Hypertrophic cardiomyopathy: genetics and haemodynamic mechanisms
THE CONTEXT
Hypertrophic cardiomyopathy is usually an autosomal dominant genetic disorder involving sarcomeric contractile proteins, with mutation-specific phenotypes.
Genetic basis
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Inheritance: Transmission is usually autosomal dominant, with high penetrance and variable expression.
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Molecular basis: Most patients have a single-point mutation in a gene encoding a sarcomeric contractile protein.
Mutation-associated phenotypes
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Beta-myosin heavy-chain mutations: These are associated with marked ventricular hypertrophy.
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Troponin mutations: These cause little or no hypertrophy but are associated with marked myocardial fibre disarray, exercise-induced hypotension and a high risk of sudden death.
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Myosin-binding protein C mutations: These tend to present late in life and are often associated with hypertension and arrhythmia.
Mechanisms of functional impairment
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Diastolic filling: In all subtypes, a stiff, non-compliant left ventricle impedes diastolic filling and may lead to heart failure.
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Outflow obstruction: Septal hypertrophy may cause dynamic left ventricular outflow tract obstruction, termed hypertrophic obstructive cardiomyopathy.
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Mitral regurgitation: Abnormal systolic anterior motion of the anterior mitral valve leaflet can cause mitral regurgitation.