title: Effects of Cardiac Resynchronization Therapy on Cardiac Remodeling and Contractile Function: Results From Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE).
abstract: BACKGROUND
  Cardiac resynchronization therapy results in improved ejection fraction in patients with heart failure. We sought to determine whether these effects were mediated by changes in contractility, afterload, or volumes.
  
  
  RESULTS
  In 610 patients with New York Heart Association class I/II heart failure from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study, we performed detailed quantitative echocardiography assessment prior to and following cardiac resynchronization therapy. We derived measures of contractility (the slope [end-systolic elastance] and the volume intercept of the end-systolic pressure-volume relationship, stroke work, and preload recruitable stroke work), measures of arterial load and ventricular-arterial coupling, and measures of chamber size (volume intercept, end-systolic and end-diastolic volumes). At 6 and 12 months, cardiac resynchronization therapy was associated with a reduction in the volume intercept and end-systolic and end-diastolic volumes (P<0.01). There were no consistent effects on end-systolic elastance, stroke work, preload recruitable stroke work, or ventricular-arterial coupling. In the active cardiac resynchronization therapy population, baseline measures of arterial load were associated with the clinical composite score (odds ratio 1.30, 95% CI 1.04 to 1.63, P=0.02). The volume intercept was associated with mortality (hazard ratio 1.90, 95% CI 1.01 to 3.59, P=0.047) and more modestly with the combined end point of mortality or heart failure hospitalization (hazard ratio 1.48, 95% CI 0.8 to 2.25, P=0.06). In contrast, end-systolic elastance, stroke work, preload recruitable stroke work, and ventricular-arterial coupling were not associated with any outcomes.
  
  
  CONCLUSIONS
  In patients with NYHA Class I/II heart failure, cardiac resynchronization therapy exerts favorable changes in left ventricular end-systolic and end-diastolic volumes and the volume intercept. The volume intercept may be useful to gain insight into prognosis in heart failure.
  
  
  BACKGROUND
  URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00271154.
authors.affiliation: Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (M.S.J.S., J.A.C., B.K.).
authors.forename: Martin
authors.initials: M
authors.lastname: St John Sutton
authors.affiliation: Medtronic, Inc, Minneapolis, MN (J.C.).
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cerkvenik
authors.affiliation: Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.).
authors.forename: Barry A
authors.initials: BA
authors.lastname: Borlaug
authors.affiliation: Département de Cardiologie, Centre Hospitalier Universitaire de Caen, Rennes, France (C.D.).
authors.forename: Claude
authors.initials: C
authors.lastname: Daubert
authors.affiliation: Division of Cardiology, Medical University of South Carolina, Charleston, SC (M.R.G.).
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gold
authors.affiliation: Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (S.G.).
authors.forename: Stefano
authors.initials: S
authors.lastname: Ghio
authors.affiliation: Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (M.S.J.S., J.A.C., B.K.).
authors.forename: Julio A
authors.initials: JA
authors.lastname: Chirinos
authors.affiliation: Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (C.L.) Department of Medicine, Karolinska Institutet, Stockholm, Sweden (C.L.).
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (M.S.J.S., J.A.C., B.K.).
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ky
mesh_terms: D000368:Aged; D058406:Cardiac Resynchronization Therapy / Q000009:adverse effects / Q000401:mortality; D018450:Disease Progression; D005060:Europe; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009656:North America; D016017:Odds Ratio; D010359:Patient Readmission; D016016:Proportional Hazards Models; D020127:Recovery of Function; D012307:Risk Factors; D013318:Stroke Volume; D013599:Systole; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
keywords: cardiac resynchronization; echocardiography; heart failure