTS ARE VITAMIN D DEFICIENT AND HYPERPARATHYROID, WITH LEVELS OF EACH RELATED TO MARKERS OF SEVERITY
doi:10.1136/heartjnl-2011-300198.106

1 2
Conclusions Calculating plasma volume status in CHF patients appears prognostically useful and suggests that dehydration is better tolerated than volume excess in these individuals and that targeting therapy to achieve a plasma volume status #178 ml might increment survival.
G A Begg, 1L Kearney, 2A C Wheatcroft, 1R Byrom, 1S Barnes, 1J Gierula, 2J Barth, R Cubbon, 2M T Kearney, 2K K Witte. 1Leeds General Inrmary, Leeds, UK; 2University of Leeds, Leeds, UK
105
CLINICAL AND ECHOCARDIOGRAPHIC DETERMINANTS OF N-TERMINAL PRO B-TYPE NATRIURETIC PEPTIDE LEVEL IN PATIENTS WITH STABLE CHRONIC OBSTRUCTIVE AIRWAYS DISEASE: A PROSPECTIVE OBSERVATIONAL STUDY OF 140 PATIENTS
doi:10.1136/heartjnl-2011-300198.105
1 6
C P Gale, J White, A Hunter, J Owen, J Watson, 5I R Pearson, 4I Holbrook, N Durham, 6M Pye. 1Division of Biostatistics, University of Leeds, Leeds, UK;
Background The vitamin D-parathyroid (PTH) axis is increasingly recognised as potentially being involved with many of the features of the syndrome of CHF. We wanted to explore the relationship between vitamin D and PTH levels in a group of CHF patients and relate these to markers of severity. Methods We analysed serum 25(OH) vitamin D3 levels in 406 consecutive attendees of the Leeds Advanced Heart Failure clinic (310 men) and correlated these to clinical markers of severity. Results Mean age (SE) was 69 (3) years, mean left ventricular ejection fraction (LVEF) 31 (2)%, mean serum creatinine 117 mmol/l (2.4), median vitamin D levels (IQR) 30 (20e43) nmol/l (normal for skeletal health>75 nmol/l) and median parathyroid levels 8.8 (6.2e13.5) pmol/l (normal<6.5 pmol/l). Aetiology was ischaemic
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BCS Abstracts 2011

heart disease in 63% and 23% had diabetes mellitus. Patients were optimally treated (84% on b-blockers, 88% on ACE inhibitors, and 46% on spironolactone). The mean daily dose of furosemide was 60 (3) mg. Very few patients (5%) were sufcient in vitamin D. Patients with worse symptoms as measured by NYHA status had lower vitamin D levels and higher PTH levels (Abstract 106 gures 1 and 2). There was also a negative relationship between furosemide dose and vitamin D (Abstract 106 gure 3) and, in an unselected subset of 160 patients (mean peak oxygen uptake (pVo2) 16.6 (0.5) ml/kg/ min), there was a positive relationship between pVo2 and vitamin D (Abstract 106 gure 4). Patients with diabetes had lower vitamin D levels than non-diabetics (p<0.001) and there was a negative correlation between vitamin D and fasting glucose levels (r0.13; p0.02). There was no relationship between vitamin D levels and age, calcium, creatinine or CRP, and no differences between those patients taking and those not taking b-blockers and ACE inhibitors. In 8 unselected patients we found a negative relationship between tumour necrosis factor-alpha (TNF-a) levels and vitamin D (r0.62; p0.05). Although there was no relationship between vitamin D levels and baseline LVEF, in a subgroup of 150 patients followed up one year after titration to optimal CHF therapy, there was a signicant positive relationship between change in LV dimensions and vitamin D levels at the time of the baseline scan (p<0.05). Conclusions The vitamin D-PTH axis is abnormal in CHF, related to the severity of the condition. Our data suggest that reverse remodelling in response to optimal drug titration is greater in those with higher vitamin D levels. Whether vitamin D deciency is causally related to CHF remains unknown and requires a long-term, randomised, placebo-controlled study in CHF patients with efcacy and mechanistic outcomes, using a dose of vitamin D capable of normalising both vitamin D and PTH levels.
107
EXPANSION OF THE RED CELL DISTRIBUTION WIDTH AND EVOLVING IRON DEFICIENCY AS PREDICTORS OF POOR OUTCOME IN CHRONIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.107
N Aung, 1H Z Ling, 1,2S Aggarwal, 1,2J Flint, 1,2S Weissert, 1,2A Cheng, 1T Richards, D P Francis, 3J Mayet, 1,2M Thomas, 1,2,4D O Okonko. 1University College London Hospital, London, UK; 2The Heart Hospital, London, UK; 3International Center for Circulatory Health, NHLI Imperial College London, London, UK; 4NHLI Imperial College, London, UK
3

Background Red cell distribution width (RDW) is a surrogate of many aberrations (inammation, malnutrition, iron deciency (ID)) that may drive chronic heart failure (CHF) progression. While an elevated RDW and iron deciency at baseline predict mortality in CHF, little is known about the prognostic implications of their temporal trends. Methods We analysed the relation of red cell indices on rst consultation and over time with mortality in 274 outpatients with CHF (mean (6SD) age 70614 years, LVEF 2868%, NYHA class 261, 54% ischaemic). The combination of a rising RDW and a falling mean cell volume (MCV) identied evolving ID. Results On initial consultation, an RDW >15%, Hb<12.5 g/dl, and MCV <80 were evident in 41%, 46%, and 8% of patients. Over a median (6IQR) follow-up of 15617 months, 60 (22%) patients died. On Cox proportional hazards analyses, a higher RDW independently predicted increased mortality (HR 1.21, p<0.0001). Over time, 51%, 58%, 40%, and 23% of patients had a rise in RDW, a fall in Hb, a fall in MCV, and evolving ID, respectively. A rising RDW predicted death (HR 1.18, p0.002) independently of baseline RDWs and changes in Hb, with an absolute increase >1% conferring a twofold escalated risk of mortality (Abstract 107 gure 1A). Evolving ID was also associated with poorer survival (HR 2.89, p<0.0001, Abstract 107 gure 1B).
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Results Signicant vortical ow in any segment (dened as ow disturbance occupying more than one half of the aortic lumen) was present in all patients with MFS, but in only 7/18 controls (p<0.0005). The severity of ow disturbance was greater in MFS patients than controls (median severity score 3 for Marfan patients, 1 for controls, p<0.0005). There was marked regional variation in the prevalence of major ow disturbance (Abstract 108 gure 2), with the sinuses of Valsalva and proximal descending aorta being most frequently affected. Prior repaired aortic dissection was associated with marked abnormalities of blood ow (Abstract 108 gure 1C), with corresponding increases in axial WSS within the true lumen of the dissected aorta (typical axial WSS in the dissected ascending aorta was +0.9 N/m2, compared to +0.54 N/m2 in healthy controls). Aortic ow disturbance in MFS was of one of three types: Type A: ow disturbance conned to the sinuses of Valsalva, Type B: ow disturbance conned to the proximal descending aorta, Type C: ow disturbance in both the sinuses of Valsalva and the proximal descending aorta.

Conclusions An expanding RDW and evolving iron deciency over time predict an amplied risk of death in CHF and could be utilised for risk stratication or therapeutically targeted to improve outcomes.
108
4D-FLOW CMR DEMONSTRATES THE REGIONAL DISTRIBUTION OF AORTIC FLOW DISTURBANCE IN MARFAN SYNDROME
doi:10.1136/heartjnl-2011-300198.108
A Pitcher, T E Cassar, J Suttie, J M Francis, 2P Leeson, 3E Blair, 4B P Wordsworth, J C Forfar, 6M Markl, 1S N Neubauer, 7S E Petersen. 1Oxford Centre for Clinical Magnetic Resonance Imaging, Oxford, UK; 2Department of Cardiovascular Medicine, University of Oxford, Oxford, UK; 3Department of Clinical Genetics, Churchill Hospital, Oxford, UK; 4Nufeld Department of Medicine, University of Oxford, Oxford, UK; 5John Radcliffe Hospital, Oxford, UK; 6University Hospital, Freiburg, Germany; 7Centre for Advanced Cardiovascular Imaging, William Harvey Research Institute, London, UK
5
Background Marfan syndrome (MFS) commonly leads to progressive aortic dilation, aneurysm formation and aortic dissection, particularly at the aortic sinuses (w60% of dissections), and descending thoracic aorta (w30% of dissections). Abnormal aortic blood ow patterns may contribute to the enlargement and dissection of an inherently weak aorta, or to late complications after aortic dissection. Methods 18 patients with MFS (3 with a prior history of aortic dissection and aortic root surgery, 15 with no such history) and 18 healthy volunteers matched for age, sex and height underwent CMR at 3T, using a time-resolved 3-dimensional ow technique. The aorta was segmented into regions on the basis of anatomic features (Abstract 108 gure 1A). Each segment was visualised using streamlines (Abstract 108 gure 1B) and particle traces, and was rated as normal or abnormal, (dened as the presence of turbulent ow vortices) and, where abnormal, extent of abnormality was classied on a 4-point scale determined by the extent of radial involvement of the aortic lumen. Wall shear stress (WSS) quantication was undertaken at predened aortic locations (Abstract 108 gure 1A).
Abstract 108 Figure 2 Prevalence of vortical ow disturbance occupying >50% luminal diameter for each aortic region for Marfan patients and controls.
Conclusion Patients with MFS commonly show aortic ow disturbance. The sinuses of Valsalva and proximal descending aorta are most frequently affected. Flow disturbance can be categorised into one of three categories, and we anticipate that ow abnormalities within a segment will predict progressive aortic dilation and dissection in an ongoing follow-up study.
109
3T MRI OF ACUTE ATHEROSCLEROTIC PLAQUE RUPTURE AND DOWNSTREAM EMBOLIC INJURY

doi:10.1136/heartjnl-2011-300198.109
A C Lindsay, L Biasiolli, J M Lee, I Kylintireas, H Watt, W Kuker, A Handa, M D Robson, S Neubauer, J Kennedy, R P Choudhury. University of Oxford, Oxford, UK
Abstract 108 Figure 1 A. Planes for aortic segmentation and WSS quantication. B. Flow visualisation in a healthy volunteer. C. Flow visualisation in a patient with prior aortic dissection fullling the Ghent Criteria for Marfan syndrome.
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Introduction Luminal stenosis is a poor predictor of the risk posed by any given atherosclerotic plaque, therefore current angiographic imaging techniques cannot reliably determine which patients are most likely to suffer future ischaemic events. However, MRI may be able to detect features of atherosclerotic plaque rupture that have been associated with an increased risk of recurrent atherothrombosis.
BCS Abstracts 2011

Hypothesis 3T MRI of the carotid artery can identify atherosclerotic plaque rupture in patients presenting with TIA or minor stroke. Methods 81 patients with carotid artery disease were recruited; 41 presented acutely with TIA or minor stroke and 40 asymptomatic patients acted as the control group. Median time from symptom onset to MRI in the symptomatic group was 2.1 days (range 0.17e7.0). All patients underwent T1, T2 and proton densityweighted turbo spin echo MRI to 10 mm either side of the carotid. As part of a combined scan protocol, study participants then underwent diffusion-weighted imaging (DWI) and Fluid-Attenuated Inversion Recovery (FLAIR) imaging of the brain to assess acute and chronic injury, respectively. If physically able, patients underwent follow-up scanning a minimum of six weeks later. Plaques were graded according to the MRI modied American Heart Association (AHA) system by two independent reviewers blinded to the clinical status of the patient. Statistical analysis was performed using the Wilcoxon sign rank test and Fisher9 s exact test to compare plaques, in addition to the Mann Whitney U test to compare cerebral injury. Results AHA type VI (ruptured) plaque was seen in 22/41(54%) in the symptomatic group vs 8/41(20%) in the asymptomatic group (p<0.05), either due to intra-plaque haemorrhage (34% vs 18%, p0.08; Abstract 109 gure 1A), surface rupture (24% vs 5%, p0.03; Abstract 109 gure 1B), or luminal thrombus (7% vs 0%, p0.24; Abstract 109 gure 1C). Of particular note, 17/30 (57%) cases of AHA VI (ruptured) plaque were seen to cause <70% stenosisthe current cut-off for surgical treatment. At follow-up scanning a minimum of 6 weeks later, only two cases of AHA VI plaque showed evidence of full healing. Of the 41 patients in the acute group, evidence of cerebral injury on DWI imaging was seen in 32/41 patients; the median number of lesions per patient was 7 and the median total lesion volume was 10.62 ml (range 0e522 ml). No signicant associations were noted between AHA plaque type and downstream cerebral injury, however the presence of plaque surface rupture independently predicted a higher number of DWI lesions, a higher total DWI burden at presentation, and higher total cerebral FLAIR signal at follow-up when compared to all other plaque types (p<0.05). there was already evidence of early changes in systolic function related to subclinical atherosclerosis. Methods We studied 81 individuals (44 females, 37 males) without cardiovascular risk factors and with a mean age of 28.4265.36 years (mean6SD). Peak mid-ventricular myocardial circumferential systolic strain and left ventricular mass adjusted for body surface area (LVM) were assessed by CMR. Carotid IMT was measured as a marker of subclinical atherosclerosis using ultrasound. Demographic and anthropometric characteristics were measured as well as metabolic parameters and peripheral and central blood pressure. Results Individuals with reduced peak myocardial circumferential systolic strain had higher carotid IMT (r0.392, p<0.001). Total cholesterol level and waist to hip ratio were both signicantly associated with reduced myocardial strain. Increased LVM, central and peripheral systolic blood pressure, peripheral pulse pressure, glucose, triglycerides, age, body mass index and waist to hip ratio, as well as reduced high-density lipoprotein, were all signicantly associated with increased carotid IMT (p<0.01). Males also had higher carotid IMT than females (mean6SD 0.5460.068 mm vs 0.4760.042 mm, p<0.001). The association between carotid IMTand peak myocardial circumferential systolic strain was independent of gender, smoking, LVM as well as peripheral and central blood pressure measures. Conclusions We have shown for the rst time that subclinical changes in cardiac function and subclinical atherosclerosis are closely interrelated in young adults, with associations that extend to those in the normal range of cardiovascular risk. This study further establishes the ability of CMR to detect early changes in cardiovascular disease development.
111
SINGLE CENTRE PROSPECTIVE CARDIAC CT STUDY TO DETERMINE THE PREVALENCE OF PATIENTS WITH CORONARY ARTERY DISEASE WITH A ZERO CORONARY ARTERY CALCIUM SCORE AND ASSOCIATED NON-CARDIAC INCIDENTAL FINDINGS
doi:10.1136/heartjnl-2011-300198.111
A J Shah, D R Obaid, D Gopalan, J Babar, J H F Rudd. Addenbrookes Hospital, Cambridge, UK

Conclusion Acute atherosclerotic plaque rupture can be visualised using 3T MRI. In particular, MRI can provide detailed information on plaque morphology that can predict downstream embolic injury, independent of the degree of luminal stenosis caused.
110
MYOCARDIAL SYSTOLIC STRAIN AND SUBCLINICAL ATHEROSCLEROSIS IN YOUNG ADULT LIFE

doi:10.1136/heartjnl-2011-300198.110
A J Lewandowski, M Lazdam, E Davis, R Poole, J Diesch, J Francis, D Augustine, R Banerjee, J Suttie, S Neubauer, P Leeson. Cardiovascular Medicine, University of Oxford, Oxford, UK
Background In the elderly, reduced left ventricular function is related to elevated carotid intima media thickness (IMT), a well-established subclinical marker of atherosclerosis. Cardiovascular magnetic resonance (CMR) allows for precise quantication of changes in myocardial structure and function. We therefore sought to determine if in young adults, without overt cardiovascular risk factors,
Introduction Cardiac CT, incorporating coronary artery calcium (CAC) scoring and angiography, is being increasingly used to evaluate patients with chest pain and exclude coronary artery disease (CAD), as recommended in the recent NICE guidelines. Calcication of the coronary arteries is an excellent marker of underlying atherosclerosis, but a zero CAC score does not completely exclude the diagnosis as potentially signicant non-calcied plaques will not be detected by CAC scoring. CT imaging may also identify non-cardiac incidental ndings that can lead to further downstream testing and medical expense. Objectives (1) To evaluate the probability of CAD in patients with a CAC score of zero. (2) To determine the incidence of non-cardiac incidental ndings on cardiac CT and to quantify resulting investigations. Methods 116 symptomatic patients undergoing cardiac CT to exclude CAD from November 2009 to October 2010 were prospectively enrolled. Patients underwent CAC scoring and had contrastenhanced, 128-slice, dual source CT coronary angiography (CTCA Siemens Flash). Scans were dual-reported by a cardiac radiologist and a cardiologist. Statistical analysis was performed using GraphPadPrism. Results 62/116 patients had a CAC score of zero. Of these, 57 (91.9%) patients had normal coronary arteries, 4 (6.5%) patients had nonobstructive CAD (stenosis <50%), and 1 patient (1.6%) had signicant obstructive CAD (stenosis>50%). This patient with obstructive CAD had a high grade lesion in the proximal left anterior descending artery that required intervention. 54/116 had non-zero CAC scores. Of these, 13 (24%) had obstructive CAD and 41 (76%) nonobstructive CAD. 42/116 (36%) patients had incidental ndings on
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cardiac CT that are summarised in Abstract 111 table 1. These incidental ndings resulted in further investigations, documented in Abstract 111 table 2. The mean radiation dose (6 SEM) for CAC scoring was 0.6160.03 mSv. The mean radiation dose (6 SEM) for subsequent CTCA was 2.66 6 0.32 mSv in high pitch ash mode (n27), 5.8660.50 mSv in prospective mode (n64) and 17.1561.68 mSv in the retrospective mode (n25). if strong clinical suspicion remains in patients with a CAC score of zero further coronary investigation may be warranted. Incidental ndings are common, and can result in multiple further investigations for patients. Further research is needed to evaluate the added cost, clinical benets and radiation exposure created by investigation of such incidental ndings in the context of cardiac CT.
Abstract 111 Table 1

Area Chest (n27)
Incidental ndings on cardiac CT

Structure Lung parenchyma Incidental Finding Nodule <1 cm Emphysema Atelectasis Fibrosis Tumour recurrence Bronchiectasis Pleura Lymph node Liver Adernal Effusion Calcication Adenopathy Cyst/Nodules Adenoma/metastasis Hiatus Hernia Dilatation Aneurysm Stenosis Stenosis n 5 3 6 4 1 2 2 2 2 6 1 5 8 1 1 1
112
COMPUTED TOMOGRAPHIC CORONARY ANGIOGRAPHY TO SCREEN FOR ALLOGRAFT VASCULOPATHY AFTER HEART TRANSPLANTATION
doi:10.1136/heartjnl-2011-300198.112
M G Panicker, A G Mitchell, N R Banner, T K Mittal. Hareeld Hospital, Hareeld, UK
Abdomen (n7) Diaphragm (n5) Vasculature (n11)
Aorta Renal Coeliac
Abstract 111 Table 2 Cardiac CT

Investigation Bone scintigraphy Chest clinic referral CT chest DMSA MR adrenals MRA renal Nephrology clinic referral Pleural uid aspiration Ultrasound kidneys Ultrasound liver
Further investigation of incidental ndings on

n 1 2 4 1 1 1 1 1 1 3
Abstract 111 Table 3 incidental ndings

Investigations or referrals Bone scintigraphy Chest clinic referral CT chest DMSA MR adrenals MR cardiac MRA renal Nephrology clinic referral Pleural uid aspiration Ultrasound kidneys Ultrasound liver
Investigations and referrals generated by

Number 1 2 4 1 1 2 1 1 1 1 3
Objective To evaluate ComputedTomographic Coronary Angiography (CTA) as an alternative to Invasive Coronary Angiography (ICA) for the detection of Cardiac Allograft Vasculopathy (CAV). Background CAV is an important cause of late mortality after heart transplantation (HT). Because patients are often asymptomatic, surveillance ICA is performed in our institution. CTA is effective for the diagnosis of coronary disease in non-transplant patients, but few studies have been done after HT. Methods 117 HT patients, 1 to 24 years post transplant (mean12 years SD6 6) underwent CT coronary artery calcication (CTCAC) followed by retrospective ECG gated coronary angiogram on a 64slice scanner without the use of any b-blockers. Majority (89%) of patients had CTA within 24 h before ICA. The Agatston calcium score (CS) was calculated for all patients. The CTA images were systematically analysed for image quality and the presence of CAV (graded as signicant if >50% luminal stenosis) using a fteen coronary segments model by an independent investigator blinded to the results of ICA. Results CS ranged from 0 to 1681 (Mean91.76275). Out of 77 patients with absent CS, 3 had signicant CAV on ICA. Despite a mean resting heart rate of 82 bpm SD613 and body mass index of 27 kg/m2 SD 65, 81% of the CTA images were graded as excellent or satisfactory. For all the 1755 segments assessed by CTA irrespective of the image quality, CTA had sensitivity, specicity, positive and negative predictive values of 71%, 79%, 72% and 78% respectively for the detection of any CAV found by ICA. On a patient basis, CTA best performed in diagnosing CAV of more than 25% with sensitivity, specicity, positive and negative predictive values of 74%, 94%, 79%, and 92% respectively. None of the 61 patients with completely normal CTA had CAV on ICA. 83 (92%) out of 90 patients who responded to a patient survey preferred CTA to ICA as a screening test for CAV. Non-coronary cardiac and non-cardiac abnormalities were identied in 18% and 14% patients respectively. Conclusion The study shows that CTA compares favourably with ICA in detecting CAV in heart transplant recipients, and may be a preferable screening technique because of its non-invasive nature, patient preference and yield of additional information. One has to exercise caution in just using CS in these patients as signicant CAV can be missed out.
113
DUAL ENERGY CT IMPROVES DIFFERENTIATION OF CORONARY ATHEROSCLEROTIC PLAQUE COMPONENTS COMPARED TO CONVENTIONAL SINGLE ENERGY CT
doi:10.1136/heartjnl-2011-300198.113
D R Obaid, P A Calvert, J H F Rudd, D Gopalan, 1M R Bennett. 1University of Cambridge, Cambridge, UK; 2Papworth Hospital NHS Trust, Cambridge, UK
Conclusions Despite 62 patients having a reassuring CAC score of zero, 8% of this group had evidence of non-calcied plaque, with one patient having obstructive CAD that required intervention. We conclude that
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Introduction Vulnerable plaques have a relatively high necrotic core area and low brous tissue content. Although CT can identify plaque components on the basis of their x-ray attenuation, there is
BCS Abstracts 2011

signicant overlap between their attenuation ranges, most crucially between necrotic core and brous plaque. Recently introduced dual energy CT (DECT) permits acquisition of 2 different energy data sets simultaneously, with the change in attenuation of plaque components to different energies depending upon their material composition. We therefore examined whether DECT was better than single energy CT in determining plaque components dened by virtual histology IVUS. Methods 20 patients underwent DECT and 3-vessel VH-IVUS. CT data was obtained at peak voltages of 100 kV and 140 kV. 52 plaques were chosen with either homogenous brous plaque or conuent areas of calcied plaque or necrotic core as dened by VH-IVUS. VHIVUS images were co-registered and orientated with the corresponding CT images using distance from coronary ostia and duciary markers (Abstract 113 gure 1). Multiple regions of interest (ROI) were placed within the plaque components or in lumen on cross sectional CT images pre-classied by VH-IVUS (Abstract 113 gure 1). ROI densities were measured (in Hounseld Units) and assigned to the plaque component. A dual energy index (DEI) was created for each component, dened as the ratio of the difference in attenuation at 2 different energies / sum of attenuation with 1000 added to each attenuation value to avoid negatives. data sets permitted resolution of necrotic core and brous plaque without overlap (Abstract 113 gure 2B).
Abstract 113 Figure 2 (A) Dened CT attenuation spectra of plaque components using a single energy (140kV), calcied plaque is distinguishable from all others but necrotic core and brous plaque overlap. (B) The use of dual energy index from the attenuation data at 2 energies (100/140kV) allows signicant separation of necrotic core and brous plaque (p<0.05) (Tukeys multiple comparison test). Abstract 113 Table 1
Plaque Component Necrotic Core Fibrous Plaque Calcied Plaque Lumen 100 kV mean HU (SD) 57.26 (42.20) 148.30 (49.47) 733.10 (226.7) 411.5 (82.27) 140 kV mean HU (SD) 42.69 (31.51) 84.60 (30.34) 582.20 (194.9) 282.90 (55.93) Mean Difference (100e140 kV) 14.57 63.69 150.9 128.6 Dual Energy Index (mean) 0.0071 0.0283 0.0450 0.0483
Conclusions The additional attenuation data provided by DECT improves the differentiation of plaque components when compared to conventional single energy CT. In particular, DECT may allow better differentiation of necrotic core and brous plaque, a weakness of conventional cardiac CT, allowing for more accurate non-invasive identication of vulnerable plaques.
114
RADIATION DOSES TRENDS FROM CARDIAC CT USING A CARDIAC SPECIFIC CONVERSION FACTOR: SYSTEM UNDERSTANDING & AN OPTIMISATION STRATEGY SIGNIFICANTLY REDUCES THE DOSE TO THE PATIENTS IN A CLINICAL SERVICE
doi:10.1136/heartjnl-2011-300198.114
O E Gosling, S Iyengar, R Loader, G Morgan-Hughes, 2W D Strain, 3C Roobottom. Plymouth Hospitals NHS Trust, Plymouth, UK; 2Peninsula College of Medicine and Dentistry, Exeter, UK; 3Peninsula College of Medicine and Dentistry, Plymouth, UK
1
Abstract 113 Figure 1 Demonstration of plaque co-registration between VH-IUS and 140kV/100kV CT data sets. Calcied plaque is identied 5mm from side branch adjacent to characteristic calcication (yellow line). Cross section taken through this plaque (blue arrow) and following orientation with VH-IVUS cross section HU region of interest sampling is performed in calcied plaque.
Results Attenuation values for 1088 ROIs were measured from 70 paired data sets at 100 kV and 140 kV creating 70 DEIs (12 necrotic core, 11 brous plaque, 29 calcied plaques and 18 lumen). Values obtained using a single energy data set showed good differentiation between calcied plaque and all others (p<0.05), but considerable overlap between necrotic core and brous plaque (pns) (Abstract 113 gure 2A) (Abstract 113 table 1). In DECT, lumen (iodinated contrast) showed the greatest change in attenuation and hence had the highest DEI. Necrotic core had the lowest DEI and could be distinguished from all other components (p<000.1) Importantly, in contrast to the single energy data, DEI derived from both energy
Background CT coronary angiography CTCA now has an established role in the investigation of patients with chest pain. Under the IRMER regulations radiation doses to patients should be kept as low as reasonably practical (ALARP). Previous publications have used a chest conversion factor to calculate the effective dose (mSv) from CTCA. We have previously demonstrated that chest conversion factors signicantly under-estimate the effective dose to the patient when applied to CTCA and have calculated a cardiac specic conversion factor of 0.028 mSv (mGy.cm)-1. Our department follows the ALARP ethos and has implemented new technologies together with physician training to reduce the radiation dose from CTCA. We aimed to investigate what impact the implementation of new technologies has had on the radiation dose of CTCA. Method All patients who were coded as attending for a cardiac CT scan on the PACS and CRIS systems were included in the analysis. Scan indication included: rule out coronary artery disease, CABG assessment, pre-EP studies and problem solving. CT scanning
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between September 2007 and August 2010 was included; the total dose for the whole examination is used including the scout and nonenhanced scan (calcium score). Scans were performed on a Lightspeed VCT or HD750 (GE Healthcare). To calculate the effective dose a conversion factor was applied to the dose length product of each examination. The DLP is the radiation dose in one CT slice multiplied by the length of the scan. A cardiac specic conversion factor was used rather than a chest conversion factor (0.014) which signicantly underestimates the effective dose from CTCA. Data was transformed and expressed as a geometric mean with 99% CI. For each analysis period all scans were included; retrospective, prospective, low kV and zero padding. Results In the 3-year period 1736 scans were performed. The mean radiation dose in the rst 6 months of the study (retrospective gating) was 29.6 mSv; using the accepted conversion factor at the time the mean dose was 14.9 mSv. In March 2008 prospective ECG gating was installed; this resulted in a halving of the mean radiation dose to 13.6 mSv. In March 2009 the scanner parameters was set to zero padding and 100 KV reducing the dose to 7.4 mSv. For the nal 6 months the mean radiation dose for a cardiac scan was 5.9 mSv; this Abstract 114 gure 1 incorporates scans performed with standard ltered back projection, iterative reconstruction, high denition scanning and retrospective ECG gating for a variety of differing clinical scenarios.
115
ATRIAL HIGH RATE EPISODES AND ATRIAL FIBRILLATION BURDEN: DO THEY HAVE SIMILAR ASSOCIATION WITH CARDIAC REMODELLING?
doi:10.1136/heartjnl-2011-300198.115
C W Khoo, S Krishnamoorthy, G Dwivedi, B Balakrishnan, H S Lim, G Y H Lip. University Department of Medicine Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
Background and Objectives Contemporary pacemaker devices allow quantication of atrial high-rate episodes (AHREs) and atrial brillation burden (AFB) accurately. Cumulative ventricular pacing (Vp) is associated with development of atrial brillation, but it is not clear if AHREs and AFB share similar pathophysiologic associations with left atrium (LA) and ventricle (LV) function and remodelling. Methods In total, 87 patients with dual-chamber pacemaker underwent two-dimension (2D) and tissue Doppler imaging (TDI) echocardiography. LA volume (LAV) was evaluated by area-length method and indexed to body surface area. Septal A9 was used to measured regional LA function. LV systolic and diastolic parameters were evaluated by mitral inow velocity (E, A, E/A), LV ejection fraction (biplane Simpsons) and septal TDI velocity. The presence of AHREs (dened by atrial-rate $220 beats/min and $5 minutes) and AFB were derived from pacemaker diagnostics. Plasma markers of remodelling, matrix metalloproteinases-1 (MMP1) and tissue inhibitors of metalloproteinases-1 (TIMP1), were analysed by ELISA. Results Baseline characteristics and comorbidities were comparable between groups (Abstract 115 table 1). Patients with AHREs had signicantly larger indexed LAV (p0.011) and higher cumulative Vp (p0.012), but this was not associated with elevation of MMP1 and TIMP1. Plasma markers, LV systolic and diastolic parameters were comparable between groups. In patients with AHREs, the AFB ranged from 0 to 99% and correlated with E/A (r0.966, p<0.001), and inversely correlated with late acceleration velocity (A) (r0.612, p0.009). On linear regression analysis, A, E/A, septal A9 were independently associated with AFB (all p<0.01). Conclusion Cumulative Vp and increased LAV are associated with the development of AHRE, but AFB is independently associated with changes in LA function and LV diastolic function. This study suggests AHREs and AFB have dissimilar pathophysiologic associations with left atrium and ventricle remodelling.

No AHRE (n[70) AHRE (n[17) 75.468.8 27.664.7 34.869.4 55.169.2 1.060.6 7.962.6 6.561.4 14.163.5 98.6 (41.0e99.9) p Value 0.1 0.38 0.01 0.4 0.23 0.16 0.71 0.74 0.01
Effective dose (mSv) by protocol period.
Age (years) Body mass index (kg/m2) Indexed LA volume (ml/m2) LV ejection fraction (%) E/A Septal A (cm/s) Septal S (cm/s) Septal E/E Percentage Vp
71.0611.6 26.464.4 27.467.9 52.8611.9 0.860.2 8.962.2 6.661.8 13.766.2 21.9 (1.8e99.0)
Conclusion The introduction of dose saving strategies and appropriate physician training has lead to a signicant reduction in the radiation dose from cardiac CT. As CTCA programmes become established in hospitals around the UK it is important that clinicians have the appropriate training and experience to keep the radiation dose to the patients as low as reasonably practical.

Retrospective Gatingddose modulation 150 29.6 33 26.6 Prospective gating 489 13.6 14.9 12.5 Zero paddingd 100 kV 636 7.4 8 6.8 Final 6 months 461 5.9 6.5 5.3
116
Scanning protocol Number of Patients Mean Effective Dose (mSv) CIs (99%) (mSv)
CRT OPTIMISATION: IMPROVING ECHOCARDIOGRAPHIC TECHNIQUES BY ACCOMMODATING BIOLOGICAL VARIABILITY WITHIN DIFFERENT ECHOCARDIOGRAPHIC PARAMETERS
doi:10.1136/heartjnl-2011-300198.116
P A Pabari, A Kyriacou, M Moraldo, B Unsworth, N Sutaria, J Mayet, A D Hughes, D P Francis. Imperial College London, London, UK
Background In optimisation of CRT (and even selection for implantation) we may have underestimated the impact of beat-to-beat
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variation on echocardiographic measurements. This can be quantied most clearly in the optimisation process, in which genuine small changes in cardiac function (signal) must be detected among potentially large beat-to-beat variation (noise). Methods and Results In this large study of biological variability, we performed over 2000 echocardigraphic measurements in 12 patients. We performed separate, replicate measurements at a series of interventricular delays of each potential optimisation modality at rest. This included (i) 3D systolic dyssynchrony index, (ii) aortic preejection time, (iii) interventricular mechanical delay, (iv) LVOT VTI and (v) QRS width. The equivalent of 31 optimisations per patient were performed. For single measurements at each setting, agreement between successive optimisations was low, at 39% for SDI, 41% for aortic pre-ejection time, 32% for IVMD, 54% for LVOT VTI and 58% for QRS width. Agreement between one method and another, using single replicates, was similarly low, with the average agreement between optima by two methods being only 18% similar to pure guesswork. The intraclass correlation coefcient was low for all methods at 0.11, 0.51, 0.30, 0.50 and 0.55 respectively. The intraclass correlation coefcients improved to 0.19, 0.63, 0.42, 0.54 and 0.66 (p0.001) when averages of paired measurements were used. To optimise within 20 ms or 10 ms of the true optimum, requires a greater number of measurements, as seen in Abstract 116 gure 1, dependant on the intraclass correlation coefcient. The scatter of optima obtained reduced (improved) signicantly when using averaged pairs of measurements compared to single measurements from 23 ms to 18 ms (3D SDI), 14 ms to 10 ms (aortic pre-ejection time), 28 ms to 22 ms (IVMD), 21 ms to 16 ms (LVOT VTI) and 14 ms to 10 ms QRS duration (p0.0002).
117
TRICUSPID VALVE ANNULAR DYNAMICS IN NORMAL VS DILATED RIGHT HEARTS; A 3D TOE STUDY
doi:10.1136/heartjnl-2011-300198.117
L Ring, B Rana, R A Rusk. Papworth Hospital NHS Foundation Trust, Cambridge, UK
Background The tricuspid valve annulus (TVA) is a complex three dimensional structure that is non-planar, and is incompletely understood. The dynamics of the normal TVA has not been described in any signicant detail, nor has the impact of abnormal right hearts on the TVA been described. This study was designed to assess the feasibility of assessing the TVA throughout the cardiac cycle using 3D transoesophageal echo (TOE). Methods 20 patients were included, divided into 2 groups: normal right hearts (n10), and dilated right hearts (n10). 3D zoom images of the TVA were acquired using an iE33 imaging platform and X7-2t transducer (Phillips, Andover, Massachusetts, USA). Antero-posterior (AP) diameter, septo-lateral (SL) diameter, area and height were measured at 6 points of the cardiac cycle adapting commercially available software designed for assessing the mitral valve (MVQ, Phillips). The eccentricity ratio was calculated as AP/SL. Results TVA area decreases during systole in both groups, and is greatest in mid-diastole. The area is signicantly larger in the abnormal group (mean 1795 mm2 abnormal vs 1204 mm2 normal; p<0.01). The SL diameter increased more in the abnormal group, resulting in a circular orice and lower eccentricity ratio throughout the cycle (mean 0.91 abnormal v 1.22 normal; p<0.01, see graph). Annular height is similar in both groups but has an upward trend in systole in normals and reduces in abnormals, reaching signicance at end systole (6.7 mm vs 4.9 mm; p0.046). Conclusions In patients with abnormal right hearts, the TVA dilates in a septo-lateral direction, resulting in a more circular orice. The dynamic changes of the TVA are similar in dilated vs normal right hearts, with the exception of annular height. This pilot study suggests that 3D TOE provides insight into understanding tricuspid annular dynamics.

Conclusions Because of beat-to-beat variability, VV delay optimisation by any of the echocardiographic techniques is not realistic unless multiple replicates are performed and averaged. Smoothing biological variation by averaging multiple measurements allows the full potential of echocardiographic optimisation to be achieved and improves the consistency of optimisation. Trying to save time by performing inadequate numbers of replicates is a false economy and leads to optimisation being a form of randomisation. These observations may also cast light on to why attempts to identify future responders from CRT has not e when tested in externally monitored randomised trialsdbeen fruitful: dyssynchrony assessment to select patients for implantation may need averaging too, and of far more replicate measurements than is current practice. Integration of this biological insight into technological achievements of clinical imaging is necessary, if reliable predictors of which patients will benet from CRT, are to be developed.
Abstract 117 Figure 1 Eccentricity ratio of the tricuspid valve annulus during the cardiac cycle: normal vs dilated rated hearts.
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BCS Abstracts 2011

118
HIGH-RESOLUTION CARDIAC MAGNETIC RESONANCE PERFUSION IMAGING VS POSITRON EMISSION TOMOGRAPHY FOR THE DETECTION AND LOCALISATION OF CORONARY ARTERY DISEASE
doi:10.1136/heartjnl-2011-300198.118 G D J Morton, M Ishida, A Chiribiri, A Schuster, S Baker, S Hussain, D Perera, M ODoherty, S Barrington, E Nagel. Kings College London, London, UK
supplied by stenotic arteries by PET and 76% by CMR. Remote ischaemia was detected in 24% of territories by PET and 16% by CMR.

Characteristic Male Number (percentage) of affected patients 25 (81%) 12 (39%) 10 (32%) 22 (71%)
Background Non-invasive imaging has a key role in the detection of coronary artery disease (CAD). Its importance has been afrmed by recent National Institute of Clinical Excellence (NICE) guidelines. Localisation of ischaemia to a coronary territory is also important in patient management. Cardiac Magnetic Resonance (CMR) perfusion imaging is a well-established and radiation-free test for these purposes. However, there are few data comparing perfusion CMR with Positron Emission Tomography (PET), which is widely regarded as the non-invasive gold standard. Furthermore novel CMR methods, including those based on k-t acceleration techniques, allow myocardial perfusion imaging with unprecedented spatial resolution. Methods 31 patients with known or suspected CAD referred for diagnostic x-ray coronary angiography (XCA) underwent both CMR and PET examinations. Both PET and CMR protocols included adenosine stress and rest perfusion imaging. CMR perfusion imaging was performed at 1.5T with a k-t-accelerated steady-state free-precession sequence. PET imaging was performed with 13NAmmonia. The Abstract 118 gure 1 shows an example. Experts blinded to the clinical data analysed the imaging data and experts blinded to the imaging results visually analysed the XCA data. A signicant coronary artery stenosis was dened as $70% reduction in diameter or a fractional ow reserve <0.8 where available. Sensitivity and specicity for PET and CMR vs invasive angiography were calculated. Localisation of ischaemia was assessed in patients with CAD by classifying myocardial territories as either supplied by, or remote from, a stenotic artery.
Diabetes Previous PCI Hypertension
Conclusions CMR is at least as accurate as PET for the diagnosis of CAD and also for the localisation of ischaemia to coronary territories. Relatively low numbers mean that CIs are wide and further work is required. Using an anatomic test as the reference-standard for functional tests has well-described limitations. Remote ischaemia is likely to occur for several reasons including underestimation of disease severity at XCA, microvascular disease and also false positive results.
119
CARDIOVASCULAR MAGNETIC RESONANCE IMAGING (CMR) DETECTS SUBCLINICAL CARDIOMYOPATHY IN ASYMPTOMATIC PATIENTS WITH LEFT BUNDLE BRANCH BLOCK (LBBB) AND NORMAL ECHOCARDIOGRAPHY
doi:10.1136/heartjnl-2011-300198.119
M Mahmod, T D Karamitsos, J J Suttie, S G Myerson, S Neubauer, J M Francis. University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Oxford, UK

Results Patient characteristics are shown in the Abstract 118 table 1. Mean age 6 SD was 6469 years. One CMR examination was nondiagnostic. The interval between PET and CMR was 266 days (77% same day), between PET and XCA 22628 days and between CMR and XCA 22629 days. The prevalence of CAD was 81%. For the detection of CAD PET sensitivity was 80% (95% CI 59% to 92%) and specicity was 67% (24% to 94%). CMR sensitivity was 83% (95% CI 62 to 95%) and specicity was also 83% (36% to 99%). In patients with CAD ischaemia was localised to 63% of the territories
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Introduction Asymptomatic left bundle branch block (LBBB) is a common indication for referral for cardiovascular magnetic resonance (CMR) imaging. However, it is not known whether referral for LBBB returns a high diagnostic yield. We evaluated the diagnostic value of CMR in these patients. Methods All clinical CMR referrals for LBBB from January 2005 to November 2010 were reviewed by two independent investigators. Only patients with asymptomatic LBBB and normal echocardiograms (echos) who underwent complete CMR evaluation were included in the study. Patients were excluded if they had cardiac symptoms or known coronary artery disease. Anthropometric data, pre-existing conditions, medications, smoking status, family history and echocardiographic data were recorded. Results From January 2005 to November 2010, 63 asymptomatic patients with LBBB were referred to our institution for CMR from a total of 3596 CMR referrals. Of these, 34 had normal echos; 20 subjects who had abnormal echos and 9 who had no echos at presentation were excluded from further analysis. Mean age of the 34 patients with normal echos was 5469 years, and 19 (56%) were men. Demographic data and left ventricular (LV) measurements are presented in the Abstract 119 table 1. The most common associated medical conditions were hypertension (11 patientsd33%) and hyperlipidaemia (8 patientsd24%). Ten subjects (30%) had a family history of heart disease. Nine (27%) patients underwent coronary angiography which was normal. Of the 34 patients, 14 (41%) were found to have pathological ndings on CMR. The commonest abnormalities were dilated cardiomyopathy (DCM) (23%), followed by LV hypertrophy (LVHddened as LV wall thickness >13 mm) (9%), arrhythmogenic right ventricular cardiomyopathy (ARVC) (6%) and Ebstein anomaly (3%). Two patients (6%) had mid wall late gadolinium enhancement. In the remaining 20 (59%) patients, no abnormalities on CMR were detected.
BCS Abstracts 2011

All patients Normal CMR Abnormal CMR (n[34) (n[20) (n[14) p value Age (years (median, IQR)) Male gender (no, %) BMI (mean, kg/m2) LVEDV (ml (median, IQR)) LVESV (ml (median, IQR)) LVEF (ml (mean, SD)) 54.368.9* 19 (55.8%) 57.5 (19.7) 11 (55.0%) 48.5 (17.0) 8 (57.1%) 29.366.5 182.5 (60.5) 71.5 (39.5) 55.7613.6 12.5 (9.4) 83.0 (14.5) 0.6 0.59 0.37 0.012 0.005 0.004 0.059 0.001
28.365.6 27.664.9 155.0 (58.0) 133.0 (41.5) 51.0 (26.0) 60.6613.9 48.0 (12.5) 66.165.5
LV thickness (mm (median, IQR)) 11.0 (7.4) 9.0 (6.1) LVMI (g/m2 (median, IQR)) 72.5618.1* 64.0 (15.0) *mean, SD. IQR.
Conclusions There is a high rate of sub-clinical cardiomyopathy (41%) detected by CMR in asymptomatic patients with LBBB despite normal echocardiograms. These ndings support the claim that CMR is a valuable adjunct to conventional investigations in asymptomatic LBBB. Further studies are needed to evaluate the prognostic implications of CMR abnormalities in this cohort of patients.
The MBH SR curves were ltered with a moving average (MA) to reduce noise sensitivity, results from a sample width of three and ve were examined. Differences between SBH and MBH were assessed using Wilcoxon signed-rank test as not all measures were normally distributed. Reproducibility assessments were carried out on all techniques. Results PeakEcc was signicantly higher with MBH vs SBH, but reproducibility was slightly worse. Results are summarised in Abstract 120 table 1. Systolic SR was approximately equal with all techniques although MBH using MA of ve led to a borderline signicant reduction. Diastolic SR was higher when measured with MBH although only signicant using MA of three. Systolic and diastolic SR measures were more reproducible with MBH compared with SBH, except for the diastolic SR using MA of three, which was substantially worse. Strain and SR curves for the same patient are shown in Abstract 120 gure 1.

Peak systolic strain (%) SBH MBH (MA of three) e13.762.4 e15.163.1 (p0.023 vs SBH) MBH (MA of ve) e15.163.1 (p0.023 vs SBH) SBH reproducibility 0.5061.52; 11.1%; (MD6SD; CoV; B-A) e2.5 to 3.5 Peak systolic strain rate (1/s) e0.7460.15 e0.7360.11 (p0.877 vs SBH) e0.6960.10 (p0.049 vs SBH) e0.0160.13; 18.1%; e0.26 to 0.28 Peak diastolic strain rate (1/s) 0.7560.27 1.1260.54 (p0.017 vs SBH) 0.9160.36 (p0.535 vs SBH) e0.0460.16; 21.0%; e0.36 to 0.27 e0.1360.44; 39.0%; e1.00 to 0.75 0.0960.15; 16.9%; e0.39 to 0.22
Abstract 119 Figure 1 CMR ndings in asymptomatic patients with LBBB and normal echocardiogram.
MBH reproducibility (MA of three) (MD6SD; CoV; B-A) MBH reproducibility (MA of ve) (MD6SD; CoV; B-A) MD6SDmean difference 6 SD
1.1362.23; 14.7%; 0.0660.04; 5.3%; e3.3 to 5.6 e0.02 to 0.14 1.1362.23; 14.7%; 0.0460.05; 7.8%; e3.3 to 5.6 e0.07 to 0.15 CoVcoefcient of variation BeABlandeAltman 95% limits of agreement
120
COMPARISON AND REPRODUCIBILITY OF STANDARD AND HIGH TEMPORAL RESOLUTION MYOCARDIAL TISSUE TAGGING IN PATIENTS WITH SEVERE AORTIC STENOSIS
doi:10.1136/heartjnl-2011-300198.120
C D Steadman, 2N A Razvi, 1K I E Snell, 3J P A Kuijer, 3A C van Rossum, G P McCann. 1Leicester Cardiovascular Biomedical Research Unit, Leicester, UK; 2 Department of Cardiovascular Sciences, University Hospitals of Leicester, Leicester, UK; 3Department of Physics and Medical Technology, ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands; 4University Hospitals of Leicester, Leicester, UK
4
Objectives The aim of this study was to compare and assess the reproducibility of left ventricular (LV) circumferential peak systolic strain (PeakEcc) and strain rate (SR) measurements using standard and high temporal resolution myocardial tissue tagging in patients with severe aortic stenosis (AS). Background Myocardial tissue tagging with cardiac magnetic resonance (CMR) can be used to quantify strain and SR, however, there are little data on the reproducibility. Diastolic SR may be of particular interest as it may be the most sensitive marker of diastolic dysfunction often occurring early in the course of disease. Methods Eight patients with isolated severe AS without obstructive coronary artery disease were prospectively enrolled. They underwent CMR in a 1.5T scanner (Siemens Avanto) on two separate occasions, median interval 12 days. Complementary tagged (CSPAMM) images were acquired with both a single breath-hold (SBH: temporal resolution 42 ms), and a multiple brief expiration breath-hold (MBH: high temporal resolution 17 ms) sequence. Midwall PeakEcc was measured in the LV at mid-ventricular level with HARP Version 2.7 (Diagnosoft, USA). SR was calculated from the strain data; SREcc2-Ecc1/Time2-Time1. PeakEcc, peak systolic and diastolic SR were read from curves of strain and SR against time.

Conclusions It is likely than SBH may be adequate or even superior to MBH for assessment of PeakEcc. The increased temporal resolution of MBH may be advantageous for examining systolic and diastolic SR; a MA of ve for diastolic SR may be the preferred method for quantication given the improved reproducibility of this measure.
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BCS Abstracts 2011

121
INCIDENTAL EXTRA-CARDIAC FINDINGS ON CLINICAL CMR; A COMPARISON OF 3 HASTE TECHNIQUES
doi:10.1136/heartjnl-2011-300198.121 R B Irwin, 2T Newton, 3C Peebles, 4A Borg, 5D Clark, 4C Miller, 6N Abidin, M Greaves, 4M Schmitt. 1Wythenshawe Hospital, Manchester, UK; 2Royal Blackburn Inrmary, Blackburn, UK; 3Southampton General Hospital, Southampton, UK; 4 Wythenshawe Hospital, University Hospitals of South Manchester NHS Trust, Manchester, UK; 5Alliance Medical, Wythenshawe Hospital CME unit, Manchester, UK; 6Salford Royal Hospital, Salford, UK
4 1
Introduction Cardiac magnetic resonance (CMR) is an increasingly important imaging modality, which by necessity incorporates a large eld of view. Both localiser and multiple slice half-fourier spin echo (eg, HASTE) sequences provide coverage of the thorax and upper abdomen. Such imaging may reveal hitherto unexpected incidental extra-cardiac ndings (IEF). First we sought to assess the frequency of IEF found on clinically indicated CMR scans. Second we compared the 3 clinically used HASTE acquisition protocols in this context. Lastly we determined the impact of the 3 different protocols on acquisition time and image quality. Methods Three subsequent groups of 238 patients (714 patients in total), all referred for clinically indicated CMR, were scanned with either breath-hold (BH) HASTE (Group 1), free breathing (FB) HASTE (Group 2) or diaphragmatic navigated (NAV) HASTE (Group 3). Additionally localiser sequences performed in 3 orthogonal planes were analysed. All 714 clinical reports were reviewed regarding the presence of IEF. These were categorised as either minor, or major if recommendations for further investigation, follow-up, and/or clinical correlation were made. Finally, to determine the impact of each HASTE protocol on acquisition time and image quality, an additional cohort of 15 patients underwent 3 protocols back to back in a random fashion. The length of each acquisition was timed and image quality was reviewed and scored externally. Results A total of 180 IEF were found in 162 (22.7%) out of 714 patients. There was no signicant difference in frequency of IEF between the 3 HASTE groups. Out of 180 IEF, 88 were considered minor and 92 major ndings. Of the latter, 8 (1.1%) were considered highly signicant. These included one bronchoalveolar carcinoma stage 1B requiring lobectomy, 2 cases of orid sarcoidosis in patients presenting with VT and structurally normal hearts on echocardiography, one case of pulmonary aspergillosis, 2 cases of advanced pulmonary brosis, one ascending thoracic aortic aneurysm and a case of iatrogenic liver haemorrhage following placement of a pericardial drain. FB HASTE acquisition (6962.5 s) was signicantly faster than BH (10563.8 s) and NAV (12162.7 s), p<0.001, but also produced the lowest image quality on a 5 point scale; 3.5 (FB) vs 3.9 (BH) vs 3.8 (NAV), p0.08. Conclusion Overall, IEF are common and lead to follow on investigations in a substantial minority of cases. However, the overall incidence of highly signicant ndings in the current study was low (w1%). There was no difference in the frequency of incidental extracardiac ndings between the 3 HASTE protocols. While the free breathing HASTE technique is statistically signicantly faster than breath hold and navigated HASTE, the absolute time saving is small and probably out-weighted by lesser image quality.
sclerosis via a direct paracrine or vasocrine route. Excess adipose tissue accumulation leads to adipose tissue dysfunction characterised by a pro-inammatory and potentially pro-atherogenic pattern of adipokine secretion. We used MRI for PVAT imaging and quantication and evaluated the effects of obesity and increased perivascular adiposity on the relationship of PVATwith the function and structure of the underlying vessels. Methods We measured peri-aortic fat, aortic stiffness and atheroma burden by MRI in 128 cardiovascular patients and in 18 healthy lean subjects at baseline and in 22 healthy obese subjects (before and after weight loss intervention (diet or bariatric surgery). Fat around the brachial artery and FMD of the brachial artery was measured among 75 cardiovascular patients. Results There was good inter-observer and intra-observer reproducibility (coefcient of variance (CV) <6% and<5%) and inter-scan repeatability (CV<8%) of the measurement of PVAT. After adjustment for anthropometric indices, demographics and cardiovascular risk factors as appropriate: I) A positive independent association between PVAT and aortic atheroma was detected among obese participants (BMI$30 kg/m2)(p<0.005) but not among individuals with intermediate (BMI<30 and $26) and low BMI (BMI<26). II) Perivascular fat was independently, inversely associated with aortic stiffness among lean patients (p<0.0005) while the association was independent and positive for obese participants (p<0.05). III) An independent, negative linear correlation between peri-brachial fat and FMD was noted among overweight and obese subjects (BMI$26) (p<0.001), but not among normal weight participants (BMI<26). IV) PVAT was an independent negative predictor of aortic elasticity among healthy obese individuals (BMI$30) (p<0.01) while it was positively and independently associated with aortic elasticity among lean healthy controls (BMI#18) (p<0.05). V) Following weight loss intervention, PVAT reduction was an independent predictor of aortic elasticity improvement in the obese group (p<0.05). Conclusions Our results suggest an inuence of both generalised and regional excess adiposity on the functional state and the effects of perivascular adipose tissue on dysfunction and remodelling of the underlying vessels.
123
CARDIOVASCULAR RISK IN ASYMPTOMATIC POTENTIAL SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANT RECIPIENTS IS DETERMINED BY MYOCARDIAL PERFUSION SCINTIGRAPHY
doi:10.1136/heartjnl-2011-300198.123
V M S Stoll, N S Sabharwal, O O Ormerod. The John Radcliffe Hospital, Oxford, UK
122
OBESITY AND PERIVASCULAR ADIPOSITY IN ATHEROSCLEROSIS

doi:10.1136/heartjnl-2011-300198.122
I Kylintireas, C Shirodaria, O Rider, J M Lee, I Bechar, J Digby, M D Robson, S Neubuer, R P Choudhury. University of Oxford, Oxford, UK
Introduction It has been proposed that perivascular adipose tissue (PVAT) contributes to inammation and advancement of atheroA70
Introduction More than 50% of renal transplant recipients will die as a consequence of cardiovascular disease (CVD). Type I diabetics undergoing simultaneous pancreas-kidney transplantation (SPK) are at an even greater risk of CVD. Optimising a patient9 s cardiovascular status is necessary before SPK transplant surgery. Patients can remain on transplant waiting lists for years. There is little evidence as to how frequently repeat cardiovascular risk assessments are required in asymptomatic patients. Myocardial perfusion scintigraphy is used in SPK patients to detect any asymptomatic myocardial ischaemia or abnormal left ventricular function. This study analyses data from a SPK transplant centre with an annual surveillance programme to aim to establish the suitable frequency of MPS. Methods Potential SPK transplant recipients who had undergone two perfusion scans were included for analysis. An abnormal MPS was dened as either showing a regional wall motion abnormality, inducible ischaemia, or impaired left ventricular function. The scan results were both documented and compared. Angiography results from the study period were also recorded. Results 99 out of 130 patients on the SPK waiting list in November 2009 had undergone two perfusion scans as part of their
BCS Abstracts 2011

pre-transplant assessment. The median age was 45 yrs (range 26e63), with 41% female and a median time between scans of 1.4 yrs (range 0.6e3.0). 59 patients (60%) had two consecutive normal scans. The remaining 40 patients had at least one abnormal scan. 16% of patients with a normal 1st scan developed an abnormal 2nd scan within a median period of 1.4 years. 28 (70%) of the patients with an abnormal MPS underwent angiography, of these 12 required revascularisation (either PCI or CABG). Of the remaining 16 patients; 1 died before angiography and the other 15 patients were treated with medical therapy. Of the 59 patients with two normal scans; 3 underwent angiography during the study period (for new symptoms), 1 of these patients required revascularisation after presenting with an ACS. 2 had minor plaque disease. Conclusions 40% of SPK patients on the waiting list have an abnormal MPS. Of the patients with normal scans 5% required an angiogram because of new symptoms with only 2% requiring revascularisation. Of the patients undergoing angiography driven by MPS 43% subsequently underwent revascularisation. The current screening interval is successfully monitoring changes in the patients cardiovascular status with only one patient requiring an intervention which was not predicted by MPS. Therefore a near annual MPS is a useful, non-invasive means by which to monitor patients at very high risk of asymptomatic cardiovascular disease while awaiting a SPK transplant.

Results Patient characteristics are summarised in the Abstract 124 table 1. 2 patients were excluded (1 claustrophobia; 1 incomplete imaging data). Mean interval 6 SD between CMR and coronary angiography was 40647 days. 13 patients (22%) with no history of myocardial infarction had CMR evidence of prior infarction. There was a strong correlation between the BCIS JS and myocardial ischaemic burden: Pearsons r0.75, p<0.00001 (Abstract 124 gure 2). The BCIS JS was also correlated with the combined burden of scar and ischaemia: r 0.77, p<0.00001. There was no difference between 3T and 1.5T CMR imaging. Area under the receiver-operating characteristic curve for BCIS JS to detect $10% myocardial ischaemic burden was 0.87 (95% CI 0.77 to 0.97). BCIS JS $6 predicted $10% myocardial ischaemic burden with sensitivity 68% and specicity 90%.
124
VALIDATION OF THE BCIS-1 MYOCARDIAL JEOPARDY SCORE USING CARDIAC MRI

doi:10.1136/heartjnl-2011-300198.124
G D J Morton, 2K De Silva, 1M Ishida, 1A Chiribiri, 1A Indermuhle, 1A Schuster, S Redwood, 1E Nagel, 1D Perera. 1Kings College London, London, UK; 2Guys and St Thomas NHS Foundation Trust, London, UK
2
Introduction The recently described angiographic BCIS-1 Myocardial Jeopardy Score (BCIS JS) was designed to classify the extent of coronary artery disease (CAD). It provides a semi quantitative estimate of the amount of myocardium at risk as a result of severe coronary stenoses (0no jeopardy; 12maximum jeopardy). Advantages include ease of use and universal applicability including classication of left main stem disease and CABG. However anatomic tests, including the BCIS JS, do not incorporate myocardial ischaemia and scar, which are important for management and prognosis. Cardiac magnetic resonance (CMR) imaging allows reliable assessments of myocardial ischaemia and scar in a single examination and was used to examine the functional relevance of the BCIS JS. Methods 60 consecutive patients with angina and known or suspected CAD referred for diagnostic x-ray coronary angiography underwent CMR examination at a single UK centre. CMR included standard functional and scar imaging and also high-resolution k-t accelerated adenosine stress and rest perfusion imaging at 1.5T (40 patients) or 3T (20 patients). Expert observers blinded to the clinical data analysed the angiographic and CMR data. The BCIS JS was calculated from visual analysis of the coronary angiogram. CMR perfusion and scar data were segmented according to the standard 17-segment model excluding the apex. Segments were subdivided into equal endo- and epicardial sub-segments, each assigned 3% of the total myocardial volume and classied as normal, ischaemia or scar. Myocardial ischaemia and scar burden were calculated and correlated with the BCIS JS individually and as a combined score (Abstract 124 gure 1).
Abstract 124 Figure 2 burden and BCIS JS.
Correlation between myocardial ischemic
Conclusions The BCIS JS correlated well with ischaemic burden on CMR. A BCIS JS $6 predicts the prognostically important ischaemic threshold of 10% with high specicity. As expected, the correlation is imperfect which is likely to be a result of difculty predicting haemodynamic effects of angiographically moderate disease, microvascular disease and limitations of CMR imaging.
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BCS Abstracts 2011

Characteristic Age (mean6SD) Left ventricular ejection fraction (mean6standard deviation) Male Diabetes Previous CABG Previous percutaneous coronary intervention Previous MI Hypertension Number of patients 65610 59614% 48 (83%) 17 (29%) 13 (22%) 22 (38%) 10 (17%) 38 (66%)
125
ASSESSING PATIENT BENEFIT FROM THE REVASCULARISATION OF CHRONICALLY OCCLUDED CORONARY ARTERIES BY ADVANCED CARDIOVASCULAR MRI TECHNIQUES
doi:10.1136/heartjnl-2011-300198.125
PCI and 3 with CABG). In those with successful revascularisation by PCI LV volumes reduced (EDV 185 (54) vs 174 (50) p<0.05; ESV 85(60) vs 77(58) p<0.001) and the left ventricular ejection fraction improved (56.5(12)% vs 58.9(12)% p0.01). During adenosine stress imaging there was a signicant improvement in absolute myocardial blood ow in the revascularised segments (from 1.87(0.51) to 3.77 (0.67) ml/g/min p<0.001) but not in the remote regions (from 3.76 (0.52) to 3.95(0.58) ml/g/min pns). LGE was only present in 25 (20%) revascularised segments. In these segments there was a strong inverse correlation between the extent of scar and improvement in segmental systolic thickening (r0.736, p<0.001). There was a weaker association between the segmental response to low dose dobutamine and the degree of functional improvement following successful revascularisation (Pearson r0.249, p<0.01). Conclusion Following revascularisation of CTO, myocardial perfusion increases and both regional and global systolic function improves. While the majority of subjects in this study had no scar on LGE imaging, when segments are scarred there is a negative correlation with improvement in regional systolic thickening.
N J Artis, 2A Crean, 1A Zaman, 1S Sorbron, 1A N Mather, 1S G Ball, 1S Plein, J P Greenwood. 1University of Leeds, Leeds, UK; 2Toronto General Hospital, Toronto, Canada
1
Background Cardiovascular magnetic resonance (CMR) imaging can provide an array of information about cardiac function and anatomy. The utility of CMR in the setting of coronary artery chronic total occlusion (CTO) has not been fully investigated. We set out to examine the ability of CMR to show regional improvements in left ventricular (LV) function and perfusion and to investigate if any features were able to predict those that benet from revascularisation. Methods Twenty-seven patients with single vessel CTO were recruited from clinical waiting lists and underwent a comprehensive CMR assessment prior to and 6 months following attempted CTO revascularisation. A multi-parametric CMR protocol was performed which included cine imaging to assess regional wall thickness/ thickening and global LV function, rest and adenosine stress perfusion imaging (Fermi model), low dose dobutamine stress to assess inotropic reserve, and late gadolinium enhancement (LGE) imaging to determine scar location and extent. Using the AHA 16 segment model only segments supplied by the CTO artery were studied for functional improvement. Data are presented as mean (SD). Results Procedural success in terms of revascularisation of the occluded artery was achieved in 23 of the 27 patients (85%, 20 with
Abstract 125 Figure 2 Relationship of improvement in segmental systolic thickening against segmental scar (top panel) and change in thickening with low dose dobutamine (bottom panel).
126
THE IMPACT OF NICE GUIDELINES FOR THE INVESTIGATION OF CHEST PAIN ON OUTPATIENT CARDIOLOGY SERVICES IN THE UK
doi:10.1136/heartjnl-2011-300198.126
Abstract 125 Figure 1 Changes observed in the CTO and a remote territory following attempted revascularisation. (non-revascularisedd black lines). Adenosine stress increases perfusion only in the CTO territory with no change in resting perfusion.
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1 C Patterson, 2E Nicol, 3L Bryan, 4T Woodcock, 1S Padley, 1D Bell. 1Imperial College, London, UK; 2Royal Brompton Hospital, London, UK; 3Chelsea and Westminster Hospital, London, UK; 4NIHR CLAHRC for Northwest London, London, UK
BCS Abstracts 2011

Introduction The National Institute for Health and Clinical Excellence (NICE) have released guidelines for the investigation of chest pain of recent onset (1). There is concern that the guidelines will increase the burden on cardiac imaging, requiring service reconguration and investment (2, 3). This study was performed to assess the impact of the guidelines on outpatient cardiology services in the UK. Methods 595 consecutive patients attending chest pain clinics at two hospitals over six months preceding release of the NICE guidelines (51% male; median age 55 yrs (range 22e94 yrs)) were risk stratied using NICE criteria. Preliminary cardiac investigations recommended by NICE were compared with existing clinical practice and the relative costs calculated. Results NICE would have recommended 443 patients (74%) for discharge without cardiac investigation, 10 (2%) for cardiac computed tomography (CCT), 69 (12%) for functional cardiac imaging and 73 (12%) for invasive coronary angiography (ICA). Relative to existing practice there would have been a trend towards reduced functional cardiac imaging (24%; p0.06) and increased CCT (+43%; p0.436) but a signicant increase in ICA (+508%; p<0.001). The cost of investigations recommended by NICE would have been 15 881 greater than existing practice. Conclusions This study suggests implementation of the NICE guidelines will require investment in cardiology services, particularly ICA. It will be necessary to establish and maintain CCT for relatively few patients; also to establish and maintain functional cardiac imaging even though referrals are likely to decline. Individual hospitals should assess their local populations prior to service reconguration. acquired at 1 week were better predictors of LVEF and infarct size at 3 months than data collected at day 2. Conclusions The extent of myocardial oedema and infarct size decrease signicantly during the rst week after reperfusion for AMI and these changes are associated with a signicant improvement in LVEF over the same interval. These ndings have implications for the timing of CMR studies in the early post-infarct period. We found that the percentage myocardial salvage index did not change signicantly between day 2 and 1 week. Therefore, accurate assessment of the efcacy of reperfusion therapy can be made up to one week after revascularization. In addition, CMR data acquired at 1 week were better predictors of CMR endpoints measured at 3 months. Thus, we conclude that the optimal time point to image patients post-reperfusion therapy for AMI is at 1 week.
128
BRIGHT BLOOD T2 WEIGHTED MRI HAS HIGHER DIAGNOSTIC PRECISION AND ACCURACY THAN DARK BLOOD STIR MRI FOR ASSESSMENT OF THE ISCHAEMIC AREA-AT-RISK AND MYOCARDIAL SALVAGE IN ACUTE MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.128
A R Payne, 1M Casey, 1J McClure, 2R McGeoch, 2A Murphy, 2R Woodward, 2A Saul, J Gilchrist, 2C Clark, 2K G Oldroyd, 1N Tzemos, 1C Berry. 1University of Glasgow, Glasgow, UK; 2Golden Jubilee National Hospital, Glasgow, UK
2
Abstract 126 Table 1 Preliminary cardiac investigations undertaken (pre-NICE) compared with those recommended by NICE (N595)
Pre-NICE No investigation Cardiac CT Functional cardiac assessment Invasive angiography 33 7 91 12 NICE 443 10 69 73 % change +1242% (p<0.001) +43% (p 0.436) 24% (p 0.06) +508 (p<0.001)
127
TIMING OF CARDIOVASCULAR MRI AFTER ACUTE MYOCARDIAL INFARCTION: EFFECT ON ESTIMATES OF INFARCT CHARACTERISTICS AND PREDICTION OF LATE VENTRICULAR REMODELLING
doi:10.1136/heartjnl-2011-300198.127
A N Mather, T A Fairbairn, N J Artis, J P Greenwood, S Plein. University of Leeds, Leeds, UK
Background The pathophysiological remodelling processes associated with acute myocardial infarction (AMI) evolve over time and the optimal acute imaging time point to predict medium-term surrogates for outcome has not been established. This study aimed to dene the evolution of infarct characteristics by cardiovascular magnetic resonance (CMR), and to assess whether CMR data acquired at day 2 or at 1 week post-AMI are stronger predictors of infarct size and left ventricular (LV) function measured at 3 months. Methods Fifty-seven patients were recruited with rst presentation ST elevation AMI treated successfully with primary percutaneous coronary intervention. Cine, T2- weighted and late gadolinium enhancement CMR imaging were performed at days 2, 7, 30 and 90 after index presentation. Results Infarct size and extent of myocardial oedema decreased signicantly between day 2 and 1 week (mean %LV-scar (SD) 27.2 (13.9) vs 21.6 (14.1), p<0.001 and %LV-AAR (Area At Risk) (SD), 37.9 (15.2) vs 32.3 (14.3), p0.003). These changes were accompanied by a signicant improvement in LV ejection fraction (%LVEF (SD), 41.7 (9.6) vs 44.6 (10.1), p<0.001). CMR data
Background T2-weighted MRI reveals myocardial oedema and enables estimation of the ischaemic area-at-risk and myocardial salvage in patients with acute myocardial infarction (MI). We compared the diagnostic accuracy of a new bright blood T2-weighted with a standard black blood T2-weighted MRI in patients with acute MI. Methods A breath hold bright blood T2-weighted ACUTE pulse sequence with normalisation for coil sensitivity and a breath hold T2 dark blood short s inversion recovery (STIR) sequence were used to depict the area-at-risk in 54 consecutive acute MI patients. Infarct size was measured on gadolinium late contrast enhancement images. Results Compared with dark blood T2-weighted MRI, consensus agreements between independent observers for identication of myocardial oedema were higher with bright blood T2 -weighted MRI when evaluated per patient (p<0.001) and per segment of left ventricle (p<0.001). Compared to bright blood T2-weighted MRI, dark blood T2-weighted MRI under-estimated the area-at-risk compared to infarct size (p<0.001). The 95% limits of agreement for inter-observer agreements for the ischaemic area-at-risk and myocardial salvage were wider with dark blood T2-weighted MRI than with bright blood T2-weighted MRI. Bright blood enabled more accurate identication of the culprit coronary artery with correct identication in 94% of cases compared to 61% for dark blood (p<0.001). Conclusion Bright blood T2-weighted MRI has higher diagnostic accuracy than dark blood T2-weighted MRI. Additionally, dark blood T2-weighted MRI may underestimate area-at-risk and myocardial salvage.
129
MYOCARDIAL SALVAGE DURING PRIMARY PCI CAN BE PREDICTED IN THE CATH LAB
doi:10.1136/heartjnl-2011-300198.129
A R Payne, 1C Berry, 1O Doolin, 2M B McEntegart, 2R Woodward, 2A Saul, 2S D Robb, M C Petrie, 1I Ford, 2K G Oldroyd. 1University of Glasgow, Glasgow, UK; 2Golden Jubilee National Hospital, Glasgow, UK
2
Objectives This study investigated the relationship between the index of microcirculatory resistance (IMR) and myocardial salvage as determined by T2-weighted and contrast-enhanced cardiac magnetic resonance (CMR) imaging in patients undergoing primary percutaneous coronary intervention (pPCI) for ST elevation myocardial infarction (STEMI).
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Background IMR is a simple invasive measure of microvascular function available at the time of pPCI. T2-weighted non-contrast CMR can reveal myocardial oedema, and in the post-infarct population this represents the ischaemic area at risk (AAR). Contrastenhanced CMR delineates the area of myocardial infarction. The volume of myocardium within the AAR, but not contained within the infarct area is salvaged myocardium. Methods 108 patients with STEMI underwent invasive coronary physiology measurements during pPCI and had a subsequent CMR scan at a median of 19 h post pPCI. Short axis non-contrast T2weighted images were acquired and delayed enhancement imaging was performed following administration of intravenous gadolinium (0.1 mmol/kg). AAR was determined and myocardial salvage was calculated as AARdinfarct area. Results IMR was 29 (21), AAR 32% (13%) and myocardial salvage 6% (9%)dall mean (SD). Spearman rank correlation between IMR and AAR was 0.27 (p 0.02) and between IMR and salvage was 0.31 (p 0.01). IMR was also a multivariate predictor of AAR (p 0.01) and a negative multivariate predictor of myocardial salvage (p 0.02). Conclusions IMR measured acutely correlates with AAR and correlates negatively with myocardial salvage as determined by MRI. repeatability co-efcient (RC) 2.14; intra-observer R0.99, RC 1.49). Reproducibility of global ecc measurements by HARP was somewhat lower, but still high (inter-observer R0.89, RC 4.80; intraobserver R0.98, RC 2.73). There was much greater variability in segmental ecc measurements using both methods, particularly with HARP (Abstract 130 gure 2).
130
COMPARISON OF HARMONIC PHASE IMAGING WITH LOCAL SINE WAVE MODELLING FOR THE ASSESSMENT OF CIRCUMFERENTIAL MYOCARDIAL STRAIN USING TAGGED CARDIOVASCULAR MAGNETIC RESONANCE IMAGES
doi:10.1136/heartjnl-2011-300198.130
Abstract 130 Figure 1 Abstract 130 Table 1

Analysed segment for circumferential strain Anterior Anterolateral Inferolateral Inferior Inferoseptal Anteroseptal All 6 segments pooled HARP vs SinMod Mean Difference SD (%) 1.6866.38 3.1868.07 1.4868.24 1.3366.17 1.6665.63 2.4766.77 0.9967.11 HARP vs SinMod 95% Limits of agreement (%) 14.18 to 10.82 18.99 to 12.64 14.67 to 17.62 10.76 to 13.42 12.68 to 9.37 15.73 to 10.79 14.92 to 12.95 HARP vs SinMod Correlation Coefcient 0.59 0.22 0.24 0.48 0.59 0.52 0.43
A N Borg, 1C A Miller, 2C D Steadman, 2G P McCann, 1M Schmitt. 1University Hospital of South Manchester, Manchester; 2NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK
p-value for correlation 0.001 0.25 0.21 0.008 0.001 0.007 <0.001
Introduction Assessment of myocardial strain promises to become an important quantitative tool in early diagnosis of cardiac disease and treatment monitoring. Advances in image processing software have facilitated rapid and clinically feasible analysis of strain from tagged cardiac magnetic resonance (CMR) images. Harmonic Phase Analysis (HARP) or Local Sine Wave Modelling (SinMod) can be used for automated derivation of strain. We obtained tagged CMR images to compare measurements of left ventricular (LV) circumferential strain obtained using a HARP with a SinMod method. Methods Ten normal controls, 10 hypertrophic and 10 dilated cardiomyopathy patients (mean age 46.6614.8 years) were included. Spatial modulation of magnetisation using short-axis LV slices at mid-ventricular level, with a temporal resolution of 30e50 mS, were obtained using a 1.5 Tesla scanner (Siemens Avanto) with a 32-channel coil. Global and segmental transmural peak circumferential strains (ecc) were measured using HARP (Diagnosoft, USA, version 2.7) and SinMod (InTag, University of Lyons, France, version 3.6.1). Prior to running the algorithm, both methods involve manual tracing of the endocardial and epicardial borders, and localisation of right ventricle-to-septum insertion points, in one frame. Agreement between HARP and SinMod was assessed by Spearmans correlation co-efcient R and Bland Altman methods. Repeated measurements were carried out on 10 randomly selected scans to assess reproducibility. Results There was a high level of agreement between HARP and SinMod for global ecc (HARPdSinMod mean difference: 0.12%, 95% limits of agreement: 5.69% to 5.45%, R0.83, p<0.001) (Abstract 130 gure 1). Agreement was much lower for segmental ecc, ranging from very poor in lateral segments to modest in inferoseptal segments (Abstract 130 table 1). Analysis time using SinMod was signicantly shorter than for HARP (84642 vs 2016120 S, p0.02). Inter- and intra-observer reproducibility were extremely high for SinMod measurements of global ecc (inter-observer R0.99,
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Abstract 130 Figure 2 Inter- and intra observer variability for HARP local sine wave modelling: repeatability co-efcients.
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Conclusions HARP and SinMod methods show a high level of agreement for assessment of global mid-ventricular transmural circumferential strain, with good reproducibility for both individual methods. Agreement is much lower for segmental measurements; poor reproducibility for segmental measurements using both techniques probably reect user variability in identication of right ventricular septal insertion points and contour tracing.
132
NON-SYNONYMOUS SMAD6 MUTATIONS IMPAIRED INHIBITION OF BMP SIGNALLING IN PATIENTS WITH CONGENITAL CARDIOVASCULAR MALFORMATION
doi:10.1136/heartjnl-2011-300198.132
131
AETIOLOGICAL ROLE OF FOLATE DEFICIENCY IN CONGENITAL HEART DISEASE: EVIDENCE FROM MENDELIAN RANDOMISATION AND META-ANALYSIS
doi:10.1136/heartjnl-2011-300198.131
H L Tan, E A Glen, A L Topf, D H Hall, J J OSullivan, 2L Sneddon, 2C Wren, P Avery, 4R J Lewis, 5P ten Dijke, 1H M Arthur, 1J A Goodship, 1B D Keavney. 1 Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK; 2 Freeman Hospital, Newcastle upon Tyne, UK; 3School of Mathematics & Statistics, Newcastle University, Newcastle upon Tyne, UK; 4Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK; 5Department of Molecular Cell Biology and Center for Biomedical Genetics, Leiden University, Leiden, UK
3
V Mamasoula, T Pierscionek, D Hall, J Palomino-Doza, A Topf, T Rahman, J Goodship, B Keavney. Institute of Human Genetics, Newcastle upon Tyne, UK
Background The existence of a causal relationship between lower levels of plasma folate and congenital heart disease (CHD) remains contentious. Randomised trials of this question are not possible, in view of the known protective effect of folate against neural tube defects (NTDs). Folate fortication of our is known to reduce the incidence of NTDs, but it is not known whether there is any effect on CHD. Clarity regarding the relationship between folate and CHD could potentially inform the practice of folate fortication. We present a genetic approach using Mendelian randomisation to determining the causality of folate in CHD risk. Methods We compared genotype frequencies at the methylene tetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism (SNP) in 1186 CHD cases and 4168 controls. The TT genotype at MTHFR C677T is known to be associated with lower activity of MTHFR and plasma folate, and higher levels of plasma homocysteine. The effect of TT genotype on plasma folate levels is greater in conditions of folate deciency. Thus, if lower plasma folate had a causal effect on CHD risk, a higher frequency of TT genotype among CHD cases than among healthy controls would be anticipated, and this would be expected to be more marked in conditions of folate deciency. We placed our results in the context of a meta-analysis of all previously published studies of this question (to September 2010), which together included 1883 cases and 3069 controls in 25 studies. Thus, the combined analyses included 3069 CHD cases and 7271 controls. We used randomeffects models to combine the data. We conducted sensitivity analyses to examine folate fortication of our as a potential source of heterogeneity. Results The primary genotyping data in 1186 cases and 4168 controls revealed a trend towards increased risk with the TT genotype, but this did not reach statistical signicance (OR 1.15 (95% CI 0.94 to 1.40)). Combination of our primary data with previous studies, however, revealed association in the larger dataset (OR 1.45 (95% CI 1.12 to 1.89); p0.005). The population attributable fraction for the TT genotype was 3% of CHD. There was no evidence of publication bias among the contributing studies. We discovered folate fortication status to be a signicant source of heterogeneity. Studies conducted in countries with mandatory folate fortication showed no effect of C677T genotype on CHD risk (OR 0.96 (95% CI 0.64 to 1.44)), whereas studies conducted in countries without mandatory fortication showed a signicant effect of genotype (OR 1.63 (95% CI 1.19 to 2.25)). These ORs were signicantly different from each other (p0.032). Conclusions We demonstrate genetic evidence in favour of a causal relationship between plasma folate and CHD. The absence of a genetic association in countries practicing folate fortication suggests that fortication largely abrogates the risk of CHD attributable to folate deciency.
Introduction Congenital cardiovascular malformation (CVM) exhibits familial predisposition but the specic genetic factors involved are unknown. Bone morphogenetic proteins (BMPs) regulate many processes during development, including cardiac development. Five genes of the BMP signalling were surveyed for novel variants predisposing to CVM risk. One of the genes, SMAD6, functions as an inhibitory SMAD which preferentially inhibits BMP signalling. The SMAD6 knockout mouse is characterised by cardiac valve and outow tract defects, including aortic ossication. We hypothesised that rare functional variation in SMAD6 could predispose to congenital cardiovascular malformation (CVM). Methods The coding regions of BMP2, BMP4, BMPR1A, BMPR2 and SMAD6 were sequenced in 90 unrelated Caucasian cases of CVM. The MH2 domain of SMAD6 were further sequenced in additional 346 CVM patients. Functional effects of the wild-type and variant SMAD6 proteins were expressed in C2C12 cells and their capacity to inhibit ALK3 activated expression of a BMP-responsive reporter, or to inhibit osteogenic differentiation (using an alkaline phosphatase assay) was assessed. Results We identied two novel non-synonymous variants, P415L and C484F, that were not present in 1000 ethnically-matched controls. P415L was identied in a patient with congenital aortic stenosis and C484F was identied in a patient with coarctation and calcication of the aorta. Both mutations are in evolutionarily conserved amino acid residues and are predicted to be damaging by in silico analysis. This was conrmed in functional assays as both SMAD6 variants failed to inhibit BMP signalling compared with wild-type SMAD6. The P415L mutant appeared to be hypomorphic whereas C484F appeared to be a null allele in the luciferase assay. The C484F mutant had a signicantly (p<0.05) lower capacity to inhibit alkaline phosphatase generation in response to BMP signalling. Conclusions This is the rst time that functional mutations in SMAD6 have been described in patients with CVM, specically those with calcic aortic malformations. Our data suggest that inadequate inhibition of BMP signalling pathway due to genetic variation in SMAD6 may be an important factor in CVM.
133
ACTIVITY AND PSYCHOSOCIAL HEALTH IN ADOLESCENTS WITH CONGENITAL HEART DISEASE (CHD)
doi:10.1136/heartjnl-2011-300198.133
M L Morrison, A J Sands, C G McCusker, 2P P McKeown, 1M McMahon, J Gordon, 1B G Craig, 1,2F A Casey. 1Royal Belfast Hospital for Sick Children, Belfast, UK; 2The Queens University of Belfast, Belfast, UK
1
1,2
Many patients with CHD are now adolescents. Like other patients with chronic illnesses they may be at higher risk of psychological/ emotional problems. Ability to exercise is an important quality of life measure and indicator of physical health. We aimed to ascertain if activity and psychosocial health were reduced in adolescents with major CHD compared to those with a minor diagnosis. Patients aged 12e20 years were identied using the Northern Ireland regional database (HeartSuite). Participants were categorised as having major or minor CHD and divided into four diagnostic
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subgroups. Participants completed validated, age-appropriate questionnaires examining standard psychological parameters. Participants also underwent an evaluation of exercise, including formal exercise stress testing and measurement of free-living activity using an ActiGraph accelerometer. Results were analysed using parametric methods. 143 patients (mean age 15.6 years) consented to participate, 86 were male (60%) and 105 had major CHD (73%). Diagnostic subgroups included 39 acyanotic (27.3%), 61 acyanotic corrected (42.7%), 30 cyanotic corrected (21.0%) and 13 (9%) cyanotic palliated patients. Beck Youth Inventory demonstrated that individuals with major CHD, particularly cyanotic palliated patients, had higher anxiety scores (p value 0.01 (8.42, 1.13)). There were no signicant differences across study groups for selfesteem or other psychological parameters. 134 participants (93.7%) took part in regular exercise each week. There was no signicant difference in activity score between study groups. On formal exercise testing, more complex patients performed worse at peak exercise. Exercise time for acyanotic group 11.73 mins (sd 3.74) compared to 8.26 mins (sd 4.08) in cyanotic palliated group, p value 0.002 (1.32, 5.61)). However, patients with major CHD had significantly higher activity counts. Correlation analysis showed that selfesteem and health locus of control were important predictor variables for activity. Self-esteem and mood seem well preserved in adolescents with CHD as a whole. The majority of young people with CHD, in this group, take part in regular exercise. Surprisingly, complex patients rate themselves to be as active as those with minor CHD. While accelerometer data indicate that the group may be more active day to day, they are limited in terms of peak exercise duration. The experience of growing up with a chronic condition may therefore have a positive effect on psychological health and interventions targeted around this area may inuence activity. example of mutations in a sarcomere protein causing congenital heart malformation.
135
GENE SCREENING OF THE SECONDARY HEART FIELD NETWORK IN TETRALOGY OF FALLOT PATIENTS
doi:10.1136/heartjnl-2011-300198.135
A Topf, H R Grifn, D H Hall, E Glen, B D Keavney, J A Goodship; The Change Study Collaborators. Institute of Human Genetics, Newcastle upon Tyne, UK
134
MUTATIONS IN THE SARCOMERE PROTEIN GENE MYH7 IN EBSTEINS ANOMALY

doi:10.1136/heartjnl-2011-300198.134
T Rahman, 1J Goodship, 2A Postma, 2K Engelen, 2B Mulder, 3S Klaassen, 4B Keavney. Institute of Human Genetics, Newcastle upon Tyne, UK; 2Academic Medical Centre, Amsterdam, The Netherlands; 3Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany; 4Institute of Human Genetics, Newcastle upon Tyne, UK
1
Background Ebsteins anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaets of the tricuspid valve to the underlying myocardium. As there have been reports of abnormal left ventricular morphology and function in patients with Ebsteins anomaly we hypothesised that mutations in the b-myosin heavy chain (MYH7) may be associated with Ebsteins anomaly. Methods MYH7 mutation analysis was undertaken in 141 unrelated affected individuals with Ebsteins anomaly using next-generation sequencing on the 454 platform. 64 probands had no associated cardiac anomalies. The most common associated cardiac malformation were atrial septal defect (48 probands) and left ventricular non-compaction (LVNC) (7 probands). Where mutations were discovered, family studies were undertaken and the segregation of the mutation with disease was investigated. Results Heterozygous mutations were identied in eight of the probands including six of the seven with LVNC. Two patients had the same mutation; of the seven distinct mutations, ve were novel (four missense changes and an in-frame deletion) and two have been previously reported in patients with hypertrophic cardiomyopathy. Family studies revealed additional members with LVNC for three of the probands, one of whom also had a relative with Ebsteins anomaly. In these three pedigrees the mutation segregated with disease. Conclusions Mutations in MYH7 occur relatively frequently in Ebsteins anomaly accompanied by LVNC. This study is another
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Background Tetralogy of Fallot (TOF) is the most common cyanotic heart defect, affecting 3e6 infants for every 10 000 births. TOF is phenotypically well dened; it consists of four heart abnormalities: a VSD, an over-riding aorta, a narrowed pulmonary valve and right ventricular hypertrophy. During heart development two heart elds can be distinguished. The rst one gives origin to the left ventricle and contributes to the right and left atria. The secondary heart eld gives origin to the right ventricle and the outow tract. Each of these elds can be identied by the expression of specic markers. As TOF is a malformation of the outow tract, we hypothesised genes involved in the regulatory network of the secondary heart eld were particularly good candidates for TOF susceptibility. Methods We examined by standard Sanger method the full exonic and intron boundary regions of 14 secondary heart eld genes, namely NKX2-5, GATA4, TBX20, MEF2C, BOP, HAND2, FOXC1, FOXC2, TBX1, FOXA2, FGF10, FGF8, ISL1 and FOXH1, in a panel of 93 TOF patients. All newly discovered rare variants were checked in a panel of 1000 control chromosomes by multiplex Sequenom assays. When available, parents of cases were screened to assess inheritance of the rare variant. Results We re-sequenced a total of 80 exons and w30 Kb. Among the 14 genes studied we found a total of 50 new variants, of which 23 were exclusive to the patient population, ie, were absent from 1000 normal chromosomes. Nine of these variants cause change in the aminoacid sequence. We found a functional 19aa deletion of a highly conserved region of TBX1. In FOXC1 we found a contraction of both alanine and glycine tracts. An alanine expansion, usually known to be deleterious, was found in HAND2. Four non-synonymous changes were found in FOXA2. Most patients presented just one variant, however 3 patients presented two, and one patient presented up to 3 variants. All patients were heterozygotes for the variants, and had inherited them from one of their phenotypically normal parents (when parental information was available). In addition, 75% of the variants were inherited from the mother. Conclusions Although genes of the secondary heart eld seemed good candidates for TOF susceptibility, thus far we have not found any strong indication of unique causal effect, as all variation found in probands was also present in their unaffected parents. However, the presence of multiple variants in the same proband may result in the disruption of gene-gene interactions in the secondary heart eld pathway, which in turn may lead to outow tract defects. Based on our results, it would seem more likely that susceptibility to TOF be determined by a larger number of small genetic contributions which are also modied by environmental factors. It is evident that larger scale analysis of signicant numbers of whole genomes/exomes will be necessary to better understand the molecular aetiology of TOF.
136
SHOULD FAMILIAL SCREENING BE ROUTINELY OFFERED TO PATIENTS WITH BICUSPID AORTIC VALVE DISEASE?
doi:10.1136/heartjnl-2011-300198.136
R Panayotova, S Hosmane, A Macnab, P Waterworth. University Hospital of South Manchester, Manchester, UK
Background Bicuspid aortic valve (BAV) disease is one of the most common congenital cardiac abnormalities with prevalence in the
BCS Abstracts 2011

general population of up to 2%. There has been growing evidence supporting its familial predisposition with an autosomal dominant pattern of inheritance. It is often associated with ascending aortic dilatation and dissection, occurring at a younger age than in patients with idiopathic aortic aneurysms. BAV disease carries a 6% lifetime risk of aortic dissection, 9 times higher than that of the general population. Thus, the presence of BAV and dilatation of the ascending aorta requires regular monitoring with a view to timely pre-emptive surgery. Current ACC/AHA guidelines state that echocardiographic screening of rst degree relatives of patients with BAV is recommended. This, however, to our knowledge, is not routinely done within the UK. Methodology and Results We set out to explore the practicalities of running a routine echocardiographic screening programme for rst degree relatives of patients with BAV disease. We identied a total of 47 patients who had undergone aortic valve surgery performed by the same Consultant Cardiothoracic Surgeon in the context of BAV disease in the period May 2007eSeptember 2009. Screening of rst degree relatives was offered to these patients. 24 patients (51%) gave us information regarding family members who would like to attend for an echocardiogram. A total of 75 rst degree relatives were referredean approximate average of 3 per patient. Out of these, 52 relatives (70%) actually attended for an appointment. The remainder did not undergo testing with us as they either lived in a different geographic region or expressed a personal preference not to be scanned at this time. The incidence of newly diagnosed bicuspid aortic valve disease in our cohort of rst degree relatives was 8% (4 out of 52 relatives). One of these asymptomatic individuals had a signicant ascending aortic aneurysm, which required prompt surgery. Among the relatives of the 24 index patients, there were a total of 8 cases (3: 1 ratio) of bicuspid aortic valve diseasedeither known or newly diagnosed via screening. Conclusions There is a relatively high prevalence and incidence of bicuspid aortic valve disease among rst degree relatives of patients with this common congenital cardiac abnormality. Routine echocardiographic screening should be offered to these families. Implementing such a programme is limited by adequate motivation to attend for a screening test if well, and by varying clinical practice in different geographic regions. Patients with bicuspid aortic valve disease should be made aware of its familial pattern of inheritance and screening of their rst degree relatives should be actively pursued in order to reduce the potential morbidity and mortality associated with this condition and its related aortopathy. left-right patterning and placental development makes it difcult to identify a later specic role for Cited2 in myocardial development. To overcome this problem we therefore investigated the role of Cited2 in the myocardium by conditional deletion in cardiomyocyte precursors. Methods Cited2 was selectively deleted from cardiomyocytes by intercrossing mice transgenic for Cited2 and Nkx2-5Cre. Embryos were collected and processed for analysis by histology, MRI, X-Gal staining, quantitative reverse transcriptase PCR (Q-RTPCR), chromatin immunoprecipitation and transient transfection assays. Results The cardiomyocyte specic knockout of Cited2 results in abnormal myocardial compact zone growth and ventricular septal defects. This is associated with a decreased ratio in the number of small vessels to large vessels, and a reduction in Vegfa expression. We also show that CITED2 is present at the Vegfa promoter in mouse embryonic hearts, and that it stimulates human VEGFA promoter activity in cooperation with TFAP2 transcription factors in transient transfection assays. However, we observed no change in the myocardial expression of the left-right patterning gene Pitx2c, a known target of Cited2. Conclusions The myocardial and capillary defects observed in myocardial loss of Cited2 are not associated with Pitx2c deciency and suggests that Cited2 can cause myocardial and vascular defects via a mechanism that is distinct from its effect on the left-right patterning pathway. Our results delineate a novel mechanism of Vegfa regulation by CITED2 and TFAP2 transcription factors, and indicate that coupling of myocardial and coronary vascular growth in the developing mouse heart occurs, at least in part, through a Cited2->Vegfa pathway. This pathway may be targeted for the treatment of heart failure resulting from ischaemic heart disease.
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CELL-SPECIFIC ROLE OF NOX2 NADPH OXIDASE IN DEVELOPMENT OF ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS IN VIVO
doi:10.1136/heartjnl-2011-300198.138
S Chaubey, C E Murdoch, A Ivetic, B Yu, D Vanhoutte, 2S Heymans, 1A Brewer, A M Shah. 1Kings College London BHF Centre of Excellence, London, UK; 2University Hospital Maastricht, Maastricht, The Netherlands
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A CITED2->VEGFA PATHWAY COUPLES MYOCARDIAL AND CORONARY VASCULAR GROWTH IN THE DEVELOPING MOUSE HEART
doi:10.1136/heartjnl-2011-300198.137
1 1
S D Bamforth, 1S T MacDonald, 1J Braganca, 1C-M Chen, 1C Broadbent, J E Schneider, 2R Schwartz, 1S Bhattacharya. 1University of Oxford, Oxford, UK; 2 Texas A&M Health Science Centre, Houston, Texas, USA
Introduction Myocardial development is dependent on the concomitant growth of cardiomyocytes and a supporting vascular network. The coupling of myocardial and coronary vascular development is mediated in part by VEGFA signalling. Cited2 is a transcriptional cofactor that can inhibit hypoxia-activated transcription and also acts as a co-activator for transcription factors such as TFAP2. Genetic evidence indicates that Cited2 is essential for cardiac left-right patterning via regulation of the Nodal-Pitx2c left-right patterning pathway. Zygotic and epiblastic deletion of Cited2 results in atrioventricular septation, outow tract and aortic arch abnormalities, as well as left-right patterning defects such as right-isomerism. Cited2 is also essential for adrenal, neural crest, liver, lung, lens and placental development. However, the early requirement of Cited2 in
Introduction Mice globally decient in Nox2 are protected against cardiac brosis in response to chronic AngII infusion even though the degree of hypertrophy was unaltered. The selective effect of Nox2 on brosis may reect its activation in a non-cardiomyocyte cell type. We hypothesised that Nox2, which is expressed in endothelial cells and inammatory cells, may be important for cardiac brosis in these cell types. Methods To investigate the role of Nox2 in inammatory cells, we generated chimeric mice by irradiation (10Gy, 15 min) to deplete resident bone marrow cells, followed by bone marrow (BM) transplantation, using the following permutations: wild-type (WT) recipient with either KO or WT BM, and KO recipients with WT BM. To assess the role of endothelial Nox2, we used transgenic mice with endothelial-specic overexpression of Nox2 (TG) utilising the tie2 promoter construct. Result AngII (1.1 mg/kg/day, 14-day) infusion caused similar increase in systolic hypertension and cardiac hypertrophy in all 3 chimeric groups. However, cardiac brosis assessed by Sirius red staining was signicantly lower in KO mice receiving WT BM (0.560.1%) compared to the WT:WT group (2.760.7%) or in WT receiving KO BM (2.360.6%). These data suggested that resident Nox2-expressing cells are responsible for the protective effect observed in global Nox2 KO mice. TG mice developed the same level of systolic hypertension and hypertrophy as WT littermates after AngII infusion. However, the extent of cardiac brosis was signicantly greater in TG than WT by w2-fold (p<0.05). This was associated with a greater degree of inltration by CD45+
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inammatory cells (w1.8-fold, p<0.05) and 30% (p<0.05) more VCAM-1 positive blood vessels in AngII treated TG hearts. Furthermore, isolated TG endothelial cells recruited w2-fold (p<0.05) more leukocytes than WT upon AngII treatment. Conclusion These results indicate there is a cell-specic role of endothelial Nox2 in the development of brosis. Endothelial Nox2 enhances AngII-induced cardiac brosis, possibly by enhancing inammatory cell recruitment and inux via VCAM-1 expression. Although inammatory cells may be important for the development of brosis, our results indicate that Nox2 in these cells is not essential for any pro-brotic effect. cantly reduced cardiac function following myocardial infarction. In rat cardiac broblasts, endoglin expression is up regulated following stimulation with angiotensin II and TGFb, resulting in reduced expression of MMP1 and increased expression of collagen I. These effects are inhibited by an endoglin specic antibody. Using our conditional endoglin knockout mice we sought to investigate the role of endoglin in cardiac healing following myocardial infarction. Adult Eng / Rosa26-CreERT2 or control (Eng /) mice were treated with intraperitoneal injection of tamoxifen for 5 days to activate CreERT2 and deplete endoglin by Cre-lox recombination. Mice then underwent surgical coronary artery ligation or sham operation. Cine cardiac MRI was performed 28 days after injury. Measurement of left ventricular (LV) volumes and myocardial mass were made using ImageJ, and parameters of cardiac function were calculated. We found that LV volumes and mass were signicantly increased (p<0.001) and ejection fraction signicantly reduced (p0.005) in endoglin decient mice compared to controls. However, we also noticed LV volume and mass were increased in sham operated endoglin decient mice. This led us to investigate the effect of endoglin knockdown on normal heart structure and function in adult mice. Cine cardiac MRI was therefore performed on mice without any surgical procedure after endoglin knockdown. We found that in the endoglin decient mice, LV volume and mass were again signicantly increased (p<0.03). However, ejection fraction did not differ signicantly from controls. These results demonstrate that depletion of endoglin results in signicant left ventricular remodelling and suggest that endoglin plays an essential role in the maintenance of normal cardiac structure. The fact that cardiac function was preserved indicates that this is not a cardiomyopathic process and we hypothesise that the increased left ventricular volume in the endoglin-decient mice may be the result of alterations in the extracellular matrix. We are currently investigating this potential molecular mechanism for left ventricular remodelling in the absence of endoglin.
139
ENDOTHELIAL SPECIFIC INSULIN RESISTANCE PROMOTES THE DEVELOPMENT OF ATHEROSCLEROSIS

doi:10.1136/heartjnl-2011-300198.139
1 1
M C Gage, 1N Yuldasheva, 2C Jackson, 1M Kearney, 1H Imrie, 1H Viswambharan, M Kahn, 1J Smith, 1S Galloway, 1R Cubbon, 1P Sukumar, 1A Aziz, 1S Wheatcroft. 1 Leeds University, Leeds, UK; 2University of Bristol, Bristol, UK
Background Global insulin resistance and endothelial dysfunction have been identied as predisposing factors for atherosclerosis. However, it is unclear whether selective insulin resistance in endothelial cells alone, is sufcient to promote atherosclerosis. Here we addressed this question by crossing Endothelial Specic Mutant Insulin Receptor Over-expressing (ESMIRO) mice with ApoE null mice. ESMIRO mice over-express a human insulin receptor with Ala-Thr1134 mutation in the tyrosine kinase domain (which disrupts insulin signalling) selectively in endothelial cells under the control of the tie-2 promoter/enhancer. Methods Male ApoE/ESMIRO mice were compared with sexmatched littermate ApoE/ mice (both on a C57Bl6 background) after feeding a Western-style diet for 12 weeks. Results ApoE/ESMIRO mice were morphologically indistinguishable from ApoE/ control littermates, with normal development and no difference between groups in body mass. Heart rate, systolic blood pressure, glucose tolerance, insulin sensitivity and fasting glucose levels were similar in ApoE-/-ESMIRO and ApoE/ mice. Aortic lipid deposition, assessed by en-face oil red O staining, was similar in ApoE/ESMIRO and ApoE/ mice (6.4%60.5% vs 5.8%60.5%; p0.39). However, atherosclerotic lesion area in cross sections of aortic sinus was signicantly increased in ApoE/ ESMIRO mice compared to ApoE/ controls (24.8%62.4% vs 16.6%62.4%; p0.02). Absolute plaque size was also signicantly increased in ApoE/ESMIRO mice compared to ApoE controls (226 448.9616 154 mm2 vs 149 424.41624 221 mm2; p0.01). Conclusions Endothelial specic insulin resistance is sufcient to promote atherosclerosis and increase lesion area in ApoE null mice. This suggests that enhancing endothelial insulin sensitivity may be an appropriate target to prevent atherosclerosis in insulin-resistant conditions.
141
TISSUE FACTOR PATHWAY INHIBITOR REGULATES VASCULAR DEVELOPMENT IN ZEBRAFISH

doi:10.1136/heartjnl-2011-300198.141
E W Holroyd, C K Pierret, V M Bedell, J Townend, 2S C Ekker, 2R D Simari. 1Queen Elizabeth Hospital, Birmingham, UK; 2Mayo Clinic, Rochester, UK; 3Queen Elizabeth Hospital, Rochester, UK
140
IN VIVO DEPLETION OF ENDOGLIN RESULTS IN SIGNIFICANT LEFT VENTRICULAR REMODELLING

doi:10.1136/heartjnl-2011-300198.140
B J Davison, R Redgrave, B Keavney, A Blamire, 1H Arthur. 1Institute of Human Genetics, Newcastle University, Newcastle Upon Tyne, UK; 2Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
Endoglin, a TGFb co-receptor, is essential for cardiovascular development. However, endoglin also has an important role in brosis in adult life. Endoglin heterozygous mice have been shown to have reduced brosis in response to renal injury. They also have signiA78
Introduction Angiogenesis requires the coordinate regulation of multiple biological pathways, including haemostasis. Tissue factor pathway inhibitor (TFPI) is a potent anticoagulant molecule, inhibiting tissue factor-led coagulation. However, the role of TFPI in vascular development is unknown. Zebrash (Danio rerio) provide a unique model system to study vascular development in vertebrates. Despite the divergence of jawed sh (teleosts) over 430 million years ago, there is notable conservation of the constituent molecules of the clotting cascade. Multiple features make this vertebrate model unique, including its genetic accessibility, the ability to titrate the degree of genetic knock-down, external embryonic development, and the transparent nature of the embryos. Methods Using in-situ hybridisation techniques, we demonstrate TFPI expression during early vertebrate development. We then utilise transgenic sh with labelled endothelium (Fli1GFP) and erythrocytes (GATA1dsRed), to study in real time, concomitant uorescent imaging of both structural development and dynamic blood ow observation, in living zebrash embryos. Results TFPI expression was identied at 24 h post fertilisation (hpf) in the pronephros (Abstract 141 gure 1ddark blue staining denotes TFPI expression; none seen in control embryos). Subsequently, TFPI mRNA became more abundant, localising to
BCS Abstracts 2011

2EFHIK&L) were seen by 48hpf. TFPI MO induced coagulopathy (a spontaneous clot or bleed; white arrows Abstract 141 gure 2GJMP) in 25.262.3% (p<0.01 cf. uninjected controls) at 3 ng and 23.865.8% (p<0.01) at 9 ng. Control embryos did not demonstrate signicant signs of coagulopathy (3.363.3%). Extra arteries occurred in 26.462.6% (p<0.001 by ANOVA cf. uninjected controls) of embryos injected with 3 ng of TFPI MO. To further dene the role of TFPI in vascular function, RNAi-mediated knockdown of TFPI was performed in human endothelial cells (EC). Knockdown of TFPI resulted in enhanced EC tube formation on Matrigel and EC migration in injury model associated with increased phosphorylation of Vascular Endothelial Growth Factor Receptor-2. Conclusion These data represent the rst demonstration of TFPI expression in zebrash and the rst description of a unique phenotype following TFPI knockdown. They support a model in which TFPI acts a molecular break to angiogenesis both in vivo, during early vertebrate embryogenesis, and in vitro in mature human endothelial cells, secondary to constitutive regulation of VEGF signalling.
142
ATRIAL SOURCES OF REACTIVE OXYGEN SPECIES VARY WITH THE SUBSTRATE AND DURATION OF ATRIAL FIBRILLATION: IMPLICATIONS FOR THE ANTIARRHYTHMIC EFFECT OF STATINS
doi:10.1136/heartjnl-2011-300198.142
S Reilly, 1R Jayaram, 2C Anroniades, 3S Verheule, 1K M Channon, 1N J Alp, U Schotten, 1B Casadei. 1University of Oxford, John Radcliffe Hospital, Oxford, UK; 2 First Department of Cardiology, University of Athens, Athens, Greece; 3Department of Physiology, University of Maastricht, Maastricht, The Netherlands
3
developing kidney, gut, and vasculature. Morpholino (MO)-based knockdown of TFPI resulted in coagulopathy and disordered vascular development (Abstract 141 gure 2. left column: green endothelial Fli1GFP, right column: red erythrocytes. AB: uninjected controls. CD: MO controls. EeP: TFPI knockdown). Abnormally targetted (ie, vessels sprouting from normal site but growing in abnormal direction; grey arrows) and extra vessels (ie, superuous vessels not seen in controls; white arrows in Abstract 141 gure

Background Atrial brillation (AF) is the most common sustained cardiac arrhythmia and is associated with altered nitric oxide (NO)redox balance. The molecular mechanisms and implications of this phenomenon in the management of patients with AF are poorly understood. Statins improve NO-redox imbalance and decrease the occurrence of postoperative AF but are less effective in the secondary prevention of AF, suggesting that the sources of reactive oxygen species might vary with the substrate and duration of AF. Methods and Results We investigated atrial tissue from 130 patients undergoing cardiac surgery (26 with permanent AF, 32 who developed AF post-operatively and 72 who were in normal sinus rhythm before and after surgery), and from goats in sinus rhythm (SR, n19) with or without atrial structural remodelling secondary to surgical AV block (AVB, n10) or after 2 weeks (2W, n15) or 6 months (6M, n10) of pacing-induced AF. Atrial NADPH oxidase activity (chemiluminescence and 2-OH ethidium, Abstract 142 gures 1 and 2), NOX2 & p22phox protein level were increased after 2W-AF and in patients who developed AF post-operatively (n32). In contrast, the increased superoxide production in atrial tissue from goats with AVB or 6M-AF was exclusively driven by mitochondrial oxidases and uncoupled NOS (secondary to a reduction in atrial BH4 level and an increase in arginase activity). These ndings were recapitulated in the right atrial appendage of patients. Increase in basal superoxide production in postoperative AF was associated with an apocynin-reversible increase in NADPH oxidase activity and protein level of the NOX2 and p22phox subunits. NOS activity remained coupled despite the increase in superoxide production. In line with this, atrial BH4 content was unaltered. In contrast, in patients with permanent AF, increased superoxide production was not reversed by apocynin, and was maintained by mitochondrial oxidases and uncoupled NOS (secondary to BH4 deplition). Ex-vivo inhibition of HMG-CoA reductase with atorvastatin (20 mMol/l) inhibited NADPH oxidase activity (via reducing activity of Rac1 and membrane translocation of cytosolic subunit p47phox and p67phox of NADPH oxidase) and caused a mevalonate-reversible reduction in
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superoxide release in atrial samples of patients with post-operative AF but had no effect in patients with permanent AF. Similarly, atorvastatin did not induce a mevalonate-reversible changes in the atrial BH4 concentration and NOS uncoupling in neither group. Conclusions Together, these ndings indicate that upregulation of NOX2-NADPH oxidases is an early but transient event in the natural history of AF, as mitochondrial oxidases and uncoupled NOS account for the statin-resistant increase in atrial superoxide production in permanent AF. Variation in atrial sources of reactive oxygen species with the duration and substrate of AF may explain the reported variability in the effectiveness of statins in the prevention and management of AF.
143
TISSUE FACTOR PATHWAY INHIBITOR REGULATES ANGIOGENESIS INDEPENDENTLY OF TISSUE FACTOR VIA INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR SIGNALLING
doi:10.1136/heartjnl-2011-300198.143
1 E W Holroyd, 2K Larsen, 2R G Vile, 2D Mukhopadhyay, 2R D Simari. 1Queen Elizabeth Hospital, Birmingham, UK; 2Mayo Clinic, Rochester, Minnesota, USA
Introduction The biological systems of coagulation and angiogenesis show considerable interdependence. Proteases and inhibitors within the tissue factor (TF) pathway of coagulation have emerged as potential regulators of angiogenesis. Tissue factor pathway inhibitor (TFPI), as the primary physiological inhibitor of tissue factor (TF)mediated coagulation, is ideally situated to modulate the proangiogenic effects of TF. However, TFPI may also have effects on angiogenesis independent of its anti-TF ability. Methods We determined the effects of altered TFPI expression on the regulation of angiogenesis in vivo using genetically-modied murine models of vascular overexpression (SM22TFPI strain) and endothelial-specic deletion of the TF-binding domain of TPFI (Tie2TFPI). We then dened the mechanism of these effects in vitro using Human Umbilical Vein Endothelial Cells (HUVECs) overexpressing TFPI or via exogenous addition of TFPI-derived peptides in assays of angiogenesis. Results Vascular-directed over-expression of TFPI (SM22TFPI strain) inhibited angiogenesis in vivo (Abstract 143 gure 1). SM22TFPI showed signicantly impaired recovery from ischaemia in the hindlimb ischaemia model after 3 days (p<0.05, n5 per group), which persisted throughout the experiment. Survival (until 1-cm tumour dimension) of SM22TFPI mice vs wild-type control (median survival 14 cf. 10 days) following s.c. B16 melanoma injection (n7 per group, c24.325, *p<0.05). Endothelial-specic deletion of the TF-binding domain of TFPI failed to reveal a proangiogenic phenotype. This led us to suspect that the anti-angiogenic action of TFPI may be independent of TF. Systemic delivery of the murine TFPI carboxyl-terminus (mTFPIct) replicated the effects of endogenous overexpression. In vitro, overexpression of TFPI inhibited endothelial cell tube formation on Matrigel and migration using an injury migration model. Human TFPIct (hTFPIct) inhibited tube formation and migration through inhibition of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) tyrosine-951 phosphorylation, a key event in migration. hTFPIct did not inhibit VEGF121-induced migration, which lacks the heparin-binding domain of VEGF165. Utilising the chimeric receptor, EGDR, which contains the extracellular domain of epidermal growth factor (EGF) and the intracellular domain of VEGFR2/KDR, a direct effect of TFPIct on the intracellular domain of VEGFR2 was excluded (Abstract 143 gure 2) TFPIct did not block phosphorylation of EGDR when stimulated with EGF.
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Conclusion Angiogeneis is a key biological system in health and disease; enabling cells in a hypoxic environment to stimulate new blood vessel growth. These data demonstrate, both in vivo and in vitro, an inhibitory role for TFPI in angiogenesis that is TF-independent. In addition to it classical role as a TF-antagonist, TFPI, via TFPIct, interferes with the interaction of VEGF165 with the extracellular domain of VEGFR2, thereby limiting angiogenesis.
144
A DRUGGABLE INHIBITOR OF CARDIAC HYPERTROPHY IDENTIFIED THROUGH AN INNOVATIVE CHEMICAL LIBRARY SCREEN
doi:10.1136/heartjnl-2011-300198.144
R Abou Leisa, T M A Mohamed, D Oceandy, S Prehar, M Zi, F Baudoin, L Neyses, E J Cartwright. Manchester University, Manchester, UK
Cardiac hypertrophy is a prerequisite for the development of heart failure. It currently affects almost one million people in the UK. Few effective anti-hypertrophic agents with druggable properties have been identied. Recently, our group showed that plasma membrane calcium ATPase isoform 4 (PMCA4) knockout mice showed a reduced response to hypertrophic stress prompting us to hypothesise that a novel PMCA4 specic inhibitor would modify the development of cardiac hypertrophy. A library of 1280 medically optimised compounds was screened using a novel in vitro assay which measures the Ca2+ dependent ATPase activity of PMCA4. The compound AP2 was identied, which inhibited PMCA4 activity with high afnity (IC50300 nM) but not other PMCAs (PMCA1, PMCA2 and PMCA3) or related ATPases which are expressed in the heart including the sarcoplasmic reticulum calcium ATPase and Na/K ATPase. In isolated neonatal rat cardiomyocytes (NRCM), AP2 showed dose dependent inhibition of phenylephrine-induced hypertrophy, indicated by an 85% reduction in cell surface area as well as in BNP activity. In vivo studies showed that AP2 (5 mg/kg body weight/day IP) signicantly reduced pressure-overload induced hypertrophy following 2 weeks transverse aortic constriction (TAC) (heart weight/tibia length (mg/ mm): sham, 5.560.3, vehicle treated TAC mice, 8.7 60.2, AP2 treated TAC mice, 7.0 60.5, n10 in each group, p<0.01). AP2 treated TAC
BCS Abstracts 2011

mice showed a signicant reduction in the cardiomyocyte cross sectional area (sham, 26763.4 mm2, vehicle treated TAC mice, 48065.8 mm2, AP2 treated TAC mice, 31963.9 mm2). A signicant reduction in the expression of the hypertrophic marker ANP and BNP and in the percentage of brosis was also observed in these mice compared with vehicle treated TAC mice. AP2 treatment led to a signicant reduction in the expression of the bona de calcineurin target RCAN1.4 and a reduction in the NFAT phosphorylation level in vivo and the NFAT transcriptional activity in vitro. In conclusion, we have identied AP2 as a novel PMCA4 specic inhibitor and shown its potential to modify the development of cardiac hypertrophy likely through inhibition of calcineurin/NFAT signalling. This compound has drug-like properties and thus lays the basis for a novel approach for treating cardiac hypertrophy and failure through PMCA4 inhibition.
145
CHARACTERISATION OF FRACTIONATED ATRIAL ELECTROGRAMS CRITICAL FOR MAINTENANCE OF AF: A RANDOMISED CONTROLLED TRIAL OF ABLATION STRATEGIES (THE CFAE AF TRIAL)
doi:10.1136/heartjnl-2011-300198.145
Abstract 145 Figure 1 Impact of CFAE grade on the proportion of lesions causing AF cycle length prolongation.
R J Hunter, I Diab, M Tayebjee, L Richmond, S Sporton, M J Earley, R J Schilling. Barts and The London NHS Trust, London
146
Introduction Targeting complex fractionated atrial electrograms (CFAE) in the ablation of atrial brillation (AF) may improve outcomes, although whether this is by eliminating focal drivers or simply de-bulking atrial tissue is unclear. It is also uncertain what electrogram morphology should be ablated. This randomised study aimed to determine the impact of ablating different CFAE morphologies compared to normal electrograms (ie, de-bulking normal tissue) on the cycle length of persistent AF (AFCL). Methods After pulmonary vein isolation CFAE were targeted systematically throughout the left then right atrium, until termination of AF or abolition of CFAE prior to DC cardioversion. 10 s electrograms were classied by visual inspection according to a validated scale, with Grade 1 being most fractionated and grade 5 normal. Patients were randomised to have CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). Because grade 5 electrograms were considered normal, only 5 were ablated. Mean AFCL was determined manually over 30 cycles from bipolar electrograms recorded at the left and right atrial appendages before and after each CFAE was targeted. Lesions were regarded as individual observations, and a resultant increase in mean AFCL $5 ms was regarded as signicant. The randomised strategy rst controlled for any cumulative effect of ablation on AFCL, and second allowed assessment of the order of ablation on the number of CFAE lesions required. Results 20 patients were randomised. The CFAE grade determined by rapid visual inspection for the 968 electrograms targeted agreed with that at off-line manual measurement in 92.7% (l0.91). AFCL increased after targeting 49.5% of grade 1 CFAE, 33.6% of grade 2, 12.8% of grade 3, 33.0% of grade 4, and 8.2% of grade 5 CFAE (p<0.0001 for grades 1, 2, and 4 vs 5, 3 vs 5 not signicant). Binary logistic regression conrmed the effect of CFAE grade, but showed no effect of electrogram amplitude, location in the left or right atrium, or the order in which CFAE were targeted. There was no difference between groups in the number of grade 1 or 2 CFAE encountered, but there were fewer grade 3 and 4 CFAE in group 2 than group 1 (both p<0.01), translating to fewer CFAE targeted per patient in group 1 compared to group 2 (37614 and 58618 respectively; p0.015). Conclusion Targeting CFAE is not simply atrial de-bulking. Ablating certain grades of CFAE caused AFCL prolongation, suggesting they are more important in maintaining AF. Targeting these CFAE may reduce unnecessary left atrial destruction. (ClinicalTrials.gov number, NCT00894400).
IS THERE AN ASSOCIATION BETWEEN THROMBOGENESIS MARKERS AND ATRIAL FIBRILLATION BURDEN IN PACEMAKER POPULATION?
doi:10.1136/heartjnl-2011-300198.146
C W Khoo, S Krishnamoorthy, G Dwivedi, B Balakrishnan, HS Lim, G Y H Lip. University Department of Medicine Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
Background and Objectives Contemporary pacemaker devices are able to quantify atrial high-rate episodes (AHREs) and atrial brillation burden (AFB) accurately. In this study, we aim to assess the relationship of thrombogenesis markers in association with AHREs and AFB. Methods We studied 87 patients with dual-chamber pacemaker. Patients on warfarin were excluded. AHREs were dened as atrialrate $220 beats/min and $5 minutes. AFB and percentage of cumulative pacing were derived from pacemaker diagnostics. Plasma levels of von Willebrand factor (vWf), tissue factor (TF), soluble P-selectin (P-sel) and D-dimer (DDM) were analysed using ELISA. Results Baseline characteristics and co-morbidities were comparable between groups (Abstract 146 table 1). Patients with AHREs had signicantly higher cumulative percentage ventricular pacing (p0.012). There were no signicant differences in levels of vWf, TF, P-sel and DDM between patients with and without AHREs. The AFB ranged from 0 to 99% in AHRE group. TF (r0.516, p0.086), P-sel (r0.795, p<0.001) and DDM (r0.643, p0.045) correlated with AFB. On linear regression analysis, both P-sel and DDM were independently associated with AFB (p<0.05).

No AHRE (n[70) Age, years Hypertension, (%) Antiplatelet, (%) Percentage atrial pacing Percentage ventricular pacing vWf, IU/dl TF, ng/ml P-sel, ng/ml DDM, ng/ml 71.0611.6 38, (54) 53, (76) 34.6 (6.8e81.5) 21.9 (1.8e99.0) 94.2616.2 0.2 (0.1e0.3) 47.6615.8 180.0 (82.0e390.0) AHRE (n[17) 75.468.8 12, (71) 14, (82) 22.1 (6.9e65.0) 98.6 (41.0e99.9) 93.9633.7 0.1 (0.0e0.2) 63.4629.7 152.5 (82.5e307.5) p value 0.096 0.116 0.739 0.414 0.012 0.977 0.105 0.055 0.553
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Conclusion AFB is independently associated with increased indices of P-sel and D-dimer which indicate platelet activation and thrombosis respectively.

CHADS2 Score Zero One Two Three Four Five Six None (%) 27.0 4.7 0.0 0.0 0.0 0.0 0.0 Aspirin (%) 70.3 45.1 7.8 0.8 0.0 0.0 0.0 Aspirin or Warfarin (%) 1.3 43.2 32.2 11.5 5.3 2.9 2.9 Warfarin (%) 1.3 7.0 60.0 87.7 94.7 97.1 97.1
147
THROMBOEMBOLIC RISK STRATIFICATION, ANTITHROMBOTIC AND ANTICOAGULATION USE FOR PATIENTS WITH ATRIAL FIBRILLATION, A CLINICAL AUDIT
doi:10.1136/heartjnl-2011-300198.147
R A Veasey, R Kulanthaivelu, P Patel, D W Harrington. Kent and Sussex Hospital, Tunbridge Wells, UK
Introduction Atrial brillation (AF) is the most prevalent arrhythmia in primary and secondary healthcare settings. Thromboembolic (TE) risk assessment and initiation of anti-thrombotic or anticoagulation (AT/AC) therapy, according to level of risk, is recommended in both national and international guidelines. NICE guidance straties patients with AF in to low, moderate or high risk categories and recommends aspirin, aspirin or warfarin or warfarin therapy respectively. ACC/ESC guidance endorses use of the CHADS2 scoring system and for scores of 0, 1, or $2 recommends aspirin, aspirin or warfarin or warfarin therapy respectively. In addition, it is recommended that AF episode frequency or subtype (paroxysmal (PAF), persistent (PersAF) or chronic (CAF)) does not inuence TE risk assessment. We audited UK cardiologists and general practitioners (GPs) to assess adherence to these guidelines. Methods We designed an audit questionnaire assessing: (1) use of risk stratication tools, (2) choice of AT/AC for increasing levels of risk, and (3) choice of therapy for a number of hypothetical patients with variable TE risk and variable AF subtype. The questionnaire was distributed by electronic or postal mail to 1176 cardiologists and 621 randomly selected GPs. Results In total, 421 responses were received (306 cardiologists, 115 GPs). Overall, 91.4% of responders reported use of TE risk stratication tools (97.1% cardiologists, 76.5% GPs, p<0.001). NICE risk assessment is used by 26.6% of responders (24.5% cardiologists, 32.2% GPs, p0.14), CHADS2 by 79.3% (90.2% cardiologists, 50.0% GPs, p<0.001). The frequency of reported use of AT/AC for each risk level of the NICE assessment and CHADS2 score are shown in Abstract 147 tables 1 and 2 respectively. Type of AF (PAF/PersAF/ CAF) reportedly inuences the use of AT/AC for 34.3% or responders (24.2% cardiologists, 46.3% GPs, p0.001). Abstract 147 gure 1 demonstrates AT/AC usage for each of the following hypothetical patients: 1. 61 year old, hypertension, PAF episodes twice a year lasting 1e2 h (NICE risk: mod, CHADS2 score 1/6). 2. 43 year old, diabetes, PAF episodes weekly lasting 10e12 h (NICE risk: mod, CHADS2 score 1/6). 3. 53 year old, hypertension, CAF (NICE risk: mod, CHADS2 score 1/6). 4. 78 year old, no other risk factors, CAF (NICE risk: mod, CHADS2 score 1/6). 5. 76 year old, hypertension, diabetes, PAF episodes 3e4 times per year lasting <1 hour (NICE risk: high, CHADS2 score 3/6). 6. 77 year old, hypertension, diabetes, PAF episodes occurring weekly and lasting several hours (NICE risk: high, CHADS2 score 3/6). 7. 80 year old, previous TIA, CAF (NICE risk: high, CHADS2 score 3/6).

Conclusions TE risk stratication tools are reportedly widely used in UK clinical practice. AT/AC use for NICE and CHADS2 risk levels are mostly appropriate, although warfarin is under recommended for patients with a CHADS2 score of 2/6. In addition, the use of AT/ AC is inuenced, inappropriately, by AF episode frequency and subtype.
148
THE ASSESSMENT OF TRANSIENT LOSS OF CONSCIOUSNESS: WERE STILL NOT ASKING THE RIGHT QUESTIONS
doi:10.1136/heartjnl-2011-300198.148
A E Bewick, A Gasson, L Ala, R A Bleasdale. Royal Glamorgan Hospital, Cardiff, UK

NICE Risk Low Moderate High None (%) 16.7 0.6 0.0 Aspirin (%) 78.3 3.5 0.0 Aspirin or Warfarin (%) 2.9 66.9 4.4 Warfarin (%) 2.1 28.7 95.6
Accurately diagnosing patients with TLOC can be achieved in most cases with a detailed clinical history. We set out to assess how patients were assessed in the setting of a district general hospital (DGH) with 570 beds, receiving an unselected intake via general practice and an A&E. Using the ESC guidelines of 2009 we generated a 22-question study proforma for a retrospective review of the medical records. We identied 322 cases for possible inclusion over a 4 month period. 26 of the case notes were not available to analyse, 8 had insufcient details to identify the relevant patient. Therefore in total 288 notes were reviewed. Inclusion required the TLOC to be complete, of rapid onset and short duration with spontaneous complete recovery. A further 123 patients were therefore excluded. This left 165 data sets (58% male). The age distribution was a typical bimodal distribution with 16% between 10 and 29 years of age and 48% over the age of 70 years. 73% were assessed in A&E, 18% were assessed in the Acute Medical Unit (AMU) and 7% were assessed in rapid access ambulatory clinics. Only 4% of the initial assessments were undertaken by consultants, 12% by a Specialist Registrar (SpR), 21% by a year 1 foundation program (FP1) doctor and the majority was assessed by FP 2 or core medical trainees (CMT). Key diagnostic elements of the history are still being neglected. For example, the symptoms at the onset of the TLOC were documented in only 58% of cases; the recovery symptom
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prole was reported in only 37%. Only 47% (n78) of records described a witness account. Within the witness accounts that were recorded, key elements remained un-reported for example skin complexion was only reported in 35% of the 78. The duration of the TLOC was recorded in only 44%, Tongue biting in 27% and the presence or absence of abnormal movements was recorded in only 12% of this 78 patients. The presence or absence of a family history of sudden cardiac death was only reported in 2% cases. The family history of a cardiomyopathy was only recorded in 1% and a family history of TLOC was recorded in 1%. A patient past history of cardiac disease was asked about in 40% of cases while a past history of TLOC was only asked about in 35%. In this majority elderly study population, a recent change in drug therapy was only asked about in 2% of cases. This study highlights that in a DGH environment, the initial assessment of patients with TLOC is undertaken by junior medical staff who often do not document key diagnostically differentiating elements of the history and examination indicating an ongoing lack of adequate training regarding the most appropriate and accurate techniques for differentiating the causes of TLOC.
Abstract 149 Figure 1 Comparison of pre-ablation and post-ablation % scar using xed threshold.
149
AUTOMATED ANALYSIS OF ATRIAL ABLATION-SCAR USING DELAYED-ENHANCED CARDIAC MRI

doi:10.1136/heartjnl-2011-300198.149
1 1
L Malcolme-Lawes, R Karim, C Juli, P B Lim, 2T V Salukhe, 2D W Davies, D Rueckert, 1N S Peters, 2P Kanagaratnam. 1Imperial College London, London, UK; 2 Imperial College Healthcare, London, UK
Introduction Visualisation of the ablation-related atrial scar using delayed-enhanced MRI (DE-MRI) may reveal important underlying causes for atrial brillation (AF) recurrence following ablation. In order to develop and objective method for delineating ablation-scar we compared pre and post DE-MRI after Cryo-balloon lesion on the basis that a more predictable lesion set would be created for validation. Methods and Results 12 patients undergoing cryoablation for PAF were enrolled in the study, and underwent pre-ablation DE-MRI scans. Pulmonary vein isolation (PVI) was conrmed in all patients at the end of the cryoablation procedure using a circular mapping catheter. Additional ablation by RF or Freezer Max was required to achieve PVI in 59%. No ablation was performed in any region other than the PV ostia. Post-ablation DE-MRI was performed at 3 months. An automatic segmentation of the LA was produced with custom software from the MRA sequence. The preablation and postablation free breathing late gadolinium enhanced sequence was registered to the MRA and the maximum intensity within the LA wall was projected onto the post ablation LA surface. The blood pool was identied automatically using custom software as the region 1 cm inside the wall of the LA, and its mean (BPM) and SD used as a baseline. To identify a universal threshold for scar, regions of brightest myocardium were initially selected in pre and post ablation MRIs. The brightest regions were 1.961.2 vs 8.763.1 SDs above the BPM in pre-and post-ablation MRIs respectively (p0.001). A threshold of 5 SDs above the BPM was therefore programmed into our custom software to identify regions of scar for all patients. The ostial regions were dened as extending 1 cm both proximal and distal to the PVeLA junction, and selected manually for left and right sided veins prior to scar projection. (See Abstract 149 gure 1). The scar proportion within these regions was calculated using commercially available software ITK-SNAP. Total LA scar proportion was 0.260.02% vs 6.360.75% in pre and post ablation scans respectively. The increase in scar seen in the PV ostia was 24.661.38% compared with 2.661.28% in the rest of the LA (p0.01) (See Abstract 149 gure 2).

Conclusion We have demonstrated the feasibility an objective, automated method of DE-MRI analysis of left atrial ablation-scar. This technique will now need to be validated against clinical outcomes.
150
IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR LEAD COMPLICATIONS AND CLINICAL EFFECTIVENESS IN PATIENTS WITH INHERITED CARDIAC CONDITIONS
doi:10.1136/heartjnl-2011-300198.150
R Bastiaenen, 1S Ben-Nathan, 2S Jones, 2D Ward, 2M Gallagher, 1,2S Sharma, E R Behr. 1St Georges University of London, London, UK; 2St Georges Hospital, London, UK
1,2
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Background Implantable cardioverter-debrillator (ICD) therapy can reduce sudden death due to ventricular arrhythmia (VT/VF) but is not without complication, particularly in young patients who live for many years with a device in situ. We aimed to determine the ICD complication rate in our inherited cardiac condition (ICC) population compared with international reports. Particular importance was given to inappropriate shock therapy due to lead failure as there are new ICD technologies available. Methods Patients with ICCs who had ICD implantation or box change between January 2006 and September 2009 were included. Data on clinical characteristics, complications and ICD therapies were obtained from pacing and hospital records. We compared our data with several ICD studies of patients with specic ICCs (Abstract 150 table 1).
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BCS Abstracts 2011

Long QT SGH ICC Syndrome HCM ARVC patients patients patients patients (n[101) (n[51) (n[506) (n[106) Follow-up (months; mean6SD) 74653 Appropriate therapy (%) 26 Inappropriate therapy (%) Lead failure (%) Complication rate excluding lead failure (%) 18 21 26 87 24 29 25 31 44633 20 27 7 n/a 58635 24 19 2 34 Brugada Syndrome patients (n[220) 38627 8 20 9 20
Results 101 patients (mean age 44.1614.8 years; 59 male) were included (idiopathic VF 15%; DCM 17%; ARVC 22%; HCM 21%; long QT syndrome 17%; Brugada syndrome 6%; others 2%). During a mean follow-up of 74.0653.2 months 2 patients died (1 inappropriate shocks; 1 stroke). Indications were secondary prevention in 71.3% of patients. ICD types were 56.4% single chamber; 39.6% dual chamber; 4.0% biventricular. Appropriate therapy successfully terminated VT/VF in 27 (26.7%) patients 34.7% of secondary and 6.9% of primary prevention patients received appropriate therapy. Inappropriate therapy occurred in 18 (17.8%) patients and lead failure (noise/wear/fracture) in 22 (20.8%) patients (Abstract 150 table 2). 12 out of 18 inappropriate shocks were due to lead failure, 5 sensing errors (1 T-wave oversensing; 4 AF), 1 generator fault. 10/22 leads that failed were Medtronic Sprint Fidelis and these were responsible for 8/12 patients receiving inappropriate shocks including one death due to lead fracture. Comparison with other studies indicates a high lead failure rate due to the long follow-up period, similar to the LQT Study which reports 25% lead failure over 87 months (Abstract 150 table 1). With lead failure excluded the complication rate is comparable to shorter follow-up studies. Inappropriate and appropriate therapy rates are similar among all studies.
extraction. There are limited clinical data on the optimal time for device re-implantation. A small series reported good results with simultaneous contralateral implantation. We evaluated this approach in our institution for patients without signs of systemic sepsis. We present clinical outcomes and completeness of extraction. Methods The clinical records of all patients undergoing lead extraction in our institution since January 2008 were reviewed. Results 68 patients underwent CIED extraction for infection during this time period (see Abstract 151 table 1). In 34 cases, the device was removed with simple traction, 9 with locking stylet, 22 with locking stylet and laser sheath, 1 with locking stylet and mechanical sheath and 2 with femoral snare. There was complete hardware removal in 64 cases (94%). One patient with lead related endocarditis required a subsequent surgical procedure to remove a lead fragment and in 4 other patients who had erosion, pocket infection or threatened erosion, a small fragment of lead remained. 18/68 patients were re-implanted with a new device on the contralateral side on the same day as the extraction. 28/68 patients received a new device between 1 and 227 days later and 22/68 have not undergone reimplantation. An active xation bipolar TPW (temporary pacing wire) was used in 6 patients for a mean 7.862.7 days. 3 patients had a further device related procedure during a mean follow-up of 4456304 days: 1 lead reposition, 1 pocket washout and 1 extraction. Of the 2 procedures carried out for recurrent infection, 1 was managed with a TPW for 7 days prior to reimplantation and 1 underwent reimplantation at 14 days without TPW. In addition, the patient requiring pocket washout had a fragment of lead remaining following their initial extraction.

Indication for device extraction Erosion Pocket infection Lead infection Threatened erosion Number of patients, n[80 (%) 31 (39) 25 (31) 7 (9) 4 (5) 1 (1)

Complication Lead failure Inappropriate shock Lead displacement Infection Pneumothorax/Haemothorax Box/Wound/Other revision procedure Thrombosis (venous/lead) Haematoma Chronic abdominal cavity postexplant Number of patients 21 18 5 5 5 7 2 5 1 % of patients 20.8 17.8 4.9 4.9 4.9 6.9 1.9 4.9 0.9
Pain
Conclusions There is a signicant rate of ICD lead failure in patients with ICCs, which may be expected given the high frequency of Sprint Fidelis leads implanted during this period and the long followup. Our results compare favourably to other similar studies. The high rate of appropriate therapy highlights the clinical effectiveness of ICD intervention in secondary prevention. Lead complications may be lower with the use of new ICD technology in selected patients.
Conclusion We report low rates of recurrent infections following CIED extraction. None of the 18 individuals simultaneously reimplanted with a new device on the contralateral side needed any further procedures during the follow-up period. This approach may be appropriate, particularly in pacing dependant patients who would otherwise require a TPW with its associated risks. In those individuals who required a TPW, the risk of recurrent infection in our series was 17% despite our use of an active xation pacing lead and externalised pulse generator which has a lower reported complication rate. Only one of the 4 patients with a residual lead fragment required reintervention for recurrent infection. This provides some supportive evidence that in patients with high surgical risk and pocket abnormalities, if fragments of lead may remain, the patient may be treated conservatively and monitored for signs of recurrent CIED infection.
152
REAL-TIME CARDIAC MR ANATOMY AND DYSSYNCHRONY OVERLAY TO GUIDE LEFT VENTRICULAR LEAD PLACEMENT IN CRT
doi:10.1136/heartjnl-2011-300198.152
151
RISK OF RECURRENCE FOLLOWING EXTRACTION OF CARDIAC IMPLANTABLE ELECTRONIC DEVICES FOR INFECTION: WHEN SHOULD A NEW DEVICE BE RE-IMPLANTED?
doi:10.1136/heartjnl-2011-300198.151
A Shetty, S Duckett, M Ginks, Y Ma, 1,2M Sohal, 1,2P Mehta, 1,2S Hamid, J Bostock, 1,2G Carr-White, 1,2K Rhode, 1,2R Razavi, 1,2C A Rinaldi. 1Guys and St Thomas Hospital NHS Foundation Trust, London, UK; 2Kings College London, London, UK
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1,2
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H E Thomas, M Das, D Twomey, C J Plummer, E J Shepherd. Freeman Hospital, Newcastle upon Tyne, UK
Background The recommended management of cardiac implantable electronic device (CIED) infection is complete system
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Introduction Optimal left ventricular (LV) lead placement via the coronary sinus (CS) is a critical factor in dening response to cardiac resynchronisation therapy (CRT). Using novel semi-automated image acquisition, segmentation, overlay and registration software
BCS Abstracts 2011

we set out to guide lead placement by avoiding scar and targeting the region of the LV with the latest mechanical activation. Methods 17 patients underwent cardiac magnetic resonance (CMR) scans. 3D whole heart images were segmented to produce high delity anatomical models of the cardiac chambers and coronary veins. 2, 3, 4 chamber and short axis cine images were processed using Tomtec software to give a 16 segment time volume-dyssynchrony map. In patients with myocardial scar the late gadolinium enhancement images were manually segmented and registered to the anatomical model along with the dyssynchrony map. The 3 latest mechanically activated segments with <50% scar were identied and this information was overlaid at CRT implant on to live uoroscopic images using a prototype version of the Philips EP Navigator software. Subsequently, the x-ray C-arm and table could be moved freely while automatically maintaining a registered roadmap. We used a high delity pressure wire to assess the acute haemodynamic response to pacing in different regions of the overlaid 16 segment model. All dP/dt measurements were compared to baseline AAI or VVI (for those patients in AF) pacing at 5e10 beats/min above intrinsic rate. Results 15 of the 17 patients underwent successful placement of a LV pacing lead via the CS with satisfactory pacing parameters and no phrenic nerve stimulation at implant. The mean time from insertion of the CS guide catheter into the venous sheath to successful cannulation of the CS was 1.361.0 min. In 2 patients we were unable to place a LV lead successfully in any branch of the CS. We paced in at least one of our 3 target segments in 11 patients. 67% of patients were responders as dened by a 10% increase in +dP/dt over baseline. The mean change in +dP/dt for the best lead position vs baseline+dP/dt was 15.9611.3% for DDDLV pacing. This compares to a mean change in+dP/dt of 14.9612.3% when the CMR dyssynchrony-map dened target region was paced DDDLV. The region of best+dP/dt response was postero-lateral, lateral or posterior in all cases. Conclusion We have shown it is feasible to acquire, overlay and accurately register cardiac MR data on to uoroscopic images at the time of CRT implant. Our data suggest that it is also possible to identify and place the LV lead in at least one target region in most patients. This appears to give close to the best acute haemodynamic response that can be achieved in any branch of the CS. The initial results of this pilot study suggest that a MR dyssynchrony guided approach to LV lead placement may allow ideal LV lead positioning (Abstract 152 gures 1 and 2).
153
VENTRICULAR PACING ALONG INDIVIDUAL BRANCHES OF THE CORONARY SINUS USING A QUADRIPOLAR LV PACING LEAD
doi:10.1136/heartjnl-2011-300198.153
A K Shetty, 1,2P Mehta, 1,2S Duckett, 1,2J Bostock, 1,2M Ginks, 1,2S Hamid, M Sohal, 1,2R Razavi, 1,2Y Ma, 1,2K Rhode, 1,2A Arujuna, 1,2C A Rinaldi. 1Guys and St Thomas Hospital NHS Foundation Trust; 2Kings College London, London, UK
1,2
1,2

Introduction Cardiac resynchronisation therapy (CRT) usually involves placing the left ventricular (LV) pacing lead in the posterolateral or lateral region of the LV epicardial surface as this is thought likely to re-coordinate myocardial contraction most effectively. The LV lead is standardly placed in a position with the best pacing parameters and satisfactory stability. It is not known, however, whether there is a signicant difference in haemodynamic response to LV pacing in different regions of the same coronary sinus (CS) vein. In this study we aimed to evaluate the difference in acute haemodynamic response to pacing along individual branches of the CS. Methods 16 patients underwent an acute haemodynamic study during their CRT-debrillator implant. We used a high delity pressure wire to assess the acute haemodynamic response (AHR) to pacing in different branches of the coronary sinus. We used a novel quadripolar lead (Quartet, St Jude Medical, Sylmar, California, USA) that has four poles on the LV leaddistal tip and 3 ring electrodes. The 3 ring electrodes are spaced 20 mm, 30 mm and 47 mm from the distal tip electrode and the four poles allow bipolar pacing between them. It was thus possible for us to test pacing parameters and AHR along a signicant proportion of a CS branch without having to reposition the LV lead. Results DDDLV pacing was attempted in as many different CS branches as possible in each patient (total 56 different positions used). The mean overall percentage difference in AHR (measured by change in +dP/dt compared to baseline AAI pacing or VVI pacing in AF patients) between an individual CS branch bipole with the lowest +dP/dt and that with the highest was 6.665.6%. Much larger differences in change in +dP/dt were seen, however, between different branches of the CS in the same patient with a mean difference in change in +dP/dt in the best CS vein compared to the worst CS vein of 16.766.3%. Although the difference in AHR seen between different bipoles within the same vein were not large, we did nd that in some cases no pacing capture was found with one
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BCS Abstracts 2011

bipole but was found with another. Furthermore, differences in whether phrenic nerve stimulation (PNS) occurred were seen when using different LV lead bipoles within the same branch of the CS. Conclusion Our data suggest that only a small difference in AHR is seen when pacing along the same branch of the CS compared to pacing within different branches of the CS within the same patient. This means that although the site of LV lead placement is important, a proximal or distal position within a CS branch is much less important than choosing the right branch in terms of acute haemodynamic response. A choice of bipoles on the LV lead may mean, however, that problems with capture thresholds or PNS can be overcome without the need to reposition the LV lead. mortality rate. In an unselected population of patients with pacemakers, we have established that the amount of RV pacing is related not only to important surrogate measures of outcome such as exercise tolerance and LVEF but also mortality. Whether an aggressive policy of limiting RV pacing in patients at risk reduces mortality is unknown.
155
INCIDENCE SCREENING OF PATIENTS FOLLOWING ST ELEVATION MYOCARDIAL INFARCTION FOR PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER DEFIBRILLATOR (ICD) IMPLANTATION HAS A LOW THERAPEUTIC YIELD
doi:10.1136/heartjnl-2011-300198.155
154
PATIENTS RECEIVING STANDARD PACEMAKER GENERATOR REPLACEMENTS FREQUENTLY HAVE IMPAIRED LEFT VENTRICULAR FUNCTION AND EXERCISE INTOLERANCE, RELATED TO THE PERCENTAGE OF RIGHT VENTRICULAR PACING
doi:10.1136/heartjnl-2011-300198.154
E L Berry, H C Padgett, A J Ahsan, A D Staniforth. Nottingham University Hospitals NHS Trust, Nottingham, UK
1 2
G A Begg, 1J Gierula, 1Z L Waldron, 2K K Witte. 1Leeds General Inrmary, Leeds, UK; University of Leeds, Leeds, UK
Background Right ventricular (RV) pacing is an accepted treatment for symptomatic bradycardia. However, long-term RV pacing is increasingly recognised to be detrimental to left ventricular (LV) systolic function. We wanted to establish the prevalence, associated features and predictors of LV systolic dysfunction (LVSD) and outcome in a contemporary group of patients with longeterm RV pacemakers. Methods We prospectively recruited consecutive patients listed for PGR between 2008 and 2010 at Leeds General Inrmary. We performed echocardiography, exercise testing and recorded indications for pacing, pacing variables and duration of pacing, comorbidities, current medication and renal function. Results Of 399 PGR procedures 342 subjects (86%), 184 men, attended. Non-attendees had similar pacing variables and were of similar age as attendees. Mean age (SE) was 76 (1), and mean duration of pacing was 10 (0.3) years. Comorbidites were common: diabetes mellitus in 11%, previous myocardial infarction in 15%, previous cardiac surgery in 26% and atrial brillation (AF) in 26%. Medical therapy included b-blockers in 60% and ACE inhibitors in 70%. Dual chamber devices were implanted in 77% (45% of all patients had rate responsive (RR) pacing programmed). Mean percentage of ventricular pacing (%VP) was 61 (2)%. Mean left ventricular ejection fraction (LVEF) was 49 (1)%, (44% had an LVEF <50%). Mean peak oxygen uptake (pVo2) (in 107 subjects) was 17 (1) ml/kg/min and mean creatinine was 108 (3) mmol/l. There was an inverse relationship between LVEF and %VP (0.42; p<0.0001), and years since rst implanted (p0.09) but there was no effect on LVEF of age, the presence of AF and the pacing mode. In single chamber devices, RR pacing was associated with higher %VP (p0.01), and a trend to worse LVEF (p0.09). These differences were not seen in RR programmed dual chamber devices. There was a negative relationship between pVo2 and %VP (r0.21; p<0.03). Even with a short follow-up period of 16 (0.5) months, 23 (7%) patients are dead. Patients dead at the censor date were older at the time of the assessment (p<0.005), had a higher %VP (p<0.03) and worse renal function (p<0.001), but did not have signicantly worse LVEF or pVo2. The presence of a single chamber device was associated with a poorer outcome (p<0.002) despite patients with a single chamber device being of similar age as those with a dual chamber device. Conclusions Patients receiving standard pacemaker generator replacements frequently have cardiovascular comorbidities, left ventricular dysfunction and impaired pVo2 and suffer a high
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Introduction The ICD implant rate for the United Kingdom is low compared with the European Union and United States of America. National Institute of Clinical Excellence guidance TAO95 (NICE 2006) makes recommendations for primary prevention ICD implantation. Our study investigated the feasibility of systematically screening patients following an acute ST elevation myocardial infarction (STEMI) to improve local ICD implant rates. Method A prospective single centre study was performed over 14months, in tertiary centre setting. All patients with a diagnosis of an acute STEMI had an echocardiogram at 6 weeks to assess left ventricular ejection fraction (LVEF). Patients with impaired LVEF then underwent screening for primary prevention ICD as per TA095 recommendations (Abstract 155 gure 1).

BCS Abstracts 2011

Results 326 STEMI patients were identied. Of these 12(3.7%) declined investigation. 25(7.8%) died during the investigation period (22 died during their initial acute event, 3 died of non cardiac causes following discharge). 10(3.1%) requested follow-up in another geographical area. 26(8%) patients were identied as LVEF<35%; 2(0.6%) patients were assessed as not clinically suitable for further investigation. 2(0.6%) had LVEF<30% and QRS>120 ms, both proceeded to have a primary prevention ICD implanted. 24(7.4%) patients had Holter monitors; 2(0.6%) were identied as having episodes of NSVT. Both patients had EPS; 1(0.3%) had inducible VT and proceeded to have a primary prevention ICD implanted. 1 patient (0.3%) self presented with a cardiac arrest before completion of their screening tests and received a secondary prevention ICD. In total, 3(0.9%) primary prevention ICDs were implanted (Abstract 155 gure 2). patients had associated symptoms of hyperadrenergic surges. Holter monitoring prior to treatment demonstrated sinus tachycardia. Resting pre-treatment mean 24 h HR was 94610 (range 75e100) and mean HR on minimal exertion was 157620 (range 130e176). All patients had a structurally normal heart on echocardiogram. Tilt table testing was considered in 3 patients due to their symptoms and it excluded postural orthostatic tachycardia syndrome. Pretreatment with b-blockers had been unsuccessful in 5/6 patients. The remaining patient had symptomatic asthma and was therefore unable to tolerate b-blockers. Ivabradine was exclusively used in 3 patients and clonidine in 2. 1 patient was started with Ivabradine but later switched over to clonidine as it was ineffective. All 4 patients taking Ivabradine failed to gain symptom relief with no signicant reduction in mean 24-h HR parameters. Mean resting HR after 3 months of Ivabradine therapy was 9569 (range 88e105) and mean HR on exertion was 159623 (range 128e180). 2/4 patients subsequently had complete sinus node ablation and AAIR pacemaker. In contrast, the 3 patients on clonidine had greater symptom resolution and fall in resting and exercise heart rates at 3 months follow-up. Resting mean HR was 8163 (range 78e83) and mean HR with exertion was 144618 (range 132e164). The HR variability pre and post treatment is shown in Abstract 156 gure 1.

Conclusion The yield from this study was low; 3 patients (0.9%) proceeded to primary prevention ICD. It should also be noted that the methodology resultant from TA095 guidelines was labour and resource intensive. An alternative approach of opportunistic screening in patient groups with a high prevalence of impaired LV function might give a higher yield than our approach looking at disease incidence.
156
A SINGLE CENTRE EXPERIENCE OF IVABRADINE AND CLONIDINE FOR INAPPROPRIATE SINUS TACHYCARDIA
doi:10.1136/heartjnl-2011-300198.156
P P Sadarmin, T R Betts. John Radcliffe Hospital, Oxford, UK

Discussion In our case series of 6 patients, Clonidine was more effective than Ivabradine both in terms of reducing heart rate and treating symptoms for patients with inappropriate sinus tachycardia. Patients with coexisting hyperadrenergic symptoms may benet the most. A trial of Clonidine can be recommended before considering sinus node ablation. Formal randomised controlled trials are needed to conrm our ndings.
Introduction Inappropriate sinus tachycardia (IST) is a relatively rare disease that manifests with resting tachycardia, a rapid increase in heart rate (HR) with minimal exertion, a normal ECG and absence of structural heart disease. Treatment options include b-blockade or sinus node modication which are not 100% successful. Newer agents like sinus node inhibitor (Ivabradine) or a centrally acting a-2 sympathomimetic (Clonidine) can be used but there is no success outcome data for either and there is also no evidence that one is better than the other. We present our experience of managing 6 patients with a diagnosis of IST with either Ivabradine or Clonidine or both. Methods We identied 6 patients from 2005 to 2009 with a diagnosis of IST (according to accepted international guidelines) who had been treated with either Ivabradine or Clonidine or both. Medical case records were reviewed for each patient. Results 5 out of 6 patients were women with a mean age of 27.5 years (range 16e40 years). All patients had been symptomatic for alteast 6 months before presentation to our tertiary centre. 2
157
AN INSIGHT INTO IMPLANTERS PRACTICES OF ICD IMPLANTATION: A PHYSICIAN SURVEY

doi:10.1136/heartjnl-2011-300198.157
P P Sadarmin, K C K Wong, K Rajappan, Y Bashir, T R Betts. John Radcliffe Hospital, Oxford, UK
Introduction The Implantable cardioverter debrillator (ICD) is the mainstay of treatment for the prevention of sudden cardiac death (SCD) and the management of tachyarrhythmias. Informed patient
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BCS Abstracts 2011

consent is an essential part of the implant process. Our aim was to get an insight into implanters (Imp) practices prior to an ICD implantation. Methods A questionnaire survey was sent to UK ICD Imp to test their knowledge of the risk and benets of an ICD in patients who satisfy trial and national guideline criteria and the incidence of implant complications. Information of the style and language of consent was requested. This questionnaire was specically aimed at Imp and was part of the larger questionnaire looking at knowledge, attitudes and factors inuencing ICD prescription in the UK. Results Replies were received from 23 implanters. 35% of the responders were between the age of 30e39 years and 39% were between 40 and 49 years. 83% of the responders were Consultants and 96% were working in an implantating centre. 83% of Imp were fully aware of Primary Prevention (PP) NICE guidelines while 78% were fully aware of Secondary Prevention (SP) NICE guidelines. There was widespread use of information leaets (87%) and specialist ICD nurses (83%) to disseminate information to patients. All responders said they would personally discuss the therapy with the patient prior to the implantation regardless of the referral source. A discussion regarding the prevention of SCD, inappropriate shocks and driving restrictions were performed by 96% of responders and device infections and lead failures discussed by 91%. Use of absolute risk reduction in percentages and number needed to treat while explaining the risks and benets gained from ICDs were used by 22% and 26% respectively. There was widespread use of phrases like small risk or moderate risk (61%) and life prolongation (eg, lets you live longer by an average of 3 months) (30%). Replies also indicated that Imp under-estimate overall mortality in medicallytreated and ICD-treated patients, lead dislodgement requiring re-positioning and major haematoma requiring reoperation. Imp overestimate infections leading to device removal and the incidence of pneumothorax when compared to published trial or study data. Conclusion The majority of implanters are aware of UK ICD guidelines. The patient consent process is not universal. Guidelines and awareness about end-of-life care in ICD patients is needed and should be part of the initial consent process. Evidence based use of risk and benet terminologies like ARR and NNT are needed to better inform the patient rather than abstract phrases. Increasing awareness of ICD complication rates can help patients and physicians balance risk against benet which could lead to improved patient satisfaction with their therapy.
158
IS IT COST EFFECTIVE TO USE A PLUGGED LV PORT?

doi:10.1136/heartjnl-2011-300198.158
M A Jones, T R Betts, K Rajappan, Y Bashir, K C K Wong, N Qureshi. John Radcliffe Hospital, Oxford, UK

Estimate of ICD complications Death as a complication of device implant Lead dislodgement requiring lead repositioning Lead failure requiring extraction or additional lead insertion Major haematoma requiring reoperation Device infection requiring removal/extraction Cardiac tamponade Pneumothorax Inappropriate shocks Mean % 0.3760.48 3.562.08 5.467.28 2.7263.07 2.2762.4 Published/Trial data % 0.77% (Circulation.1998;98:663e670); 2.08% (Br Heart J.1995:73:20e24) 5% (PACE.2005; 28:926e932); 10% (Circulation.1998;98:663e670) 4.3% (PACE.2005;28:926e932) 5.8% (JAMA.2006:295:1901e1911) 0.5% (PACE.2005:28:926e932); 0.77% (Circulation.1998;98:663e670);0.7% (MADIT2 trial) 0.2% (PACE.2005;28:926e932); 0.64% (Circulation.1998;98:663e670) 1.1% (PACE.2005; 28:926e932); 0.89% (Circulation.1998;98:663e670) 12% (PACE.2005; 28:926e932); 14.91% (Circulation.1998;98:663e670); 18% (Z Kardiol.1996;85:809e819) 13e38% (Clin Cardiol 1999;22:481e9)
Background Many patients receiving ICD implants do not meet criteria for CRT therapy, yet are often felt likely to benet from CRT in the future. The reasons for this include less severe NYHA class of HF symptoms at the time of implant, narrow QRS, and (progressive) atrio-ventricular conduction delay. Management options include only implanting DDD / VVI devices, and then upgrading to CRT if required; implanting CRT-D devices but without an LV lead, with the LV port plugged, such that if an upgrade were to become necessary, only a new LV lead (and implant kit) would be required; and nally, implanting CRT-D devices with LV leads in all patients in the rst instance, as has been suggested by the recent Madit-CRT and RAFT studies. It is not clear which of these strategies is superior in terms of the cost-benet ratio. Purpose This study analyses a retrospective cohort of patients who received CRT-D devices but without LV leads, to examine the cost implications of this approach, and to compare this cost to that of merely implanting a DDD device, or implanting a full CRT-D system initially. Method A retrospective analysis of all patients receiving CRT-ICDs with plugged LV ports between September 2004 and June 2009 at our institution. Patient characteristics, indication for a plugged LV port, subsequent addition of a LV lead and reasons for doing so were taken from patient records. The total cost (surgery and hardware) was compared with the estimated cost of initially implanting single or dual chamber ICDs and upgrading the entire system, and to the cost of implanting full CRT-D systems up front. Results 35 patients (27 male) were identied. Mean (SD) age was 6768 years. 26 had ischaemic heart disease and 9 non-ischaemic dilated cardiomyopathy. All had LV EF<30%. Indications for a plugged LV port were LBBB and NYHA class I or II symptoms in 29 and NYHA class I or II with a narrow QRS but a high chance of becoming pacemaker dependent in 6. During a mean (SD) FU of 40 616 months, 6 (17%) patients had an LV lead added, all for the development of NYHA III symptoms, at 10, 11, 15, 17, 17 and 21 months respectively. Total cost at end of FU period was 654 000. If all patients had initially been implanted with VVI or DDD ICDs and 6 new CRT systems implanted, the estimated cost would have been 598 000. If all patients had received full CRT-D the cost would have been 665 000. Taking into account the time to develop symptoms, it is predicted that an upgrade rate of 26%e31% would be required before using a plugged LV port becomes cost-effective. Furthermore, full CRT-D system implantation is even less cost effective. Conclusion In this series of ICD patients with potential CRT indications but minimal heart failure symptoms, only a small proportion subsequently required biventricular pacing. Using a CRT-ICD with a plugged LV port is not a cost effective strategy (Abstract 158 gure 1).
0.761.07 1.6861.17 14.8610.92
Psychological problems associated with the device
22.6626.68

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Per cent freedom from upgrade to LV lead.

BCS Abstracts 2011

159
PILOT STUDY EXPLORING THE REGIONAL REPOLARISATION INSTABILITY INDEX IN RELATION TO MYOCARDIAL HETEROGENEITY AND PREDICTION OF VENTRICULAR ARRHYTHMIA AND DEATH
doi:10.1136/heartjnl-2011-300198.159 W B Nicolson, 1C D Steadman, 1P Brown, 2M Jeilan, 2S Yusuf, 2S Kundu, A J Sandilands, 2P J Stafford, 1F S Schlindwein, 2G P McCann, 1G A Ng. 1University of Leicester, Leicester, UK; 2University Hospitals of Leicester NHS Trust, Leicester, UK
2 1

Variable Age (years) Sex (% male) QRSD(ms) EF(%) PES result (positive/total) R2I2>median EDV index (ml/cm) SV index (ml/cm) Follow-up (months) PIZ % Scar % Whole Group (n[30) 6769 97 107620 31614 12/30 14/29 1.4860.41 0.4260.14 24 (18) 7.8 (10.7) 10.9 (16.5) No VA/death (n[23) 6569 96 107621 32.4615 7/23 8/22 1.4960.41 0.4360.14 24 (16) 7.5 (8.4) 9.67 (13.5) VA/death (n[7) 7268 100 106615 2767.5 5/7 6/7 1.4560.45 0.3960.15 16 (16) 13.6 (8.5) 21.9 (17.8) p 0.055 0.95 0.34 0.068 0.031 0.84 0.47 0.088 0.093 0.16
Introduction There is a need for better sudden cardiac death (SCD) risk markers. Mounting evidence suggests that the mechanism underlying risk of ventricular arrhythmia (VA) is increased heterogeneity of electrical restitution. We investigated a novel measure of action potential duration (APD) restitution heterogeneity: the Regional Repolarisation Instability Index (R2I2) and correlated it with peri-infarct zone (PIZ) a cardiac magnetic resonance (CMR) anatomic marker of VA risk. Methods Blinded retrospective study of 30 patients with ischaemic cardiomyopathy assessed for an implantable cardioverter debrillator. The R2I2 was derived from high resolution 12 lead ECG recorded during programmed electrical stimulation (PES). ECG surrogates were used to plot APD as a function of diastolic interval; the R2I2 was the maximal value of the mean squared residuals of the mean points for anterior, inferior and lateral leads normalised to the mean value for the total population. PIZ was measured from late gadolinium enhanced CMR images using the full width half maximum technique. Results Seven patients reached the endpoint of VA/death (median follow-up 24 months). R2I2 > median was found to be predictive of VA/death independent of PES result, left ventricular ejection fraction and QRS duration (6/14 vs 1/15 p0.031). Modest correlation was seen between the R2I2 and PIZ (r0.41 p0.057) (Abstract 159 gure 1).
160
HIGH DOSE OCTREOTIDE; A NOVEL THERAPY FOR THE TREATMENT OF DRUG REFRACTORY POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME IN PATIENTS WITH JOINT HYPERMOBILITY SYNDROME
doi:10.1136/heartjnl-2011-300198.160
A E French, C Shepherd, A Horne, C Parker, J Tagney, J Pitts-Crick, T Johnson, G Thomas. Bristol Heart Institute, Bristol, UK
Conclusions In this pilot study of ischaemic cardiomyopathy patients, the R2I2 was shown to be an electrical measure of VA/ death risk with a moderately strong correlation with an anatomic measure of arrhythmic substrate, the extent of PIZ. The R2I2 may add value to existing markers of VA/death and merits further investigation.
Introduction Postural orthostatic tachycardia syndrome (POTS) is dened as symptomatic orthostatic intolerance with an increase in heart rate of 30 beats per minute within 10 min of head up tilt (HUT). This dysautonomia causes wide-ranging symptoms including palpitations, presyncope, chronic fatigue, headache and cognitive difculties. When POTS occurs in patients with preexisting Joint Hypermobility Syndrome (JHS), symptoms begin approximately a decade earlier than non-JHS patients with a preponderance of neurological features, secondary to cerebral hypoperfusion. Vascular laxity with splanchnic venous pooling has been implicated as a causative factor thus measures to expand plasma volume (thereby increasing mean arterial pressure and restoring cerebral perfusion) form the mainstay of therapy. Symptomatic improvements have been previously reported in POTS patients with the somatostatin analogue Octreotide, a powerful splanchnic vasoconstrictor. We report the rst UK series of JHS patients with drug refractory POTS treated with high-dose octreotide. Methods Six patients (female, aged 21e52) were referred to our institution. All had known JHS (4 requiring a wheelchair), neurological symptoms (headache and cognitive impairment) and diagnostic tilt-table testing with a mean increase in heart rate of 64 beats/min (range 47e73) with head-up tilt (HUT). All patients had remained symptomatic despite pre-treatment with a mean of 5 POTS medications (range 5e7) including udrocortisone, midodrine, propranolol, ivabradine, selective serotonin reuptake inhibitors, gabapentin and erythropoietin. Octreotide was commenced using a short-acting preparation given 3 times daily (dosage 50e250 mg according to body mass) in conjunction with a longacting (monthly), intramuscular injection (dosage 10e30 mg). The short-acting preparation was weaned following the second monthly injection. Results During follow-up of 3 months (range 1e8), 3 (50%) patients reported a complete resolution of all postural and neurological symptoms which corresponded with a normalised response to HUT. The remaining patients reported a dramatic improvement but ongoing postural symptoms. No patients developed supine hypertension. Side effects including mild abdominal discomfort and transient diarrhoea were reported in 3 (50%) patients. Conclusion Octreotide is increasingly recognised as an effective therapy in POTS patients. Both short-acting, subcutaneous (0.9 mg/ Kg) and long-acting, intramuscular (10e20 mg) preparations have
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previously been reported. We conclude that higher dosages of both preparations when administered together are effective and well tolerated in JHS patients with drug refractory POTS.
162
THE CLINICAL MANAGEMENT OF RELATIVES OF YOUNG SUDDEN ARRHYTHMIC DEATH VICTIMS; ICDS ARE RARELY INDICATED
doi:10.1136/heartjnl-2011-300198.162
J C Caldwell, Z Borbas, N Moreton, N Khan, 2L Kerzin-Storrar, 2K Metcalfe, W Newman, 1C J Garratt. 1Manchester Heart Centre, Central Manchester University NHS Foundation Trust, Manchester, UK; 2Department of Clinical Genetics, St Mary9 s Hospital, Central Manchester University NHS Foundation Trust, Manchester, UK
2
161
CATHETER ABLATION OF ATRIAL FIBRILLATION ON UNINTERRUPTED WARFARIN USING STANDARD AND DUTY CYCLED RADIOFREQUENCY ENERGY: SAFE AND EFFECTIVE
doi:10.1136/heartjnl-2011-300198.161
J R J Foley, N C Davidson, B D Brown, D J Fox. University Hospital of South Manchester, Manchester, UK
Introduction Catheter ablation (CA) for atrial brillation (AF) is growing exponentially. Although ablation for paroxysmal AF (PAF) is associated with shorter procedure times and less extensive left atrial ablation vs persistent AF thromboembolic complications can occur in both sub-groups. Inadequate anticoagulation leads to thrombotic complications and excessive anticoagulation can lead to bleeding risks. Many centres adopt a policy of discontinuing warfarin in the immediate run-up to the procedure, covering the procedure with unfractionated heparin and bridging postoperative patients with low molecular weight heparins (LMWH) back onto warfarin. We wished to determine the safety of CA for AF with a therapeutic INR using both the single transseptal approach and duty cycled radiofrequency energy (RF) with non irrigated PVAC catheters and the double transseptal puncture technique using irrigated RF catheters and either CARTO or NAVX electroanatomical mapping. Methods A retrospective analysis of 173 patients who underwent CA for AF while taking uninterrupted warfarin. Procedural target International Normalised Ratio (INR) was 2e3 with a peri-procedural target ACT of 300e350 s. In sub therapeutic INR patients weight adjusted LMWH was used post procedure with warfarin until INR was >2. Standard technique employed was large area circumferential ablation using conventional RF energy or pulmonary vein isolation using duty cycled RF energy. Data was gathered for demographics, procedural INR, total dose of unfractionated heparin, uoroscopy time, and type of radiofrequency energy used. Endpoints were minor bleeding, major bleeding (requiring transfusion), vascular complications, pericardial tamponade and stroke/ TIA within 28 days of the procedure. Results There were 128/173 male patients, age range between 21 and 73 years (mean 57 years). 122 underwent ablation for PAF and 51 for persistent AF. Mean procedural INR was 2.4 (range 1.7e3.9). Mean unfractionated heparin dose was 6000 units (range 1000e14 500). Mean uoroscopy time for the PVAC group was 23.4 mins (range 8.3e50.1 mins). Mean uoroscopy time for CARTO/NAVX group was 31mins (range 14.10e58.44 mins). There were no major bleeding complications. There was 1 minor bleeding complication with a groin pseudoaneurysm. There were 2 cases of pericardial tamponade (2/173%e1.2%) both managed with percutaneous pericardial drainage. There were no stroke/TIAs. Conclusion These data demonstrate that CA for AF by both single and double transseptal technique using both standard RF and duty cycled RF while maintaining a therapeutic INR is a safe procedure. Maintaining a therapeutic INR reduces the risk of embolic events associated with bridging heparin without an increase in bleeding complications. This technique is convenient for patients and avoids switching between LMWH and warfarin and ensures patient safety by maintaining therapeutic anticoagulation before, during and after the procedure.
Introduction Following National Service Framework guidance on the management of sudden cardiac death (SCD), regional inherited cardiac conditions clinics were established to identify and treat those at increased risk of dying from an arrhythmic condition. Studies have examined the yield of different diagnostic strategies but the outcome of management in these patients has not been reported. Methods We present data on 193 consecutive patients (108 families) referred to a regional inherited cardiac conditions clinic because of SCD/aborted cardiac arrest of a relative. The mean age on referral was 38617 yrs and mean duration of follow-up was 15 months (range 1 day to 56 months). All individuals underwent clinical assessment by history, examination, ECG and echo. If treadmill exercise test had not previously been performed this was undertaken. Further imaging by CMR or contrast echo was performed in those with structurally abnormal hearts or with T wave inversion in V2/V3. Ajmaline provocative testing was performed in those with a history and/or ECG suggestive of Brugada syndrome. Results Of the 193 patients, 43 individuals (22%) from 36 families (33%) were diagnosed with an inheritable cause of SCD and 145 patients were clinically normal (see Abstract 162 table 1). Five patients were found to have other conditions (LV non-compaction, AVNRT, skeletal myopathy, mild AS and congenital sub-aortic membrane). Of the 43 patients diagnosed with an inheritable condition, 21 had medication commenced by the clinic (b-blockers (21), ACEi/ARB(2), Spironolactone[1]). ICDs were implanted as per HRUK guidelines, resulting in 4 patients having an ICD inserted on clinic recommendation (2 HCM, 1 DCM, 1 ARVC). To date no appropriate therapies have been administered (follow-up 8e29 months) but there was 1 inappropriate shock from a fractured lead. Three individuals had b-blockade withdrawn after negative genetic testing for an established familial mutations (2 CPVT, 1 LQT), one ICD was removed and one deactivated (both negative for CPVT). Of the 145 patients thought to be clinically normal, 85 were reassured and discharged, 13 failed to return to clinic and 47 are regular reviewed as the risk of developing an inheritable condition cannot be excluded; this includes those with family histories of HCM (7), ARVC (12), DCM (9), CPVT (5), Brugada (4) and LQT(1). To date no deaths have occurred in those diagnosed with inherited causes of SCD (follow-up mean 20, 1e52 range) or those clinically normal with ongoing review (follow-up mean 22 months, 1e56 range).

Diagnosis of patient Clinically normal LQTS Brugada CPVT ARVC DCM HCM Numbers 145 12 2 5 7 7 10
Conclusion A diagnosis of an inheritable cause of SCD was obtained in 22% of individuals and 33% families with a history of SCD/ aborted cardiac arrest in a relative. The number of ICDs inserted was very small (2%) and there have been no appropriate therapies in this
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group. Two ICDs have been removed/deactivated after exclusion of a known familial mutation. Conclusions The UK TAVI Registry has successfully captured the entire TAVI activity of England and Wales incorporating the learning curves of every centre. Outcomes following TAVI are excellent in a high risk patient population. Outcomes are better in the population who are suitable for a transfemoral approach (with less comorbidity) than those treated with the transapical approach. These data suggest that careful proctoring allows the introduction of a new treatment method without an adverse effect on patient outcome, and we have demonstrated no systematic difference in outcome between the two commercially available technologies.
163
THE UNITED KINGDOM TRANSCATHETER AORTIC VALVE REGISTRY - OUTCOMES TO DECEMBER 2009 AND UPDATE
doi:10.1136/heartjnl-2011-300198.163
P F Ludman. On Behalf of the UK TAVI Steering Group, Birmingham, UK
Introduction The United Kingdom Transcatheter Aortic Valve (TAVI) Registry was established to dene the clinical and procedural details of all patients being treated by TAVI, regardless of access route or technology used, and to assess their outcomes. The registry has captured all cases in England and Wales. Methods For every TAVI performed, all centres complete an agreed dataset. The data are encrypted and sent electronically to servers at the Central Cardiac Audit Database (CCAD) for analysis. A unique patient identier (the NHS number) is used to link with the NHS Central Register to track mortality. This analysis is based on all procedures performed up to 31st December 2009. Results 25 centres in England and Wales performed a total of 877 procedures in 870 patients; 66 in 2007, 273 in 2008 and 538 in 2009. Median number of cases per centre was 24. Median (IQR) age was 82 (78e87) yrs. 52% were male, and mean logistic Euroscore (LES) was 22.2%. 68% were transfemoral, the remainder being mainly transapical. 90% of CoreValve implants and 46% of Edwards used a transfemoral approach. Patients needing a transapical route had more comorbid conditions than those treated by a transfemoral route (LES 25.2% vs 20.9%). Mortality tracking was successful in 100% of patients. Survival at 30 days was 93.1%, 78.9% at 1 year (443 at risk) and 72.3% at 2 years (114 at risk). Survival was signicantly poorer in those needing non-transfemoral approaches (1 year survival 73.5% vs 81.4%). Survival was also poorer in those with poorer LV ejection fraction, with moderate or severe post procedural aortic regurgitation and with a LES>40. Survival was not associated with age, NYHA class, or the presence of concomitant coronary artery disease, and not different between those with a LES<21 compared with LES 21e40. There was also no difference in survival between patients treated with CoreValve or Edwards technologies, or between proctored and non proctored cases. There was a signicant improvement in survival over the 3 years of the registry, and a change in demographics with the proportion of patients with prior CABG rising from 16.4% in 2007 to 29.9% in 2009. The total number of cases in the UK TAVI registry has risen to 1490 as of 29 Nov 2010. More details of the 2010 cohort will be available at the time of presentation (Abstract 163 gure 1).
164
EARLY HAEMODYNAMIC CHANGES AND MYOCARDIAL INJURY AFTER TRANSFEMORAL TRANSCATHETER AORTIC VALVE IMPLANTATION (TAVI)
doi:10.1136/heartjnl-2011-300198.164
R Dworakowski, A Bhan, B Brickham, O Wendler, M Monaghan, A M Shah, P MacCarthy. Kings College Hospital, Kings Health Partners, London, UK
Purpose Transfemoral (TF) TAVI is a novel procedure for the treatment of severe aortic stenosis, without the need for thoracotomy or cardiopulmonary bypass. The procedure results in almost instantaneous normalisation of transvalvular gradients, but little is yet known about the periprocedural haemodynamic effects. We aimed to describe these effects using 3D and tissue Doppler (tD) transthoracic echocardiography (TTE) and Cardiac Output monitoring. Methods In 16 patients undergoing TF TAVI haemodynamics were characterised with a number of tD and 3D TTE measurements.


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These were taken at multiple time points (baseline, 6 and 24 hours post procedure). Calculated volumetric parameters included 3D enddiastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV) and 3D LA volume (LAV). Diastolic function was monitored using the indices mean E:E9 and systolic function/ contractility was measured with dP/dt max and early peak systolic velocity (S9 ). The FloTrac system (consisting of the Vigileo monitor and sensor), uses a clinically validated algorithm to provide continuous cardiac output (CO), stroke volume (SV) and systemic vascular resistance in real-time. Results TAVI resulted in an immediate increase in cardiac output (3.7 (baseline), 4.6 (6 h) 4.5 l/min (24 h), p<0.5 baseline vs 6 h and 24 h) with no signicant change in systemic vascular resistance (1162, 1292 and 1367 dyn*s/cm5). However, 6 h post-TAVI there was a signicant decrease in systolic function as measured by dP/dt max/EDV (see Abstract 164 gure 1A) and co-existent impairment of diastolic function as indicated by medial E:E9 values (see Abstract 164 gure 1B), which was associated with an appropriate increase in LA volume (70.3, 82.6 and 72.8 ml, p<0.05 baseline vs 6 h). Following this, there was a recovery of both systolic and diastolic indices. In addition, another marker of systolic function, S9 increased after 24 h (6.4, 6.6, 8.2 cm/s, p<0.05 baseline vs 24 h and 6 h vs 24 h). Concurrent with this recovery, we observed a signicant decrease in EDV and ESV at 24 h post-TAVI (EDV: 94.9 to 83.4 ml (p<0.05); ESV 41.9 to 33.5 ml (p<0.05)). These changes in haemodynamics were associated with signicant increase of troponin I levels at 24 h and increase in CK-MB at 6 h after the procedure (troponin: 0.06 vs 1.19 mg/l, p<0.05; CK-MB 1.6 vs 6.6 mg/l, p<0.05). Conclusion Successful TF TAVI results in an immediate improvement in cardiac output. However, overlying this, within the rst 24 h both systolic and diastolic dysfunction occurs. The rise in the markers of myocardial injury suggest this may be due to myocardial stunning and/or some periprocedural myocardial damage. Recovery of contractility is observed after 24 hours. British Society of Echocardiography guidelines. The threshold for inclusion in the screen positive group was deliberately low to capture all manifestations of VHD. Participants were given preliminary results, before completing a shortened Spielberger STAI questionnaire. Results Uptake was 46% (age range 65e96 years; male to female ratio 1:1.1). VHD was detected in 33% of participants and prevalence increased with increasing age (see Abstract 165 gure 1). Mitral regurgitation and aortic regurgitation were the most common lesions detected (present in 17% and 14% respectively). The majority of VHD was graded as mild (84%); only 1% of VHD detected was severe. The majority of participants (99%) described themselves as calm or relaxed at the time of screening; none expressed signicant levels of worry or tension. 98% would be prepared to undergo repeat echocardiography as screening for VHD.
Prevalence of VHD in $65s by age group.
165
THE OXVALVE STUDY: ECHOCARDIOGRAPHIC SCREENING FOR VALVULAR HEART DISEASE IN THE COMMUNITY SETTING: METHODOLOGY, FEASIBILITY AND PRELIMINARY RESULTS
doi:10.1136/heartjnl-2011-300198.165
Conclusions The prevalence of VHD in adults aged over 65 in the Oxfordshire population, using a low threshold for detection, is approximately 33% and increases with age. Mitral regurgitation is the most common lesion, and the majority of detected VHD is mild. Echocardiographic screening for VHD is feasible in the primary care setting and acceptable in this group of patients.
J L dArcy, D Ebbs, P Grimwade, A J Farmer, 4D Mant, 1B D Prendergast. 1John Radcliffe Hospital, Oxford, UK; 2Didcot Health Centre, Oxford, UK; 3Bampton Medical Practice, Oxford, UK; 4Department of Public Health and Primary Care, University of Oxford, Oxford, UK
166
CARDIOVASCULAR MAGNETIC RESONANCE (CMR) TAGGING IDENTIFIES DIFFERENTIAL VENTRICULAR REMODELLING IN PATIENTS WITH BICUSPID VS TRICUSPID AORTIC VALVE DISEASE
doi:10.1136/heartjnl-2011-300198.166
Introduction Valvular heart disease (VHD) is poorly researched in comparison with other areas of cardiovascular disease. Principle limitations are the diverse nature of patients with VHD, inability to identify individuals at the earliest stages of disease and lack of an appropriate investigational infrastructure. Studies addressing the contemporary epidemiology and natural history of VHD are scarce but demonstrate an increasing prevalence in the elderly, associated with signicant morbidity and mortality. Cohort studies in the USA are ongoing but there are no European or UK studies to date. We have developed a large scale, prospective community echocardiographic screening study within the adult Oxfordshire population, to determine the epidemiological characteristics of VHD in the UK for the rst time, to assess the acceptability of echocardiographic screening for VHD, and establish cohorts with well-characterised genetic and echocardiographic phenotypes for future study. Herein, we present preliminary data for the rst 1050 patients, with enrolment ongoing. Methods Patients >65 years, registered with participating general practices (GP) and with no known VHD, were invited to attend their GP surgery where routine demographic and cardiac data were collected and a focused examination undertaken. Participants underwent a standard transthoracic echocardiogram (TTE) according to
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S Bull, J Suttie, N Blundell, J M Francis, T D Karamitsos, A Pitcher, J DArcy, B Prendergast, S Neubauer, S G Myerson. John Radcliffe Hospital, Oxford, UK
Background Bicuspid aortic valves (BAV) are a common inherited abnormality with a very high rate of adverse cardiac events at an earlier age than tricuspid aortic valves (TAV). Risk stratication for moderate to severe aortic stenosis, in both bicuspid and tricuspid disease, remains a signicant clinical challenge. It is unknown whether pathological left ventricular (LV) remodelling, a strong predictor of adverse cardiac events, differs between patients with bicuspid and tricuspid valvular disease with comparable transvalvular gradients. Cardiovascular magnetic resonance (CMR) tagging provides detailed characterisation of global and regional contractility, and is a powerful investigative tool in the assessment of myocardial disease. We therefore assessed left ventricular strain (using CMR tagging), valve morphology and LV hypertrophy in patients with bicuspid and tricuspid aortic valve disease matched for transvalvular gradient. Methods 42 subjects were recruited in total: 24 patients with moderate to severe BAV (age 55 615 yrs, female 21%, peak transHeart June 2011 Vol 97 Suppl 1
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aortic velocity 3.160.6/ms, LV mass 172648 g; SBP 127 614 mm Hg DBP 76 610 mm Hg) and 18 patients with velocity-matched TAV (age 74 66 years, female 28%, velocity 3.160.6/ ms, LV mass 147627 g; SBP 136617 mm Hg; DBP 7967 mm Hg; Abstract 166 table 1). Patients were scanned using a 1.5 T Avanto scanner (Siemens Healthcare, Erlangen, Germany) and basal, mid-ventricular and apical short axis tagging images were acquired. Peak systolic global circumferential strain was calculated at each ventricular level using CimTag2D software v.7 (Auckland MRI Research Group, New Zealand).
167
AORTIC REGURGITATION QUANTIFICATION WITH CARDIOVASCULAR MAGNETIC RESONANCE PREDICTS CLINICAL OUTCOME
doi:10.1136/heartjnl-2011-300198.167
S G Myerson, J DArcy, R Mohiaddin, J P Greenwood, 1T D Karamitsos, J M Francis, 1A P Banning, 4J P Christiansen, 1S Neubauer. 1John Radcliffe Hospital & University of Oxford, Oxford, UK; 2CMR Unit, Royal Brompton Hospital and the National Heart and Lung Institute, London, UK; 3University of Leeds, Leeds, UK; 4North Shore Hospital, Auckland, New Zealand
1
Bicuspid vs tricuspid aortic valve disease

Bicuspid aortic valve (BAV) 55615 21 3.160.6 172648 127614 76610 2063 1962 1764 Tricuspid aortic valve (TAV) 7466 28 3.160.6 147627 136617 7967 2263 2162 1963
Morphology Age (yrs) Female (%) Transvalvular velocity (ms1) Left ventricular mass (g) Systolic blood pressure (SBP) Diastolic blood pressure (DBP) Basal circumferential systolic strain (%) Mid ventricular circumferential strain (%) Apical ventricular circumferential strain (%)
p Value <0.01 0.31 0.50 0.04 0.04 0.15 0.04 0.07 0.04
Results Patients with BAV had signicantly greater left ventricular hypertrophy (BAV 172 648 g vs TAV 147627 g; p0.04) despite similar degrees of valve stenosis. Peak systolic circumferential strain was lower (ie, reduced contractility) in patients with BAV than TAV (Basal BAV 2063% vs TAV 2263% P0.04; Mid BAV 19 6 2% vs TAV 21 6 2% p0.07; apical BAV 1764% vs TAV 1963%; p<0.04), despite the younger age and lower blood pressure. Conclusion Ventricular remodelling differs between BAV and TAV patients with equivalent transvalvular gradients. BAV patients, despite being younger and having lower systolic blood pressure, have more severe hypertrophy and lower myocardial contractility. This nding may have implications for monitoring disease progression or more timely medical or surgical intervention in patients with BAV.
Background The timing of valve surgery in asymptomatic patients with signicant aortic regurgitation can be challenging. Current indications focus on symptoms and left ventricular (LV) dilation/ dysfunction, but prognosis is already reduced by this time. Quantication of the regurgitation has not previously been used to guide management, likely due to the difculty of achieving this with echocardiography. Cardiovascular magnetic resonance (CMR) can accurately quantify aortic regurgitation and LV volumes, and we examined whether either could predict symptom development and the need for aortic valve surgery. Methods 94 asymptomatic patients with moderate or severe aortic regurgitation on echocardiography were identied from four high volume CMR centres. CMR scans were performed to quantify aortic regurgitation and LV volume indices, and subsequent clinical followup occurred for up to 7 years (mean 2.662.1 years). The best predictors of progression to symptoms and other conventional indications for surgery were determined. Results Aortic regurgitant fraction was the best predictor of clinical outcome; area under the curve (AUC) on receiver operating characteristics analysis 0.93 (p<0.0001), with a specicity of 93% and sensitivity of 78% for predicting the progression to symptoms and surgery. Survival without surgery was 88% for patients with a regurgitant fraction <37%, compared to 6% for those with a regurgitant fraction $37% (see Abstract 167 gure 1). Regurgitant volume >38 mls and regurgitant volume index >25 ml/m2 were also good predictors (AUC 0.91 and 0.90 respectively), though regurgitant fraction had signicantly greater predictive power (OR 1.26 compared to 1.09 for regurgitant volume). LV volumetric indices also predicted outcome, but less strongly than measures of regurgitation: LV end-diastolic volume >267 mls (AUC 0.85), LV end-systolic volume >88 mls (AUC 0.78). Regurgitant fraction and volume were the only independent outcome predictors on multiple logistic regression analysis. The predictive ability of CMR applied to patients with both moderate and severe aortic regurgitation on echocardiography. Supporting data also comes from a comparison
Abstract 166 Figure 1 Velocity matched tricuspid and bicuspid aortic valves showing valve morphology, tagging and cine imaging.
Abstract 167 Figure 1 Kaplan-Meier survival curve showing survival without surgery for conventional indications.
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with patients already planning to undergo surgery at the time of CMR scanning, which showed similar regurgitant fractions in the surgical group (mean 6SD: 45.4%612.1%) compared to the initially asymptomatic patients who developed symptoms or other indications for surgery (42.8%610.4%); p0.32. Subjects who remained asymptomatic had a signicantly lower regurgitant fraction: 25.368.6% (p<0.0001 vs both the planned surgical group and the symptom progression group). Conclusions CMR quantication of aortic regurgitation and LV volumes accurately predicts the progression to symptoms/surgery. Its use in patients with aortic regurgitation should be encouraged. ciated with an adverse prognosis in a range of other cardiac conditions. Using late gadolinium enhancement, we sought to assess the prognostic signicance of mid-wall and infarct patterns of myocardial brosis in aortic stenosis. Methods Between January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis (aortic valve area <1.5 cm2) underwent cardiovascular magnetic resonance with assessment of myocardial brosis by late gadolinium enhancement. Patients were categorised into absent, mid-wall or infarct patterns of late gadolinium enhancement by blinded independent observers. Patient follow-up was completed using the National Strategic Tracing Scheme. Results 143 patients (aged 68614 years; 97 male) were followed up for 2.061.4 years. 81 patients had coronary artery disease, 72 underwent aortic valve replacement and 27 died. Compared to those with no late gadolinium enhancement (n49), univariate analysis revealed that patients with mid-wall brosis (n54) had an eightfold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n40) had a six-fold increase. Mid-wall brosis (HR, 5.35 (95% CI, 1.16 to 24.56); p0.03) and ejection fraction (HR 0.96 (95% CI, 0.94 to 0.99); p0.01) were independent predictors of all cause mortality by multivariate analysis. Conclusion: Mid-wall brosis is an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratication in patients with advanced disease (Abstract 169 gure 1).
168
b-BLOCKER THERAPY IMPROVES CLINICAL OUTCOMES IN

PATIENTS WITH MODERATE TO SEVERE MITRAL REGURGITATION
doi:10.1136/heartjnl-2011-300198.168
A Nadir, D H Elder, M G MacArtney, S D Pringle, A M Choy, A D Struthers, C C Lang. University of Dundee, Dundee, UK
Background Volume overload seen in mitral regurgitation (MR) leads to neuro-endocrine activation including heightened sympathetic activity. Experimental data have reported protective effects of beta-blockers (BBs) on myocardial function in MR suggesting that BB therapy may be benecial in MR. However, the effect of BB therapy on clinical outcomes in MR has not been dened. Hence, in this large observational study we investigated the impact of BB therapy on clinical outcome in patients with moderate to severe MR. Methods The Health Informatics dispensed prescribing, morbidity and mortality database for the population of Tayside, Scotland was linked through a unique patient identier to the Tayside echocardiography database (>110 000 scans). Patients with a diagnosis of moderate or severe MR from 1993 to 2008 were identied. Cox regression model (adjusted for age, gender, left ventricular dimensions and function, left atrial diameter, cardiovascular (CV) history and concurrent CV medications) was used to assess the impact of BB therapy on all-cause mortality and cardiovascular events (CV death or hospitalisations). Results A total of 4437 patients with moderate to severe MR (mean age 74 611 years, 46% males) were identied. MR was categorised as functional in 2523 (57%) and organic in 1894 (43%) while 1324 (30%) were on BBs. Over a mean follow-up of 3.9 years there were 2287 (51%) all-cause deaths and 2333 (52%) CV events. Those treated with BBs had a signicantly lower all-cause mortality with an adjusted HR of 0.65 (95% CI 0.56 to 0.75, p<0.0001) and fewer CV events with an adjusted HR of 0.79 (95% CI 0.69 to 0.90, p<0.0001). Conclusions This large observational study suggests that BB therapy is associated with an improved survival and a lower risk of CV events in patients with moderate to severe MR. These observations needs to be conrmed in prospective studies and support the rationale for undertaking a future randomised clinical trial.
Abstract 169 Figure 1 Kaplan-Meier curves of cardiac mortality (left) and all cause mortality (right) according to pattern of LGE (A No LGE, B Infarct LGE, C Mid-wall LGE).

No LGE Number of patients Mean age yrs Documented CAD % Ejection fraction % Aortic valve area Indexed LV mass g/m2 Mortality rate (deaths / 1000 pt years) 49 64616 37 69613 1.0560.37 92.6* (86.0, 99.6) 15.7 * Geometric mean (95%) Mid-wall LGE 54 70611 42 58621 1.0060.31 113.7* (104.5, 123.8) 142.7 Infarct LGE 40 70613 98 44618 0.9160.26 97.8* (90.9, 105.2) 173.7 p Value e 0.031 <0.001 <0.001 0.111 0.005
169
MID-WALL FIBROSIS IS AN INDEPENDENT PREDICTOR OF MORTALITY IN PATIENTS WITH AORTIC STENOSIS

doi:10.1136/heartjnl-2011-300198.169
1,2 1
M R Dweck, S Joshi, T Murigu, A Gulati, F Alpendurado, R Mohiaddin, J Pepper, 1D Pennell, 2D Newby, 1S Prasad. 1Royal Brompton Hospital, London, UK; 2 Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
Introduction Predicting adverse clinical outcomes in aortic stenosis is challenging. Late gadolinium enhancement (LGE) has been asso-
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170
ETHNIC DIFFERENCES IN PHENOTYPIC EXPRESSION OF HYPERTROPHIC CARDIOMYOPATHY
doi:10.1136/heartjnl-2011-300198.170 N Sheikh, M Papadakis, N Chandra, H Raju, A Zaidi, S Ghani, M Muggenthaler, S Gati, S Sharma. St. Georges University of London, London, UK
Purpose Hypertrophic Cardiomyopathy is a heterogeneous condition with variable phenotypic expression. Current studies are based on predominantly Caucasian cohorts (white patients; WP), therefore the phenotypic manifestations of HCM in individuals of African/Afro-Caribbean origin (black patients; BP) are not fully realised. Data in athletes and hypertensive patients indicate that black ethnicity is associated with a greater prevalence of repolarisation abnormalities on the ECG as well as a greater magnitude of left ventricular hypertrophy (LVH), highlighting the importance of dening the HCM phenotype in this ethnic group. Methods Between 2001 and 2010, 155 consecutive patients with HCM (52 BP, 103 WP) were assessed in 3 specialist cardiomyopathy clinics in South London. All individuals underwent comprehensive

Black HCM (n[52) Demographics Age of diagnosis (years) Gender (males) FH of HCM/SCD NYHA functional class III or IV Patients on treatment B-blockers Calcium antagonists Amiodarone Diuretics Disopyramide Intracardiac debrillator in situ Echocanliographic characteristics Ao (mm) LA (mm) LVED (mm) mLVWTd (mm) LV mass (g) FS (%) E wave (m/s) A wave (m/s) E/A SAM LVOT gradient 30 mm Hg LVH pattern ASH Concentric Apical No hypertrophy Echocanliographic characteristics LVH (Sokolow & Lyon) Left atrial enlargement Pathological Q waves Left axis deviation Inverted T-waves T-wave inversions in V1eV4 T-wave inversions in inferior leads T-wave inversions in lateral leads Deep T-wave inversions ST-segment elevation ST-segment depression 25% 44.2% 28.8% 1.9% 53.8% 44.2% 9.6% 11.5% 82.7% 3.8% 1.9% 76.9% 69.2% 9.6% 50% 57.3% 30.1% 11.7% 1.0% 35.9% 49.5% 23.3% 17.2% 69.9% 3.9% 5.8% 60.2% 51.5% 9.7% 35.0% 0.033 0.534 0.039 0.270 0.086 0.991 0.269 0.038 0.035 0.985 0.071 0.004 white HCM (n[103) p Value
cardiac evaluation including 12-lead ECG and echocardiography. Patients subject to therapeutic interventions potentially affecting repolarisation patterns were excluded. Results Black patients revealed signicantly different echocardiographic patterns of LVH, with more concentric (44.2% vs 30.1%) and apical (28.8% vs 11.7%) hypertrophy compared to WP who exhibited more asymmetric septal hypertrophy (57.3% vs 25.0%) (p0.004). Black patients exhibited a similar magnitude of LVH compared to WP (17.364.9 vs 18.864.1 mm, p0.069). Relating to ECG repolarisation abnormalities, BP exhibited more T wave inversions in the lateral leads (76.9% vs 60.2%, p0.038) and deep ($0.2 mV) T-wave inversions (69.2% vs 51.5%, p0.035). Black patients also tended to display more ST segment depression (50.0% vs 35.0%, p0.071), although this was not statistically signicant. In contrast, WP had signicantly more pathological Q waves (23.3% vs 9.6%, p0.039). Conclusions Ethnicity appears to exert a signicant effect on ECG and echocardiographic patterns in patients with HCM. A signicant proportion of black patients exhibit concentric LVH, highlighting the diagnostic challenges in distinguishing HCM from hypertensive heart disease and physiological adaptation to exercise in black individuals. The greater prevalence of deep T wave inversions and T wave inversions in the lateral leads underscores the importance of further evaluation of black individuals with such ECG repolarisation abnormalities, which may represent the initial expression of HCM.
48.1617.1 61.5% 34.6% 7.7% 55.8% 28.8% 26.9% 7.7% 13.5% 3.8% 5.8% 31.363.7 40.967.3 44.066.1 17.364.9 279.66106.5 40.469.1 0.7060.18 0.6760.18 1.1160.44 23.1% 23.1%
50.5616.5 62.1% 32.0% 7.8% 46.6% 39.1% 12.6% 1.9% 9.7% 9.7% 5.8% 33.265.8 39.967.3 44.466.1 18.864.1 287.66112.7 39.868.3 0.7460.20 0.6660.27 1.2260.58 37.9% 34.0%
0.552 0.942 0.747 0.987 0.281 0.445 0.026 0.080 0.480 0.197 0.989 0.123 0.593 0.787 0.069 0.767 0.641 0.443 0.851 0.422 0.064 0.163
171
THE RIGHT VENTRICLE OF THE ENDURANCE ATHLETE: THE RELATIONSHIP BETWEEN MORPHOLOGY AND DEFORMATION
doi:10.1136/heartjnl-2011-300198.171
D Oxborough, 2R Shave, 3G Whyte, 1K Birch, 4N Artis, 3K George, 5S Sharma. University of Leeds, Leeds, UK; 2UWIC, Cardiff, UK; 3Liverpool John Moores University, Liverpool, UK; 4Leeds Teaching Hospitals NHS Trust, Leeds, UK; 5St Georges University Hospital, London, UK
1
Introduction It is well established that endurance exercise results in cardiac adaptation including eccentric hypertrophy of the left ventricle which can complicate the differential diagnosis of the athletic heart from some cardiac pathologies that may pre-dispose to sudden cardiac death. The impact of physiological conditioning on RV structure and function, and a similar diagnostic challenge with arrhythmogenic right ventricular cardiomyopathy (ARVC), has received less attention. A recent guideline paper from the American Society of Echocardiography (ASE) has provided a range for normal RV dimensions and functional deformation. These guidelines suggest the RV inow (RVI) should be <42 mm while the proximal outow tract (RVOT) <35 mm. A recent paper also suggested that an RVOT dimension >36 mm or 21 mm/m2 is a major criterion for the diagnosis of ARVC and furthermore longitudinal RV deformation has been shown to be impaired in these patients. In view of this, the aims of this study are twofold:
1. To provide a range of absolute values for RV dimensions in 102 endurance athletes as well as providing a range of data indexed for body surface area (BSA). 2. To provide normal athlete data for indices of RV strain (3) and strain rate (SR).
Methods and Results One hundred and two (102) endurance athletes (86 males and 16 females) with a broad age range (mean 6 SD age (range)36 6 11 (21e71) years) volunteered and were consecutively enrolled in the study. All subjects were either endurance runners or cyclists and were scanned at peak condition. Echocardiography provided measurements of RVI, RV length, RVOT and RV diastolic area (RVDarea). A 2D strain technique was utilised to provide indices of RV3 and systolic and diastolic SR. The values for RVI
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ranged from 30 to 55 mm with 57% of the population having values greater than the normal range. Proximal RVOT ranged from 26 to 49 mm with 40% of the population above the normal range. 28% of the population had RVOT values greater than the proposed major criteria for ARVC. RV length ranged from 70 to 110 mm and RVDarea from 13 to 38 cm2 with values falling above ASE cut-offs in 69% and 59% of the population, respectively. When indexed (ratio scaling) for BSA proximal RVOT ranged from 13 to 25 mm/m2 with 6% of the population meeting the major criteria for ARVC. Peak RV3 ranged from 18 to 41% and peak RV SRS9 from 0.75 to 2.65 l/s, consistent with normal ranges proposed by the ASE. RV diastolic deformation indices displayed marked individual variability with a dominant SRE9 (mean 6 SD2.060.61 l/s) and smaller SRA9 (1.2560.56 l/s). Conclusion RV dimensions in endurance athletes are higher than those proposed as normal and likewise may be consistent with the criteria for ARVC. Despite this enlargement, RV function in endurance athletes is preserved and therefore the role of RV strain imaging may provide additional diagnostic value in differentiating physiological from pathological adaptation.

Parameter RVOT (mm) RVDI (mm) RV Length (mm) RVDarea (cm2) RV 3 (%) RVSRS9 (l/s) RVSRE9 (l/s) RVSRA9 (l/s) RVSR E9 /A9 Mean SD (range) 3465 (26 to 49) 4465 (30 to 55) 9269 (70 to 110) 2665 (13 to 38) 2766 (18 to 41) 1.5360.43 (0.75 to 2.63) 2.060.61 (0.87 to 3.76) 1.2560.56 (0.28 to 2.88) 1.8961.03 (0.49 to 7.25) ASE Normal Values <35 <42 <86 <25 18 to 39 0.7 to 2.54 N/A N/A N/A Indexed (ratio scaling) for BSA 1763 (13 to 25) mm/m2 2263 (15 to 30) mm/m2 4565 (32 to 61) mm/m2 12.862 (8.7 to 17.6) N/A N/A N/A N/A N/A
172
INCREASING ANTI-OXIDANT CAPACITY REVERSES IRON OVERLOAD MEDIATED DYSFUNCTION IN CARDIOMYOCYTES

doi:10.1136/heartjnl-2011-300198.172
1 az. F R Millar, 1D T Baptista-Hon, 2S C O9 Neill, 1M E D 1University of Edinburgh, Edinburgh, UK; 2University of Manchester, Manchester, UK
Introduction Iron overload-cardiomyopathy (IOCM) is an increasing clinical problem worldwide. 70% of patients who receive compulsory blood transfusion die of IOCM, with increased susceptibility to arrhythmias and sudden death. We have previously found that iron exposure impairs cardiomyocyte Ca homeostasis. However, the cellular mechanisms responsible are unknown. Iron is known to participate in the Fenton reaction to produce reactive oxygen species (ROS), which mediate oxidative damage. We therefore tested the hypothesis that increasing the anti-oxidant capacity of cardiomyocytes, with the ROS scavenger Tempol, could be cardioprotective in the presence of iron. Methods Single rat ventricular cardiomyocytes were loaded with uo-3 to monitor intracellular Ca changes upon stimulation while bathed in control Tyrode solution and after adding ferrous iron (iron II). Sarcoplamic reticulum (SR) Ca load and sarcolemmal Ca extrusion rates were estimated during exposure to caffeine, which empties SR Ca stores. The ROS scavenger tempol was used to dissect ROS-mediated pathways from the direct effects of iron II on Ca handling. Data are provided as mean6SEM. Signicance was tested using paired student t test and dened as p<0.05. Results Iron II exposure signicantly increases systolic Ca transient amplitude (mean increase 82.8621.8%, n9) and causes spontaneous arrhythmogenic Ca release events (SACRE). These changes corresponded with increased SR Ca content (mean increase 21.065.7%, n8), which is known to impact on systolic Ca release and spontaneous activity in cardiomyocytes. Sarcolemmal Ca extrusion rate was also signicantly reduced upon iron II exposure (measured as the rate of fall of the caffeine response; mean decrease 48.765.5%, n8), consistent with an overall gain of Ca by the cardiomyocyte. The onset of these Ca disruptions was signicantly delayed in the presence of the ROS scavenger tempol (p<0.001). Without tempol, SACRE onset occurred after 6.960.6 min (n22) following iron II exposure. The same manoeuvre in in tempol delayed the onset of SACRE to 17.861.8 min (n7). Furthermore, increasing ROS scavenging reversed the increase in systolic Ca transient amplitude, as well as SACRE upon washout of iron II. In contrast, in cardiomyocytes not exposed to tempol, the effects of iron II were irreversible. Conclusions Our data show that iron II disrupts cardiomyocyte Ca handling. This is mediated via inhibition of sarcolemmal Ca extrusion, leading to SR Ca overload and SACRE. These are the initiators of most fatal non-reentrant arrhythmias and cardiac sudden death in
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experimental models. The observed effects are partly due to iron IImediated oxidative damage. This was conrmed by the presence of a ROS scavenger delaying the onset of the effects of iron II, and crucially rendering the effects reversible upon iron-washout. These effects of tempol suggest a novel therapeutic target for the treatment of IOCM patients. Cardiac power output (CPO) was calculated as the product of CO and mean arterial pressure. A composite endpoint including maternal death, fetal death, emergency caesarean section for maternal distress and signicant morbidities was determined. Results All tests were performed without signicant complications. Employing data from a previous study of haemodynamics during labour in healthy women, the mean CPO required during peak labour is 2.6 W. This value was adopted for investigation as the minimum required for an average woman to cope with the circulatory demands of normal labour. The healthy controls had a mean peak CPO (PkCPO) of 3.7960.6 W and all non-pregnant women had PkCPO exceeding 2.6 W. The majority of heart disease patients were able to achieve PkCPO values overlapping their healthy counterparts. Only a small proportion of the cardiac patients had PkCPO values lower than the 2.6 W cutoff. Women were signicantly more likely to have uncomplicated pregnancy, labour and puerperium if able to achieve PkCPO>2.6 W (OR 8.1, 95% CI 1.8 to 37.0, p0.023). Pregnant women in NYHA class I had PkCPO values indistinguishable from controls (mean 3.9860.77 W, NS); whereas symptomatic pregnant women had signicantly lower values (mean 3.1560.71W, p<0.005). Conclusions Direct measurement of cardiac functional reserve capacity can be performed by maximal cardiopulmonary exercise testing with non-invasive assessment of PkCPO, which can be safely undertaken during pregnancy. A cutoff value of PkCPO 2.6 W was identied as the lower limit for healthy women, corresponding to that required for normal labour. Most cardiac patients studied had PkCPO values comfortably above this cutoff, and all asymptomatic (NYHA I) and low risk cardiac patients had PkCPO values similar to controls. Measurement of PkCPO allows pregnant patients to be further classied into those with adequate vs limited cardiac reserve, supplementary to existing risk stratication methods.
173
A GENERIC METHOD TO ASSESS THE ADEQUACY OF INDIVIDUAL MATERNAL CARDIAC RESERVE TO TOLERATE THE DEMANDS OF PREGNANCY AND LABOUR
doi:10.1136/heartjnl-2011-300198.173
1 D Barker, 2N Lewis, 2G Mason, 2L B Tan. 1Liverpool Heart and Chest Hospital, Liverpool, UK; 2Leeds General Inrmary, Leeds, UK
Introduction Clinicians often feel apprehensive when managing pregnant patients with heart disease. To complement current evaluation, we have developed a new method of directly assessing the individual patients cardiac functional reserve through stress testing. Pregnant mothers with and without heart disease were studied to test the hypothesis that pregnant cardiac patients who possess cardiac reserve equivalent to that of controls can tolerate the usual demands of pregnancy, labour and puerperium. Methods Fifty-one pregnant women with heart disease (mean age 30.766.5 (range 21e42), mean gestation 25.668.6 weeks) and 102 healthy pregnant women (mean age 31.465.0, (range 19e41), mean gestation 25.169.2 weeks) underwent maximal symptom-limited treadmill cardiopulmonary exercise testing. Fifty-nine non-pregnant women (mean age 32.765.1 (range 20e41) years) were similarly tested and used as a control group. Cardiac output (CO) was measured at peak exercise using the CO2 re-breathing method.
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Author index
The number next to the author indicates the page number, not the abstract number. Abbas A, A1, A3 Abidin N, A70 Abozguia K, A55 Abu-Own H, A25 Adam Z, A5 Adams PC, A39 Aggarwal R, A22, A30 Aggarwal S, A60, A61 Ahmed R, A43 Ahsan AJ, A86 Aitma TJ, A4 Akhtar M, A9 Al Fakih K, A36 Ala L, A82 Alahmar A, A27 Alamgir MF, A23 Alp NJ, A79 Alpendurada F, A53 Alpendurado F, A94 Amersey R, A15 Anand A, A7 Angelini G, A24 Anroniades C, A79 Antoniou S, A5 Appleby C, A27 Archbold A, A46 Archbold RA, A5 Arthur H, A78 Arthur HM, A75 Artis N, A95 Artis NJ, A72, A73 Arujuna A, A85 Augustine D, A63 Aung N, A60, A61 Austin D, A5 Avery P, A75 Awan M, A5 Ayers L, A50 Aziz A, A78 Babar J, A63 Baker CSR, A18 Baker S, A68 Balakrishnan B, A66, A81 Baliga V, A56 Ball SG, A35, A41, A72 Balmforth AJ, A35, A41 Bamforth SD, A77 Banerjee A, A40 Banerjee G, A7 Banerjee R, A63 Banerjee S, A7 Banner NR, A48, A49, A64 Banning AP, A12, A93 Banypersad SM, A59 Bapat V, A19 Baptista-Hon DT, A96 Barker D, A57, A97 Barker J, A7 Barmby D, A21 Barnes S, A60 Barrington S, A68 Barsan A, A49 Barth J, A60 Barth JH, A8, A17 Baruah R, A51, A58 Basavarajaiah S, A33 Bashir Y, A87, A88 A98 Bastiaenen R, A33, A38, A83 Baudoin F, A80 Baumbach A, A24 Bawamia BR, A10 Beadle RM, A55 Beatt K, A24 Bechar I, A70 Bedell VM, A78 Begg G, A56 Begg GA, A60, A86 Begley D, A50 Behan M, A16 Behar J, A15 Behar JM, A25 Behr E, A38 Behr ER, A33, A83 Bell D, A72 Bell J, A45 Bellamy MF, A18 Ben-Nathan S, A83 Bennett MR, A2, A64 Berry C, A16, A73 Berry EL, A86 Betts TR, A87, A88 Bewick AE, A82 Bhabra M, A19, A40 Bhan A, A91 Bhattacharya S, A77 Biasiolli L, A62 Bijnens BH, A52 Birch K, A95 Blackman DJ, A21 Blair E, A62 Blake J, A11 Blamire A, A78 Bland MB, A37 Blaxill JM, A21 Bleasdale RA, A34, A82 Bloomer LDS, A41 Blundell N, A92 Bonser RS, A36, A48 Borbas Z, A90 Borg A, A70 Borg AN, A74 Bostock J, A52, A84, A85 Boston-Grifths E, A30 Bowater S, A55 Bowen TS, A56 Braganca J, A77 Braganza D, A2 Braund PS, A41, A42 Brewer A, A77 Brewster S, A46 Brickham B, A91 Broadbent C, A77 Brown AJ, A29 Brown BD, A90 Brown P, A89 Bryan L, A72 Buchanan L, A23 Bull S, A92 Byrom R, A60 Caldwell JC, A90 Calver A, A16 Calvert PA, A2, A64 Camara O, A52 Campbell M, A11 Cannon DT, A56 Caplin JL, A23 Carr-White G, A52, A84 Carre F, A38 Carrick D, A16 Carter J, A5 Cartwright EJ, A41, A80 Casadei B, A79 Casey FA, A75 Casey M, A73 Cassar TE, A62 Chalmers RTA, A3 Chambers J, A43 Chandra N, A33, A38, A95 Channon K, A12 Channon KM, A79 Chaubey S, A77 Chaudhry U, A27 Chen C-M, A77 Cheng A, A60, A61 Chico TJA, A43 Chinchapatnam P, A52 Chinnappa S, A57 Chiribiri A, A68, A71 Chong E, A24 Choudhury RP, A12, A62, A70 Chowienczyk P, A28, A32 Choy AM, A94 Choy AMJ, A58 Christiansen JP, A93 Christie J, A16 Christodou P, A41 Churchhouse AMD, A7 Clack L, A19 Clapp B, A24, A32 Claridge S, A36 Clark C, A73 Clark D, A70 Clarke B, A26 Clarke SC, A2 Cleary N, A46 Clesham G, A30 Codd V, A42 Collerton J, A57 Connelly K, A22 Connolly S, A7 Cook DG, A41 Cook S, A43 Cook SA, A4 Corbett S, A16 Cotton J, A19 Cowie MR, A53 Cox RD, A41 Craig BG, A75 Crean A, A72 Crossman D, A13 Cruddas E, A24 Cubbon R, A1, A3, A60, A78 Cunliffe E, A52 Curzen N, A16 DArcy J, A92, A93 dArcy JL, A92 az D ME, A96 DallArmellina E, A12 Damm E, A30 Danesh J, A43 Das D, A43 Heart June 2011 Vol 97 Suppl 1
Author index
Das M, A84 Davidson C, A14 Davidson J, A35 Davidson NC, A90 Davies DW, A51, A83 Davies J, A22, A30, A45, A54 Davies JE, A10 Davies MJ, A6 Davis E, A37, A63 Davison BJ, A78 Dawson A, A34 de Belder A, A45 de Belder MA, A5 De Silva K, A24, A28, A71 Deaneld JE, A41 Deaton C, A26 Debiec R, A41 Densem CG, A2 Dent H, A16 Denvir MA, A7, A53 Dhillon OS, A10 Diab I, A81 Dick AJ, A22 Dick KJ, A42 Dickens C, A11 Diesch J, A37, A63 Digby J, A70 Dinh DT, A9 Dixit A, A26 Dixon G, A45 Dobrzynski H, A4 Doherty PD, A37 Donald A, A32 Donald AE, A41 Donin A, A41 Doolin O, A73 Douglas-Hill C, A19 Drury-Smith M, A19 Duckett S, A84, A85 Duckett SG, A52 Dungu J, A18, A59 Durham N, A60 Dutka DP, A50 Dweck M, A3 Dweck MR, A94 Dwivedi G, A66, A81 Dworakowski R, A91 Earley MJ, A81 Ebbs D, A92 Eccleston D, A38 Edmunds L, A45 Edwards R, A10, A29 Eftychiou C, A21 Ekker SC, A78 El-Omar M, A26 Elder DH, A94 Elder DHJ, A34, A58 Ellins E, A41 Emin A, A48 Engelen K, A76 Englyst N, A16 Eve S, A47 Fairbairn TA, A73 Farmer AJ, A92 Fath-Ordoubadi F, A11 Ferguson E, A5 Ferreira V, A12 Finch S, A46 Flather M, A13, A24, A38 Heart June 2011 Vol 97 Suppl 1 Flint J, A60, A61 Foley C, A13 Foley JRJ, A90 Foo F, A16 Ford I, A73 Forfar C, A12 Forfar JC, A62 Fox DJ, A90 Fox K, A13 Fox KAA, A7 Fox KF, A7 Frampton C, A11 Francis DP, A49, A50, A51, A58, A60, A61, A66 Francis J, A37, A63 Francis JM, A12, A62, A68, A92, A93 Frangi AF, A52 Fraser AG, A34 Fraser D, A26 Freemantle N, A49 French AE, A89 Frenneaux MP, A55 Gage M, A1, A3 Gage MC, A78 Gale CP, A8, A17, A60 Gale CPG, A37 Gallagher M, A83 Gallagher S, A15, A31 Gallagher SM, A5 Galloway S, A78 Gamble D, A7 Garden OJ, A3 Garratt CJ, A90 Gasson A, A82 Gati S, A31, A95 George DA, A40 George K, A95 Ghani S, A31, A95 Gholap NN, A6 Gibbins A, A45 Gibbons SM, A41 Gibbs SDJ, A59 Gierula J, A60, A86 Gilchrist J, A73 Gill JS, A52 Gill PS, A59 Gillivray TJMac, A3 Gillmore JD, A59 Ginks M, A52, A84, A85 Glen E, A76 Glen EA, A75 Goodall AH, A42 Goodship J, A75, A76 Goodship JA, A75, A76 Gopalan D, A63, A64 Gordon B, A49 Gordon J, A75 Gosling O, A20 Gosling OE, A65 Graham A, A13, A15 Graham C, A7 Graham TR, A36 Gray C, A3, A43 Gray H, A16 Greaves M, A70 Greenwood JP, A13, A21, A72, A73, A93 Grifn HR, A76 Grimwade P, A92 Guha K, A53 Guilcher A, A28 Gulati A, A94 Gunn J, A13 Guttmann O, A9 Guttmann OP, A31 Haga KK, A53 Hall A, A13 Hall AS, A8, A17, A35, A41 Hall ASH, A37 Hall D, A75 Hall DH, A75, A76 Hall JA, A5 Hall R, A24 Hamid S, A84, A85 Hamid SG, A52 Hancock J, A19 Handa A, A62 Haq IU, A39 Haran H, A19 Hards R, A49 Harrington DW, A82 Harwood SM, A17 Hawkins NM, A30 Hawkins PN, A59 Hayward PA, A9 Hedger M, A49 Hegab Z, A41, A44 Heneghan C, A40 Heymans S, A77 Hobson A, A16 Hodson J, A36 Holbrook I, A60 Holroyd EW, A78, A80 Horne A, A89 Hosmane S, A76 Hoye A, A23 Hughes A, A49 Hughes AD, A50, A66 Hunt J, A32 Hunter A, A60 Hunter RJ, A81 Hussain S, A68 Iles-Smith H, A11 Imrie H, A1, A3, A78 Indermeuhle A, A24 Indermuhle A, A71 Ingram TE, A34 Irwin RB, A70 Ishida M, A68, A71 Ivetic A, A77 Iyengar S, A65 Jackson C, A78 Jagger C, A57 Jain A, A13, A15, A25, A31 Jain AK, A5, A9, A15 James PE, A34 Jamieson S, A10 Jamshidi Y, A4 Jayaram R, A79 Jeilan M, A89 Johnson T, A89 Jones D, A5 Jones DA, A9, A13, A15, A25, A31 Jones JD, A30 Jones MA, A88 Jones S, A83 Joshi NV, A10 Joshi S, A94 Joysurry D, A41 Juli C, A83 Kahn M, A1, A78 A99
Author index
Kahn MB, A3 Kaier T, A39 Kanagaratnam P, A51, A83 Kapetanakis S, A52 Kapur A, A17, A24, A31 Kapur AK, A25 Karamitsos TD, A12, A68, A92, A93 Karia N, A12 Karim R, A83 Kearney L, A60 Kearney M, A1, A78 Kearney MT, A3, A60 Keavney B, A57, A75, A76, A78 Keavney BD, A75, A76 Kellman P, A12 Kelly B, A37 Kelly P, A22, A30 Kemp I, A27 Kemp S, A31 Kennedy J, A62 Kenny A, A57 Kervio G, A38 Kerzin-Storrar L, A90 Kesavan S, A24 Kettle AJ, A11 Khan FZ, A50 Khan MF, A23 Khan N, A90 Khan S, A39 Kharbanda RJ, A12 Khattar R, A26 Khawaja MZ, A19 Khimdas K, A46 Khogali S, A19 Khoo CW, A66, A81 Khunti K, A6 Kilcullen N, A8 Kingston A, A57 Kirkwood T, A57 Klaassen S, A76 Knight C, A5, A9, A13, A15, A25, A31 Knight CJ, A25 Kooner J, A43 Kotecha D, A38 Krishnamoorthy S, A66, A81 Krum H, A38 Kuehl M, A55 Kuijer JPA, A69 Kuker W, A62 Kulanthaivelu R, A82 Kumar D, A46 Kundu S, A89 Kylintireas I, A62, A70 Kyriacou A, A50, A51, A66 Lachmann HJ, A59 Lang CC, A35, A58, A94 Langrish JP, A3 Larsen K, A80 Lazdam M, A37, A63 Leadbeater P, A16 Lee JM, A62, A70 Lee KK, A7 Lees B, A13 Leeson P, A37, A62, A63 Leisa RA, A80 Leon FL, A55 Lewandowski AJ, A37, A63 Lewin BL, A37 Lewinter CL, A37 Lewis N, A57, A97 Lewis RJ, A75 Leyva F, A48 Lim HS, A66, A81 Lim PB, A83 Lindsay A, A12 Lindsay AC, A62 Ling HZ, A60, A61 Lip GYH, A59, A66, A81 Little A, A46 Liu A, A21 Llewellyn-Grifths H, A54 Loader R, A65 Lockie TPE, A28 Loh PH, A23 Lovell MJ, A5 Lowdell M, A20 Lucas A, A37 Ludman A, A9 Ludman PF, A91 Lundmark P, A42 Ma Y, A84, A85 MacArtney MG, A94 MacCarthy P, A91 MacDonald ST, A77 MacDonald TM, A35 Macgillivray K, A19 Macgilivray TJ, A3 MacGowan G, A48, A49 MacLeod M, A7 Macnab A, A76 Mahadevan V, A26 Maher A, A19 Mahmod M, A68 Majumder B, A20 Makri L, A21 Malcolme-Lawes L, A83 Malik N, A22 Mamas M, A26, A44 Mamas MA, A41 Mamasoula V, A75 Manisty C, A50 Manisty CH, A58 Mant D, A92 Marber M, A28 Margulescu A, A34 Markl M, A62 Marshall CJ, A11 Mascaro J, A36 Masi S, A41 Mason G, A97 Mather AN, A72, A73 Mathur A, A5, A9, A13, A15, A25, A31 Mavroudis C, A27 Mavroudis CA, A20 May S, A13 Mayet J, A50, A51, A58, A60, A61, A66 McCann GP, A69, A74, A89 McCarthy CA, A59 McCarthy MI, A43 Mcclean DR, A11 McClure J, A73 McCormick LM, A29 McCusker CG, A75 McDiarmid A, A49 McDonagh T, A53 McEntegart MB, A73 McGeoch R, A73 McGill LA, A15, A25 McGowan L, A11 Mckenzie JL, A11 McKeown PP, A75 McKillop G, A3 McLenachan JM, A21 McMahon M, A75 McNab D, A2 Mehta P, A84, A85 Mehta RL, A6 Menon A, A36 Metcalfe K, A90 Millar FR, A96 Miller C, A70 Miller CA, A74 Mills NL, A7 Mitchell AG, A64 Mittal TK, A64 Moccata T, A11 Mohamed TMA, A80 Mohammed TMA, A41, A44 Mohiaddin R, A93, A94 Mohiddin S, A5, A9, A13 Mole G, A14 Monaghan M, A91 Moraldo M, A50, A66 Moreton N, A90 Morgan-Hughes G, A65 Morrell C, A8 Morrice D, A40 Morrison ML, A75 Morton AC, A13 Morton G, A24 Morton GDJ, A68, A71 Muckett P, A43 Muckett PJ, A4 Muggenthaler M, A33, A95 Muir DF, A5 Mukhopadhyay D, A80 Mulder B, A76 Mullen LJ, A29 Murdoch CE, A77 Murgatroyd SR, A56 Murigu T, A94 Murphy A, A73 Murray SA, A53 Musameh MD, A35 Myerson SG, A68, A92, A93 Nadir A, A35, A94 Nadra I, A19 Nagel E, A68, A71 Nair S, A26 Nallaratnam M, A11 Narayan HK, A10 Nayar V, A50 Nelson CP, A41, A42 Ness A, A53 Neubauer S, A12, A37, A62, A63, A68, A92, A93 Neubauer SN, A62 Neubuer S, A70 Nevill AM, A40 New G, A38 Newby D, A94 Newby DE, A3, A7 Newman D, A40 Newman W, A90 Newton T, A70 Neyses L, A26, A41, A44, A80 Ng GA, A89
A100
Author index
Ng LL, A10 Nicol E, A72 Nicolson WB, A89 Nightingale CM, A41 Nijjar M, A30 Nijjer SS, A7, A49 Norrie J, A16 Nyawo B, A29 OCallaghan P, A55 ODoherty M, A68 ODonnell M, A53 OSullivan JJ, A75 OSullivan M, A2 O9 Neill SC, A96 Obaid DR, A2, A63, A64 Oceandy D, A80 Okonko DO, A60, A61 Oldroyd K, A16 Oldroyd KG, A73 Oliver M, A54 Oliver RM, A23 Ordoubadi F, A26 Oriolo V, A47 Ormerod OO, A70 Owen CG, A41 Owen J, A60 Oxborough D, A95 Pabari P, A49, A51, A58 Pabari PA, A50, A66 Padgett HC, A86 Padley S, A72 Pagano D, A36 Palmieri V, A49 Palomino-Doza J, A75 Panayotova R, A76 Panicker MG, A64 Panoulas V, A33, A38 Papadakis M, A33, A38, A95 Parameshwar J, A48 Parker C, A89 Parry G, A49 Pashaei A, A52 Patel P, A82 Paterson E, A7 Patterson C, A72 Paul GA, A22 Payne AR, A73 Pearson IR, A8, A17, A60 Peebles C, A70 Pennell D, A94 Penswick A, A46 Pepper J, A94 Perera D, A24, A28, A68, A71 Perry R, A30 Perry RA, A27 Peters NS, A4, A51, A83 Petersen SE, A62 Petrie MC, A73 Pettit S, A30 Pierret CK, A78 Pierscionek T, A75 Pinney JH, A59 Pitcher A, A62, A92 Pitts-Crick J, A89 Plein S, A72, A73 Plummer CJ, A84 Poole R, A37, A63 Popov AF, A49 Postma A, A76 Heart June 2011 Vol 97 Suppl 1 Prasad S, A53, A94 Pravanec M, A4 Prehar S, A41, A80 Prendergast B, A12, A92 Prendergast BD, A92 Prescott M, A41 Pretsell G, A45 Pringle SD, A58, A94 Pugh PJ, A50 Pye M, A60 Quinn PA, A10 Qureshi AC, A17 Qureshi N, A88 Rahman T, A75, A76 Rajappan K, A87, A88 Raju H, A31, A33, A38, A95 Rajwani A, A1, A3 Rakhit RD, A20, A27 Rampat R, A17 Rana B, A67 Rapala A, A41 Rashid S, A3 Rathod B, A15, A31 Rathod K, A13, A25, A31 Rathod KR, A15 Rathod KS, A9, A15 Rathod VS, A15 Rawling A, A50 Rawlins J, A33, A38 Ray KK, A2 Raybould A, A54 Razavi R, A84, A85 Razavi RS, A52 Razvi NA, A69 Redgrave R, A78 Redwood S, A19, A24, A28, A71 Rees I, A55 Reid CM, A9 Reid J, A53 Reilly S, A79 Rekhraj S, A35 Rhode K, A84, A85 Richards JMJ, A3 Richards M, A11 Richards T, A61 Richmond L, A81 Rider O, A70 Rinaldi CA, A52, A84, A85 Ring L, A67 Robb SD, A73 Robinson N, A49 Robson MD, A12, A62, A70 Rogers C, A11 Rogers CA, A48 Rogers T, A36 Rolandi C, A28 Roobottom C, A65 Rooney SJ, A36 Rose H, A45, A54 Rossiter HB, A56 Rothman A, A13 Rothman M, A46 Roughton M, A17 Rudd JHF, A63, A64 Rudnicka AR, A41 Rueckert D, A83 Rusk RA, A67 Russell S, A46, A54 Russell SJ, A45, A55 Sabharwal NS, A70 Sadarmin PP, A87 Salaheen D, A43 Salukhe TV, A83 Samani NJ, A35, A41, A42 Sambu N, A16 Sammut E, A15, A25 Sammut EC, A13 Sanderson JE, A48 Sandilands AJ, A89 Sands AJ, A75 Sattianayagam P, A59 Saul A, A73 Sayan S, A51 Sayer J, A22, A30 Schilling RJ, A81 Schlindwein FS, A89 Schmitt M, A70, A74 Schneider JE, A77 Schoeld PM, A2 Schotten U, A79 Schueler S, A48, A49 Schuster A, A68, A71 Schwartz R, A77 Sehmi J, A43 Semple SI, A3 Sermesant M, A52 Shah A, A7 Shah AJ, A63 Shah AM, A77, A91 Shah NH, A23 Shantsila E, A59 Shapiro LM, A2 Shardey GC, A9 Sharma R, A53 Sharma S, A31, A33, A38, A83, A95 Shave R, A95 Sheikh N, A31, A38, A95 Shelton RJ, A21 Shepherd C, A89 Shepherd EJ, A84 Shetty A, A52, A84 Shetty AK, A85 Shi WY, A9 Shirodaria C, A70 Shome J, A5 Showkathali R, A22, A30 Sicard P, A24 Siebes M, A28 Sim V, A54 Simari RD, A78, A80 Simon A, A48 Simon AR, A49 Simpson I, A16 Singh R, A19 Singhal A, A37 Sinha M, A47 Sivananthan UM, A8, A17 Skinner JS, A39 Smith EJ, A25 Smith J, A78 Smith JA, A9 Sneddon L, A75 Snell KIE, A69 Sohal M, A84, A85 Somauroo J, A31 Somers K, A21 Sorbron S, A72 Spath N, A33 A101
Author index
Sporton S, A81 Squire IB, A6, A10 Stables RH, A27 Stafford PJ, A89 Staniforth AD, A86 Steadman CD, A69, A74, A89 Stegemann B, A49 Stoll VMS, A70 Strain WD, A65 Strauss BH, A22 Struck J, A10 Struthers AD, A34, A35, A58, A94 Sukumar P, A78 Suresh V, A20 Surr J, A1, A3 Sutaria N, A66 Suttie J, A62, A63, A92 Suttie JJ, A68 Sutton AGC, A5 Swanson NM, A5 Syvanen AC, A42 Szwejkowski BR, A34, A58 Topf A, A76 Taggu W, A22 Tagney J, A47, A89 Tai ES, A43 Tan HL, A75 Tan LB, A57, A97 Tan YT, A48 Tayebjee M, A81 Taylor R, A29 Templeton C, A34 ten Dijke P, A75 Thackray S, A23 Thomas G, A89 Thomas HE, A84 Thomas HL, A48 Thomas M, A19, A24, A60, A61 Thompson CA, A25 Tilling LM, A32 Tomaszewski M, A35, A41 Tooze P, A21 Topf A, A75 Topf AL, A75 Townend J, A78 Tsui S, A48 Twomey D, A84 Tzemos N, A73 Ungvari T, A23 Unsworth B, A58, A66 Van den Bruel A, A40 van Eeden FJ, A43 van Rossum AC, A69 Vanhoutte D, A77 Veasey RA, A82 Venables P, A20 Verheule S, A79 Vile RG, A80 Virdee MS, A50 Viswambharan H, A1, A3, A78 Viswanathan K, A8 Waldron ZL, A86 Walker S, A7 Wallace W, A3 Wang WYS, A35 Ward D, A83 Ware JS, A4 Warner T, A16 Wassef N, A59 Waterworth P, A76 Watson D, A14 Watson J, A60 Watson OJ, A43 Watt H, A62 Wechalekar A, A59 Weerackody R, A15, A25, A46 Weissert S, A60, A61 Wells TA, A47 Wendler O, A91 Wenzelburger FWG, A48 West NEJ, A2, A29 Westwood M, A5 Wheatcroft AC, A60 Wheatcroft S, A1, A3, A78 Wheatcroft SB, A21 Whelan CJ, A59 Whincup PH, A41 Whinnett Z, A51 Whinnett ZI, A58 White J, A60 Whyte G, A95 Wicks E, A31 Wilkinson S, A4 Williams C, A34 Williams LK, A55 Williams M, A3 Williams P, A26 Williams R, A28, A39 Willson K, A51 Wilson IC, A36 Wilson K, A19 Wilson SJ, A20 Wiper A, A26 Witte KK, A56, A60, A86 Woldman S, A60 Wong KCK, A87, A88 Woodcock T, A72 Woodward R, A73 Wordsworth BP, A62 Wragg A, A9, A13, A15, A25, A31 Wren C, A75 Wright GA, A22 Wright RA, A5 Wrightson N, A49 Yap CH, A9 Yaqoob MM, A17 Yellowlees D, A53 Yeo Y, A43 Young C, A19 Young S, A45 Yousaf F, A57 Yousef ZR, A45, A46, A54, A55 Yu B, A77 Yuldasheva N, A3, A78 Yusuf S, A89 Zaidi A, A31, A33, A95 Zaman A, A10, A72 Zhang W, A43 Zi M, A41, A80 Zych B, A49
A102

2AC Heartjnl BCS Abstracts 2011

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97

June 2011 Volume 97 Supplement I

Volume 97 Supplement I Pages A1A104 HEART June 2011

Young Research Workers Prize

Young Research Workers Prize

Young Research Workers Prize

Young Research Workers Prize

INTEGRATIVE GENOMICS APPROACHES IDENTIFY NEW GENES CONTROLLING HEART RATE

Heart June 2011 Vol 97 Suppl 1

BCS Abstracts 2011

p 0.02 0.05 0.20

Heart June 2011 Vol 97 Suppl 1

BCS Abstracts 2011

Inclusion and exclusion criteria for HACX

Abstract 2 Figure 1 angiography.

Time from ED presentation to coronary

BCS Abstracts 2011

Heart June 2011 Vol 97 Suppl 1

BCS Abstracts 2011

Heart June 2011 Vol 97 Suppl 1

BCS Abstracts 2011

MACE after primary PCI.

BCS Abstracts 2011

19 (57.6%) 2 (6.1%) 1 (3.0%) 11 (33.3%)

Heart June 2011 Vol 97 Suppl 1

BCS Abstracts 2011

BCS Abstracts 2011

BCS Abstracts 2011

Abstract 15 Table 1 secondary outcomes

Log transformed values for the primary and

MACE and other SAE

BCS Abstracts 2011

Heart June 2011 Vol 97 Suppl 1

BCS Abstracts 2011

All cause mortality after PCI for STEMI.

BCS Abstracts 2011

Abstract 19 Figure 1 disease.

Comparison of MACE between multivessel

Breakdown of MACE at 5 years.

BCS Abstracts 2011

BCS Abstracts 2011

J Dungu, C S R Baker, M F Bellamy. Hammersmith Hospital, Imperial College London, London, UK

Change in MR grade post-Mitraclip.

Change in NYHA class post-Mitraclip.

BCS Abstracts 2011

0.03 0.03 0.03 0.36

BCS Abstracts 2011

BCS Abstracts 2011

< Age < Weight (Kg) < Height (cm)

< < < <

< Need to increase screening frame rate

BCS Abstracts 2011

No. of patients Death Cardiac death Re-infarction Unplanned TVR Stroke

968 52 (5.4%) 45 (4.7%) 16 (1.7%) 12 (1.2%) 56 (5.8%)

882 46 (5.2%) 39 (4.4%) 14 (1.6%) 10 (1.1%) 54 (6.1%)

Abciximab + UFH (n[346) 3.8 5.2 3.5 0.9 0 5.8 3.8

BCS Abstracts 2011

BCS Abstracts 2011

Abstract 33 Figure 1 tion Index (RI). Abstract 33 Table 2

Cumulative survival according to Revascularisa-

BCS Abstracts 2011

All cause mortality after PCI for elective patients.

BCS Abstracts 2011