Phenotyping of Exercise Response in FORMs of Arrhythmogenic CardioMyopathy: PERFORM-ACM

Patients with arrhythmogenic cardiomyopathy (ACM) are advised to perform no more than moderate-intensity exercise, but whether such exercise acutely alters hemodynamic, electrophysiological, or cardiac biomarker profiles is unknown. We investigated whether moderate-intensity isometric, resistance, or aerobic exercise induces exercise pulmonary hypertension (exPH, mean pulmonary artery pressure to cardiac output slope >3 mmHg/L/min), troponin T elevation, or changes in late potentials (LP) in definitive or probable ACM. Twenty patients (13 definitive, 7 probable ACM; age 42.2 ± 10.7 years) underwent exercise right heart catheterization during isometric handgrip (HG) and bicep curl (BC) (1 minute each at 70% of maximal voluntary contraction), followed by 2 × 20 minutes of supine cycling (CYC) at the first ventilatory threshold. Central hemodynamics and cardiac biomarkers were measured during each condition, and high-density right ventricular electroanatomical mapping was performed before and after exercise. exPH did not occur in either group (all <3 mmHg/L/min), whereas troponin T rose progressively without group differences (p=0.880). LP within the "arrhythmogenic triangle" decreased in probable (mean change -1.95 ± 1.59%) but increased in definitive ACM (mean change 2.72 ± 2.16%, p<0.001). In conclusion, moderate-intensity HG, BC, and CYC exercise were not associated with exPH in probable or definitive ACM. Despite similar hemodynamic and biomarker responses, post-exercise LP diverged between groups, decreasing in probable but increasing in definitive ACM. This observation warrants validation in larger cohorts with better control for baseline substrate and longitudinal clinical outcomes.