Abstract 13018: Clinical Impact of Desmosomal and Titin Gene Mutations on the Natural History of Arrhythmogenic Right Ventricular Cardiomyopathy
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is caused by abnormalities in desmosomal proteins of the intercalated disc and desmosomal gene mutations are the principal cause of ARVC. Recently novel variants were discovered in the sarcomeric gene titin (TTN) that are associated with ARVC. Whether known mutation carriers differ clinically from non-carriers is not well known. To address this question, we analyzed clinical outcomes in our ARVC population based on mutation status.
Methods: Thirty-eight ARVC families (66 patients) were analyzed, with a median follow-up of 77 months. Genotype-phenotype association analysis was performed, and multiple variables including symptoms, electrocardiogram/echocardiogram abnormalities, arrhythmias, pacemaker and/or ICD implantation and survival time free from death or heart transplant were compared between desmosomal mutation carriers, TTN carriers and non-carriers.
Results: Seven patients (11%) harbored rare genetic variants in desmosomal genes (DSP, PKP2, DSG2, and DSC2), 14 (21%) carried TTN variants and 45 (68%) were non-carriers. Desmosomal carriers (DC) had a higher prevalence of inverted T waves in V2-3 in the absence of RBBB (100% vs. 32%, p=0.001) and epsilon waves (57% vs. 14%, p=0.007) compared to non-carriers. The TTN group had significantly more supraventricular arrhythmias (atrial fibrillation, atrial tachycardia) (43% vs. 0%, p=0.04) and required more pacemakers (57% vs. 0%, p=0.018). Conversely, DC required more heart transplants relative to non-carriers (57% vs. 11%, p=0.03) and exhibited a worse survival free from death or heart transplant (63% vs. 88% at 30 years and 42% vs. 88% at 50 years, p≤0.001).
Conclusions: This study provides valuable insights into the clinical consequences of gene mutations in individuals with ARVC. TTN rare variants confer greater risk for supraventricular arrhythmias and the need for pacemaker implantation relative to DC, while DC portends a greater risk for electrocardiogram abnormalities and the combined end-point of heart transplant or death compared to non-carriers.
- © 2013 by American Heart Association, Inc.