Repolarization patterns in right-sided precordial leads in relation to genotype and structural substrate in patients with arrhythmogenic right ventricular cardiomyopathy

Background Repolarization ECG abnormalities in precordial ECG leads is a diagnostic marker of arrhythmogenic right ventricular cardiomyopathy (ARVC) included in the diagnostic task force criteria (TFC2010). Right-sided precordial leads (RSPL) are likely to be more sensitive for detection of right ventricular substrate, however, they are rarely recorded in clinical practice. Derived RSPL computed from the standard 12-lead ECG using ECG signal-processing have been shown to contain prognostic information for ARVC patients with subtle ECG abnormalities in the standard leads, however, their relation to the structural substrate in patients with ARVC has not been studied. Objective We aimed to investigate how repolarization characteristics in synthetized RSPL relate to the genotype and structural ventricular abnormalities in patients with ARVC. Methods Patients with definite ARVC by TFC2010 from the Nordic, Canadian and Dutch ARVC registries were included if they had digital ECG recordings registered within one year from diagnosis. Complete right bundle branch block or low ECG quality were exclusion criteria. RSPL (V3R-V6R) were derived from digitally recorded eight linearly independent leads (I, II and precordial V1 to V6) of the standard ECG using a linear ECG transformation matrix. The matrix was previously developed based on a library of body surface potential maps from a mixed group of healthy subjects and patients with cardiac diseases using multivariate linear regression and QRS-T data obtained from averaged beats of RSPL and the basis leads. T-wave inversion (TWI) was defined if there was a negative inflation exceeding 0.1 mV. The presence and distribution of late gadolinium enhancement (LGE) and wall motion abnormalities (WMA) was assessed from the cardiac magnetic resonance (CMR) examinations. Results In total 215 patients were included (mean age at diagnosis 42±17 yrs, 39% females, 59% probands, 30% with major repolarization ECG criterion. Genotype testing was performed in 199 patients. The TWI expansion to RSPL was more typical for PKP2 and DSC2/DSG2 carriers whereas DSP and PLN carriers more often demonstrated the TWI in leads V4-V6 (Table 1). CMR parameters of interest were available for 90 patients. TWI was most frequently registered in leads V5R through V2 in case of the isolated RV abnormalities and leads V3R through V4 in case of biventricular involvement (Table 2). The specificity of TWI in leads with the highest sensitivity (V3R to V1) did not exceed 50%. Conclusions RSPL repolarization pattern in patients with ARVC contains useful information regarding the presence of structural abnormalities in the right ventricle in patients with ARVC and can be more sensitive for the diagnosis of isolated RV involvement than standard precordial leads.