CARDIAC RESYNCHRONIZATION THERAPY-PACEMAKERS IN HEART FAILURE PATIENTS WITH LEFT BUNDLE BRANCH BLOCK AND LEFT VENTRICULAR EJECTION FRACTION 36-50%: THE DESIGN OF THE MIRACLE EF STUDY
C. Linde1, A.B. Curtis2, G.C. Fonarow3, K. Lee4, W Little5, A Tang6, F. Leyva7, S. Momomura8, T. Bergemann9, C.M. Manrodt9, M. Cowie10
1Karolinska University, Stockholm, Sweden 2University at Buffalo, Buffalo, NY 3UCLA, Los Angeles, CA 4Duke Clinical Research Institute, Durham, NC 5University of Mississippi, Jackson, MS 6University of British Columbia, Victoria, BC, Canada 7Queen Elizabeth Hospital, Birmingham, UK 8Jichi Medical University, Saitama, Japan 9Medtronic, Inc. Mounds View, MN 10The Royal Brompton Hospital, London, UK
Purpose: The benefits of Cardiac Resynchronization Therapy (CRT) for New York Heart Association (NYHA) Class II-III heart failure (HF) patients with a wide QRS, reduced left ventricular ejection fraction (LVEF ?35%), and optimal medical therapy has been well established. Recent studies indicate large benefits in patients with left bundle branch block (LBBB). Sub-studies from the REVERSE and PROSPECT trials indicate that CRT benefit may be present among patients with LVEFs >35%. Symptomatic patients with NYHA Class II-III HF and mid-LVEF remain at high risk of mortality/morbidity, but have few established treatments, compared to low-LVEF HF patients. Therefore, the aim of the MIRACLE EF study is to test the hypothesis that CRT benefit reduces time to death or HF event in patients with NYHA Class II-III HF and LVEF of 36 to 50% and LBBB.
Methods: The MIRACLE EF study is a prospective, randomized, controlled, double-blinded, global multi-center study to evaluate CRT-P ON vs CRT-P OFF in NYHA II-III HF patients with LBBB and LVEF of 36% to 50%. Patients in persistent atrial fibrillation or already indicated for cardiac pacing or ICD therapy are excluded.
Following baseline assessment, eligible subjects are implanted with a CRT-P and randomized 2:1 to either treatment (CRT-P ON) or control (CRT-P OFF) groups. Subjects are followed for a minimum of 24 months or until study closure, and remain in their randomized groups until the study is stopped or until their 60 month visit, whichever comes first. The primary endpoint is a composite endpoint of time to first HF event and all-cause mortality. Secondary endpoints include mortality, time to first event defined as death, HF event or worsening systolic function, recurrent HF events, quality of life, healthcare system cost-effectiveness and echocardiography data.
Results: The MIRACLE EF study, which includes heart failure patients with LBBB and LVEF 36-50%, is currently enrolling, and is expected to be conducted at up to 275 centers worldwide. Approximately 2,900 subjects are to be enrolled to reach approximately 2,300 randomized subjects. This sample size provides 90% power to detect a hazard ratio of 0.75 or less if 10% of the control group per year experiences an event. The results are expected to emerge in 2018.
Conclusions: If trial results of this prospective randomized trial are positive, the indications for CRT may become wider and accessible to HF patients with mild to moderately reduced LVEF. (clinicaltrials.gov NCT 01735916).
