Hypertrophic Cardiomyopathy

Case
17 yo male professional basketball player with no known past medical hx collapses on the playing floor during practice and subsequently arrests. He had been having some exertional dyspnea for a few months prior to this incident but it did not affect his activity level. He was told growing up that he had a heart murmur that was never formally investigated. He was taking no medications, and there was no family history of cardiac disease in his family. An autopsy later revealed that the patient had hypertrophic cardiomyopathy.

Background

Prevalence of HCM: 1:500 to 1:1000 individuals

This occurrence is higher than previously thought, suggesting a large number of affected but undiagnosed people

Global disease with most cases reported from USA, Canada, Western Europe, Israel, & Asia

Historical Perspective

HCM was initially described by Teare in 1958

Found massive hypertrophy of ventricular septum in small cohort of young patients who died suddenly

Braunwald was the first to diagnose HCM clinically in the 1960s Many names for the disease
Idiopathic hypertrophic subaortic stenosis (IHSS) Muscle subaortic stenosis Hypertrophic obstructive cardiomyopathy (HOCM)

Genetic Basis of HCM

Causes: Inherited, acquired, unknown Autosomal dominant inheritance pattern >450 mutations in 13 cardiac sarcomere & myofilament-related genes identified ?? Role for environmental factors

Alcalai et al. J Cardiovasc Electrophysiol. 19(1): Jan 2008.

Genetics of HCM

Alcalai et al. J Cardiovasc Electrophysiol 2008;19:105.

Pedigree

autosomnal dominant passed on from affected males and females The disease does not skip generations

Pathophysiology of HCM
The pathophysiology of HCM involves 4 interrelated processes: Left ventricular outflow obstruction Diastolic dysfunction Myocardial ischemia Mitral regurgitation

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 & spade-like left ventricular cavity: more benign.

LV Outflow Obstruction in HCM

Long-standing LV outflow obstruction is a major determinant for heart failure symptoms and death in HCM patients Subaortic outflow obstruction is caused by systolic anterior motion (SAM) of the mitral valve leaflets move toward the septum

LV Outflow Obstruction in HCM

Physiological Consequences of Obstruction

Elevated intraventricular pressures Prolongation of ventricular relaxation Increased myocardial wall stress Increased oxygen demand Decrease in forward cardiac output

The myocardial disarray

Microscopic examination of the heart muscle shows that it is abnormal. The normal alignment of muscle cells is absent and this abnormality is called myocardial disarray. This disarray can contribute to an irregular heartbeat (arrhythmia) in some people.

Massive left ventricular hypertrophy, mainly confined to the septum

Histopathology showing significant myofiber disarray and interstitial fibrosis

Cell Research. 2003;13(1):10.

Pathophysiology of HCM

Diastolic Dysfunction
Contributing factor in 80% of patients Impaired relaxation

High systolic contraction load Ventricular contraction/relaxation not uniform

Accounts for symptoms of exertional dyspnea

Abnormal diastolic filling increased pulmonary venous pressure

Pathophysiology of HCM

Myocardial Ischemia
Often occurs without atherosclerotic coronary artery disease Postulated mechanisms

Abnormally small and partially obliterated intramural coronary arteries as a result of hypertrophy Inadequate number of capillaries for the degree of LV mass

Pathophysiology of HCM

Mitral Regurgitation
Results from the systolic anterior motion of the mitral valve Severity of MR directly proportional to LV outflow obstruction Results in symptoms of dyspnea, orthopnea in HCM patients

Integrated Pathophysiology

Braunwald. Atlas of Heart Diseases: Cardiomyopathies, Myocarditis, and Pericardial Disease. 1998.

Clinical Presentation

Dyspnea on exertion (90%), orthopnea, PND Angina (70-80%) Syncope (20%), Presyncope (50%)

outflow obstruction worsens with increased contractility during exertional activities

Sudden cardiac death

HCM is most common cause of SCD in young people, including athletes

Physical Examination

Carotid Pulse

Bifid short upstroke & prolonged systolic ejection

Prominent a wave decreased ventricular compliance Double or triple S4 usually present due to hypertrophy

Jugular Venous Pulse

Apical Impulse

Heart Sounds

Physical Examination

Murmur
Medium-pitch crescendo-decrescendo systolic murmur along LLSB without radiation Dynamic maneuvers Murmur intensity increases with decreased preload (i.e. Valsalva) Murmur intensity decreases with increased preload (i.e. squatting, hand grip)

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

Physical Examination in HCM

Braunwald E. Atlas of Internal Medicine. 2007.

Diagnostic Evaluation

Electrocardiogram Echocardiogram Catheterization

Electrocardiogram in HCM

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

Echocardiography in HCM

Transesophageal Echo

Cardiac Catheterization
Coronary angiography is not typically necessary in HCM

Hyperdynamic systole function results in almost complete obliteration of the LV cavity

Disease Progression in HCM

ACC Consensus Document. J Am Coll Cardiol. 2003;42(9):1693.

Sudden Cardiac Death in HCM

Most frequent in young adults <30-35 years old Primary VF/VT Tend to die during or just following vigorous physical activity Often is 1st clinical manifestation of disease HCM is most common cause of SCD among young competitive athletes

J Am Coll Cardiol. 2003;42(9):1693.

SCD in Competitive Athletes

Maron B. Atlas of Heart Diseases. 1996

Natural History of HCM

Heart Failure

Atrial Fibrillation

Only 10-15% progress to NYHA III-IV Only 3% will become truly end-stage with systolic dysfunction

Prevalent in up to 30% of older patients Dependent on atrial kick CO decreases by 40% if AF present
25% of HCM patients Associated with poor prognosis

Endocarditis

Autonomic Dysfunction

4-5% of HCM patients Usually mitral valve affected

Treatment of HCM

Medical therapy Device therapy Surgical septal myectomy Alcohol septal ablation

Medical Therapy

Beta-blockers
Increase ventricular diastolic filling/relaxation Decrease myocardial oxygen consumption Have not been shown to reduce the incidence of SCD

Verapamil

Augments ventricular diastolic filling/relaxation

Disopyramide
Used in combination with beta-blocker Negative inotrope

Diuretics

Dual-Chamber Pacing

Proposed benefit: pacing the RV apex will decrease the outflow tract gradient Several RCTs have found that the improvement in subjective measures provided by dual-chamber pacing is likely a placebo effect Objective measures such as exercise capacity and oxygen consumption are not improved No correlation has been found between pacing and reduction of LVOT gradient

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

Surgical Septal Myectomy

Nishimura RA et al. NEJM. 2004. 350(13):1320.

Alcohol Septal Ablation

Braunwald. Atlas of Heart Diseases: Cardiomyopathies, Myocarditis, and Pericardial Disease. 1998.

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.

Alcohol Septal Ablation

Successful short-term outcomes

LVOT gradient reduced from a mean of 60-70 mmHg to <20 mmHg Symptomatic improvements, increased exercise tolerance

Long-term data not available yet Complications

Complete heart block Large myocardial infarctions

No randomized efficacy trials yet for alcohol septal ablation vs. surgical myectomy

Efficacy of Therapeutic Strategies

Nishimura et al. NEJM. 2004. 350(13):1323.

Implantable Cardioverter
Defibrillators in HCM
Primary & Secondary Prevention

Risk Stratification ICDs

Primary Prevention Risk Factors for SCD

Premature HCM-related sudden death in more than 1 relative History of unexplained syncope Multiple or prolonged NSVT on Holter Hypotensive blood pressure response to exercise Massive LVH

HCM vs. Athletes Heart

Circulation 1995;91.

Differential Diagnosis:
HCM

Athletic heart

Can be asymmetric Wall thickness: > 15 mm LA: > 40 mm LVEDD : < 45 mm Diastolic function: always abnormal

Concentric & regresses < 15 mm < 40 mm > 45 mm Normal

Thank You!