Hypertrophic cardiomyopathy

Definition

Hypertrophic cardiomyopathy (HCM) is a mostly genetic myocardial disorder with left ventricular hypertrophy. In adults a maximal diastolic wall thickness of 15 mm or more (echocardiography or MRI) without an alternative cause is considered diagnostic; with a family history or a proven pathogenic sarcomeric variant a threshold of 13 mm or more is sufficient. This differs from hypertrophy due to pressure overload (e.g. aortic stenosis, hypertension).

Classification

• Obstructive HCM (HOCM): peak left ventricular outflow tract (LVOT) gradient of 30 mmHg or more at rest or with physiological provocation; gradients of 50 mmHg or more are generally considered sufficient to cause symptoms.
• Non-obstructive HCM.
• Morphology: most commonly asymmetric hypertrophy of the basal septum; also focal or symmetric forms, apical HCM (without outflow tract obstruction, more common in people of Asian descent) and midventricular obstruction, often with an apical aneurysm.

Occurrence & epidemiology

HCM is the most common monogenic cardiac disorder, with an estimated prevalence of 1:200 to 1:500 adults. About two-thirds of patients have dynamic outflow tract obstruction. Symptoms usually appear in early to mid-adulthood (30s to 50s).

Aetiopathogenesis

• Genetics: pathogenic variants in genes of the cardiac sarcomere, most frequently MYBPC3 and MYH7, are found in about 35 % of tested patients with clinical HCM; penetrance and expression vary markedly.
• Phenocopies: Fabry disease, Danon disease, Andersen disease and other glycogen storage diseases can mimic HCM.
• Pathophysiology: excessive actin-myosin cross-bridge formation and abnormal calcium handling cause hypercontractility and reduced compliance. The stiff chamber fills poorly, and end-diastolic and pulmonary venous pressures rise.
• Outflow tract obstruction: interplay of the thickened basal septum and systolic anterior motion (SAM) of the often elongated anterior mitral leaflet, with accompanying posteriorly directed mitral regurgitation.
• Ischemia despite normal epicardial coronary arteries due to microvascular dysfunction, capillary-myocyte mismatch and increased oxygen demand.

Clinical features

• Highly variable presentation; symptoms frequently on exertion: dyspnea, chest pain (usually resembling typical angina), palpitations, syncope.
• Exertional syncope results from outflow tract obstruction or arrhythmia and is an important warning sign of sudden cardiac death.
• Symptoms are aggravated by conditions that reduce preload or afterload and increase heart rate and contractility.
• Auscultation: dynamic late-peaking systolic murmur at the left sternal border in the 3rd or 4th intercostal space; louder with the Valsalva maneuver and on standing up from squatting, softer with handgrip, prolonged squatting or passive leg raising; possibly an additional mitral regurgitation murmur at the apex; often a fourth heart sound.
• Pulse: with obstruction a brisk upstroke, bifid peak and rapid downstroke; sustained apex beat; blood pressure and heart rate usually normal.

Histology

Classic findings are cardiomyocyte hypertrophy, disorganized arrangement of myocytes ("myocyte disarray"), interstitial fibrosis and thick-walled intramural coronary arteries.

Diagnosis

• History: syncope and other symptoms; three-generation family history (HCM, unexplained sudden cardiac death).
• Echocardiography: extent and distribution of hypertrophy, outflow tract gradient at rest and with provocation, systolic anterior motion of the mitral valve, mitral regurgitation; usually a small cavity with normal or hyperdynamic systolic function.
• Cardiac MRI: precise wall thickness measurement including segments difficult to visualise; apical aneurysms; late gadolinium enhancement reflecting fibrosis.
• ECG: frequently left ventricular hypertrophy with repolarisation abnormalities (deep T-wave inversion, ST depression), Q waves, signs of left atrial enlargement; sometimes bundle branch block or pre-excitation.
• Ambulatory ECG over 24–48 hours: atrial arrhythmias and ventricular tachycardia (a risk factor).
• Exercise testing: provocation of outflow tract obstruction, functional capacity.
• Chest X-ray: often normal, possibly an enlarged left atrium.
• Genetic testing and examination of relatives.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Hypertrophic Cardiomyopathy
2. StatPearls: Hypertrophic Cardiomyopathy

Cross-references