Original Article

Ventricular Tachycardia Ablation in Severe Heart Failure

An International Ventricular Tachycardia Ablation Center
Collaboration Analysis
Wendy S. Tzou, MD; Roderick Tung, MD; David S. Frankel, MD; Marmar Vaseghi, MD, MS;
T. Jared Bunch, MD; Luigi Di Biase, MD, PhD; Venkatakrishna N. Tholakanahalli, MD;
Dhanunjaya Lakkireddy, MD; Timm Dickfeld, MD, PhD; Anastasios Saliaris, MD;
J. Peter Weiss, MD; Nilesh Mathuria, MD; Usha Tedrow, MS, MD;
Mohammed R. Afzal, MD; Pasquale Vergara, MD, PhD; Koichi Nagashima, MD, PhD;
Mehul Patel, MD; Shiro Nakahara, MD, PhD; Kairav Vakil, MD; J. David Burkhardt, MD;
Chi-Hong Tseng, PhD; Andrea Natale, MD; Kalyanam Shivkumar, MD, PhD;
David J. Callans, MD; William G. Stevenson, MD; Paolo Della Bella, MD;
Francis E. Marchlinski, MD; William H. Sauer, MD
Downloaded from http://circep.ahajournals.org/ by guest on January 15, 2017

BackgroundVentricular tachycardia (VT) radiofrequency ablation has been associated with reduced VT recurrence and
mortality, although it is typically not considered among New York Heart Association class IV (NYHA IV) heart failure
patients. We compared characteristics and VT radiofrequency ablation outcomes of those with and without NYHA IV in
the International VT Ablation Center Collaboration.
Methods and ResultsNYHA IIIV patients undergoing VT radiofrequency ablation at 12 international centers were
included. Clinical variables, VT recurrence, and mortality were analyzed by NYHA IV status using KaplanMeier
analysis and Cox proportional hazard models. There were significant differences between NYHA IV (n=111) and NYHA
II and III (n=1254) patients: NYHA IV had lower left ventricular ejection fraction; more had diabetes mellitus, kidney
disease, cardiac resynchronization implantable cardioverterdefibrillator, and VT storm despite greater antiarrhythmic
drug use (P<0.01). NYHA IV subjects required more hemodynamic support, were inducible for more and slower VTs,
and were less likely to undergo final programmed stimulation. There was no significant difference in acute complications.
In-hospital deaths, recurrent VT, and 1-year mortality were higher in the NYHA IV group, in the context of greater
baseline comorbidities. Importantly, NYHA IV patients without recurrent VT had similar survival compared with NYHA
II and III patients with recurrent VT (68% versus 73%). Early VT recurrence (30 days) was significantly associated with
mortality, especially in NYHA IV patients.
ConclusionsDespite greater baseline comorbidities, VT radiofrequency ablation can be safely performed among NYHA
IV patients. Early VT recurrence is significantly associated with subsequent mortality regardless of NYHA status.
Elimination of recurrent VT in NYHA IV patients may reduce mortality to a level comparable to NYHA II and III with
arrhythmia recurrence.(Circ Arrhythm Electrophysiol. 2017;10:e004494. DOI: 10.1161/CIRCEP.116.004494.)
Key Words: catheter ablation heart failure tachycardia, ventricular

V entricular tachycardia (VT) ablation among patients with

structural heart disease has evolved from a procedure of
last resort to one that is recommended as first-line therapy in
certain patients.1 Still, ablation is often deferred even after
implantable cardioverterdefibrillator (ICD) therapies have
been delivered because of perceived risks and efficacy con-
cerns.2 Patients with heart failure (HF) and New York Heart
Association class IV (NYHA IV) functional status represent a
special population for whom this procedure is often deferred
because of elevated risk, even though significant benefit may
be derived.3 Despite this potential benefit, there are limited
data in this patient population because of safety concerns and
exclusion from industry-sponsored clinical research evaluat-
ing catheter ablation of ventricular arrhythmias (VT/ventricu-
lar fibrillation [VF]).
During the past decade, there have been advances in the
ability to minimize hemodynamic instability during catheter
ablation, including improved methods for substrate-based

Received July 15, 2016; accepted November 30, 2016.

For the author affiliations, please see the Appendix.
Guest Editor for this article was Gerhard Hindricks, MD.
The Data Supplement is available at http://circep.ahajournals.org/lookup/suppl/doi:10.1161/CIRCEP.116.004494/-/DC1.
Correspondence to Wendy S. Tzou, MD, Section of Cardiac Electrophysiology, University of Colorado, 12401 E 17th Ave, B136, Aurora, CO 80045.
E-mail wendy.tzou@ucdenver.edu
2017 American Heart Association, Inc.
Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org DOI: 10.1161/CIRCEP.116.004494

1
 2 Tzou et al VT Ablation in Severe Heart Failure
WHAT IS KNOWN
Catheter ablation of VT is an effective treatment for
VT, and lack of recurrent VT after ablation has been
associated with improved survival.
VT ablation is often avoided among patients with
NYHA IV HF because of a perception of prohibi-
tively high risk:benefit ratio.
WHAT THE STUDY ADDS
VT ablation can be performed safely among patients
with advanced HF, and lack of recurrent VT among
these patients is associated with improved survival
Early recurrence of VT after ablation in NYHA IV
patients is strongly associated with subsequent mor-
tality and should prompt consideration for advanced
HF therapies.
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ablation.48 In addition, use of percutaneous left ventricular
assist devices (LVADs) during ablation, in selected cases, has
helped to minimize hemodynamic compromise.9,10 Not only
has the need for repeated VT induction and activation map-
ping been minimized with contemporary approaches, but free-
dom from VT recurrence and outcomes have been improved.8
We sought to assess the safety and efficacy of VT ablation
in patients with NYHA IV HF and ventricular arrhythmias
refractory to medical therapy among a contemporary group of
patients included in the cohort established by the International
VT Ablation Center Collaborative Group (IVTCC).3
Methods
Study Cohort
We retrospectively analyzed data collected by the IVTCC to evaluate
the safety and efficacy of VT ablation in patients with NYHA IV HF
and structural heart disease. Details of this shared database have been
previously reported.3 Briefly, patients with structural heart disease
and refractory VT undergoing catheter ablation between 2002 and
2013 among 12 international, tertiary-care sites specializing in VT
management were included. Data collection and analysis were ap-
proved by the institutional review board of each participating center,
and all subjects gave informed consent. For this study, only patients
with NYHA IIIV HF with left ventricular ejection fraction <50%
were included, and characteristics between NYHA IV and NYHA II
and III were examined.
NYHA Classification
Investigators contributing to the IVTCC database assigned NYHA
functional class to each subject included in the database using stan-
dard classifications. NYHA I patients were those with no limitation
of physical activity. NYHA II comprised those with slight physical
activity limitation but comfortable at rest. Patients with NYHA III HF
had marked limitation of any physical activity but were asymptomatic
at rest. Patients with NYHA IV HF were those with dyspnea at rest,
inability to perform any physical activity without HF symptoms, and
were often inotrope dependent.11,12
Ablation and Procedural Data Collection
Details of ablation procedures performed and data collected have been
previously reported.3 Contemporary approaches for substrate-based
ablation guided by electroanatomic mapping, pace-mapping, and,
when feasible, activation and entrainment mapping were performed
across all centers. Specific techniques used were case and operator
dependent, including epicardial access and ablation and use of he-
modynamic support devices (extracorporeal membrane oxygenation,
Impella [Abiomed, Inc, Danvers, MA], TandemHeart [CardiacAssist,
Pittsburgh, PA] or intra-aortic balloon counterpulsation). Acute abla-
tion success was defined as noninducibility of sustained, monomorphic
VT with programmed stimulation after ablation and was performed un-
less hemodynamic instability or other patient safety risk was present.
Follow-up and End Points
All subjects included in the IVTCC database were followed in the
outpatient setting to assess for recurrent VT, transplant, and mortal-
ity.3 Outpatient assessments included device interrogations and of-
fice visits. Recurrent VT/VF was defined as spontaneous recurrence
lasting 30 seconds and documented by telemetry, ECG, or device
recording, or any appropriate ICD therapy, including antitachycardia
pacing. The date of VT recurrence, cardiac transplant, or death was
noted in addition to the last follow-up date.
Twelve-month survival in patients was assessed in those with and
those without recurrence of VT, based on NYHA IIIV classification.
Baseline, procedural, and outcome differences between NYHA IV
and NYHA II and III patients were compared. Risk factors for recur-
rence of VT and mortality were further analyzed among NYHA IV
patients.
Statistical Analyses
Continuous data are expressed as meanSD, and categorical data
are expressed as number (%). Two-sided Student t test was used for
comparison of continuous variables; the Wilcoxon rank-sum test was
used for nonparametric comparative testing. Pearson 2 test was used
for comparison of proportions. Cox proportional hazard analysis
was used to evaluate significant univariable and multivariable cor-
relates for time to ventricular arrhythmia recurrence and mortality,
and results are reported as hazard ratio (95% confidence interval).
In addition, VT recurrence as a time-dependent covariate was used
to analyze the association between VT recurrence and early VT re-
currence (30 days after ablation) with mortality in unadjusted and
multivariable analyses. Characteristics included in the multivariable
model included those that were significant in univariable analysis
(P<0.1) and those that were felt to be otherwise clinically relevant
(age and left ventricular ejection fraction). KaplanMeier survival
analysis was performed to estimate survival among patients with
NYHA IV versus NYHA II and III HF and (1) VT recurrence after
ablation, with time to death assessed from time of recurrence and
(2) lack of VT recurrence, with time to death assessed from time
of ablation. Landmark analysis was additionally performed to com-
pare survival between NYHA IV and NYHA II and III cohorts based
on early VT recurrence, after excluding those who had died before
day 30 or those without early recurrence with <1-year follow-up.
Comparisons were performed using the log-rank test. Statistical
analyses were performed using the IBM SPSS (version 24.0, New
York) statistical software program, and statistical significance was
defined as a 2-sided P<0.05.
Results
Patient Characteristics
There were a total of 2061 patients with structural heart disease
who underwent VT ablation among 12 centers in the IVTCC.
Of those, 698 had NYHA I functional status and were not
included in this study because of lack of clinical HF. There
were 1365 patients included in the present analysis, 111 who
had NYHA IV HF (Table1). Mean age was 6412 years, and
left ventricular ejection fraction was 3011%. The majority
were male (88%) and had ischemic cardiomyopathy (59%).
VT storm or incessant VT was present in 38%, and 77% had
been treated with at least 1 antiarrhythmic drug before ablation.
 3 Tzou et al VT Ablation in Severe Heart Failure

There were notable differences in baseline characteris-
tics between patients with NYHA II and III and NYHA IV
HF presenting for VT ablation (Table1). Comorbidities were
greater among patients with NYHA IV HF, with significantly
higher prevalence of diabetes mellitus, chronic kidney dis-
ease, and hyperlipidemia. Left ventricular ejection fraction
was significantly worse among patients with NYHA IV com-
pared with those with NYHA II and III HF (3011% versus
217%; P=0.001).
There were significantly more NYHA IV patients who had
cardiac resynchronization therapydefibrillators (CRT-Ds),
and they were more likely to present with VT storm or inces-
sant VT, as well as with multiple ICD shocks not meeting
criteria for storm. These presentations were more frequent
despite greater use of antiarrhythmic drugs, especially amiod-
arone (82% versus 60%; P<0.001). Sotalol was used less often
Table 1. Baseline Characteristics by NYHA Classification
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in the NYHA IV patients compared with patients with less
advanced HF (4% versus 12%; P=0.009), although there was
also significantly greater use of other -blockers in the NYHA
IV group. There were no differences observed in age, sex, or
cause of heart disease.
Procedural Characteristics Based on NYHA
Classification
There also were notable differences observed during VT abla-
tion procedures between NYHA IV and NYHA II and III
patients (Table2). There was a significantly greater use of
hemodynamic cardiac support devices among patients with
NYHA IV compared with NYHA II and III HF (22% ver-
sus 7%; P<0.001). There was no difference in the proportion
undergoing epicardial access and mapping, but more of the
NYHA IV patients required cardiothoracic surgical assistance
to obtain epicardial access. There was a trend toward greater
number of VTs induced among the advanced HF patients,

NYHA II and III NYHA IV

and VT cycle lengths were significantly slower than in the
Variable (n=1254) (n=111) P Value NYHA II and III group (37690 versus 35187 ms, fastest,
and 458110 versus 420110 ms, slowest). Programmed elec-
Age, y 6412 6511 0.317
tric stimulation after ablation was more often deferred among
Male sex 1113 (89) 95 (86) 0.350 NYHA IV patients; however, among those undergoing final
Ischemic programmed electric stimulation, there was no significant
741 (59) 68 (61) 0.688
cardiomyopathy difference observed in rates of inducible clinical/targeted VT
LVEF 3011 217 <0.001 (79% versus 82%; P=0.521). When examining baseline and
procedural differences among the minority of patients in each
Hypertension 663 (53) 57 (61) 0.132
group with nonischemic cardiomyopathy (NICM), based on
Hyperlipidemia 695 (55) 59 (69) 0.018 NYHA IV versus NYHA II and III HF, there were no signifi-
Atrial fibrillation 357 (32) 39 (40) 0.116 cant differences noted, included among the following (NICM
NYHA II and III versus NICM NYHA IV, respectively): epi-
Diabetes mellitus 280 (22) 45 (42) <0.001
cardial ablation (46% versus 54%; P=1.000), procedure time
Chronic kidney (297 versus 269 minutes; P=0.211), or acute noninducibility
432 (34) 58 (52) <0.001
disease
after ablation (55% versus 42%; P=0.114).
ICD type 0.006 Despite significant differences in baseline and proce-
None 133 (11) 5 (5) dural characteristics, the acute complication rate between
groups did not differ significantly (7% among NYHA II and
Single or Dual
Chamber
731 (58) 56 (51) III versus 10% in NYHA IV; P=0.246). The most common
complications included the following, with frequencies listed
CRT 390 (31) 49 (45) for NYHA II and III versus NYHA IV, respectively: vascu-
VT storm/incessant lar access or access-related bleeding in 31 (2.5%) versus 2
447 (36) 74 (67) <0.001
VT (1.8%); pericardial effusion leading to pericardiocentesis in
ICD shocks 750 (60) 75 (72) 0.016 27 (2.2%) versus 3 (2.7%) or surgical repair in 3 (0.2%) ver-
sus 0; thromboembolic events in 6 (0.5%) versus 3 (2.7%).
Syncope 114 (9) 8 (19) 0.055
Notably, there were 5 intraprocedural cardiac arrests that
Previous ablation 478 (38) 40 (36) 0.685 occurred in the NYHA II and III group, one of which pro-
Previous ceeded to extracorporeal membrane oxygenation and the other
409 (34) 36 (33) 0.916
cardiothoracic surgery of which ultimately underwent implantation of LVAD. There
Use of antiarrhythmic were no cardiac arrests in the NYHA IV group, either intra-
959 (81) 96 (91) 0.008
drug procedurally or immediately postprocedurally.
Amiodarone 706 (60) 86 (82) <0.001
Outcomes After VT Ablation Based on NYHA
Sotalol 139 (12) 4 (4) 0.009
Functional Class
2 239 (20) 27 (26) 0.209 Rates of in-hospital death and 1-year mortality and cardiac
-Blocker 1022 (83) 99 (90) 0.046 transplantation were significantly higher among patients
Continuous variables are reported as meanSD, unless specified. Categorical
with NYHA IV HF compared with those with NYHA II and
variables are reported as n (%). CRT indicates cardiac resynchronization therapy; III HF (Table3); these differences were consistent when
ICD, implantable cardioverterdefibrillator; LVEF, left ventricular ejection examining outcomes only among patients with NICM in
fraction; NYHA, New York Heart Association; and VT, ventricular tachycardia. each group, although there was a more dramatic difference
 4 Tzou et al VT Ablation in Severe Heart Failure

Table 2. Procedural Characteristics by NYHA Classification of hemodynamic cardiac support devices (P=0.039) were sig-
nificantly associated with VT recurrence, although the small
NYHA II and III NYHA IV
Variable (n=1254) (n=111) P Value number of subjects limited statistical power in these analyses.
Chronic kidney disease, use of intraprocedural hemody-
Use of hemodynamic
67 (7) 17 (22) <0.001 namic cardiac support devices, VT recurrence, and early (30
support device
days) VT recurrence were associated with subsequent death
Epicardial mapping 335 (29) 29 (27) 0.823 among NYHA IV patients after VT ablation in unadjusted
Surgical epicardial analyses (Table5). There was no difference in VT recurrence
25 (2) 6 (6) 0.036
access or survival based on ischemic versus nonischemic cause for
No. of VTs induced 2.22.0 2.62.3 0.057 structural heart disease. In multivariable analysis, early VT
recurrence or any VT recurrence remained significantly asso-
No. with unmappable VT 497 (57) 56 (58) 0.764
ciated with 1-year mortality among the group of patients with
Fastest VT cycle the most severe HF.
35187 37690 0.016
length, ms
Slowest VT cycle
420110 458110 0.005 Association Between Early VT Recurrence and
length, ms Mortality After Ablation
Procedure time, min 285116 280120 0.691 Mortality was significantly increased across all of the NYHA
Noninducible or functional classes when VT recurred 30 days after ablation
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inducible for nonclinical 1028 (82) 88 (79) 0.521 (P<0.001; Figure2). Early VT recurrence was strongly associ-
VT on final PES ated with mortality in this group, with a >8-fold increased risk
Final PES not performed 54 (5) 12 (11) 0.010 of mortality among NYHA IV patients (Table5; P<0.001).
Conversely, among NYHA IV patients without early VT recur-
Complications 82 (7) 11 (10) 0.246
rence, survival was similar to that of NYHA II and III patients
Continuous variables are reported as meanSD, unless specified. Categorical with early VT recurrence (86% versus 87%; Figure2).
variables are reported as n (%). NYHA indicates New York Heart Association;
PES, programmed electric stimulation; and VT, ventricular tachycardia.
Discussion
in in-hospital mortality (3% NYHA II and III versus 41% Study Results
NYHA IV; P<0.001). Among those in whom the cause of In this multicenter collaborative study of patients undergoing
in-hospital death was known, the most common included VT ablation at tertiary-care ablation centers, we found that VT
the following (NYHA II and III versus NYHA IV, respec- ablation in patients with severe HF could be safely performed,
tively): cardiogenic shock in 13 (1.0%) versus 8 (7.2%); with reasonable intermediate-term outcomes. Freedom from
recurrent VT in 8 (0.6%) versus 2 (1.8%); thromboembolic recurrent VT was achieved in 64% of patients with NYHA IV
events in 0 (0.0%) versus 2 (1.8%); and sepsis in 3 (0.2%) HF, in whom significant morbidity was present at baseline.
versus 2 (1.8%). Of those surviving to cardiac transplanta- Compared with those with mild and moderate HF (NYHA
tion after ablation, 30-day survival was equivalent in both II and III), patients with severe HF seemed to have a greater
groups (100%). One-year VT recurrence was not statisti- burden of VT and VT storm, as well as significantly greater
cally significantly higher among NYHA IV patients, but comorbidities, and the threshold for performing the procedure
when VT did recur, the time to recurrence was shorter. Early may thus have been higher for the NYHA IV patients. Despite
VT recurrence (30 days of ablation) also occurred more this higher expected morbidity, patients with severe HF and
frequently among NYHA IV patients (19% versus 10%; no VT recurrence had improved mortality compared with oth-
P=0.011) and particularly among those with NICM and ers in the same class but with recurrent VT after ablation. In
NYHA IV (35% versus 14% among those with NYHA II fact, the survival among NYHA IV patients without recurrent
and III; P<0.001). VT was similar to that among patients with less severe HF
Survival of NYHA IV versus NYHA II and III patients
was significantly worse if VT recurred after ablation (27% Table 3. Outcomes After VT Ablation by NYHA Classification
versus 71%, log-rank P<0.001; Figure1). However, despite
NYHA II and III NYHA IV
the significant baseline and procedural differences between
Variable (n=1254) (n=111) P Value
groups, 1-year survival among NYHA II and III patients with
recurrent VT was similar to the 68% survival of NYHA IV In-hospital mortality 35 (3) 19 (17) <0.001
patients without recurrent VT after ablation. Recurrent VT in 1 y 357 (29) 40 (36) 0.102
Time to VT recurrence, d 283357 6794 <0.001
Correlates of VT Recurrence and Mortality Among
Early (1 mo) VT recurrence 130 (10) 21 (19) 0.011
NYHA IV Patients
Characteristics associated with shorter time to VT Recur- Cardiac transplantation in 1 y 50 (4) 12 (11) 0.003
rence in NYHA IV patients (Table4) in unadjusted analysis One-y mortality 320 (26) 53 (48) <0.001
included presence of CRT-D, hyperlipidemia, and intraproce- Continuous variables are reported as meanSD. Categorical variables
dural use of hemodynamic cardiac support devices. In multi- are reported as n (%). NYHA indicates New York Heart Association; and VT,
variable analysis, only presence of CRT-D (P=0.020) and use ventricular tachycardia.
 5 Tzou et al VT Ablation in Severe Heart Failure
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Figure 1. KaplanMeier analysis illustrating survival of New York Heart Association class IV heart failure (NYHA IV HF) patients (blue) vs
NYHA II and III HF patients (green) from time of recurrence among those with recurrent ventricular tachycardia (VT; 27% vs 71%).

in whom VT recurred after ablation. This improvement may with advanced HF and VT have the highest rate of mortality
seem marginal, but incremental improvement in survival is with concomitant HF risk.13 Our data suggest that, at selected
significant among this very sick subset of patients. Patients ablation referral centers, VT ablation can still performed

Table 4. Correlates of VT Recurrence Among NYHA IV Patients

Univariable Analyses Multivariable Analysis
Variable HR (95% CI) P Value HR (95% CI) P Value
Age* 0.98 (0.941.01) 0.230 1.00 (0.961.05) 0.891
Ischemic cardiomyopathy 0.70 (0.371.33) 0.273
LVEF* 0.93 (0.871.00) 0.050 0.90 (0.781.05) 0.176
Presence of CRT-D* 0.52 (0.270.98) 0.045 0.33 (0.130.84) 0.020
VT storm/incessant VT 1.03 (0.512.10) 0.935
Hyperlipidemia* 3.46 (1.289.35) 0.014 2.76 (0.7510.12) 0.126
Atrial fibrillation* 0.50 (0.241.02) 0.056 0.46 (0.131.66) 0.235
Diabetes mellitus 1.63 (0.833.21) 0.160
Chronic kidney disease 0.63 (0.331.22) 0.172
Antiarrhythmic drug use 0.71 (0.252.05) 0.530
Use of hemodynamic support device* 2.98 (1.197.44) 0.020 4.23 (1.0816.66) 0.039
Partial success on final PES* 0.52 (0.261.06) 0.070 0.72 (0.252.08) 0.539
Inducible at final PES 1.23 (0.931.63) 0.145
CI indicates confidence interval; CRT-D, cardiac resynchronization therapydefibrillator; HR, hazard ratio; LVEF, left ventricular
ejection fraction; NYHA, New York Heart Association; PES, programmed electric stimulation; and VT, ventricular tachycardia.
*Variables with P<0.1 on univariable analysis, except for age, were included in multivariable model.
 6 Tzou et al VT Ablation in Severe Heart Failure

Table 5. Correlates of Mortality Among NYHA IV Patients Undergoing VT Ablation

Univariable Analyses Multivariable Analysis
Variable HR (95% CI) P Value HR (95% CI) P Value
Age 0.99 (0.961.01) 0.245
Ischemic cardiomyopathy 0.63 (0.361.10) 0.103
LVEF 0.99 (0.961.03) 0.673
Presence of CRT-D 1.22 (0.732.04) 0.440
VT storm/incessant VT 1.01 (0.561.81) 0.973
Hypertension 1.65 (0.843.24) 0.146
Diabetes mellitus* 1.62 (0.922.88) 0.098 1.79 (0.923.49) 0.088
Chronic kidney disease* 1.80 (1.013.21) 0.047 1.39 (0.712.72) 0.334
Antiarrhythmic drug use 2.52 (0.6110.41) 0.201
Amiodarone use 1.93 (0.764.88) 0.166
-Blocker use 0.54 (0.241.20) 0.131
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Use of hemodynamic support device* 2.37 (1.214.66) 0.012 1.20 (0.592.45) 0.619
Epicardial and endocardial mapping 1.26 (0.931.72) 0.133
Partial success on final PES 0.68 (0.361.31) 0.251
Inducible at final PES 1.80 (0.714.54) 0.216
VT recurrence 7.03 (3.6813.42) <0.001 4.72 (2.259.91) <0.001
Early (1 mo) VT recurrence* 10.31 (4.9921.29) <0.001 8.30 (3.5319.50) <0.001
CI indicates confidence interval; CRT-D, cardiac resynchronization therapydefibrillator; HR, hazard ratio; LVEF, left ventricular
ejection fraction; NYHA, New York Heart Association; PES, programmed electric stimulation; and VT, ventricular tachycardia.
*Variables with P<0.1 on univariable analysis were included in the multivariable model.
Time-dependent covariate was also incorporated to account for time-varying nature of VT recurrence.

safely and lead to potential survival benefit among those with
potentially reversible substrate among patients with advanced
myocardial remodeling and failure. The outlook from this
study is in contrast to ICD trials, which have suggested that
many patients with the highest disease severity may be too
sick to benefit.14,15 In other words, results from this study sug-
gest that not all patients with NYHA IV HF and VT should be
considered equal, and that there is potential benefit that may
be achieved in ablation of such patients. More specifically, the
presence of advanced HF and VT should not preclude consid-
eration for ablation.
Another important finding not previously reported is that
early VT recurrence was a significant marker of mortality
after ablation, among all patients, although especially among
patients with NYHA IV. NYHA IV patients with VT recur-
rence 30 days had a >8-fold increased risk of death in a year
compared with similar patients who did not have early recur-
rence. Notably, however, NYHA IV patients without early VT
recurrence had similar survival compared with NYHA II and
III patients with early VT recurrence. In sum, these results sug-
gest that NYHA IV patients with VT likely include a mixture
of those with irreversibly advanced or extensive midmyocardial
substrate and less advanced and treatable VT substrates; those
with NICM as the cause for structural heart disease and VT
likely comprise a significant proportion of the former, as dem-
onstrated by a more marked rate of in-hospital mortality and
early VT recurrence in this study. Among the latter, with poten-
tially less advanced or irreversible VT substrate, elimination of
VT could affect the risk of death, and ablation should not be dis-
counted for VT management solely because of the presence of
advanced HF. Conversely, recurrence of VT within 30 days of
ablation of a patient with NYHA IV HF should accelerate con-
sideration for heart transplantation or other advanced therapies.
Previous Investigations Into VT Ablation in Patients
With Severe HF
There is little information on this group of patients because
they generally have been excluded from VT ablation trials
and observational studies in the past. The only exception
to this practice may have been in the Prophylactic Catheter
Ablation for the Prevention of Defibrillator Therapy Study,
in which NYHA IV was not an exclusion criterion, but the
number included (reported together with NYHA III patients,
totaling 25 of 128 patients) was small.16 This is the first
study to exclusively evaluate the role of VT ablation in this
group of patients seldom brought to the electrophysiology
laboratory.
Catheter Ablation as a Treatment of Last
Resort for HF Patients
The threshold to offer ablation as a therapeutic option for the
management of ventricular arrhythmias is much higher for
those patients with severe HF compared with others. Even in
the IVTCC, which comprised highly experienced centers for
VT ablation, patients with severe HF only represented 5% of
the population of subjects studied. This reluctance is likely
 7 Tzou et al VT Ablation in Severe Heart Failure
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Figure 2. KaplanMeier survival curves demonstrating significantly decreased survival among patients surviving for the first 30 d after
ablation but with early (30 d) vs no early ventricular tachycardia (VT) recurrence for New York Heart Association class II and III (NYHA II
and III; green, 87% vs 94%) and NYHA IV subjects (blue, 53% vs 86%); P<0.001.
because of the concerns related to potential safety of the pro-
cedure, which can be prolonged, may involve periods of time
in VT/VF, may require multiple shocks for VT/VF termina-
tion, and may lead to progressive low-output deterioration.
Many times, by the time a patient with severe HF is offered
ablation, it is after all other therapies have been exhausted, and
the quality of life and prognosis for these patients has been
greatly diminished with VT storm or multiple shocks.
In keeping with these ideas, the patients with severe HF
in this population were more likely to have a greater num-
ber of comorbidities and severity of VT/VF. More NYHA
IV patients presented with VT storm or incessant VT, ICD
shocks, and syncope, and significantly more had failed anti-
arrhythmic drug treatment, especially amiodarone. More had
CRT-D in place and were on -blocker therapy. Although the
time course of arrhythmia development and treatments was
unable to be examined in this database, the increased preva-
lence of comorbid disease and greater VT burden suggest that
ablation in these patients may have been deferred until all
other options had been exhausted. Certainly among this group
were markers of more diseased and complex myocardial and
arrhythmogenic substrate.
Differences in Procedural Strategy to Safely
Perform Catheter Ablation in Patients
With Severe HF
Despite significant differences in baseline and procedural
characteristics, the acute complication rate between groups
did not differ significantly. Further, the 10% complication
rate observed among the NYHA IV patients was comparable
to the 6% to 15% complication rate that has been reported
in other single- and multi-center studies evaluating VT abla-
tion in patients with structural heart disease and without the
same degree of HF.4,1722 Not surprisingly, operators chose to
use hemodynamic support more often in these patients. This
procedural characteristic may have allowed for greater safety
in performing the ablation and minimizing hemodynamic
compromise because of sedation or anesthesia effects, VT
induction, and, in some cases, mapping during VT. Notably,
effective substrate-based ablation approaches that minimized
the need for repetitive inductions of VT, or mapping during
VT,46,8,16,23 were used in the majority of patients because of the
presence of unmappable VT, which likely also played a great
role in minimizing intraprocedural hemodynamic instability.
Association of Reduced Mortality With Successful
VT Ablation in Patients With Severe HF
One of the main findings of this analysis was the apparent
association between lack of recurrent VT after ablation and
reduced mortality in patients with severe HF. Successful
ablation in this group may indicate the presence of myocar-
dial substrate that is either less advanced or still amenable to
modification with ablation, as opposed to unsuccessful abla-
tion in which the substrate may be too extensive, localized to
the midmyocardium, or functionally unable to be modified.
Nevertheless, this association of improved survival with lack
of recurrent VT after ablation has been described in patients
with less severe HF; the magnitude of difference seems to
be most pronounced in NYHA IV patients. In addition, the
timing of recurrence was demonstrated to be important, with
 8 Tzou et al VT Ablation in Severe Heart Failure
greater mortality difference observed in those with VT recur-
rence within 30 days of ablation. The mean time to death after
early recurrence was 31 days, suggesting that the recurrence
itself may be closely linked to the mode of death. However,
although an association has been demonstrated, causation is
unable to be proven by our analyses.
CRT trials may provide the largest body of information
on prognosis and natural history of patients with severe HF,
with mortality rates approaching 15% to 20% at 1 year among
patients treated with optimal medical therapy.2426 However,
most of these patients did not have a history of VT/VF, and
the overwhelming majority had NYHA III HF at baseline;
thus, direct comparisons with the NYHA IV patients in this
study are limited. In a subgroup analysis of the Comparison
of Medical Therapy, Pacing, and Defibrillation in Heart
Failure trial, 1-year mortality rates of NYHA IV patients
ranged from 30% (CRT-D patients) to 44% (optimal medi-
cal therapy only patients).27 Although direct comparison is
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similarly limited in that these also were primary prevention
patients, who had not previously demonstrated VT, the high
mortality rate underscores the baseline poor prognosis and
is comparable to the death rate observed among the NYHA
IV patients in this study. Further, the improved survival after
successful VT ablation among NYHA IV patients in this
study offers hope that some degree of disease reversibility
could exist even among NYHA IV patients with refractory
ventricular arrhythmias.
Our data suggest that earlier consideration of advanced
HF treatment options, such as LVAD and transplant, should
be given in those patients who have early recurrence after VT
ablation because of the very strong association with subse-
quent mortality within the next year. Although our data are
consistent with the possibility of recurrent VT/VF as causing
earlier demise, the recurrence may also be a marker for more
complex HF morbidity. We think that there may be biologi-
cal plausibility for a potential survival benefit with success-
ful VT ablation because of the subsequent reduction in ICD
therapies and antiarrhythmic use, possibly leading to improve-
ment in cardiac function, in a group of patients with tenuous
myocardial substrate, although these beliefs at this point are
speculative. While our study is not designed to address this
specific question, clinicians caring for these patients should
note the association between early recurrence of VT/VF and
subsequent mortality regardless of its cause.
Limitations
The limitations and inherent potential biases involved in
observational research must be considered when interpreting
our results. For example, referral bias likely limits how much
our study results can be generalized to the practice of VT abla-
tion as a whole. Members of the IVTCC are all higher vol-
ume, tertiary referral VT ablation centers and thus may have
different patient populations and results compared with less
specialized, lower volume sites.19 Ablation of such patients in
this study was performed not only at tertiary referral centers
with advanced ablation experience but also with on-site capa-
bility for interdisciplinary collaboration; these factors should
all be considered and included in the management of NYHA
IV patients with VT.
Selection biases may also have been present. For example,
if ablation was only performed among NYHA IV subjects per-
ceived to be lower risk or that were otherwise anticipated to
have greater success than other NYHA IV subjects with VT/
VF, results would be biased in favor of ablation. Similarly,
if there were NYHA IV patients thought to be too high risk
for ablation, for whom ablation was not considered and who
instead underwent immediate LVAD implantation or heart
transplantation, the applicability of our results to all patients
with NYHA class IV status is limited. We feel that these poten-
tial biases do not significantly diminish our findings because
the NYHA IV subjects who did undergo ablation were fairly
representative of others with NYHA IV in terms of comor-
bidities, but with even higher acuity of presentation.24,27
In this database, outcomes on patients with early VT recur-
rence were not followed to assess the important question of
whether intermediate-term mortality could be improved with
additional ablation. Additional prospective studies should be
performed to further clarify this issue.
We were unable to differentiate between cardiac and non-
cardiac causes of death, although, assuming that some of the
mechanisms of death were either noncardiac or unrelated to
ablation, assessing all-cause mortality as the end point would
only have biased the differences observed toward the null.
Unlike other analyses of VT ablation, we did not include car-
diac transplantation as an end point with mortality.3 We think
that success in this very sick group of patients with VT should
include the potential prolongation of life by limiting VT/
VF recurrence and subsequent progression to advanced HF
therapies because pump failure and refractory HF would not
be cured with VT ablation in most of these cases. Although a
greater proportion of NYHA IV patients ultimately underwent
cardiac transplantation, there was no significant difference in
the 30-day mortality rates after transplant between the NYHA
IV and NYHA II and III groups; the effect of not censoring
these patients from analysis at the time of transplant should
thus not have significantly affected results.
Additional limitations include the fact that data specifi-
cally on change in HF status immediately after procedures
were not collected, including follow-up creatinine levels, fluid
balance, increased diuretic use, or titration of HF medications.
As reported in the current analysis, there were 2 NYHA II and
III patients who experienced intraprocedural cardiac arrest
and required either extracorporeal membrane oxygenation or
LVAD implantation, but detailed analysis of postprocedure
effects on HF was not within the scope of the current database.
Also a potential limitation of the database is that past medical
history elements were collected from chart review of docu-
mented physician assessments in medical records, which were
assumed to be correct and were not routinely double checked
for accuracy. For instance, if chronic kidney disease was docu-
mented within the past medical history, it would have been
included as a comorbidity for the subject. Finally, the mode of
death could not be demonstrated based on the data collected,
including whether ICD shocks resulting from recurrent VT
correlated with mortality.
Despite its limitations, this is the largest study to date
investigating VT ablation in patients with severe HF and pro-
vides insight into the feasibility, safety, and outcomes of VT
 9 Tzou et al VT Ablation in Severe Heart Failure
ablation, as well as offers potential direction in management
should ablation fail to control VT/VF in such patients.
Conclusions
Despite significantly greater baseline comorbidities, VT RFA
can be performed among NYHA class IV patients with a simi-
lar safety profile using strategies to minimize hemodynamic
instability compared with those with mild and moderate HF.
Recognizing that patients with severe HF have more complex
and difficult-to-treat arrhythmia substrate, VT ablation in this
group has acceptable outcomes, and there is the potential for
significant intermediate-term benefit in comparison to other
HF patients. Early VT recurrence after ablation in patients
with severe HF is strongly associated with subsequent mortal-
ity and should prompt consideration for advanced HF thera-
pies in this select population of patients. The elimination of
recurrent VT in patients with NYHA IV may reduce mortality
in those with potentially less advanced myocardial substrate
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and failure to a level comparable to NYHA II and III HF with
arrhythmia recurrence.
Appendix
From the Cardiac Electrophysiology Section, Division of Cardiology,
University of Colorado, Aurora, CO (W.S.T., W.H.S.); Division of
Cardiology, University of Chicago Medical Center, IL (R.T.); UCLA
Cardiac Arrhythmia Center, UCLA Health System, Los Angeles, CA (R.T.,
M.V., K.S.); Cardiac Electrophysiology Section, Division of Cardiology,
Hospital of the University of Pennsylvania, Philadelphia (D.S.F., D.J.C.,
F.E.M.); Intermountain Heart Institute, Intermountain Medical Center,
Murray, UT (T.J.B., J.P.W.); Division of Cardiology, Albert Einstein
College of Medicine/Montefiore Medical Center, New York, NY
(L.D.B.); St. Davids Medical Center, Texas Cardiac Arrhythmia Institute,
Austin (L.D.B., J.D.B., A.N.); Cardiac Electrophysiology Section,
Division of Cardiology, Minneapolis VA Medical Center, University of
Minnesota Medical Center (V.N.T., K.V.); University of Kansas Medical
Center (D.L., M.R.A.); Cardiac Electrophysiology Section, Division of
Cardiology, University of Maryland Medical Center, Baltimore (T.D.,
A.S.); Cardiology Division, Baylor St. Lukes Medical Center/Texas
Heart Institute, Houston (N.M., M.P.); Brigham and Womens Hospital,
Boston, MA (U.T., K.N., W.G.S.); Hospital San Raffaele, Milan, Italy
(P.V., P.D.B.); Dokkyo Medical University Koshigaya Hospital, Saitama,
Japan (S.N.); and UCLA Department of Medicine Statistics Core, Los
Angeles, CA (C.-H.T.).
Disclosures
Dr Shivkumar was supported by National Heart, Lung, and Blood
Institute Grant R01HL084261. Dr Di Biase is a consultant to
Biosense Webster, St. Jude Medical, and Stereotaxis. Dr Nagashima
is the recipient of a Medtronic Japan Fellowship. Dr Tedrow has
received honoraria from Medtronic, Boston Scientific, and St. Jude
Medical and research grants from Biosense Webster and St. Jude
Medical. Dr Burkhardt is a consultant to Biosense Webster. Dr
Dickfeld has received a research grant from, and is a consultant to,
Biosense Webster. Dr Weiss is a consultant to Stereotaxis. Dr Bunch
is a consultant to Boston Scientific. Dr Stevenson is the recipient
of a patent for needle ablation consigned to Brigham and Womens
Hospital. Dr Della Bella is a consultant to St. Jude Medical and has
received honoraria for lectures from Biosense Webster, St. Jude
Medical, and Biotronik. Dr Sauer has received research grants from
Biosense Webster and CardioNXT and educational grants from St
Jude Medical, Boston Scientific, and Medtronic. The other authors
report no conflicts.
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 Ventricular Tachycardia Ablation in Severe Heart Failure: An International Ventricular
Tachycardia Ablation Center Collaboration Analysis
Wendy S. Tzou, Roderick Tung, David S. Frankel, Marmar Vaseghi, T. Jared Bunch, Luigi Di
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Chi-Hong Tseng, Andrea Natale, Kalyanam Shivkumar, David J. Callans, William G.

Stevenson, Paolo Della Bella, Francis E. Marchlinski and William H. Sauer

Circ Arrhythm Electrophysiol. 2017;10:

doi: 10.1161/CIRCEP.116.004494
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