Hypertrophic Cardiomyopathy: Current Perspectives

Abstract

Hypertrophic cardiomyopathy (HCM) is a multifaceted genetic disorder characterized by left ventricular hypertrophy (LVH) in the absence of alternative causes, with an estimated prevalence ranging from 1 in 200 to 1 in 500 individuals. Since HCM was first characterized in 1869, a plethora of pathogenic mutations have been identified, while ongoing research continues to elucidate the various pathophysiological mechanisms present in individuals with HCM. Comprehensive physical examination findings and multimodality imaging techniques have become crucial for accurately diagnosing and risk stratifying HCM patients. Meanwhile, recent advancements in research have contributed to a more refined definition and heightened recognition of HCM, prompting further investigations into targeted therapeutic strategies. This evolution in understanding provides alternative treatment options for patients, moving beyond traditional approaches such as myectomy or septal ablation. This review aims to systematically explore the genetic and pathophysiological underpinnings of HCM, as well as the application of multimodality imaging in identifying patients at risk for sudden cardiac death (SCD). The discussion also examines contemporary management strategies for HCM, specifically highlighting novel therapies targeting the molecular mechanisms involved in this disease.

Keywords: aficamten; alcohol septal ablation; hypertrophic cardiomyopathy; mavacamten; sudden cardiac death; surgical myectomy.

Fig. 1.

Echocardiographic findings in hypertrophic cardiomyopathy. (A) showcases a patient with systolic anterior motion of the anterior mitral valve leaflet (AMV) demonstrated by M-Mode of the parasternal long axis. (B) highlights a severely obstructed outflow tract gradient (82.7 mmHg) in an HCM patient. (C) displays mild mitral regurgitation via color seen on parasternal long axis. HCM, hypertrophic cardiomyopathy; SAM, systolic anterior motion; AMV, anterior mitral valve leaflet.

Fig. 2.

Cardiac MRI Cine SSFP images showing 2,3, and 4-chamber views highlighting additional characteristics seen in hypertrophic cardiomyopathy. (A,B,D) showcases severely hypertrophied walls. (A,B) showcase mid-ventricular hypertrophy with an aneurysmal apex (A). (E) showcases apical hypertrophy with mid-wall late gadolinium enhancement. (C) shows a short-axis view with mid-wall late gadolinium enhancement of the left ventricular apex. MRI, magnetic resonance imaging; SSFP, steady-state free precession.

Fig. 3.

Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy [74, 75]. HCM, hypertrophic cardiomyopathy; CMR, cardiac magnetic resonance imaging; ECG, electrocardiogram; TTE, transthoracic echocardiography; SCD, sudden cardiac death; ICD, implantable cardioverter defibrillator; LV, left ventricular; LVEF, left ventricular ejection fraction; LGE, late gadolinium enhancement.

Fig. 4.

Evidence-based management algorithm for symptomatic hypertrophic cardiomyopathy [2, 85, 86, 87, 88, 89, 90]. HCM, hypertrophic cardiomyopathy; CMR, cardiac magnetic resonance imaging; ECG, electrocardiogram; TTE, transthoracic echocardiography; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; NYHA, New York Heart Association; FDA, Food & Drug Administration; LGE, late gadolinium enhancement.

Fig. 5.

Pre- and post-mavacamten left ventricular outflow tract gradients in the same patient with hypertrophic cardiomyopathy are illustrated. (A,B) depict the pre-mavacamten gradients at rest (A) and during Valsalva maneuver (B). (C,D) present the post-mavacamten gradients at rest (C) and with Valsalva (D). Notably, there is a significant improvement post-mavacamten, with no provokable gradient observed during the Valsalva maneuver.

Fig. 6.

Parasternal long-axis views of a patient pre- and post-myectomy are illustrated. Systolic anterior motion of the anterior mitral valve leaflet in the setting of marked basal hypertrophy in the patient pre-myectomy (A) is no longer observed after myectomy (B). IVS, interventricular septum; SAM, systolic anterior motion; LA, left atrium.