Body surface potential mapping of ventricular depolarization and repolarization in phospholamban and plakophilin-2 cardiomyopathy

Background Pathogenic variants in plakophilin - 2 ( PKP2 ) and phospholamban ( PLN ) are associated with arrhythmogenic cardiomyopathy. Early disease detection is important to prevent adverse events. Body surface potential mapping (BSPM) may detect local electrical abnormalities earlier than the 12-lead electrocardiogram. Objective This study aimed to determine abnormalities in R-, S-, and T-wave amplitudes in PKP2- and PLN- pathogenic variant carriers using BSPM. Methods 67 lead BSPM was performed in controls and PKP2 and PLN carriers. R-, S-, and T-wave amplitudes across all leads in controls were used as reference. Amplitudes of carriers exceeding these ranges were considered abnormal and assessed across disease stages (presymptomatic, electrical, and structural, as done previously). Follow-up BSPM (≥2 years) was performed in a subset of carriers. Results 152 subjects (40 [27;54] years; 51% women) (40 controls and 112 carriers [53 PKP2 and 59 PLN ]) were included. Amplitude abnormalities were most frequent in structural disease, predominantly in T waves ( PKP2 20 [10;29]; PLN 25 [22;30] leads). Abnormalities in electrical disease were more prevalent in PLN carriers than PKP2 carriers (R wave 4 [1;7] vs 13 [8;16] leads, P = .002; S wave 2 [1;3] vs 4 [3;12] leads, P < .001; T wave 1 [0;3] vs 20 [16;28] leads, P < .001). Presymptomatic carriers typically had abnormalities outside the 12-lead configuration. As the disease progressed, abnormalities became more frequent and extended toward V1–V6. Follow-up BSPM (23 PKP2 and 16 PLN ) showed consistency in locations of abnormalities with increased frequency (maximal increase 31%). Conclusion BSPM detected abnormal amplitudes within and beyond the 12-lead electrocardiogram, even in presymptomatic carriers. Follow-up BSPM suggests that these abnormalities are associated with disease progression, highlighting the potential benefit of BSPM in early disease detection.