CineECG demonstrates abnormal electrical activity in preclinical plakophilin-2-pathogenic variant carriers with a normal 12-lead ECG

Abstract

Abstract Background/introduction Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease. The presence of a pathogenic variant (PV) of the plakophilin-2 (PKP2) gene increases the likelihood of developing this disease. Although cardiac screening is routinely performed, early detection of ACM remains challenging. CineECG as a tool for analysis of the 12-lead electrocardiogram (ECG) can provide a 3D-reconstruction of the average pathway of electrical activation. With the emergence of this technique, a new insight in ventricular activation patterns can be obtained. CineECG might therefore be of aid in identifying early signs of disease in preclinical PKP2-PV carriers with a normal 12-lead ECG. Purpose This study aimed to analyze the ECG’s of preclinical PKP2-PV carriers with CineECG to determine the ventricular electrical activation patterns and to compare these patterns to the normal CineECG trajectory. Methods The 12-lead ECG’s of 19 preclinical PKP2-PV carriers were selected and evaluated by three experts on depolarization abnormalities. CineECG analysis was conducted in all preclinical PKP2-PV carriers to ascertain the average location and direction of the ventricular electrical activation. The resulting CineECG trajectory was then compared to the normal CineECG, which was previously determined from normal ECG’s from the PTB-XL database. The CineECG was considered abnormal if more than 15% of the CineECG trajectory was outside the normal distribution. Results Expert analysis of the ECG’s revealed no depolarization abnormalities (e.g. abnormal electrical heart axis, pathological Q-waves or low voltage, and ECG Task Force Criteria were absent). The CineECG trajectory was abnormal in most cases (11 out of 19 PKP2-PV carriers), while the other eight carriers exhibited normal CineECG trajectories. Figure 1 shows three examples of A) a normal case, B) a PKP2-PV carrier with a normal CineECG and C) a PKP2-PV carrier with an abnormal CineECG. In example C, the activation pattern is abnormal as the latest activation is aimed towards inferior and far to the left basal area of the heart. Conclusions CineECG analysis of the normal 12-lead ECG’s of preclinical PKP2-PV carriers resulted in the finding of abnormal electrical activation patterns in the majority of carriers. CineECG could therefore be a sensitive tool to unveil subtle and early abnormalities in the depolarization that would otherwise not be easily detected.Figure 1