Genotype and arrhythmic risk in patients with apical hypertrophic cardiomyopathy.

Background: Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM, often considered to have a benign prognosis. This study aimed to compare the clinical characteristics and genetic predisposition of apical HCM with non-apical HCM.

Methods: We included 195 patients with HCM who underwent next-generation sequencing at two tertiary centres in South Korea (2017-2024). The primary outcome was a composite of lethal arrhythmic events (LAE), including death, ventricular arrhythmia, implantable cardioverter defibrillator (ICD) implantation and appropriate ICD shock. Secondary outcomes included major adverse cardiovascular events (MACE), such as new-onset atrial fibrillation, ischaemic stroke, heart failure hospitalisation, septal reduction therapy or heart transplant.

Results: Of the 195 patients, 67 (34.4%) had apical HCM. Patients with apical HCM were older at diagnosis and had lower maximal left ventricular wall thickness compared with non-apical HCM. Disease-causing variants were less frequent in apical HCM (20.9% vs 46.9%, p<0.001). MYBPC3 and MYH7 variants were less common in apical HCM (50.0%) than in non-apical HCM (75.0%). MACE occurred less frequently in apical HCM (HR 0.38, 95% CI 0.19 to 0.75), but no difference was observed in LAE (HR 0.62, 95% CI 0.36 to 1.08). The presence of disease-causing variants was independently associated with LAE (adjusted HR 2.50, 95% CI 1.44 to 4.35).

Conclusions: Although apical HCM is associated with less hypertrophy and lower genetic yield, it is not entirely benign. The presence of disease-causing variants is an important predictor of arrhythmic risk, underscoring the value of genetic testing in all HCM patients, regardless of phenotype.