title: Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Systolic Heart Failure: The DEFEAT-HF Study.
abstract: OBJECTIVE
  The primary objective of the study was a change in left ventricular end-systolic volume index (LVESVi) from baseline to 6 months of spinal cord stimulation (SCS) therapy in the treatment arm compared to the control arm as measured by echocardiography. Secondary objectives were changes in peak oxygen uptake and N-terminal pro-B-type natriuretic peptide (NT-proBNP) between the treatment arm and control arm from baseline through 6 months.
  
  
  BACKGROUND
  Abnormal neurohormonal activation is often responsible for progression of heart failure (HF). Treatment has often included drug therapy to modulate the neurohormonal axis. The purpose of the DEFEAT-HF (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure) clinical study was to evaluate whether direct modulation of the nervous system through SCS improved HF metrics, including heart size, biomarkers, functional capacity, and symptoms.
  
  
  METHODS
  The DEFEAT-HF study was a prospective, multicenter randomized (3:2), parallel, single-blind, controlled study to investigate whether SCS was a feasible therapy for the treatment of systolic HF for patients with New York Heart Association functional class III HF, left ventricular ejection fraction (LVEF) ≤35%, QRS duration <120 ms, and left ventricular end-diastolic dimension ≥55 mm. The primary objective of the DEFEAT-HF study was to evaluate the reduction in LVESVi after 6 months of SCS therapy in the treatment arm compared to the control arm.
  
  
  RESULTS
  In total, 81 patients were enrolled, with 66 successfully randomized and implanted with the SCS device system. Seventy-six percent (50 of 66) had an implantable cardioverter-defibrillator at the baseline visit. Among randomized patients, the mean age was 61 years, 79% were male, mean LVEF was 27%, and mean QRS duration was 105 ms. The change in LVESVi over 6 months was not significantly different between randomization arms (SCS OFF: -2.2 [95% confidence interval: -9.1 to 4.6] vs.
  2.1 [95% confidence interval: -2.7 to 6.9]; p = 0.30). Analyses of secondary endpoints for the study were also not significantly different.
  
  
  CONCLUSIONS
  The present study does not provide evidence to support a meaningful change in clinical outcomes for HF patients receiving SCS. (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure [DEFEAT-HF]; NCT01112579).
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: dzipes@iu.edu.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Zipes
authors.affiliation: Na Homolce Hospital, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Neuzil
authors.affiliation: Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Theres
authors.affiliation: St. Mary's Medical Center, Huntington, West Virginia.
authors.forename: David
authors.initials: D
authors.lastname: Caraway
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.affiliation: Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Clas
authors.initials: C
authors.lastname: Mannheimer
authors.affiliation: Fletcher Allen Healthcare, Burlington, Vermont.
authors.forename: Peter
authors.initials: P
authors.lastname: Van Buren
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Linderoth
authors.affiliation: Medtronic, Minneapolis, Minnesota.
authors.forename: Fred
authors.initials: F
authors.lastname: Kueffer
authors.affiliation: Medtronic, Minneapolis, Minnesota.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sarazin
authors.affiliation: Universitair Medisch Centrum Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Michael J L
authors.initials: MJL
authors.lastname: DeJongste
mesh_terms: D000368:Aged; D004867:Equipment Design; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000628:therapy*; D006801:Humans; D058542:Implantable Neurostimulators; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016037:Single-Blind Method; D062187:Spinal Cord Stimulation / Q000295:instrumentation*; D016896:Treatment Outcome
keywords: clinical trial results; heart failure; randomized; spinal cord stimulation