Characteristics of Patients with Arrhythmogenic Left Ventricular Cardiomyopathy: Combining Genetic and Histopathologic Findings

Background - Arrhythmogenic left ventricular cardiomyopathy (ALVC) is an under-characterized phenotype of arrhythmogenic cardiomyopathy involving the LV ab initio. ALVC was not included in the 2010 International Task Force Criteria (ITFC) for arrhythmogenic right ventricular cardiomyopathy diagnosis and data regarding this phenotype are scarce. Methods - clinical characteristics were reported from all consecutive patients diagnosed with ALVC, defined as a LV isolated late gadolinium enhancement (LGE) and fibro-fatty replacement (FFR) at cardiac magnetic resonance (CMR) plus genetic variants associated with ARVC and/or of an endomyocardial biopsy (EMB) showing FFR complying with the 2010 ITFC in the LV. Results - twenty-five ALVC patients (53 [48-59] years, 60% male) were enrolled. T-wave inversion in infero-lateral and left precordial leads were the most common ECG abnormalities. Overall arrhythmic burden at study inclusion was 56%. CMR showed LV LGE in the LV lateral and/or posterior basal segments in all patients. In 72% of the patients an invasive evaluation was performed, in which electroanatomical voltage mapping (EVM) and EVM-guided EMB showed low endocardial voltages and FFR in areas of LGE presence. Genetic variants in desmosomal genes (desmoplakin and desmoglein-2) were identified in 12/25 of the cohort presenting pathogenic/likely-pathogenic variants. A definite/borderline 2010 ITFC ARVC diagnosis was reached only in 11/25 patients. Conclusions - ALVC presents with a preferential involvement of the lateral and/or postero-lateral basal LV and is associated mostly with variants in desmoplakin and desmoglein-2 genes. An amendment to the current ITFC is reasonable to better diagnose ALVC patients.