Unveiling Clinical and Genetic Distinctions in Pure-Apical Versus Distal-Dominant Apical Hypertrophic Cardiomyopathy.

Background: Original apical hypertrophic cardiomyopathy was characterized by left ventricular hypertrophy confined to the apex below the papillary muscle level. In contrast, apical hypertrophic cardiomyopathy in Western countries often includes hypertrophy extending to the midventricular septum. Recognizing these phenotypic differences is essential as they may influence the clinical prognosis. The aim of this study was to delineate the clinical and genetic disparities between the pure-apical form, according to the original definition, and the distal-dominant form, in which hypertrophy extends to the ventricular septum without basal septal hypertrophy.

Methods: A retrospective analysis was conducted for 111 consecutive patients with apical hypertrophic cardiomyopathy with assessment of hypertrophic cardiomyopathy-related adverse events including hypertrophic cardiomyopathy-related death, heart failure admission, embolic stroke admission, and sustained ventricular tachycardia with hemodynamic instability or appropriate implantable cardioverter-defibrillator discharge. Genetic testing for hypertrophic cardiomyopathy-associated genes was performed in 72 patients.

Results: Among the patients, 60 were classified as pure-apical form, and 51 were classified as distal-dominant form. The median age at diagnosis was 63 years, with a predominance of men in both groups. Over a follow-up period of 11.0 years, the incidence of hypertrophic cardiomyopathy-related adverse events was significantly higher in the distal-dominant group than in the pure-apical group (log-rank, <0.001). The detection rate of pathogenic or likely pathogenic variants was also significantly higher in the distal-dominant group than in the pure-apical group (26% versus 3%; =0.005).

Conclusions: Distinct clinical and genetic profiles of the 2 apical hypertrophic cardiomyopathy phenotypes warrant their recognition and differentiation in clinical practice due to distinct prognoses and genetic backgrounds.