All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/Guidelines See the European Heart Journal online for supplementary data that includes background information and detailed discussion of the data that have provided the basis of the guidelines.Click here to access the corresponding ESC CardioMed chapters.

Background— Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a progressive cardiomyopathy. We aimed to define long-term outcome in a transatlantic cohort of 1001 individuals. Methods and Results— Clinical and genetic characteristics and follow-up data of ARVD/C index-patients (n=439, fulfilling of 2010 criteria in all) and family members (n=562) were assessed. Mutations were identified in 276 index-patients (63%). Index-patients presented predominantly with sustained ventricular arrhythmias (268; 61%). During a median follow-up of 7 years, 301 of the 416 index-patients presenting alive (72%) experienced sustained ventricular arrhythmias. Sudden cardiac death during follow-up occurred more frequently among index-patients without an implantable cardioverter-defibrillator (10/63, 16% versus 2/335, 0.6%). Overall, cardiac mortality and the need for cardiac transplantation were low (6% and 4%, respectively). Clinical characteristics and outcomes were similar in index-patients with and without mutations, as well as in those with familial and nonfamilial ARVD/C. ARVD/C was diagnosed in 207 family members (37%). Symptoms at first evaluation correlated with disease expression. Family members with mutations were more likely to meet Task Force Criteria for ARVD/C (40% versus 18%), experience sustained ventricular arrhythmias (11% versus 1%), and die from a cardiac cause (2% versus 0%) than family members without mutations. Conclusions— Long-term outcome was favorable in diagnosed and treated ARVD/C index-patients and family members. Outcome in index-patients was modulated by implantable cardioverter-defibrillator implantation, but not by mutation status and familial background of disease. One third of family members developed ARVD/C. Outcome in family members was determined by symptoms at first evaluation and mutations.

Background-Identification of patients at risk for drug-induced torsades de pointes arrhythmia (TdP) is difficult. Increased temporal lability of repolarization has been suggested as being valuable to predict proarrhythmia. The predictive value of different repolarization parameters, including beat-to-beat variability of repolarization (BVR), was compared in this serial investigation in dogs with chronic AV block. Methods and Results-In anesthetized dogs with electrically remodeled hearts, the dose-dependent difference in drug-induced TdP (d-sotalol, 2 and 4 mg/kg IV over 5 minutes, 25% and 75% TdP, respectively) could not be accounted for by prolongation of QT c (410Ϯ37 to 475Ϯ60 versus 415Ϯ47 to 484Ϯ52 ms, respectively). BVR was quantified by Poincaré plots at baseline and immediately before onset of d-sotalol-induced extrasystolic activity. TdP occurrence was associated with an increase in short-term variability (STV) of the left ventricular monophasic action potential duration (3.5Ϯ1.5 to 5.5Ϯ1.6 versus 3.0Ϯ0.7 to 8.6Ϯ3.8 ms, respectively), which was reversible when TdP was abolished by I K,ATP activation. The absence of TdP despite QT c prolongation after chronic amiodarone treatment could also be explained by an unchanged STV. In experiments with isolated ventricular myocytes, STV increased after I Kr block and was highest in cells that subsequently showed early afterdepolarizations. Conclusions-Proarrhythmia is not related to differences in prolongation of repolarization but corresponds to BVR, here quantified as STV of the left ventricle. STV could be a new parameter to predict drug-induced TdP in patients.