Hypertrophic Cardiomyopathy

Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.

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; 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 itself has moved over time, and the movement is instructive. 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.

Shapes of hypertrophy

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.

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.

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.

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, 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. Only obstructive HCM produces a systolic murmur, and its behaviour is diagnostic: manoeuvres that reduce preload or afterload, such as Valsalva or standing, intensify it, while squatting softens it.

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.

Fibrosis and sudden death

On tissue imaging, fibrosis appears at the right ventricular insertion points and as patchy areas inside thickened segments, as explained in the cardiac MRI note. Fibrosis is the key imaging finding for risk stratification: more fibrosis means more ventricular arrhythmia and sudden death, because scar borders sustain re-entrant tachycardia — and patients without obstruction remain at risk when fibrosis is extensive.

Wall thickness also tracks risk, with 30 mm or more a recognised risk factor carrying roughly 18 sudden-death events per 1000 patient-years (about 1.8% per year) against near-zero in healthy people, graded upward from 15 mm. But thickness and fibrosis are not tightly coupled: modest hypertrophy with fibrosis can still be arrhythmic.

How it presents

Many patients live asymptomatically for decades and surface incidentally — sport screening or an abnormal ECG. Exertional syncope is a red flag that must prompt exclusion of HCM. Sudden death can be the first manifestation, classically collapse during sport in the young. Palpitations and arrhythmias including atrial fibrillation occur, heart failure symptoms come predominantly from diastolic dysfunction, and stroke follows from atrial fibrillation or from thrombus in a dilated atrium or an apical aneurysm.

The ECG is usually abnormal in pronounced disease — described in the teaching material as never normal in significant HCM — while mild disease can still show a normal tracing.

Characteristic features include high QRS voltage with the tallest R waves inferolaterally, deep giant negative precordial T waves, ST abnormalities in either direction, left axis deviation, small notches or fragmentation within the QRS from disorganised depolarisation, and broad notched P waves of left atrial enlargement. Electrical change can precede visible hypertrophy, which is why ECG screening before competitive sport in the young is the most effective case-finding tool described.

Athletic heart or HCM

Physiological hypertrophy in athletes mimics mild HCM, and the distinction decides between preventable death and wrongful exclusion from sport.

When doubt persists despite full testing, the traditional approach stops sport for 6 months and re-evaluates: regression favours athletic heart. In elite athletes who cannot pause, imaging with enhancement plus genetic testing usually settles the question.

Treatment

Without obstruction, management is often surveillance, with beta-blockers used to reduce risk though the evidence is not entirely uniform.

With obstruction, medicines come first. Beta-blockers and disopyramide lower rate and contractility and thereby shrink the dynamic gradient — acting on haemodynamics, not on the diseased protein. Myosin inhibitors are newer and act directly on the sarcomere’s myosin, modifying actin–myosin interaction; they can reduce hypertrophy and substantially lower the outflow gradient, with very good outcomes reported in studies, as daily lifelong therapy. Specific agents, dosing, and pharmacology are left to guidelines. When symptomatic obstruction resists medicines, septal reduction follows: surgical myectomy removes part of the septum through open surgery, while alcohol septal ablation infarcts the segment percutaneously through its septal perforator.

Preventing sudden death

The central decision is whether the patient needs a defibrillator. Established risk factors are prior arrest or sustained ventricular tachycardia (mandating secondary-prevention implantation), family history of sudden death, maximal thickness of 30 mm or more, unexplained syncope especially on exertion, non-sustained ventricular tachycardia on Holter — even short runs of a handful of beats, with risk rising with burden — and an abnormal blood pressure response to exercise. Notably, a patient with only a 15 mm septum but daily Holter runs can still qualify: substrate outweighs centimetres.

The HCM Risk-SCD calculator formalises 5-year risk from age, maximal thickness, left atrial size, resting outflow gradient, family history, non-sustained tachycardia, and unexplained syncope. A risk of 6% or more (some sources 5%) at 5 years favours implantation; 4–6% calls for shared decision-making; below 4% generally argues against.

Two caveats matter: the calculator gives population-derived estimates, not individual prediction, so low never means zero — and it omits fibrosis despite extensive enhancement being among the strongest individual predictors, so many clinicians let it tip borderline cases. Marked left ventricular mass increase by CMR also worsens prognosis, though normal total mass never excludes segmental disease. Exercise testing adds blood pressure behaviour and the VE/VCO2 slope, whose elevation independently predicts sudden death even in modest, asymptomatic hypertrophy.

Sport

Intensive competitive sport is generally discouraged in definite HCM, but current guidance supports individualised participation decisions after expert evaluation with shared decision-making. A defibrillator prevents death but not incapacitation during sport, which is part of why intensive competition needs careful counselling. Low-intensity recreation such as golf, bowling, or hiking is generally safe and worth encouraging. For the elite athlete earning a living through sport, the doctor’s role is clear counselling, clearly documented, so that any decision to compete is shared and informed.

Evidence anchors

• Ommen SR, et al. 2020 AHA/ACC Guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: https://www.ahajournals.org/doi/10.1161/CIR.0000000000000937
• O’Mahony C, et al. A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD): https://academic.oup.com/eurheartj/article/35/30/2010/467191
• Arbelo E, et al. 2023 ESC Guidelines for the management of cardiomyopathies: https://doi.org/10.1093/eurheartj/ehad194