The figure illustrates the limited reliability of risk scores and calculators based on data obtained by heterogeneous study cohorts, including both implantable cardioverter defibrillator recipients and non-implantable cardioverter defibrillator recipients, and study design with a composite endpoint, including appropriate implantable cardioverter defibrillator intervention. In this representative example, although the mixed arrhythmogenic right ventricular cardiomyopathy study population predominantly comprises non-implantable cardioverter defibrillator patients (60%), outcomes mostly consist of appropriate implantable cardioverter defibrillator intervention (70%), which is an endpoint achievable exclusively by implantable cardioverter defibrillator recipients. Because the vast majority of outcomes in the arrhythmogenic right ventricular cardiomyopathy mixed population study are implantable cardioverter defibrillator interventions and the pre-determinate variables entered into the prediction model are those arrhythmic risk factors, that have been previously identified by implantable cardioverter defibrillator studies and represent current indication to implantable cardioverter defibrillator therapy for primary prevention of sudden cardiac death, the predictors identified by the statistical analysis coincides with the clinical variables used to guide implantable cardioverter defibrillator implantation. As a consequence, the study does allow to identify specific predictors of less frequent arrhythmic outcomes, other than appropriate implantable cardioverter defibrillator intervention, such as sustained ventricular tachycardia and cardiac arrest form ventricular fibrillation, which almost exclusively occur in the larger population of patients at lower risk and, thus, without indication to implantable cardioverter defibrillator implantation (non-implantable cardioverter defibrillator recipients). Most important, since appropriate implantable cardioverter defibrillator intervention is a recognized poor surrogate of arrhythmic sudden cardiac death, the use of risk scores and calculators based on risk predictors of appropriate implantable cardioverter defibrillator intervention may a misleading guide to implantable cardioverter defibrillator therapy for prevention of sudden cardiac death. Homogeneous study cohorts with regard to baseline treatment (particularly implantable cardioverter defibrillator therapy) are needed to make outcome studies more scientifically rigorous and to avoid that potentially misleading risk stratification scores are incorporated into calculators, which, in turn, may lead inexpert physicians to improperly implant an implantable cardioverter defibrillator for primary prevention of sudden cardiac death in young patients with genetic arrhythmias. ICD, implantable cardioverter defibrillator; SCD, sudden cardiac death; VT, ventricular tachycardia.
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