Genotype Status and Arrhythmic Risk in Sport Participants with Hypertrophic Cardiomyopathy

Abstract Aims The impact of genotype on arrhythmic risk in sports-active hypertrophic cardiomyopathy (HCM) patients remains unclear. We compared outcomes between genotype-positive (G+) and genotype-negative (G-) athletes with HCM. Methods In this retrospective study, HCM patients actively engaged in sports underwent standardized baseline evaluation and follow-up. The primary endpoint included sudden cardiac death/arrest (SCD/SCA), appropriate implantable cardiovert-defibrillator (ICD) therapy, sustained/non-sustained ventricular tachycardia (SVT/NSVT). Secondary outcomes included a composite of ventricular arrhythmias, atrial fibrillation, ischemic stroke, and heart-failure hospitalization. Results Fifty-nine patients (age 40 years [23.2-50.0]) were followed for 6.3 years [3.0-12.6]. Twenty-nine participants (49.2%) carried a likely pathogenic or pathogenic variant, most commonly MYBPC3 (44.8%), MYH7 (24.1%) and TNNT2 (17.2%). At inclusion, median sport practice was 6.0 [3.0-10.0] hours-per-week, with 67.8% of competitors. At last follow-up, 88.1% remained active in sports. The ESC 5-years SCD risk score was slightly higher in G+ compared with G- patients (1.87% [1.47-3.67] vs 1.54% [1.24-2.20], p=0.048), but most of the participants were classified as low risk. Ventricular arrhythmias occurred in 20.7% of G+ and 23.3% of G- patients (p=0.807), with similar event–free survival (p=0.685). Most ventricular arrythmias were isolated NSVT (84.6%). Hard ventricular arrhythmic events were limited to two ICD-terminated ventricular fibrillations in G+ patients, one at rest and one during low-intensity exercise. The incidence of the composite secondary CV outcome was comparable between groups (31.0% vs. 33.3%, p=0.850). Conclusions In this exploratory cohort of sport active HCM patients, ventricular arrhythmic and cardiovascular event rates were similar between G+ and G- participants during follow-up.