098: Pre clinical mutation carriers from families with dilated cardiomyopathy and angiotensin conversion enzyme inhibitor (the PRECARDIA study)

Abstract

Dilated Cardiomyopathy (DCM) is familial in at least 30% of cases, usually with autosomal dominant inheritance, and underlying genes/mutations are increasingly identified. Familial DCM is characterized by age-related penetrance, that means that the cardiac expression of the disease is usually absent for a long period and progressively appears with advanced age, usually after 20 years of age. Study the impact of ACE inhibitors (ACEi) in subjects who carry a mutation (leading to a genetic form of heart failure) but have not yet developed DCM (cardiac expression). This is a multicentre European double-blind randomized and controlled trial with perindopril or placebo in the context of a European consortium “INHERITANCE” (FP7 European Union, HEALTH-2009-2.4.2-3, Grant agreement n° 241924). The PRECARDIA trial was recently approved by the Head of medicines Agencies in Europe (HMA) and by AFSSAPS in France. We plan to enroll 200 participants from 7 European centres/countries. Follow-up duration is 3 years after inclusion. Primary Endpoint is a composite end-point: occurrence of DCM or deterioration of LV end diastolic diameter/volume or Ejection fraction (echocardiographic or magnetic resonance imaging). Secondary Endpoints are related to the evolution of other echocardiographic parameters or hormonal biomarkers (including Mid-Regional pro-Adrenomedullin). If the hypothesis is confirmed, and as a consequence, the knowledge derived from basic research (genes identification in DCM) will be translated into clinical practice (early identification of subjects at high risk of developing heart failure through predictive genetic testing) with the development of new therapeutic management (early ACEi) that will help to decrease the morbidity and mortality associated with the disease. This will constitute a paradigm of the development of preventive medicine thanks to the development of genetics in the cardiovascular field.