Clinical Diagnosis, Imaging, and Genetics of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Abstract

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy that can lead to sudden cardiac death and heart failure. Our understanding of its pathophysiology and clinical expressivity is continuously evolving. The diagnosis of ARVC/D remains particularly challenging due to the absence of specific unique diagnostic criteria, its variable expressivity, and incomplete penetrance. Advances in genetics have enlarged the clinical spectrum of the disease, highlighting possible phenotypes that overlap with arrhythmogenic dilated cardiomyopathy and channelopathies. The principal challenges for ARVC/D diagnosis include the following: earlier detection of the disease, particularly in cases of focal right ventricular involvement; differential diagnosis from other arrhythmogenic diseases affecting the right ventricle; and the development of new objective electrocardiographic and imaging criteria for diagnosis. This review provides an update on the diagnosis of ARVC/D, focusing on the contribution of emerging imaging techniques, such as echocardiogram/magnetic resonance imaging strain measurements or computed tomography scanning, new electrocardiographic parameters, and high-throughput sequencing.

Arrhythmogenic Left Ventricular Cardiomyopathy: A Clinical and CMR Study

“…This is significantly different compared to end-stage arrhythmogenic RV dysplasia. In end-stage ARVC, the left ventricle can also be involved but compared to the right ventricle it is much less severely affected where the right ventricle is much more severely affected 3,4,30 . Using CMR feature-tracking technique, Dr. Vives-Gilabert et al reported two important mechanisms in arrhythmogenic cardiomyopathy patients with LV involvement including 1) decreased myocardial deformation with global LV affectation and 2) delayed myocardial contraction at localized regions 31 .…”

SORBS2is a susceptibility gene to arrhythmogenic right ventricular cardiomyopathy

“…Arrhythmogenic right ventricular cardiomyopathy (ARVC), also referred to as arrhythmogenic right ventricular dysplasia (ARVD), is a rare inherited cardiac muscle disorder that can lead to heart failure and sudden cardiac death (SCD) 1 . The prevalence of ARVC in the general population is between 1:1,000 and 1:5,000, accounting for up to 50% SCD in the United States 2-4 .…”

“…Current management of ARVC is mostly palliative and focuses on delaying disease progression and preventing SCD. No curative treatment is available for this life-threatening disease 1 .…”

“…Human genetic studies of ARVC probands have linked 16 genes to ARVC to date 1, 7 , among which seven encode desmosomal proteins located in the intercalated disc (ICD). Mutations in desmosomal protein coding genes, such as PKP2, DSP and DSG2 , account for up to 63% of the ARVC probands 1, 8 . A small percentage of ARVC probands have sequence variants in non-desmosomal protein-encoding genes such as CTNNA3 and CDH2 9 , 10 .…”

Reevaluating the Mutation Classification in Genetic Studies of Bradycardia Using ACMG/AMP Variant Classification Framework

“…International Journal of Genomics prevention, and treatment of certain diseases [9]. The relationships between inherited ion channel disease, such as long QT syndrome (LQTs) [10] and Brugada syndrome (BrS) [11], inherited cardiomyopathy, such as dilated cardiomyopathy (DCM) [12], hypertrophic cardiomyopathy (HCM) [13], and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) [14], and variant sequencing have been well studied. However, the role of genetic sequence variants in bradycardia is still under debate.…”