The Diagnosis and Treatment of Hypertrophic Cardiomyopathy

Abstract

Background: Hypertrophic cardiomyopathy (HCM) with or without left ventricular outflow tract (LVOT) obstruction is a common primary myocardial disease, with a prevalence of 1:500. It is characterized by thickening of the myocardium. Its diagnostic evaluation includes history-taking and physical examination, genetic studies, transthoracic echocardiography, and cardiac MRI. When optimally treated, it carries a mortality of less than 1% per year.

Methods: This review is based on pertinent publications retrieved by a selective literature search, including the current guidelines.

Results: In symptomatic patients with high LVOT gradients (≥ 50 mm Hg), the treatment of first choice is pharmacotherapy with nonvasodilating beta-blockers or non-dihydropyridine-type calcium channel antagonists. Common side effects include bradycardia and hypotension, and there is a risk of AV nodal blockade. Both substance classes lower the LVOT gradient. Beta-blockers alleviate dyspnea and improve patients' quality of life. Verapamil can increase physical resilience. A further option is mavacamten, a myosin inhibitor that gained approval in Germany in mid-2023: it, too, lowers the LVOT gradient and improves quality of life. In 7-10% of patients, there is a reversible reduction of the left ventricular ejection fraction to less than 50%. Septal reduction treatments can be considered if drug therapy fails. Attention must also be paid to the management of sequelae such as atrial fibrillation, malignant arrhythmias, and mitral valve insufficiency.

Conclusion: Patients with HCM have a near-normal life expectancy if the disease is diagnosed early and treated according to the guidelines. The treatment of HCM and HOCM (hypertrophic obstructive cardiomyopathy) have been studied in no more than a few clinical trials, and randomized studies with clinical endpoints are needed.

Figure 1

Echocardiogram showing the thickened cardiac septum of a patient with HCOM in end-diastole. AMVL, Anterior mitral valve leaflet; Ao, ascending aorta; LA, left atrium; LV, left ventricle; NCC, non-coronary cusp (of the aortic valve); PMVL, posterior mitral valve leaflet; IVS, interventricular septum; RCC, right coronary cusp; RVOT, right ventricular outflow tract *1 LVOT (left ventricular outflow tract) *2 IVST (interventicular septal thickness). The thickening of the cardiac septum (26 mm) is clear to see.

Figure 2

Flow chart for management of patients with maximal LVOT gradient ≥ 50 mm Hg as measured by Doppler sonography LVOT, Left ventricular outflow tract; max., maximal; SM, surgical myectomy; SRT, invasive septal reduction treatment; TASH, transarterial alcohol ablation of septal hypertrophy

Figure 3

Schematic diagrams of the structure of cardiac myosin and the mechanism of action of mavacamten. One mechanism for the development of HOCM is excessive formation of cross-bridges between the actin filament and the myosin head (shown in blue). Mavacamten reduces cross-bridge formation (gray myosin heads) via blockade of myosin ATPase and thus counters the mechanism behind the development of HOCM.