DR ABDUL GHANI WASEEM

TYPES
IDIOPATHIC DILATED CARDIOMYOPATHY

ETIOLOGIES OF DILATED CARDIOMYOPATHY

50 45 40 35 30 25 20 15 10 5 0 Disorder
IDCM Myocarditis Ischmic CM Infiltrative disease Peripartum CM Hypertension HIV CTD Substance abuse

IDIOPATHIC DILATED CARDIOMYOPATHY PATHOLOGY

Four chamber dilatation Mild to moderate ventricular hypertrophy Varying degrees of interstitial fibrosis and myocyte hypertrophy Functional atrioventricular regurgitation is common

IDIOPATHIC DILATED CARDIOMYOPATHY PATHOLOGIC FINDINGS

IDIOPATHIC DILATED CARDIOMYOPATHY PATHOGENESIS Familial/genetic factors Viral myocarditis and cytotoxic insults Immunologic abnormalities
Beta-receptor auto-antibodies Abnormal T-cell function

Metabolic, energetic, and contractile abnormalities

Ca2+-ATPase
Myofibrillar ATPase

Creatine Kinase

MOLECULAR DEFECTS IN DILATED CARDIOMYOPATHY

GENES Lamin A/C -sarcoglycan Dystrophin Desmin Vinculin Titin Troponin-T -tropomyosin -myosin heavy chain Actin Mitochondrial DNA mutations

FAMILIAL DILATED CARDIOMYOPATHY

COMMON ASSOCIATED ABNORMALITIES
Conduction system disease

Skeletal muscle myopathy or muscular dystrophy

X-linked and autosomal dominant inheritance

patterns are most common

Extracardiac manifestations: Sensorineural hearing loss Neutropenia

NON-INVASIVE EVALUATION OF MYOCARDITIS MRI IMAGING

Unenhanced

Enhanced

IDIOPATHIC DILATED CARDIOMYPATHY EPIDEMIOLOGY

ANNUAL INCIDENCE

5-8/100,000
36/ 100,000

PREVELANCE

INCREASED RISK ASSOCIATED WITH:

MALE GENDER BLACK RACE HYPERTENSION CHRONIC BETA-AGONIST USE

IDIOPATHIC DILATED CARDIOMYPATHY CLINICAL PRESENTATIONS

Heart failure symptoms Anginal chest pain

75%-85% 8%-20%

Emboli (systemic or pulmonary) 1%-4% Syncope Sudden cardiac death

<1% <1%

SPONTANEOUS IMPROVEMENT IN ACUTE DILATED CARDIOMYOPATHY

PATIENT POPULATION 49 patients with heart failure symptoms of less than 6 months duration were compared to a cohort of 248 chronic dilated cardiomyopathy patients
Improvement was prospectively defined as a rise in LVEF > 0.15 to a final value of > 0.30

-Steimle AE et al. JACC 1994;23:553-9

ACUTE DILATED CARDIOMYOPATHY OUTCOME

49 Patients with Recent Onset Cardiomyopathy
12 months

12 Died/10 Tx

16 Alive & Unimproved

11 Improved
2

9
18 Died/13 Tx
1115 mos

5 Alive & 5 Unimproved

27 22 mos

13 Improved
43 29 mos

Steimle et al JACC 1994;23:553-9

SPONTANEOUS IMPROVEMENT IN ACUTE DILATED CARDIOMYOPATHY

UNIVARIATE PREDICTORS OF IMPROVEMENT short duration of symptoms higher cardiac output lower NYHA functional classification smaller LV end-diastolic dimension lower filling pressures higher serum sodium concentration STEPWISE REGRESSION MODEL short duration of symptoms higher serum sodium concentration lower right atrial pressure lower pulmonary capillary wedge pressure

IDCM:PROGNOSTIC FEATURES
VENTRICULOGRAPHIC FINDINGS
Degree of impairment in LVEF Extent of left ventricular enlargement

Coexistent right ventricular dysfunction

Ventricular mass/volume ratio Global wall motion abnormalities Left ventricular sphericity

CLINICAL FINDINGS
Favorable prognosis: NYHA < IV, younger age, female

sex
Poor prognosis: Syncope, persistent S3 gallop, right-

sided heart failure, AV or bundle branch block, hyponatremia, troponin elevation, increased BNP, maximum oxygen uptake < 12 mg/kg/min

ACC/AHA HEART FAILURE EVALUATION GUIDELINES CLASS I & II RECOMMENDATIONS Laboratory Studies Blood count, urinalysis, electrolytes, renal function, glucose, LFTs (class I; level C) Thyroid stimulating hormone (class I; level C) Fe/TIBC, ferritin (class IIa, level C) Urinary screening for hemochromatosis (class IIa; level C) Measurement of ANA, rheumatoid factor, urinary VMA and metanepherines in selected patients (class IIa; level C) HIV testing (class IIb; level C)
Electrocardiogram (class I; level C)
Chest x-ray (class I; level C)

DILATED CARDIOMYOPATHY
ELECTROCARDIOGRAPHIC FINDINGS

Disease Etiology
Ischemic cardiomyopathy (n=15) Idiopathic cardiomyopathy (n=21) *LBBB (n=2); paced rhythm (n=1)
+

Pathologic Q-waves
10/12 (83%)*

2/21 (10%)+

LVH (n=10);

IVCD (n=3) # P < 0.003

SEGMENTAL WALL MOTION ABNORMALITIES IN DILATED CARDIOMYOPATHY

Regional wall motion abnormalities observed in at least

50% of patients with non-ischemic causes of dilated cardiomyopathy

Most frequent wall motion abnormalities:
anterior wall & apex

Posterior and lateral walls most likely to be preserved Type of abnormality:

hypokinesis

akinesis
dyskinesis (6%)

(83%) (11%)

Heterogeneity in regional oxidative metabolism using C-11

acetate clearance has been demonstrated in DCM

NONINVASIVE ASSESSMENT OF CORONARY ARTERY DISEASE IN NEW ONSET DILATED CARDIOMYOPATHY

Retrospective studies have shown up to 94% of patients

with idiopathic dilated cardiomyopathy will have myocardial perfusion defects

Reversible defect(s): Fixed defect(s): Reversible+ fixed defect(s):

60% 15% 25%

Global myocardial blood flow reserve (dipyridamole-

induced) is diminished in DCM patients compared to controls using PET imaging Low myocardial blood flow reserve correlates with high left ventricular wall stress and anaerobic metabolism

Ann Inter Med 1992;152:679-72; JACC 2000;35:19-28.

INDICATIONS FOR CORONARY ANGIOGRAPHY IN NEW ONSET CARDIOMYOPATHY

ACC/AHA CONSENSUS GUIDELINES (2001)
Patients with Known Coronary Artery Disease/Angina Pectoris
Revascularization recommended in vast majority of such individuals

with multivessel disease. Little role for non-invasive testing. Coronary angiography considered Class I Recommendation (Level of evidence: B)

Patients with Known Coronary Artery Disease Who Lack Angina

No controlled trials have examined whether coronary revascularization

can improve outcomes in this population Many centers first evaluate patient for myocardial hibernation Coronary angiography considered Class IIa Recommendation (Level of Evidence:C)

Patients with or without Chest Pain in Whom Coronary Artery

Disease has Not Been Evaluated

Approximately 35% of patients with IDCM will report angina-like pain Coronary angiography should be considered Class IIa recommendation

(Level of Evidence: C)

Hunt SA,et al. Circulation 2001;104:2996

ENDOMYOCARDIAL BIOPSY IN DILATED CARDIOMYOPATHY

RIGHT VENTRICULAR BIOPSY TECHNIQUE

INDICATIONS FOR ENDOMYOCARDIAL BIOPSY

Acute dilated cardiomyopathy with refractory heart failure

symptoms Rapidly progressive ventricular dysfunction in an unexplained cardiomyopathy of recent onset New onset cardiomyopathy with recurrent ventricular tachycardia or high grade heart block Heart failure in the setting of fever, rash, and peripheral eosinophilia Dilated cardiomyopathy in setting of systemic diseases known to affect the myocardium (systemic lupus erythematosus,
polymyositis, sarcoidosis)

Wu LA, et al. Mayo Clin Proc 2001;76:1030-8

SURVIVAL BY HISTOPATHOLOGICAL TYPE OF MYOCARDITIS

1.0

Proportion surviving

0.8 0.6 0.4 0.2 0.0 0 1 2 3

GCM group LM group

5
CP977755-6

Survival (yr)
Cooper, et al NEJM 1997

DILATED CARDIOMYOPATHY
PROVEN THERAPEUTIC OPTIONS TREATMENT INDICATIONS ACE Inhibitors Symptomatic heart failure and asymptomatic LV dysfunction ARBs ACE intolerance Hydralazine- nitrates ACE intolerance Diuretics Volume overload Potassium/Magnesium Diuretic-induced depletion Beta-blockers Symptomatic heart failure in addition to ACE inhibitor Digoxin Persistent heart failure despite diuretics, ACE inhibitor Warfarin Chronic or paroxysmal atrial fibrillation LV thrombus or prior embolic event ICD Cardiac arrest; uncontrolled VT

STATIN THERAPY IMPROVES VENTRICULAR FUNCTION IN DILATED CARDIOMYOPATHY

Node K, et al. Circulation 2003;108:839-43

CONTROLLED TRIAL OF IMMUNE GLOBULIN IN RECENT ONSET DILATED CARDIOMYOPATHY

Purpose: To determine whether intravenous immunoglobulin G

(IVIG) improves ejection fraction in adults with recent onset idiopathic dilated cardiomyopathy or myocarditis

Methods: 62 patients with symptomatic DCM Study Population:

Age (mean) LVEF Symptom duration Myocarditis

< 6 months and LVEF < 40% were randomized to receive IVIG 2 g/kg or placebo

43 12 yrs 25 8% 2.0 1.5 months 16%

McNamara et al. Circulation 2001;103:2254-9

IMMUNOGLOBULIN THERAPY FOR ACUTE DILATED CARDIOMYOPATHY:IMAC TRIAL RESULTS

McNamara et al. Circulation 2001;103:2254-9

IMMUNOADSORPTION THERAPY FOR DILATED CARDIOMYOPATHY 12 MONTH AUTOANTIBODY LEVELS BY TREATMENT GROUP

Muller J et al. Circulation 2000;101: 385 - 391

IMMUNOADSORPTION THERAPY FOR DILATED CARDIOMYOPATHY

12 MONTH CHANGE IN EJECTION FRACTION BY TREATMENT GROUP

Muller J et al. Circulation 2000;101: 385 - 391

EFFECT OF REMOVAL OF ANTIBODIES BY IMMUNOADSORPTION IN DILATED CARDIOMYOPATHY

n=12

Effect of column effluent on adult rat cardiocyte contractility

Felix SB, et al. JACC 2002;39:646-52

CONTROLLED TRIAL OF IMMUNOADSORPTION AND IMMUNOGLOBULIN SUBSTITUTION IN DILATED CARDIOMYOPATHY Hypothesis: Immunomodulatory therapy may decrease myocardial inflammation and improve ventricular systolic function Methods: 25 patients with DCM were randomized to immunoabsorption (IA) followed by IgG (0.5 gm/kg) replacement for 3 consecutive months (n=12) or conventional therapy (n=13): Age: 50 11 years LVEF: 20% 6% Symptom Duration: 4.0 years Fibrosis: 8.7% Primary End-points: Change in LVEF (3 month) Change in CD3+, CD4+ & CD8+ cells
Staudt A et al. Circulation 2001;103:2681-8

IMMUNOABSORPTION AND REPLACEMENT TREATMENT FOR DILATED CARDIOMYOPATHY

CHANGES IN CELLULAR INFILTRATION (3 months)

IA/IgG treatment resulted in a significant decline in all subtypes of infiltrating lymphocytes

** p < 0.05 vs baseline

++

p < 0.05 vs controls

Staudt A et al. Circulation 2001;103:2681-8

IMMUNOABSORPTION AND REPLACEMENT TREATMENT FOR DILATED CARDIOMYOPATHY

A marked decrease in myocardial HLAclass II antigen expression is evident after 3 months of treatment

(magnification X 400)

Staudt A et al. Circulation 2001;103:2681-8

CONTROLLED TRIAL OF IMMUNOADSORPTION AND IMMUNOGLOBULIN SUBSTITUTION IN DILATED CARDIOMYOPATHY CHANGE IN LEFT VENTRICULAR FUNCTION (3 Months)

**p <0.05 vs baseline

++p

< 0.01vs controls

Staudt A et al. Circulation 2001;103:2681-8

IMMUNOSUPPRESSIVE THERAPY FOR INFLAMMATORY DILATED CARDIOMYOPATHY

Purpose: To assess the efficacy of immunosuppressive therapy in patients with dilated cardiomyopathy and HLA up-regulation on biopsy. Study Population: 84 (of 202 DCM) patients had HLA class I or II expression on myocytes, endothelium or interstitial cells and were randomized to 24 months of conventional therapy [ digoxin, furosemide, spironolactone, ACE inhibitor, beta-blocker, nitrates, and amiodarone] alone or with concomitant immunosuppression [ prednisone 1mg/kg/day taper to 0.2 mg/kg/day for 90 days + azathioprine 1 mg/kg/day for 100 days].

Primary Endpoint:
Secondary Endpoints:

Death, transplantation or hospital readmission

LVEF, LVEDD, LVESD, NYHA class

Wojnicz R, et al. Circulation 2001;104:39-45

IMMUNOSUPPRESSIVE THERAPY FOR DILATED CARDIOMYOPATHY

CHANGE IN VENTRICULAR FUNCTION
Left Ventricular Ejection Fraction
45% 40% 35% 30% 25% 20% 15% 10% 5% 0%
Baseline 3 Month 6 Month 12 Month 24 Month

Placebo Immuno

Wojnicz R, et al. Circulation 2001;104:39-45

TALIAN UNCONTROLLED IMMUNOSUPPRESSIVE TRIAL OR MYOCARDITIS

112 patients had biopsy-proven lymphocytic myocarditis 41 patients had progressive symptoms for > 3 months duration and were treated with 6 months with prednisone (1 mg/kg/day x 4 wks; 0.33 mg/kg/day x 5 months) and azathioprine (2 mg/kg/day x 6 months) Efficacy of therapy was evaluated at 6 & 12 months Responders demonstrated: Decrease in NYHA class Increase in LVEF > 10 Units
Frustaci A, et al. Circulation 2003;107:857-63

ITALIAN UNCONTROLLED TRIAL OF IMMUNOSUPPRESSIVE THERAPY FOR MYOCARDITIS

50.00% 40.00% LVEF 30.00% 20.00% 10.00% 0.00% 1 2 3

BASELINE

6 MO

12 MO

Frustaci A, et al. Circulation 2003;107:857-63

IMMUNOSUPPRESSIVE THERAPY FOR MYOCARDITIS STUDY DESIGN

RESPONDERS NON-RESPONDERS

(N=21) Viral Genome 3 (14%) *

(N=20) 17 (85%) 0 (0%)

+

Cardiac Antibodies 19 (90%)#

* P < 0.001;
+ Enterovirus

# p < 0.001

5; EB virus 5; adenovirus 4; influenza 1; parvovirus 1

Frustaci A, et al. Circulation 2003;107:857-63

TREATMENT FOR IDIOPATHIC DILATED CARDIOMYOPATHY 2004 AND BEYOND

Conventional neurohormonal antagonists ? Anticoagulation (WATCH; WARCEF) ? ICD implantation (DEFINITE & SCD-HeFT) ? Immunosuppression vs immunomodulation Gene therapy (SERCA2a, phospholamban) Cellular transplantation
Fetal cardiomyocytes

Skeletal myoblasts
Adult (tissue) stem cells Embryonic stem cells

IMAC TRIAL RESULT:APOPTOSIS AND RECOVERY OF VENTRICULAR FUNCTION

Fas Expression and LV Recovery Six months Twelve months

40.0

50.0

40.0
30.0

20.0

Change in EF at 12 months (%)

30.0

20.0

10.0

10.0

0.0

0.0

-10.0 -20.0
6

-10.0
N= 8 6

N=

Low

Moderate

High

Low

Moderate

High

Fas gene expression

Fas gene expression

p=0.002

p=0.006
Sheppard, AHA 2003

Hypertrophic Cardiomyopathy

Definition

WHO

Left and/or Right ventricular hypertrophy, usually asymmetric and involves the interventricular septum.

Differential Diagnosis:
HCM
Can be asymmetric Wall thickness: > 15 mm

Athletic heart
Concentric & regresses < 15 mm

LA:

> 40 mm LVEDD : < 45 mm Diastolic function: always abnormal

< 40 mm
> 45 mm Normal

Stimulus
Unknown
Disorder of intracellular calcium metabolism Neural crest disorder Papillary muscle malpositioned and misoriented

Genetic abnormality
Autosomal dominant.
Mutations in genes for cardiac sarcomeric proteins. Polymorphism of ACE gene. -myosin heavy chain gene on chromosome 14.

Variants of HCM
Most common location: subaortic , septal, and ant. wall.
Asymmetric hypertrophy (septum and ant. wall): 70 %. Basal septal hypertrophy: 15- 20 %. Concentric LVH: 8-10 %. Apical or lateral wall: < 2 % (25 % in Japan/Asia):

characteristic giant T-wave inversion laterally & spadelike left ventricular cavity: more benign.

Hypertensive hypertrophic Cardiomyopathy

Elderly women
Simulates HCM Prognosis better than non-hypertensive HCM

Pathophysiology of HCM
Dynamic LV outflow tract obstruction
Diastolic dysfunction Myocardial ischemia Mitral regurgitation Arrhythmias

 Left ventricular outflow tract gradient

with decreased preload, decreased afterload, or

increased contractility. Venturi effect: anterior mitral valve leaflets & chordae sucked into outflow tract obstruction, eccentric jet of MR in mid-late systole.

Maneuvers that end-diastolic volume ( venous return & afterload, contractility) Vasodilators Inotropes Dehydration Valsalva Amyl nitrite Exercise HCM murmur

Arrhythmias: Sustained V-Tach and V-Fib: most likely mechanism of syncope/ sudden death.
Dependant on atrial kick: CO by 40 % if A. Fib

present.

Histology:
Myocardial fiber disarray, endocardial plaques.
Abnormal relaxation and diversely oriented

myocardial fibers. Intimal hyperplasia of intramural coronary arteries, endothelial dysfunction, myocardial perfusion defects.

Clinical presentation:
Any age
Leading cause of sudden death in competitive athletes Triad: DOE, angina, presyncope/syncope.

Physical exam:
Apex localized, sustained Palpable S4 Tripple ripple Prominent a wave Rapid upstroke carotid pulse, jerky bifid (spikeand-dome pulse) Harsh systolic ejection murmur across entire precordium apex & heart base MR: separate murmur: severity of MR related to degree of outflow obstruction

EKG:

Echocardiography:
2D-echo: Asymmetric septal hypertrophy Diffuse concentric or localized to apex/anterior wall Systolic anterior motion of MV (SAM)

Doppler Echocardiocraphy: Typical appearance: late-peaking signal daggershaped Bernoulli for peak systolic gradient (+ maneuvers) Obstructive or non-obstructive Distinguish MR and intra-cavitary obstruction (looking for the aortic closure signal)

Cardiac cath:
Not necessary

Brockenbrough response
LV systolic pressure
Ao systolic pressure gradient between LV & Ao

Post PVC

Brockenbrough response

Imitator of HCM
Amyloidosis:

Thickened walls & low voltage on EKG.

Natural history of HCM

Mortality: 3 %/year (6-8 % with NSVTach)
Poor prognosis:

- Younger age - Male sex - + family hx. of sudden death - Hx. of syncope - Genetic markers (mutations of arginine gene) - Exercise-induced hypotension (worst)

Genetic defect and prognosis

Management
All first degree relatives: screening

echocardiography/genetic counseling Avoid competitive athletics Prophylactic antibiotics before medical & dental procedures Holter x 48 hours

 - Blockers: Propranolol 200-400 mg/d

(large doses)/ Selective - B lose selectivity at high doses: Slow HR longer diastolic filling time myocardial O2 consumption myocardial ischemia & LVOT obstruction CaCh- Blockers: Verapamil 240-320 mg/d (with caution for hemodynamic deterioration) Combination of both

 Disopyramide: class I antiarrhythmic + strong ive

inotropic effect

Non-responders to Medical therapy ???

1- Surgery (Myotomy/Myectomy) +/- MVR 2- ICD 3- DDD pacemaker 4- NSRT (alcohol septal ablation)

1- Surgery:
Septal myotomy/myectomy: Patients < 40 years: mortality < 1 % Patients > 65 years: mortality 10-15 % Survival better than medically treated patients Should be considered in: resting gradient > 50 mmHg, or refractory to medical Rx. Young patients, particularly those with severe disease Additional structural abnormalities affecting the mitral valve or coronary arteries.
Complication (rare): Aortic incompetence

Myotomy/Myectomy

2- ICD:
Previous sudden death
High risk of sudden death EPS use ?

3- DDD pacemaker

Substantial gradient(~ 50 %)

Effect of DDD pacemaker in HCM

Potential Mechanisms of benefit of Pacing in HCM:

RV apical pacing & maintenance of AV synchrony

abnormal pattern of septal contraction early systolic bulging of hypertrophic subaortic septum in LVOT & Venturi forces that produce SAM. LVOT width during systole systolic hypercontractility: end-systolic volume intraventricular pressure gradients & myocardial work

 MR
May favorably alter diastolic function LVH regression

Candidates for DDD

4- Alcohol septal ablation (NSRT)

Controlled myocardial infarction

of the basal ventricular septum to gradient. First septal artery occluded with a balloon catheter and ETOH injected distally

NSRT (Non Surgical Septal Reduction Therapy)

The most appropriate candidates for NSRT should meet all of the following criteria : - HCM with severe symptoms of heart failure (NYHA class III to IV) despite adequate tolerated drug therapy - An LVOT gradient 50 mmHg at rest or after exercise or >30 mmHg at rest or 60 mmHg under stress - Basal septal thickness 18 mm - NYHA class II heart failure with a resting LVOTgradient >50 mmHg or >30 mmHg at rest and 100 mmHg with stress . - Elderly or comorbidities that may increase the risk of surgical correction.

Hypertrophic Cardiomyopathy

Definition:

WHO: left and/or right ventricular hypertrophy, usually asymmetric and involves the interventricular septum.

Differential Diagnosis:
HCM
Can be asymmetric Wall thickness: > 15 mm

Athletic heart
Concentric & regresses < 15 mm

LA:

> 40 mm LVEDD : < 45 mm Diastolic function: always abnormal

< 40 mm
> 45 mm Normal

Stimulus:
Unknown
Disorder of intracellular calcium metabolism Neural crest disorder Papillary muscle malpositioned and misoriented

Genetic abnormality:
Autosomal dominant.
Mutations in genes for cardiac sarcomeric proteins. Polymorphism of ACE gene. -myosin heavy chain gene on chromosome 14.

Most common location: subaortic , septal, and ant. wall. Variants of HCM:
Asymmetric hypertrophy (septum and ant. wall): 70 %. Basal septal hypertrophy: 15- 20 %. Concentric LVH: 8-10 %.

Apical or lateral wall: < 2 % (25 % in Japan/Asia):

characteristic giant T-wave inversion laterally & spadelike left ventricular cavity: more benign.

Hypertensive hypertrophic Cardiomyopathy

Elderly women
Simulates HCM Prognosis better than non-hypertensive HCM

Pathophysiology of HCM
Dynamic LV outflow tract obstruction
Diastolic dysfunction Myocardial ischemia Mitral regurgitation Arrhythmias

 Left ventricular outflow tract gradient

with decreased preload, decreased afterload, or

increased contractility. Venturi effect: anterior mitral valve leaflets & chordae sucked into outflow tract obstruction, eccentric jet of MR in mid-late systole.

Maneuvers that end-diastolic volume ( venous return & afterload, contractility) Vasodilators Inotropes Dehydration Valsalva Amyl nitrite Exercise HCM murmur

Arrhythmias: Sustained V-Tach and V-Fib: most likely mechanism of syncope/ sudden death.
Dependant on atrial kick: CO by 40 % if A. Fib

present.

Histology:
Myocardial fiber disarray, endocardial plaques.
Abnormal relaxation and diversely oriented

myocardial fibers. Intimal hyperplasia of intramural coronary arteries, endothelial dysfunction, myocardial perfusion defects.

Clinical presentation:
Any age
Leading cause of sudden death in competitive athletes Triad: DOE, angina, presyncope/syncope.

Physical exam:
Apex localized, sustained Palpable S4 Tripple ripple Prominent a wave Rapid upstroke carotid pulse, jerky bifid (spikeand-dome pulse) Harsh systolic ejection murmur across entire precordium apex & heart base MR: separate murmur: severity of MR related to degree of outflow obstruction

EKG:

Echocardiography:
2D-echo: Asymmetric septal hypertrophy Diffuse concentric or localized to apex/anterior wall Systolic anterior motion of MV (SAM)

Doppler Echocardiocraphy: Typical appearance: late-peaking signal daggershaped Bernoulli for peak systolic gradient (+ maneuvers) Obstructive or non-obstructive Distinguish MR and intra-cavitary obstruction (looking for the aortic closure signal)

Cardiac cath:
Not necessary

Brockenbrough response
LV systolic pressure
Ao systolic pressure gradient between LV & Ao

Post PVC

Brockenbrough response

Imitator of HCM
Amyloidosis:

Thickened walls & low voltage on EKG.

Natural history of HCM

Mortality: 3 %/year (6-8 % with NSVTach)
Poor prognosis:

- Younger age - Male sex - + family hx. of sudden death - Hx. of syncope - Genetic markers (mutations of arginine gene) - Exercise-induced hypotension (worst)

Genetic defect and prognosis

Management
All first degree relatives: screening

echocardiography/genetic counseling Avoid competitive athletics Prophylactic antibiotics before medical & dental procedures Holter x 48 hours

 - Blockers: Propranolol 200-400 mg/d

(large doses)/ Selective - B lose selectivity at high doses: Slow HR longer diastolic filling time myocardial O2 consumption myocardial ischemia & LVOT obstruction CaCh- Blockers: Verapamil 240-320 mg/d (with caution for hemodynamic deterioration) Combination of both

 Disopyramide: class I antiarrhythmic + strong ive

inotropic effect

Non-responders to Medical therapy ???

1- Surgery (Myotomy/Myectomy) +/- MVR 2- ICD 3- DDD pacemaker 4- NSRT (alcohol septal ablation)

1- Surgery:
Septal myotomy/myectomy: Patients < 40 years: mortality < 1 % Patients > 65 years: mortality 10-15 % Survival better than medically treated patients Should be considered in: resting gradient > 50 mmHg, or refractory to medical Rx. Young patients, particularly those with severe disease Additional structural abnormalities affecting the mitral valve or coronary arteries.
Complication (rare): Aortic incompetence

Myotomy/Myectomy

2- ICD:
Previous sudden death
High risk of sudden death EPS use ?

3- DDD pacemaker

Substantial gradient(~ 50 %)

Effect of DDD pacemaker in HCM

Potential Mechanisms of benefit of Pacing in HCM:

RV apical pacing & maintenance of AV synchrony

abnormal pattern of septal contraction early systolic bulging of hypertrophic subaortic septum in LVOT & Venturi forces that produce SAM. LVOT width during systole systolic hypercontractility: end-systolic volume intraventricular pressure gradients & myocardial work

 MR
May favorably alter diastolic function LVH regression

Candidates for DDD

4- Alcohol septal ablation (NSRT)

Controlled myocardial infarction

of the basal ventricular septum to gradient. First septal artery occluded with a balloon catheter and ETOH injected distally

NSRT (Non Surgical Septal Reduction Therapy)

The most appropriate candidates for NSRT should meet all of the following criteria : - HCM with severe symptoms of heart failure (NYHA class III to IV) despite adequate tolerated drug therapy - An LVOT gradient 50 mmHg at rest or after exercise or >30 mmHg at rest or 60 mmHg under stress - Basal septal thickness 18 mm - NYHA class II heart failure with a resting LVOTgradient >50 mmHg or >30 mmHg at rest and 100 mmHg with stress . - Elderly or comorbidities that may increase the risk of surgical correction.

DEFINITION WHO
RCM as a myocardial disease characterized by

restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness.

The hallmark of the restrictive cardiomyopathies is

abnormal diastolic function; the ventricular walls are excessively rigid and impede ventricular filling.

Types based on etiology

Primary or Idiopathic Familial
Secondary Amyloidosis (commonest) Sarcoidosis Endomyocardial fibrosis

 Gradually worsening shortness of breath, progressive

Symptoms

exercise intolerance, and fatigue. This exertional dyspnea reflects the left heart failure.
Fatigue and weakness are results of the decreased stroke

volume.
Patients may have distention of the abdomen and

bilateral swollen feet (right heart failure).

Angina like chest pains are observed only in patients with

amyloidosis.

 Patients may complain of palpitations (atrial fibrillation),

Symptoms

which are common in idiopathic RCM. As many as one third of patients with idiopathic RCM may present with thromboembolic complications. Patients may have a history of syncopal attacks. Conduction disturbances particularly are common in infiltrative RCM. Depending on the etiology, patients may have a prior history of radiation therapy, heart transplantation, chemotherapy, or a systemic disease.

Signs
GPE Px may be more comfortable sitting Px may have minimal to moderate ascites and pitting pedal edema

CVS Exam The pulse is low volume, consistent with decreased stroke volume.

Signs
High JVP with diastolic collapse (Friedreich's sign). JVP with rapid X and Y descents, but the most

prominent wave is the Y descent (atrium emptying into the stiff ventricle) Elevation of JVP with inspiration (Kussmaul's sign). S4 in early disease (forceful atrial contraction against a stiff ventricle). S3 in advanced disease. Murmurs due to mitral and tricuspid valve regurgitation may be present.

Signs
Resp. Exam. Reduced breath sounds because of pleural effusion Crepitations due to left heart failure

Abd. Exam. In advanced cases, liver may be palpable and pulsatile.

 The goal of treatment in RCM is to reduce symptoms

by lowering elevated filling pressures without significantly reducing the cardiac output.

Investigations
CXR Pulmonary venous congestion .The cardiac silhouette can be normal (familial) or show cardiomegaly and/or atrial enlargement. ECG usually has low-voltage and ST segment and T wave abnormalities. Echocardiogram symmetrical myocardial thickening and often a normal systolic ejection fraction, but impaired ventricular filling.

 Cardiac catheterization and haemodynamic studies

help distinction from constrictive pericarditis.

Endomyocardial biopsy in contrast with other

cardiomyopathies is often useful in this condition and may permit a specific diagnosis such as amyloidosis to be made.

DIFFERENTIAL DIAGNOSIS
Constrictive Pericarditis Pericardial calcification on x-ray, which occurs in constrictive pericarditis, is absent. Right ventricular transvenous endomyocardial biopsy (by revealing myocardial infiltration or fibrosis in restrictive cardiomyopathy) CT scan or MRI (by demonstrating a thickened pericardium in constrictive pericarditis).

pericarditis and restrictive cardiomyopathy

Clinical Features History Constrictive Pericarditis Restrictive Cardiomyopathy

Prior history of pericarditis History of systemic disease or condition that causes (eg, amyloidosis, pericardial disease hemochromatosis) Peripheral stigmata of systemic disease Pericardial knock, highfrequency sound No murmurs Pericardial calcification Presence of loud diastolic filling sound S3, Lowfrequency sound Murmurs of mitral and tricuspid insufficiency Normal results of prior chest x-ray

General examination Systemic examination Heart sounds Murmurs Prior chest x-ray

TREATMENT & PROGNOSIS

There is no specific treatment.
Cardiac failure and embolic manifestations should be

treated.
Cardiac transplantation should be considered in some

severe cases, especially the idiopathic variety.

In primary amyloidosis, combination therapy with

melphalan plus prednisolone with or without colchicine may improve survival.

 However, patients with cardiac amyloidosis have a

worse prognosis than those with other forms of the disease, and the disease often recurs after transplantation.

Liver transplantation may be effective in familial

amyloidosis (due to production of mutant prealbumin) and may lead to reversal of the cardiac abnormalities.