title: Cardiac resynchronization therapy in chronic heart failure with moderately reduced left ventricular ejection fraction: Lessons from the Multicenter InSync Randomized Clinical Evaluation MIRACLE EF study.
abstract: BACKGROUND
  The benefits of CRT for symptomatic heart failure (HF) patients with a wide QRS and reduced left ventricular ejection fraction (LVEF≤35%), are well established .Post-hoc subgroup analyses suggest that CRT benefit may extend to patients with LVEF>35%.
  
  
  METHODS
  The MIRACLE EF was a prospective, randomized, controlled, double-blinded study to evaluate CRT-P in NYHA II-III HF patients with LBBB and with LVEF of 36%-50% and no previous pacing or ICD. The primary endpoint was a composite of time to first HF event or death. All patients were implanted with a CRT-P and randomized 2:1 to CRT-P ON or CRT-P OFF groups. The minimum follow up time was 24 months.
  
  
  RESULTS
  The MIRACLE EF study was stopped for enrollment futility after 13 months and enrolling only 44 patients. The main difficulties in recruiting patients were lack of eligible patients, previous ICD implants, and the reluctance of institutions, patients or physicians to enroll in the study which included a potential 5 year CRT OFF period.
  
  
  CONCLUSIONS
  Despite a careful design, identification and randomization of eligible patients were challenging and a trial to assess morbidity and mortality trial was not feasible. The MIRACLE EF experience illustrates the difficulties of designing a scientifically robust but feasible study to assess potential new indications for implantable devices. Smaller randomized studies with surrogate endpoints may therefore be more reasonable, although the potential impact of such studies on clinical practice, guidelines, and reimbursement remain to be determined.
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden. Electronic address: cecilia.linde@ki.se.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: University at Buffalo, Buffalo, NY, USA.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Curtis
authors.affiliation: University of California, Los Angeles, USA.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: Duke Clinical Research Institute, Durham, NC, United States.
authors.forename: Kerry
authors.initials: K
authors.lastname: Lee
authors.affiliation: Wake Forest University, United States.
authors.forename: William
authors.initials: W
authors.lastname: Little
authors.affiliation: University of Western Ontario, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Tang
authors.affiliation: Birmingham, United Kingdom.
authors.forename: Francisco
authors.initials: F
authors.lastname: Levya
authors.affiliation: Jichi Medical University Saitama Medical Center, Saitama, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Momomura
authors.affiliation: Medtronic Inc., Minneapolis, MN, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Manrodt
authors.affiliation: Medtronic Inc., Minneapolis, MN, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Bergemann
authors.affiliation: Imperial College London, The Royal Brompton Hospital, London, United Kingdom.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Cowie
mesh_terms: D002037:Bundle-Branch Block / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D058406:Cardiac Resynchronization Therapy; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012008:Recurrence; D012107:Research Design; D013318:Stroke Volume / Q000502:physiology*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*
keywords: Cardiac resynchronization therapy; Heart failure; LBBB; Left ventricular ejection fraction; Mortality