Prognostic value of synthetized right-side precordial leads in arrhythmogenic right ventricular cardiomyopathy: data from nordic, dutch, and canadian ARVC registers

Abstract Background T-wave inversion (TWI) in standard ECG leads is a proven risk marker for life-threatening ventricular arrhythmias (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC). Right-sided precordial leads (RSPL), which may be more sensitive for detection of the arrhythmogenic substrate, are rarely recorded and understudied in this context. Computerized ECG signal-processing allows synthesis of right-sided precordial ECG leads derived from standard 12-lead ECG. Objective We aimed to assess the value of TWI in RSPL, synthetized from the standard 12-lead ECG, for prediction of VA risk in ARVC patients with subtle ECG phenotypes. Methods Patients with definite ARVC by TFC2010 and no history of sustained VA prior to diagnosis from the Nordic, Canadian and Dutch ARVC registries were included. Patients with major repolarization criterion or complete right bundle branch block (RBBB) were excluded. 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 the right-sided-precordial leads and the basis leads. TWI exceeding 0.1 mV in any of the synthetized leads was tested for its ability to predict sustained VA, defined as either sustained ventricular tachycardia, appropriate ICD shock, aborted cardiac arrest, or sudden cardiac death. In a similar manner, the value of TWI in any of the inferior leads III, aVF or II was assessed. Hazard ratio was calculated using Cox regression analysis adjusted for age, sex, and proband status. Results In total, 144 patients without prior VA history were identified. After exclusion of patients with major repolarization criterion (n=37) and RBBB (n=11), 96 patients comprised the study group (mean age 40±16, 42% female, 41% probands, 48% ICD carriers). Fifty-nine patients (62%) had TWI in one or more synthetized RSPL and 33 patients (34%) had TWI in any of the inferior leads. During 10 years of follow-up, 11 patients (12%) developed VA. Kaplan-Meier curve analysis showed significant association between the presence of TWI in at least one of the RSPL and the risk of VA, which remained an independent predictor in the adjusted Cox regression analysis (HR 10.6, 95%CI 1.3-84.4, p=0.026). TWI in any of the inferior leads was not associated with the risk of VA in this cohort (HR 1.2 95%CI 0.26-5.42). Conclusions Synthetized right-sided precordial leads appear to contain information potentially useful for refining risk stratification of primary prevention ARVC patients with a subtle ECG phenotype, in whom traditional repolarization markers, such as major repolarization criterion or TWI in inferior leads, are not informative.