Outcomes and Burdens to Return-to-Play for Phenotype Negative Athletes With a Genetic Heart Disease.

Background: Over the past decade, the care of athletes with a genetic heart disease (GHD) has shifted. Guidelines surrounding return-to-play (RTP) for athletes who are genotype positive but phenotype negative (G+/P-) remain variable and their management challenging. Recommendations depend on diagnosis, ranging from RTP with monitoring [hypertrophic cardiomyopathy (HCM), and long QT syndrome (LQTS)] to automatic disqualification [catecholaminergic polymorphic ventricular tachycardia (CPVT), and arrhythmogenic cardiomyopathy (ACM)].

Objectives: This study sought to examine the prevalence, management, and outcomes of athletes with G+/P- GHD using a retrospective cohort of all self-identified athletes considered G+/P- treated in Mayo Clinic's Windland Smith Rice Genetic Heart Rhythm Clinic between July 2000 and November 2023.

Methods: There were 274 G+/P- athletes [119 females (43%); mean age at diagnosis 15 ± 12 years; median follow up 32 months] participating in sports at all levels. Diagnoses included LQTS (231; 84%), CPVT (19; 7%), ACM (15; 6%), or HCM (9; 3%). Treatments initiated after our first evaluation, but required for RTP approval, included pharmacologic therapy (187; 68%), left cardiac sympathetic denervation (11; 4%), or an implantable cardioverter defibrillator (6; 2%).

Results: For 76 athletes (27%), an intentional non-therapy strategy was implemented. One in five athletes (53; 19%) specifically sought RTP approval following disqualification elsewhere.

Conclusions: Despite possessing a GHD-associated variant, a GHD-associated cardiac event or death has not occurred in over 1,300 combined years of follow-up. RTP for most G+/P- athletes is safe. Restricting such athletes based solely on a positive genetic test result should be viewed as genetic discrimination.