EPS would further characterize the mechanism and origin of this patient's ventricular arrhythmias. He underwent EPS, during which epicardial voltage mapping demonstrated a small-to-moderate area of markedly abnormal electrograms within the anterior right ventricular outflow tract (RVOT) epicardium, characterized by delayed and highly fractionated signals. This region was successfully targeted with radiofrequency ablation, resulting in a marked reduction in exertional ventricular ectopy.

This case highlights the diagnostic complexity of ventricular arrhythmias in endurance athletes, particularly when exercise-induced arrhythmias raise concern for inherited channelopathies, early arrhythmogenic cardiomyopathy, or exercise-related myocardial remodeling. He presented with exertional syncope, multifocal PVCs, nonsustained VT, and progressive exertional symptoms without overt structural heart disease on initial imaging. These findings warrant EPS to define the arrhythmogenic substrate and guide management. Of note, the prevalence of nonbenign PVCs in athletes is rare. In a study of 10,728 screening ECGs of adult athletes, only 0.24% had any PVCs, with 4% of the screened PVCs demonstrating nonbenign features.¹

Given the multifocal ventricular ectopy, repetitive exercise-induced VT, and abnormal electrical substrate on EPS, he was ultimately thought to most likely have an atypical variant of ARVC. Differential diagnosis included idiopathic RVOT VT, CPVT, and exercise-induced arrhythmogenic cardiomyopathy. Idiopathic RVOT VT is typically characterized by a focal, monomorphic morphology in structurally normal hearts and is not associated with abnormal myocardial substrate. Similarly, classic CPVT typically manifests with bidirectional or highly polymorphic VT provoked by adrenergic stimulation without evidence of structural or electrophysiologic (EP) myocardial abnormalities. In this case, the PVC morphology and abnormal epicardial substrate made CPVT less likely.

Comprehensive gene panels had negative findings; however, negative findings on genetic testing do not exclude an underlying arrhythmogenic cardiomyopathy and should be interpreted in the context of the overall clinical and EP findings. The most common genetic mutation associated with ARVC is plakophilin-2 (PKP2), which encodes desmosome proteins. Approximately 40% of patients may not test positive for a known genotypic profile.² For athletes with PKP2 phenotype–positive disease, competitive sports participation, particularly endurance, carries an increased risk of disease acceleration. The risks of competitive sports participation outweigh the benefits for these patients; however, in individuals with genotype-negative or other-genotype disease, this risk is not well established and requires expert evaluation, risk stratification, and shared decision-making.³ Exercise restriction during the diagnostic period is indicated; however, lifelong exercise restriction at this stage would be premature. Exercise recommendations would hinge on the diagnosis and response to treatment after evaluation, risk stratification, and maximal exercise testing while taking therapy.

Distinguishing physiologic exercise-induced cardiac remodeling from pathologic arrhythmogenic disease remains challenging in endurance athletes. Although endurance athletes may demonstrate RV enlargement that exceeds conventional ARVC imaging thresholds, physiologic remodeling is generally not associated with significant ventricular arrhythmias, wall motion abnormalities, or abnormal substrate. Exercise-induced arrhythmogenic cardiomyopathy has been described in endurance athletes with ventricular arrhythmias despite the absence of identifiable pathogenic variants; however, these patients are typically masters athletes with substantially greater cumulative exercise dose than this patient.

Following ablation, this patient was started on nadolol 80 mg BID. The indication for and timing of an ICD hinges on the underlying diagnosis, so EPS as the next step takes precedence; ICD placement solely to facilitate return to competition is not recommended.² Repeat exercise stress testing demonstrated only isolated PVCs without progression during exercise. ICD placement was recommended on the basis of his overall clinical risk profile; however, he declined. He was initially recommended to avoid exercise above daily activities; however, with consideration of the diagnosis, arrhythmia management, and patient goals, he resumed recreational activity and was advised to avoid high-intensity exercise. He has experienced no recurrent syncope or cardiac arrest during follow-up.

This case demonstrates the role of EPS in exertional ventricular arrhythmias and nondiagnostic structural evaluation. By identifying occult arrhythmogenic substrate, EPS can refine the differential diagnosis, guide ablation, and inform subsequent risk stratification and management, even when a definitive underlying cardiomyopathy cannot be conclusively established.

References

1. Gomez SE, Perez MV, Wheeler MT, et al. Classification of premature ventricular contractions in athletes during routine preparticipation exams. Circ Arrhythm Electrophysiol. 2024;17(9):e012835. doi:10.1161/CIRCEP.124.012835
2. Lampert R, Chung EH, Ackerman MJ, et al. 2024 HRS expert consensus statement on arrhythmias in the athlete: evaluation, treatment, and return to play. Heart Rhythm. 2024;21(10):e151-e252. doi:10.1016/j.hrthm.2024.05.018
3. Kim JH, Baggish AL, Levine BD, et al. Clinical considerations for competitive sports participation for athletes with cardiovascular abnormalities: a scientific statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol. 2025;85(10):1059-1108. doi:10.1016/j.jacc.2024.12.025