Cardiovascular magnetic resonance-GUIDEd management of mild to moderate left ventricular systolic dysfunction (CMR GUIDE): Study protocol for a randomized controlled trial

Abstract

Background: The majority of sudden cardiac death (SCD) in patients with heart failure occurs in those with mild-moderate left ventricular (LV) systolic dysfunction (LVEF 36–50%) who under current guidelines are ineligible for primary prevention implantable cardiac defibrillator (ICD) therapy. Recent data suggest that cardiac magnetic resonance (CMR) evidence of replacement fibrosis forms a substrate for malignant arrhythmia and therefore potentially identifies a subgroup at increased risk of SCD. Our hypothesis is that among patients with mild-moderate LV systolic dysfunction, a CMR-guided management strategy for ICD insertion based on the presence of scar or fibrosis is superior to a current strategy of standard care. Methods/Design: CMR GUIDE is a prospective, multicenter randomized control trial enrolling patients with mild-moderate LV systolic dysfunction and CMR evidence of fibrosis on optimal heart failure therapy. Participants will be randomized to receive either a primary prevention ICD or an implantable loop recorder (ILR). The primary endpoint is the time to SCD or hemodynamically significant ventricular arrhythmia (VF or VT) during an average 4-year follow-up. Secondary endpoints include quality of life assessed by Minnesota Living with Heart Failure Questionnaire, heart failure related hospitalizations, and a cost-utility analysis. Clinical trials.gov identifier NCT01918215. Discussion: CMR GUIDE trial will add substantially to our understanding of the role of myocardial fibrosis and the risk of developing life-threatening ventricular arrhythmias. If the superiority of a CMR-guided approach over standard care is proven, it may change international clinical guidelines, with the potential to considerably increase survival in this growing patient population.