Hypertrophic cardiomyopathy (HCM) is hypertrophy from inside the muscle, not compensation for outside load. In aortic stenosis or hypertension the wall thickens against raised afterload, the resistance the ventricle pumps against; in HCM the wall thickens because the myocardium itself is diseased — disproportionate to any haemodynamic stimulus.
The working definition is a wall thickness of 15 mm or more in at least one left ventricular segment, unexplained by loading conditions. The cutoff is understood to be imperfect: with modern imaging, earlier forms measuring 12–14 mm, or even around 11 mm, are recognised in gene carriers. Prevalence sits around 0.2% — rare, but not extremely so. Unlike the harmonious concentric thickening of hypertension, HCM is usually disharmonic: one to three segments are disproportionately thick while the rest look normal.
Classification of HCM has moved over time. The AHA in 2006 grouped HCM among genetic cardiomyopathies; the ESC in 2008 went morphology-first, defining the hypertrophic phenotype before subdividing familial and non-familial forms; the WHO in 2013 integrated morphology, organ involvement, genetics, aetiology, and stage. All three agree on the core: HCM is a primary myocardial disease, not pressure overload.
The sarcomere genetics
HCM is fundamentally a sarcomere disease: mutations in contractile-apparatus proteins produce disorganised myocyte architecture alongside hypertrophy. Inheritance is autosomal dominant, across more than 11 genes of myocardial fibre proteins. In roughly 70% of cases one of two genes is responsible — MYH7, encoding the dominant contractile protein beta-myosin heavy chain, or MYBPC3, encoding the regulatory myosin-binding protein C that modulates actin–myosin interaction. The remaining cases are spread across other sarcomere genes such as troponin T, troponin I, alpha-tropomyosin, actin, and titin, with the same functional consequence: the sarcomere assembles or contracts abnormally and the myocyte hypertrophies in response.
Strikingly, carriers of the same mutation differ — modifying and epigenetic factors decide which segments thicken and how severely, which is why one mutation produces segmental disease and varied courses within a family.
Shapes of hypertrophy
Because the thickening is segmental, its location varies, and the location decides the consequences.
Asymmetric septal hypertrophy
The most common pattern: the basal septum is markedly thickened while other walls stay relatively normal, with thickness normalising toward the usually spared apex.
Mid-ventricular HCM
Narrowing at mid level separates an apical chamber from the base; the gradient then sits inside the ventricle rather than at the outflow tract, accelerates flow through the narrowing, and produces a prominent murmur. This pattern carries particular arrhythmic concern because the pressure-loaded apical chamber can form aneurysms that harbour thrombus.
Apical HCM
Thickening confined to the apex narrows the cavity to a slit sometimes called the Prussian helmet sign; without mid-cavity obstruction there is usually no gradient, and the burden is diastolic dysfunction plus arrhythmias rather than obstruction.
Patterns that argue against HCM
Concentric thickening is rare in true HCM and should prompt suspicion of pressure overload or infiltration such as amyloidosis. Right ventricular involvement is recognised but poorly characterised — isolated right ventricular HCM is very uncommon, and the left ventricle is almost always affected far more.
Obstruction and systolic anterior motion
When basal septal hypertrophy narrows the outflow tract, systolic flow accelerates through the narrowing and drags the mitral leaflets forward — systolic anterior motion (SAM) of the valve. The resulting obstruction is dynamic, not fixed: it grows with exercise, through higher rate, stronger contractility, and lower preload (the filling of the ventricle before contraction), and it produces a gradient across the outflow tract. A resting gradient of 30 mmHg or more is considered pathological and clinically significant, though smaller resting gradients can still obstruct substantially on exercise or with preload-reducing manoeuvres.
Obstruction has consequences beyond the gradient. Extreme systolic cavity pressure can compress intramural coronaries and produce microvascular ischaemia — fibrosis and wall-motion abnormalities identical to infarction despite normal epicardial arteries — which in turn feeds fibrosis and arrhythmic substrate.
How the disease unfolds
Disease unfolds slowly: normal function for years to decades, then diastolic dysfunction as the stiff ventricle relaxes poorly, and only very late a systolic decline sometimes called burned-out HCM, occasionally with dilatation. Around 90% of patients never reach systolic dysfunction — most of the clinical burden is diastolic.