hypertrophic cardiomyopathy (HCM), including idiopathic hypertrophic subaortic stenosis (IHSS)

Etiology

• idiopathic
  • onset < 10 years of age
  • no associated hypertension
• genetic (see Genetics: below)
• acquired form in elderly patients with a long history of hypertension

Epidemiology

• from 1984-2015, 270 people received diagnoses of hypertrophic cardiomyopathy
• in 2016, estimated prevalence of 89 persons per 100,000 (0.089%)

Pathology

• myocardial hypertrophy is
  • typically predominant in the ventricular septum
  • may involve all ventricular segments equally
• left ventricular outflow obstruction (61%)
  • may occur at rest
  • secondary to thickened interventricular septum
  • obstruction increased by:
    • increased left ventricular contractility
    • decreased preload (nitrates diuretics, Valsalva)
    • decreased afterload (vasodilators, ACE inhibitors)
  • obstruction decreased by:
    • increased afterload (handgrip)
    • decreased contractility
      • (beta-blockers, Ca+2 channel blockers, disopyramide)
    • increased preload (fluid)
• ventricular diastolic dysfunction
  • delayed ventricular relaxation
  • decreased ventricular compliance
  • pulmonary congestion
• myocardial ischemia
  • myocardial oxygen supply/demand mismatch
  • endomyocardial ischemia may occur despite normal coronary arteries
• mitral regurgitation
  • systolic motion of anterior leaflet of mitral valve
• cardiac arrhythmias may result from aberrant conduction

Genetics

• autosomal dominant, variable phenotypic presentation
• mutation in myosin heavy-chain 7 (beta) gene (chromosome 14)
• troponin T mutations less common than myosin heavy chain mutations
  • subtle ventricular hypertrophy
  • few symptoms
  • ominous prognosis
• alpha-tropomyosin mutation (chromosome 15)

Clinical manifestations

• clinical presentation varies considerably
• not associated with hypertension
• exertional dyspnea (most common)
• angina pectoris
• palpitations/arrhythmias
• syncope
• heart failure
• sudden death during physical exertion
  • most common in children & young adults age 10-35
  • commonly during periods of strenuous exercise
• bifid carotid pulse with delay
• forceful, double or triple apical impulse
• coarse late-peaking systolic murmur of mitral regurgitation
  • crescendo-decresendo
  • localized along left lower sternal border
  • accentuated by maneuvers or drugs that
    • reduce preload (Valsalva maneuver, standing)
    • reduce afterload
    • increase myocardial contractility
  • attenuated by maneuvers that increase preload (leg elevation, squatting)
  • systolic anterior motion of mitral valve
  • murmur does not radiate
  • murmur may be absent in hypertrophic cardiomyopathy without obstruction
• left ventricular hypertrophy generally remains stable in older patients; progressive disease with dilatation in 5-10%
• Brockenbrough's sign

Laboratory

• hypertrophic cardiomyopathy gene mutation
• genetic testing of 1st degree relatives not indicated unless the index patient has a pathogenic genetic variant

Diagnostic procedures

• electrocardiogram
  • left ventricular hypertrophy & strain
    • increased voltage
    • ST segment & T wave changes
      • deep inverted T waves V2-V4, V3-V6
  • Q waves may mimic myocardial infarction
  • W waves, II, III, aVF & lateral leads (I, avL, V4-V6)
  • p waves suggesting LAE
  • conduction delay, ventricular ectopy
  • left axis deviation
  • left atrial enlargement
• transthoracic echocardiogram
  • doppler echocardiography at rest & with stress
  • left ventricular hypertrophy
  • interventricular septum thickening diproportionately greater than ventricular free wall
  • mitral valve function (mitral regurgitation)
  • every 1-2 years
  • screen all first degree relatives
• 48-72 hour HOLTER monitoring (risk stratification)
• exercise stress testing
  • blunted increase in systolic blood pressure (< 20 mm Hg) with exercise associated with increased risk of sudden death
  • also doppler echocardiography at rest & with stress

Complications

• sudden death
  • major risk factors
    • ventricular fibrillation, prior cardiac arrest
    • ventricular tachycardia, sustained or non-sustained
    • family history of sudden death in 1st degree relative < 40 years of age
    • unexplained syncope (> 2 episodes within 1 year)
      • especially if associated with exercise
    • left ventricular septal wall thickness > 30 mm in diastole
    • systolic blood pressure increase of < 20 mm Hg on exercise stress testing
• dilated cardiomyopathy with LVEF <= 35% & NYHA class 3 or 4 heart failure
  • possible risk factors
    • significant left ventricular outflow obstruction
    • mycardial ischemia
    • delayed gadolinium hyperenhancement on CMR imaging
  • other risk factors
    • microvascular disease
    • age < 30 years at diagnosis
    • malignant genotype
  • not risk factors: ventricular arrhythmias inducible on electrophysiologic stimulation

Differential diagnosis

• see hypertrophic cardiomyopathy vs aortic stenosis
• athlete's heart

Management

General

• relief of symptoms
  • if asymptomatic & no risk factors for sudden death, annual screening for risk factors, no therapy
• avoid strenuous physical activities, including most competitive sports
  • controversial in the absence of risk factors
  • moderate-intensity exercise results in a small increase in exercise capacity at 16 weeks

pharmacologic therapy

• beta-adrenergic antagonists
  • LVEF >= 50%, dyspnea &/or angina pectoris
  • reduce myocardial contractility
  • reduce heart rate
  • propranolol 160-320 mg/day
  • avoid vasodilating beta-blockers: carvedilol, labetolol, nebivolol
  • metoprolol lowers left ventricle outflow tract obstruction gradient at rest (25 v. 72 mm Hg), peak exercise (28 vs 62 mm Hg), & post exercise (45 vs 115 mm Hg), lowers NYHA functional class & improves quality of life, but does not improve exercise capacity, peak oxygen consumption, or serum BNP
• calcium channel antagonists
  • second line agents
  • increased left ventricular diastolic filling
    • diltiazem
    • verapamil: may be used, but may cause sudden hemodynamic deterioration in patients with high resting left ventricular outflow tract obstruction
  • avoid dihydropyridines because of vasodilatory effect
• diuretics
  • avoid diuretics
  • may improve symptoms of pulmonary congestion
  • excessive preload reduction
  • may worsen LV outflow obstruction
• avoid nitrates & vasodilators (afterload reduction)
  • includes avoid ACE inhibitors
  • may increase left ventricular outflow obstruction
  • unless LV systolic dysfunction develops
• mavacamten (Camzyos) may reduce left-ventricular outflow tract obstruction
  • mavacamten improves symptomatic hypertrophic obstructive cardiomyopathy reducing need for septal reduction therapy

arrhythmias

• common
• supraventricular arrhythmias
  • DC cardioversion if patient is unstable
  • atrial fibrillation
    • poorly tolerated
    • cardioversion if possible
    • digoxin relatively contraindicated
      • inotropic agent
      • potential to increase outflow obstruction
    • control ventricular response prior to cardioversion with:
      • diltiazem
      • verapamil
      • beta-adrenergic antagonist
    • suppression of chronic atrial fibrillation
      • procainamide
      • disopyramide (Norpace)
    • anticoagulation regardless of CHADs score
• ventricular arrhythmias
  • non-sustained ventricular tachycardia
    • increased risk of cardiac arrest
    • benefit of therapy not established
  • treat symptomatic ventricular tachycardia
  • implantable defibrillator

other considerations

• cardiogenic shock
  • volume resuscitation
  • phenylephrine (alpha-1 adrenergic receptor agonist)
    • vasoconstriction
    • sinus bradycardia
  • inotropic agents are contraindicated
• prophylaxis for bacterial endocarditis recommended prior to AHA guidelines of 2007
• anticoagulation for paroxysmal or chronic atrial fibrillation
  • dose-adusted warfarin even if CHA2DS2-VASc score = 0
• Dual chamber pacing - right ventricular pacing used to alter ventricular activation sequence may reduce left ventricular outflow obstruction due to asymmetric septal hypertrophy
• implantable cardioverter-defibrillator (ICD) for patients at risk for sudden death
  • family history of sudden death
  • prior cardiac arrest due to ventricular arrhythmia
  • ventricular tachycardia on ambulatory ECG monitoring (MKSAP17 removes qualifier recurrent)
  • unexplained syncope
  • extreme LV hypertrophy
    • wall thickness > 30 mm
    • significant outflow-tract gradient
  • exercise-induced hypotension
  • malignant genotype (not in MKSAP17)
  • diagnosis < 30 years of age (not in MKSAP17)
• surgery
  • outflow tract gradient > 50 mm Hg
  • symptoms despite maximal medical management
  • useful in treatment of symptoms
  • has not been demonstrated to improve survival
  • procedures
    • septal myotomy or myectomy (Morrow procedure)
    • mitral valve replacement (MVR)
• genetic couseling for all patients if sarcomeric mutation in index case
  • screen all 1st degree relatives with echocardiography
    • screen every 12-18 months age 12-21
    • screen every 5 years for life age > 21 years
      • screening interval regardless of prior negative screening or if only 1 family member diagnosed with HCM/IHSS
    • genetic testing of affected family member
      • if unaffected family member tests negative for mutation(s) found in affected family member(s), screening can be discontinued
• prognosis
  • death occurs mostly in patients < 60 years of age
  • survival to age 60 years implies a benign phenotype

More general terms

• cardiomyopathy
• chronic heart disease

More specific terms

• familial hypertrophic cardiomyopathy

Additional terms

• athlete's heart
• hypertrophic cardiomyopathy (HCM) vs aortic stenosis (AS)