Abstract 1050: Arrhythmogenic Right Ventricular Cardiomyopathy: Genotype-Phenotype Relation and Long-Term Follow-up of Patients with and without Plakophilin-2 Mutations (ARVC-9)
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous myocardial disease accounting for ventricular tachycardia and sudden cardiac death in a young population. Mutations in the gene encoding for plakophilin-2 (PKP2) have recently been reported by our group as the most common cause of autosomal-dominant ARVC (ARVC-9). In this study, we investigated the genotype-phenotype relationship in patients with and without a PKP2 mutation with respect to clinical characteristics, disease manifestation and progression, arrhythmia profile, and long-term follow-up.
Methods and Results: Ninety-five patients with a definite diagnosis of ARVC were divided into those with (PKP2-positive; n=30) and without (PKP2-negative; n=65) a PKP2 mutation. There were no differences in age or gender between the groups. Clinical, electrophysiological and angiographic parameters were compared during a long-term follow-up period (10.0±5.3 years). PKP2-positive patients had more pronounced right ventricular (RV) abnormalities including global RV dilatation (P<0.0005) and regional RV-dysfunction (P<0.005). Endomyocardial biopsies showed fibrotic rather than fatty tissue replacement of RV myocardium in PKP2-positive patients (P<0.001). In addition, repolarization abnormalities in right precordial leads (P<0.0002) and recurrences of sustained ventricular tachyarrhythmias during long-term follow-up (P<0.01) were more frequent in PKP2-positive patients when compared to PKP2-negative patients.
Conclusions: Patients with ARVC and a PKP2 mutation present with a more extensive disease manifestation and bear a higher risk for recurrent life-threatening ventricular tachyarrhythmias when compared to ARVC patients without a PKP2 mutation. Thus, PKP2 genotyping may provide additional information for further risk stratification of patients with ARVC.