Author + information
- Received July 24, 2015
- Revision received September 30, 2015
- Accepted October 2, 2015
- Published online February 1, 2016.
- Douglas P. Zipes, MDa,∗ (, )
- Petr Neuzil, MDb,
- Heinz Theres, MDc,
- David Caraway, MD, PhDd,
- Douglas L. Mann, MDe,
- Clas Mannheimer, MDf,
- Peter Van Buren, MDg,
- Cecilia Linde, MDh,
- Bengt Linderoth, MDh,
- Fred Kueffer, MSi,
- Scott A. Sarazin, BSi,
- Michael J.L. DeJongste, MDj,
- on behalf of the DEFEAT-HF Trial Investigators
- aIndiana University School of Medicine, Indianapolis, Indiana
- bNa Homolce Hospital, Prague, Czech Republic
- cCharité Universitätsmedizin Berlin, Berlin, Germany
- dSt. Mary’s Medical Center, Huntington, West Virginia
- eWashington University School of Medicine, St. Louis, Missouri
- fSahlgrenska University Hospital, Göteborg, Sweden
- gFletcher Allen Healthcare, Burlington, Vermont
- hKarolinska University Hospital, Stockholm, Sweden
- iMedtronic, Minneapolis, Minnesota
- jUniversitair Medisch Centrum Groningen and University of Groningen, Groningen, the Netherlands
- ↵∗Reprint requests and correspondence:
Dr. Douglas P. Zipes, Indiana University School of Medicine, Krannert Institute of Cardiology, 1800 N. Capitol Avenue, E316, Indianapolis, Indiana 46202.
Objectives 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. SCS ON: 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)
Dr. Neuzil has received research grant support from Medtronic; and has served as a consultant for Boston Scientific, St. Jude Medical, and Biosense Webster. Dr. Theres has received research grant support from and served on the advisory board for Medtronic; and has served on the Speakers Bureau for Servier. Dr. Caraway has served on the advisory board and steering committee for and received research grant support from Medtronic. Drs. Mann and Van Buren have served as consultants for Medtronic. Dr. Linde has received research grant support and honoraria from Medtronic; has served as a consultant for and received honoraria from St. Jude Medical, Novartis, Cardio3, Vifor, and Medtronic. Dr. Linderoth has served as a consultant for Medtronic, St. Jude Medical, Boston Scientific, and ElektaAB. Mr. Kueffer and Mr. Sarazin are employees of Medtronic. Dr. DeJongste has received speakers fees from Medtronic and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 24, 2015.
- Revision received September 30, 2015.
- Accepted October 2, 2015.
- 2016 American College of Cardiology Foundation