HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM)

Hypertrophic Hypertrophic Obstructive Obstructive

CardiomyopathyCardiomyopathy

Dr KURIAN JOSEPHDr KURIAN JOSEPHJOURNAL PRESENTATIONJOURNAL PRESENTATION

Historical Perspective Historical Perspective

HCM was initially described by Teare in HCM was initially described by Teare in 1958 1958

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

Braunwald was the first to diagnose HCM Braunwald was the first to diagnose HCM clinically in the 1960s clinically in the 1960s

Many names for the disease Many names for the disease Idiopathic hypertrophic subaortic stenosis (IHSS)Idiopathic hypertrophic subaortic stenosis (IHSS) Muscle subaortic stenosis Muscle subaortic stenosis Hypertrophic obstructive cardiomyopathy (HOCM)Hypertrophic obstructive cardiomyopathy (HOCM)

Background Background

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

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

Men and African-Americans affected by Men and African-Americans affected by almost 2:1 ratio over women and almost 2:1 ratio over women and Caucasians Caucasians

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

Pathophysiology of HCMPathophysiology of HCM

The pathophysiology of HCM involves The pathophysiology of HCM involves 4 interrelated processes:4 interrelated processes: Left ventricular outflow Left ventricular outflow

obstruction obstruction Diastolic dysfunction Diastolic dysfunction Myocardial ischemia Myocardial ischemia Mitral regurgitation Mitral regurgitation

Systolic Anterior Motion -Systolic Anterior Motion -SAMSAM

Subaortic outflow obstruction is Subaortic outflow obstruction is caused by systolic anterior motion caused by systolic anterior motion (SAM) of the mitral valve - leaflets (SAM) of the mitral valve - leaflets toward the ventircular septumtoward the ventircular septum

SAM is generated by SAM is generated by

Venturi effectVenturi effect

A drag effectA drag effect

LV Outflow Obstruction LV Outflow Obstruction in HCMin HCM

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

Maron MS et al. NEJM. 2003;348:295.


Diastolic Dysfunction Diastolic Dysfunction Contributing factor in 80% of patients Contributing factor in 80% of patients Impaired relaxation Impaired relaxation

High systolic contraction load High systolic contraction load Ventricular contraction/relaxation not Ventricular contraction/relaxation not

uniform uniform Accounts for symptoms of exertional Accounts for symptoms of exertional

dyspneadyspnea Abnormal diastolic filling Abnormal diastolic filling increased increased

pulmonary venous pressure pulmonary venous pressure


Myocardial Ischemia Myocardial Ischemia Often occurs without atherosclerotic Often occurs without atherosclerotic

coronary artery disease coronary artery disease Postulated mechanismsPostulated mechanisms

Abnormally small and partially obliterated Abnormally small and partially obliterated intramural coronary arteries as a result of intramural coronary arteries as a result of hypertrophy hypertrophy

Inadequate number of capillaries for the Inadequate number of capillaries for the degree of LV mass degree of LV mass


Mitral Regurgitation Mitral Regurgitation Results from the systolic anterior Results from the systolic anterior

motion of the mitral valve motion of the mitral valve Severity of MR directly proportional to Severity of MR directly proportional to

LV outflow obstruction LV outflow obstruction Results in symptoms of dyspnea, Results in symptoms of dyspnea,

orthopnea in HCM patients orthopnea in HCM patients

Integrated Integrated PathophysiologyPathophysiology

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

MicroscopyMicroscopyThe microscopy of HOCM demonstratesThe microscopy of HOCM demonstrates

Myocyte hypertrophyMyocyte hypertrophy Myocardial fibre disarryMyocardial fibre disarry Interstitial and perivascular fibrosisInterstitial and perivascular fibrosis Intimal and medial hypertrophy in Intimal and medial hypertrophy in

intramural arteries.intramural arteries.

These changes lead to These changes lead to LV diastolic dysfunction by impairing LV diastolic dysfunction by impairing relaxation and reducing compliance and relaxation and reducing compliance and scarring of the myocardium. scarring of the myocardium.

Massive left ventricular hypertrophy, mainly confined to the septum

Histopathology showing significant myofiber disarray and interstitial fibrosis

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

Genetic Basis of HCM Genetic Basis of HCM Autosomal dominant Autosomal dominant

trait trait Mutations usually in Mutations usually in B-myosin heavy B-myosin heavy

chain, Myosin chain, Myosin binding proteinC and binding proteinC and cardiac troponin T. cardiac troponin T.

>450 mutations in 13 >450 mutations in 13 cardiac sarcomere & cardiac sarcomere & myofilament-related myofilament-related genes identified genes identified

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

Genetics of HCMGenetics of HCM

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

Clinical Presentation Clinical Presentation

Dyspnea on exertion (90%), Dyspnea on exertion (90%), orthopnea, PND orthopnea, PND

Angina (70-80%) Angina (70-80%) Syncope (20%), Presyncope (50%) Syncope (20%), Presyncope (50%)

outflow obstruction worsens with outflow obstruction worsens with increased contractility during exertional increased contractility during exertional activities activities

Sudden cardiac deathSudden cardiac death HCM is most common cause of SCD in HCM is most common cause of SCD in

young people, including athletes young people, including athletes

Physical Examination Physical Examination

Carotid PulseCarotid Pulse Bifid – short upstroke & prolonged systolic Bifid – short upstroke & prolonged systolic

ejection ejection

Jugular Venous Pulse Jugular Venous Pulse Prominent Prominent a wavea wave – decreased ventricular – decreased ventricular

compliance compliance

Apical Impulse Apical Impulse Double or triple Double or triple

Heart SoundsHeart Sounds S4 usually present due to hypertrophy S4 usually present due to hypertrophy

Physical Examination Physical Examination

MurmurMurmur Medium-pitch crescendo-decrescendo systolic Medium-pitch crescendo-decrescendo systolic

murmur along LLSB without radiation murmur along LLSB without radiation Dynamic maneuvers Dynamic maneuvers

Murmur intensity increases with decreased Murmur intensity increases with decreased preload (i.e. Valsalva)preload (i.e. Valsalva)

Murmur intensity decreases with increased Murmur intensity decreases with increased preload (i.e. squatting, hand grip) preload (i.e. squatting, hand grip)

Dynamic murmur of HOCMDynamic murmur of HOCM

Smaller LV volume brings septum Smaller LV volume brings septum closer to anterior MV leaflet: more closer to anterior MV leaflet: more obstruction and louder murmur. obstruction and louder murmur.

Larger LV volume separates upper Larger LV volume separates upper septum from anterior MV leaflet: septum from anterior MV leaflet: less obstruction and softer murmur.less obstruction and softer murmur.

How to alter LV volumeHow to alter LV volume

Increase LV Increase LV volumevolume SquattingSquatting Isometric handgripIsometric handgrip Beta BlockersBeta Blockers PhenylephrinePhenylephrine Passive leg liftingPassive leg lifting Slow heart rateSlow heart rate IV volume infusionIV volume infusion

Decrease LV Decrease LV volumevolume Stand (after Stand (after

squatting)squatting) Valsalva maneuverValsalva maneuver Amyl nitrateAmyl nitrate NitroglycerinNitroglycerin Increase heart rateIncrease heart rate Volume depletioVolume depletionn IsoproterenolIsoproterenol ExerciseExercise

Physical Examination in Physical Examination in HCMHCM

Braunwald E. Atlas of Internal Medicine. 2007.

Diagnostic Evaluation Diagnostic Evaluation

ElectrocardiogramElectrocardiogram Echocardiogram Echocardiogram Catheterization Catheterization

Electrocardiogram in Electrocardiogram in HCMHCM

Echocardiography in Echocardiography in HCMHCM

Transesophageal EchoTransesophageal Echo

Coronary AngiographyCoronary Angiography

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

Coronary angiography demonstrate Septal bulge on LV cavity.

Cardiac Magnetic Cardiac Magnetic ResonanceResonance

CMR demonstrates myocardial scarring, CMR demonstrates myocardial scarring, which differentiate HCM from other LV which differentiate HCM from other LV hypertrophieshypertrophies

CMR is indicated when ECHO views are CMR is indicated when ECHO views are limited due to unusual distribution of limited due to unusual distribution of hypertrophy, or to detect milder hypertrophy, or to detect milder magnitudes of hypertrophy.magnitudes of hypertrophy.

CMR with gadolinium enhancement CMR with gadolinium enhancement imaging will detect myocardial scarring in imaging will detect myocardial scarring in about two thirds of HOCM patients. about two thirds of HOCM patients.

Sudden Cardiac Death Sudden Cardiac Death Unfortunately, SCD can be the first clinical Unfortunately, SCD can be the first clinical

manifestation. manifestation. Occur in 15% of patients with HOCMOccur in 15% of patients with HOCM SCD is seen more in young patients during and SCD is seen more in young patients during and

after physical exercise. after physical exercise. High SCD association is seen in High SCD association is seen in Prior cardiac arrestPrior cardiac arrest

First degree relative with HOCM and SCDFirst degree relative with HOCM and SCDMultiple syncope associated with syncopeMultiple syncope associated with syncopeNon sustained VTNon sustained VT

Treatment of choice is ICD.Treatment of choice is ICD.Strenuous sports should be avoided. Strenuous sports should be avoided. No evidence that medical Rx reduces the rick of SCDNo evidence that medical Rx reduces the rick of SCD

Clinical Course of HCM Clinical Course of HCM

Heart Failure Heart Failure Only 10-15% progress Only 10-15% progress

to NYHA III-IV to NYHA III-IV Only 3% will become Only 3% will become

truly end-stage with truly end-stage with systolic dysfunction systolic dysfunction

Endocarditis Endocarditis 4-5% of HCM patients 4-5% of HCM patients Usually mitral valve Usually mitral valve

affected affected

Atrial Fibrillation Atrial Fibrillation Prevalent in up to Prevalent in up to

30% of older patients30% of older patients Dependent on atrial Dependent on atrial

kick – CO decreases kick – CO decreases by 40% if AF present by 40% if AF present

Autonomic Autonomic Dysfunction Dysfunction 25% of HCM patients 25% of HCM patients Associated with poor Associated with poor

prognosis prognosis

Disease Progression in Disease Progression in HCMHCM

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

Treatment of HCM Treatment of HCM

Medical therapy Medical therapy Device therapy Device therapy Surgical septal myectomy Surgical septal myectomy Alcohol septal ablationAlcohol septal ablation

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

Medical Therapy Medical Therapy

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

of SCD of SCD Verapamil Verapamil

Augments ventricular diastolic Augments ventricular diastolic filling/relaxation filling/relaxation

Disopyramide Disopyramide Used in combination with beta-blocker Used in combination with beta-blocker Negative inotrope Negative inotrope

Septal MyectomySeptal Myectomy

In symptomatic patients despite In symptomatic patients despite medical Rxmedical Rx

With gradient >50mm Hg at rest or With gradient >50mm Hg at rest or provocationprovocation

After aortic cross-clamping and After aortic cross-clamping and aortotomy, bar of myocardium is aortotomy, bar of myocardium is excised from proximal septum.excised from proximal septum.

Complications include total AV block Complications include total AV block and VSD.and VSD.

Surgical Septal Surgical Septal MyectomyMyectomy

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

Alcohol Septal Ablation Alcohol Septal Ablation

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

Alcohol Septal Ablation Alcohol Septal Ablation

Before After

Alcohol Septal Ablation Alcohol Septal Ablation Successful short-term outcomesSuccessful short-term outcomes

LVOT gradient reduced from a mean of 60-70 LVOT gradient reduced from a mean of 60-70 mmHg to <20 mmHg mmHg to <20 mmHg

Symptomatic improvements, increased exercise Symptomatic improvements, increased exercise tolerance tolerance

Long-term data not available yet Long-term data not available yet Complications Complications

Complete heart blockComplete heart block Large myocardial infarctionsLarge myocardial infarctions

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

Circulation. 2008; 18(2): 131-9.

Dual-Chamber Pacing Dual-Chamber Pacing

Proposed benefit: pacing the RV apex will Proposed benefit: pacing the RV apex will decrease the outflow tract gradient decrease the outflow tract gradient

Several RCTs have found that the Several RCTs have found that the improvement in subjective measures improvement in subjective measures provided by dual-chamber pacing is likely provided by dual-chamber pacing is likely a placebo effect a placebo effect

Objective measures such as exercise Objective measures such as exercise capacity and oxygen consumption are not capacity and oxygen consumption are not improved improved

No correlation has been found between No correlation has been found between pacing and reduction of LVOT gradient pacing and reduction of LVOT gradient

Efficacy of Therapeutic Efficacy of Therapeutic StrategiesStrategies

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

Implantable Cardioverter Implantable Cardioverter

Defibrillators in HCMDefibrillators in HCM Primary & Secondary Primary & Secondary

Prevention Prevention

Maron BJ et al. NEJM 2000;342:365-73.

Appropriate discharges Appropriate discharges in 23% of patients in 23% of patients

Rate of appropriate Rate of appropriate discharges of 7% per discharges of 7% per year year

Of 21 patients for which Of 21 patients for which intracardiac intracardiac electrograms were electrograms were available, 10 shocks for available, 10 shocks for VT, 9 shocks for VFVT, 9 shocks for VF

Suggested role for ICDs Suggested role for ICDs in primary & secondary in primary & secondary prevention of SCDprevention of SCD

Risk Stratification – ICDs Risk Stratification – ICDs

Primary Prevention Risk Factors for SCD Primary Prevention Risk Factors for SCD Premature HCM-related sudden death in Premature HCM-related sudden death in

more than 1 relative more than 1 relative History of unexplained syncope History of unexplained syncope Multiple or prolonged NSVT on Holter Multiple or prolonged NSVT on Holter Hypotensive blood pressure response to Hypotensive blood pressure response to

exercise exercise Massive LVH Massive LVH

How many risk factors warrant ICD How many risk factors warrant ICD placement?placement?

JAMA. 2007;298(4): 405-12.

Multicenter registry Multicenter registry study w/ 506 pts study w/ 506 pts from 1986-2003 from 1986-2003

Mean follow-up 3.7 Mean follow-up 3.7 yrsyrs

Average age 41 Average age 41 years old years old

Primary Outcome: Primary Outcome: appropriate ICD appropriate ICD interventions interventions terminating VF/VT terminating VF/VT

JAMA. 2007;298(4): 405-12.

J Cardiovasc Electrophysiol 2008;19(10).

J Am Coll Cardiol 2008;51(10):1033-9.

3500 asymptomatic elite 3500 asymptomatic elite athletes (75% male), mean athletes (75% male), mean age 20.5 +/- 5.8 years, no age 20.5 +/- 5.8 years, no family hx of HCM family hx of HCM

12-lead ECG, 2D-Echo 12-lead ECG, 2D-Echo 53 athletes (1.5%) had 53 athletes (1.5%) had

LVH LVH 3 athletes (0.08%) had 3 athletes (0.08%) had

ECG and echo features of ECG and echo features of HCMHCM

HCM vs. Athlete’s Heart HCM vs. Athlete’s Heart

Circulation 1995;91.

Thank You!Thank You!

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HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM)