Right vEntricular Dysfunction in tEtralogy of Fallot: INhibition of the rEnin-angiotensin-aldosterone system (REDEFINE) trial: Rationale and design of a randomized, double-blind, placebo-controlled clinical trial

Background Renin-angiotensin-aldosterone system (RAAS) inhibition with angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors is beneficial in patients with acquired left ventricular dysfunction. Adult patients with tetralogy of Fallot (TOF) with right ventricular (RV) dysfunction are at high risk for heart failure, arrhythmias, and sudden cardiac death. However, the efficacy of RAAS inhibition has not been established in these patients. Methods The REDEFINE is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo controlled trial to study the effects of the angiotensin II receptor blocker losartan (target dosage of 150 mg once daily) in adult patients with TOF. Patients with RV dysfunction in the absence of severe valvular dysfunction are eligible for inclusion. The primary end point is the change in RV ejection fraction after 18 to 24 months, as measured by cardiovascular magnetic resonance imaging. In addition, laboratory measurements, echocardiography, and cardiopulmonary exercise testing are performed. Conclusion The REDEFINE trial will study the effects of RAAS inhibition with losartan in TOF patients with RV dysfunction.