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Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics

Author
William J McKenna, MD
Section Editors
Hugh Calkins, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Brian C Downey, MD, FACC

INTRODUCTION

Arrhythmogenic right ventricular cardiomyopathy (ARVC), also called arrhythmogenic right ventricular dysplasia (ARVD), is an under-recognized clinical entity characterized by ventricular arrhythmias and a specific ventricular pathology [1-3]. ARVC is characterized macroscopically by fibrofatty replacement of the right ventricle (RV) myocardium, which initially produces regional wall motion abnormalities that later become global, producing RV dilation. The tissue replacement can also involve areas of the left ventricle (LV), but there is usually relative sparing of the septum [4].

The prevalence in the general population is estimated to be 1:1000 to 1:2000 [1]. ARVC is an important cause of sudden cardiac death (SCD) in young adults, and in northern Italy, systematic data collection suggests that it accounts for approximately 11 percent of cases overall and 22 percent in athletes [2,5].

In contrast, ARVC has been rarely diagnosed in the United States. This may reflect a difference in genetic prevalence, but is more likely due to under-recognition of disease. In a series of 100 ARVC patients from a single referral center in the United States, clinical profiles and event rates were similar to those reported in Europe [6].

The anatomy, histology, genetics, and pathogenesis of ARVC will be reviewed here. The clinical manifestations, diagnostic criteria (including the potential role of genetic testing), evaluation, treatment, and prognosis of ARVC are discussed separately. (See "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis" and "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations".)

PATHOGENESIS

Five established disease-causing genes in arrhythmogenic right ventricular cardiomyopathy (ARVC) encode desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2, desmoglein, and desmocollin in autosomal dominant disease and plakoglobin and desmoplakin in autosomal recessive disease) and support a new model for the pathogenesis of ARVC [7]. Impaired desmosome function when subjected to mechanical stress causes myocyte detachment and cell death. The myocardial injury may be accompanied by inflammation as the initial phase of the repair process, which ultimately results in fibrofatty replacement of damaged myocytes [8].

             

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Literature review current through: Nov 2016. | This topic last updated: Wed Oct 26 00:00:00 GMT+00:00 2016.
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