Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is primarily caused by mutations in genes encoding sarcomeric proteins, most commonly MYH7 (beta-myosin heavy chain) and MYBPC3 (myosin-binding protein C). These mutations lead to impaired contractile function, energy deficit, and compensatory myocyte hypertrophy with disarray and interstitial fibrosis. The hypertrophy is typically asymmetric, involving the interventricular septum, and may cause dynamic left ventricular outflow tract obstruction due to systolic anterior motion of the mitral valve.¹ Over time, microvascular ischemia and fibrosis predispose to ventricular arrhythmias and sudden death.²

Clinical manifestations range from asymptomatic to exertional dyspnea, chest pain, palpitations, syncope, and sudden cardiac death. Diagnosis is typically established by echocardiography demonstrating left ventricular wall thickness ≥15 mm in the absence of other causes. Cardiac MRI offers superior tissue characterization, detecting fibrosis via late gadolinium enhancement, which correlates with arrhythmic risk.³ Genetic testing confirms the diagnosis and enables cascade screening of relatives, though variants of uncertain significance pose challenges.⁴

Management focuses on symptom relief and sudden death prevention. Beta-blockers and calcium channel blockers reduce outflow obstruction and improve diastolic filling. For refractory obstructive HCM, septal reduction therapy—surgical myectomy or alcohol septal ablation—is effective. Implantable cardioverter-defibrillators are recommended for high-risk patients based on risk scores incorporating age, family history, syncope, and fibrosis burden.⁵ Recent advances include cardiac myosin inhibitors like mavacamten, which reduce hypercontractility and obstruction.⁶

Beyond the classic sarcomeric mutations, HCM can arise from phenocopies such as Fabry disease, Danon disease, and cardiac amyloidosis, which require specific treatments. The first surgical myectomy was performed by Cleland in 1958, and the condition was initially described by Teare in 1958 as asymmetric hypertrophy. HCM is a leading cause of sudden death in young athletes, yet many patients have normal life expectancy. Apical HCM, more common in Asian populations, often presents with giant T-wave inversions and a benign prognosis. Additionally, a subset of patients develops end-stage HCM with systolic dysfunction, resembling dilated cardiomyopathy.⁷

Sarcomere

The basic contractile unit of cardiac muscle, composed of proteins such as myosin and actin.

Septal myectomy

Surgical removal of a portion of the thickened septum to relieve outflow obstruction.

Late gadolinium enhancement

MRI finding indicating myocardial fibrosis, used for risk stratification.