A novel desmin mutation causing severe left ventricular arrhythmogenic cardiomyopathy/dysplasia

Arrhythmogenic cardiomyopathy/dysplasia (AC) is a hereditary disorder characterized by degeneration of cardiomyocytes and their subsequent replacement by fat and fibrous tissue mainly, but not exclusively, in the right ventricle (RV) (1-3). Such changes lead to conduction abnormalities that provide the substrate for arrhythmogenesis (4,5). It is most frequently inherited in an autosomal dominant manner and is usually associated with mutations in genes encoding for desmosomal proteins (6,7), although non-desmosomal and ion channels gene mutations have also been described (8-10). Diagnosis is made according to the 2010 modified Task Force Criteria (11) and the average risk of ventricular arrhythmia can be very high, ranging from 3.7% to 10.6% per year depending on the specific AC population (12). The initial reported cases of AC affected exclusively the RV (13). However, over the recent years, cases of AC involving both ventricles or indeed only the left ventricle (LV) have been reported (14-17). Risk stratification of asymptomatic patients, however, remains a significant unresolved clinical problem. Consequently, the specific population who is at high risk of sudden cardiac death (SCD) and therefore will be benefit from an implantable cardioverter defibrillator (ICD) implantation is not well determined. A recent meta-analysis concluded that male gender, unexplained syncope, the extent of T-wave inversion, right ventricular dysfunction and previously documented VT/VF were significantly associated with higher risks of ventricular arrhythmias in AC patients (12). In addition to these established risk factors, strenuous exercise and inducibility of arrhythmia at electrophysiological studies also confer a higher arrhythmic risk even in borderline AC patients. Moreover, the presence of symptoms was linked to adverse outcomes in mutation carriers (12). However, reduced LV ejection fraction was not apparently associated with increased arrhythmic risk in definite and borderline AC patients (12)