title: Left ventricular ejection fraction normalization in cardiac resynchronization therapy and risk of ventricular arrhythmias and clinical outcomes: results from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial.
abstract: BACKGROUND
  Appropriate guideline criteria for use of implantable cardioverter-defibrillators (ICDs) do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-defibrillator.
  
  
  RESULTS
  Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial who survived and had paired echocardiograms at enrollment and at 12 months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF ≤35% [reference], 36%-50%, and >50%) on outcomes of ventricular tachyarrhythmias (VTAs), VTA ≥200 bpm, ICD shock, heart failure or death, and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization (>50%). The average follow-up was 2.2±0.8 years. The risk of VTA was reduced in patients with LVEF >50% (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.07-0.82; P=0.023) and LVEF of 36% to 50% (HR, 0.44; 95% CI, 0.28-0.68; P<0.001). Among patients with LVEF >50%, only 1 patient had VTA ≥200 bpm (HR, 0.16; 95% CI, 0.02-1.51), none were shocked by the ICD, and 2 died of nonarrhythmic causes. The risk of HF or death was reduced with improvements in LVEF (LVEF >50%: HR, 0.29; 95% CI, 0.09-0.97; P=0.045; and LVEF of 36%-50%: HR, 0.44; 95% CI, 0.28-0.69; P<0.001). For inappropriate ICD therapy, no additional risk reduction for LVEF>50% was seen compared with an LVEF of 36% to 50%. A total of 6 factors were associated with LVEF normalization, and patients with all factors present (n=42) did not experience VTAs (positive predictive value, 100%).
  
  
  CONCLUSIONS
  Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present, and these patients could be considered for downgrade from CRT-defibrillator to CRT-pacemaker at the time of battery depletion if no VTAs have occurred.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00180271.
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.). mruwald@hotmail.com.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Elyse
authors.initials: E
authors.lastname: Foster
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Valentina
authors.initials: V
authors.lastname: Kutyifa
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Ruwald
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Saadia
authors.initials: S
authors.lastname: Sherazi
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Christian
authors.initials: C
authors.lastname: Jons
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.affiliation: From the Heart Research Follow-up Program, Division of Cardiology, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.R., S.S., S.M., A.J.M., W.Z.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.R., C.J.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S.); and Division of Cardiology, Department of Medicine, University of California, San Francisco (E.F.).
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
mesh_terms: D000368:Aged; D058406:Cardiac Resynchronization Therapy / Q000379:methods* / Q000401:mortality; D017147:Defibrillators, Implantable / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000401:mortality / Q000628:therapy; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D020127:Recovery of Function / Q000502:physiology; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology*; D017180:Tachycardia, Ventricular / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000628:therapy*; D014693:Ventricular Fibrillation / Q000401:mortality / Q000628:therapy; D016277:Ventricular Function, Left / Q000502:physiology*
keywords: arrhythmias, cardiac; cardiac resynchronization therapy; defibrillators, implantable; prognosis; ventricular dysfunction, left