Abstract Body (Do not enter title and authors here): Background: Although exercise stress testing (EST) has shown to unmask latent electrical substrates in PKP2-mediated arrhythmogenic cardiomyopathy (ACM), the prognostic role of EST-induced ventricular arrhythmia (VA) patterns in PKP2-ACM patients is unclear.
Objective: To examine the exercise-induced VA patterns observed during EST in PKP2-ACM patients and explore their correlation with major VA outcomes.
Methods: We retrospectively analyzed 621 patients with either genotype-positive ACM or genotype-positive dilated cardiomyopathy evaluated between 01/2015 and 04/2024 to identify those with a disease-causative variant in PKP2 (N = 108). After exclusion of 38 PKP2-ACM patients without EST data, demographic and electrocardiographic data was extracted from the electronic medical record. The arrhythmic burden [premature ventricular contractions (PVCs), PVCs in bigeminy, PVC couplets, non-sustained VT (NSVT), sustained VT, ventricular fibrillation (VF), and PVCs/minute] during each EST phase (baseline, peak, active and passive recovery) were reviewed and correlated with major VA outcomes [sudden cardiac arrest (SCA), sustained VT, and appropriate implantable cardioverter-defibrillator (ICD) shocks].
Results: A total of 186 exercise tests from 70/108 (65%) PKP2-ACM patients (mean age 36 ± 20 years, 40 % male) were analyzed. The presence and burden of PVCs occurring singly, bigeminy, couplets. and NSVT were more prevalent during the recovery phase, specifically the passive recovery phase (Table). PKP2-ACM patients with structural disease (64%) were more likely to have an increased VA burden during recovery than those without structural disease [28/45 (62%) vs 4/25 (16%); p<0.001]. Interestingly, the presence of an increased arrhythmic burden (worsening PVCs/min or complex PVCs) during the recovery was associated with major VA over a median follow-up of 47 months (HR 8.576 [1.015-72.449]; p= 0.019).
Conclusion: Increased arrhythmic burden during the recovery phase (late > early) is associated with an increased risk of major VAs in PKP2-ACM. Further studies are needed to understand if this observation extends to other ACM genotypes and whether EST-induced VA patterns can be used to assess therapeutic efficacy in PKP2-ACM.