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25: Hypertrophic Cardiomyopathy

Polakit Teekakirikul; Christine E. Seidman; Carolyn Y. Ho

Key Points

  • Disease summary:

    • Hypertrophic cardiomyopathy (HCM) is an inherited disorder of cardiac muscle characterized by left ventricular hypertrophy (LVH) in the absence of other cardiovascular or systemic conditions (eg, valvular heart diseases or long-standing hypertension).

    • The histopathologic hallmarks include myocyte hypertrophy, myocardial disarray, and fibrosis.

    • The prevalence of HCM is 1:500 in the general population, with at least 60% caused by mutation in one of the genes encoding different components of the sarcomere protein (see Molecular Genetics section).

  • Hereditary basis:

    • HCM is inherited in an autosomal dominant manner with age-dependent penetrance and variable expressivity.

  • Differential diagnosis:

    • It is clinically important to distinguish HCM from acquired LVH (eg, physiologic hypertrophy from athletic training, hypertensive heart disease), inherited LVH with multisystem involvement (eg, metabolic cardiomyopathy, cardiac amyloidosis) and syndromes with LVH as a presenting feature. Such diseases with similar cardiac morphologic finding can have different modes of inheritance, natural histories, and therapeutic strategies (Table 25-1).

Table 25-1Genetic Differential Diagnosis
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Table 25-1 Genetic Differential Diagnosis
Syndrome Symbol of Associated Gene Associated Findings
Hypertrophic cardiomyopathy see Molecular Genetics section Isolated cardiac hypertrophy
Fabry disease GLA LVH, acroparesthesias, angiokeratomas, hypohidrosis, ocular involvement, renal insufficiency (proteinuria to end-stage renal disease), cerebrovascular disease
Danon disease LAMP2 (X-linked) LVH, ventricular pre-excitation and arrhythmias, rapid progression of heart failure, extracardiac manifestations (skeletal and neurologic)
PRKAG2 cardiomyopathy PRKAG2 LVH and cardiac conduction system defects (including pre-excitation) due to excessive glycogen accumulation
Cardiac amyloidosis (Familial) TTR LVH, sensorimotor neuropathy, autonomic neuropathy, due to amyloid infiltration
Friedreich ataxia (FRDA) FXN Slowly progressive ataxia of gait and limbs, depressed tendon reflexes, dysarthria, muscle weakness, spasticity, optic nerve atrophy, scoliosis, bladder dysfunction, loss of position, and vibration sense. Two-thirds of patients have cardiomyopathy

Gene names: GLA, alpha-galactosidase A; LAMP2, lysosomal-associated membrane protein 2; PRKAG2, gamma-2 regulatory subunit of AMP-activated protein kinase (AMPK); TTR, transthyretin; FXA, frataxin.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for Hypertrophic Cardiomyopathy

Presence of the following

  • Unexplained LVH with nondilated left ventricular chamber

    • Although asymmetric septal hypertrophy is most common, the patterns of hypertrophy are variable and can include concentric and apical hypertrophy.

    • Most often diagnosed by echocardiography; cardiac MRI may be used to further evaluate left ventricular morphology and to assess for myocardial scar.

    • Additional findings may include systolic anterior motion (SAM) of the mitral valve with associated left ventricular outflow tract obstruction and mitral regurgitation, mid ventricular obstruction, and diastolic dysfunction.

    • Less than 10% of patients may develop a burnt-out or end-stage phase characterized by systolic dysfunction, occasionally with regression of LVH and left ventricular dilatation.

  • Pathognomonic histopathologic features: myocyte disarray, hypertrophy, and cardiac fibrosis

Other findings associated with HCM include

  • Prominent apical impulse or lift

  • Brisk, occasionally bifid carotid upstroke

  • A harsh crescendo-decrescendo systolic murmur from ...

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