LAUSR

BACKGROUND Desmoplakin (DSP) genetic variants have been reported in Arrhythmogenic Cardiomyopathy (ACM) with particular regard to predominant left ventricular involvement. OBJECTIVE To improve our understanding of clinical phenotype and outcome of DSP variant carriers. METHODS Clinical picture and outcome of 73 patients (36% probands) harboring a pathogenic/likely pathogenic (P/LP) DSP variant were evaluated. RESULTS The phenotype during follow-up (mean 11 years, range 1-39) changed in 25 patients (35%), Arrhythmogenic Left Ventricular Cardiomyopathy (ALVC) forms being the most frequent (n=26, 36%), followed by biventricular forms (BIV n=20, 27%) and Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC, n=16, 22%). Major ventricular arrhythmias were detected in 21 patients (29%), and they were more common in ARVC (56%) and BIV (40%) than in ALVC (15%) forms. In ALVC patients, major ventricular arrhythmias occurred in the setting of a normal/mildly reduced systolic function. Heart failure (HF) occurred in 8 patients, none affected with ALVC. Females showed more commonly a LV involvement, while ARVC forms were more frequently detected in males (61% vs 38%, p=0.147). Males showed a higher incidence of major ventricular arrhythmias (52% vs 24%, p=0.036), HF (31% vs 3%, p=0.004) and cardiac death (31% vs 0%, p<0.001). CONCLUSIONS Clinical phenotype in P/LP DSP variant carriers is wide. Although most patients show a LV involvement, 22% has RV abnormalities in keeping with a "classical" ACM form. In ALVC, HF and major ventricular arrhythmias seem less common compared to RV and BIV variants. Females show more frequently a LV involvement and a better outcome.