ARVC and the importance of fibro-fatty infiltrate and inflammation

Project: Research

Investigators

  • Sunil Krishna Vasireddi (PI)

Description

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a genetic disorder of mutations in desmosomal and structural proteins, which accounts for 10-20% of sudden cardiac deaths (SCD) in healthy young patients, and no cure is available. Basic studies in ARVC myocytes and animal models thus far have mostly demonstrated conduction abnormalities (reduced sodium current and uncoupling of gap junctions). However, these abnormalities cannot fully explain the dependence of the ARVC clinical phenotype on high premature ventricular contraction (PVC) burden. It is important to note that fibrofatty infiltrate and inflammation are characteristic features of ARVC. These regions are routinely found to be an arrhythmia focus targeted for ablation during electrophysiological (EP) studies in patients with ARVC. Furthermore, fibrofatty infiltrate and inflammation are found in other diseases associated with arrhythmias (e.g. MI, AF). This close association between fatty infiltrate, inflammation, and arrhythmia, and the inability of basic studies to fully explain the clinical phenotype, suggests that the myocyte may not be solely responsible for arrhythmias in ARVC patients. Indeed, our preliminary results show that adipocytes and inflammation can independently create multiple arrhythmia substrates, including that for PVC mediated ectopy. Based on this we hypothesize that fibrofatty infiltrate and inflammation play a key mechanistic role in creating arrhythmia substrates in ARVC.
Award amount$114,368.00
Award date07/01/2017
Program typeClinical Scientist Training Program
Award ID17CPOST33650005
Effective start/end date07/01/201706/30/2019
StatusFinished