Mutation of desmoplakin gene and assessment of right ventricle function in patients with arrhythmogenic right ventricular cardiomyopathy

Abstract

Purpose: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by life-threatening ventricular arrhythmias. Approximately 50% of symptomatic individuals harbor a mutation in one of the five major components of the cardiac desmosome, among which desmoplakin (DSP) is the common mutation genes. Litter is known about desmosomal protein gene mutation in Chinese ARVC patients. Pathologically, ARVC is characterized by a progressive replacement of myocytes of the right ventricle (RV) with fibrous and fatty tissue. Assessment of the RV by two-dimensional (2D) echocardiography is the most important screening method, but the identification of RV abnormalities using echocardiography is still challenging. We here sought to delineate the clinical characteristics and genetics of ARVC patients and characterize whether Doppler tissue imaging and 2D speckle tracking could usefully assess right ventricle function in Chinese ARVC patients. Methods: Forty subjects fulfilling modified Task Force criteria were included. Genomic DNA was screened for mutations in DSP gene. Information on Doppler tissue imaging and 2D speckle tracking of cases was underwent investigation Results: Average follow-up period from onset was 57.5±42.6 months. Ventricular tachycardia with left bundle branch block morphology was subsequently documented in a total of 28 (70%) subjects during a study period. The cumulative mortality rate was 7.5%. Six DSP mutations were identified in 7/32 (21.9%) unrelated participants, three being novel. Compound heterozygotes exhibited a severe phe-notype in three patients. RV dimensions were significantly increased in patients with ARVC (RV inflow tract 48.41±10.44 vs. 39.30±3.23mm, P<0.01; RV outflow tract 33.05±2.76 vs. 29.53±3.50mm, p<0.01 in ARVC patients, and tricuspid annular plane systolic excursion was degraded (16.08±5.25 vs. 22.92±4.07, P<0.01 compared to controls. Strain and strain rate values were significantly lower in ARVC patients in inferior wall (-16.18±3.53 vs. -25.14±3.42, p<0.01) The strain value in right ventricular inferior wall showed the best receiver operating characteristics (area under the curve 0.94) with an optimal cutoff value of -19.5%. Conclusions: ARVC is associated with early mortality that is different to other countries population. Doppler tissue imaging and speckle tracking were useful to assesse RV function in patients with ARVC. In combination with genetic testing this quantitate technique may be diagnosis ARVC at the early stage.