Author + information
- Received April 13, 2018
- Revision received April 24, 2018
- Accepted April 24, 2018
- Published online May 10, 2018.
- William T. Abraham, MDa,∗ (, )
- Karl-Heinz Kuck, MDb,
- Rochelle L. Goldsmith, PhDc,
- JoAnn Lindenfeld, MDd,
- Vivek Y. Reddy, MDe,
- Peter E. Carson, MDf,
- Douglas L. Mann, MDg,
- Benjamin Saville, PhDh,
- Helen Parise, ScDi,
- Rodrigo Chan, MDj,
- Phi Wiegn, MDk,
- Jeffrey L. Hastings, MDk,
- Andrew J. Kaplan, MDl,
- Frank Edelmann, MDm,
- Lars Luthje, MDm,
- Rami Kahwash, MDn,
- Gery F. Tomassoni, MDo,
- David D. Gutterman, MDp,
- Angela Stagg, BSq,
- Daniel Burkhoff, MD, PhDr and
- Gerd Hasenfuß, MDs
- aDivision of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio
- bDepartment of Cardiology, ASKLEPIOS Klinik St. Georg, Hamburg, Germany
- cExercise Physiology Laboratory, Columbia University Medical Center, New York, New York
- dDepartment of Heart Failure and Transplant, Vanderbilt Heart, Nashville, Tennessee
- eDepartment of Cardiac Arrhythmia Services, The Mount Sinai Hospital, New York, New York
- fMedical Intensive Care Unit, Washington VA Medical Center, Washington, DC
- gDivision of Cardiovascular, Washington University School of Medicine, St. Louis, Missouri
- hBerry Consultants, Austin, Texas
- iBiostatistics and Clinical Trials Consultant, Las Vegas, Nevada
- jChan Heart Rhythm Institute, Mesa, Arizona
- kDepartment of Clinical Cardiac Electrophysiology, Dallas VA Medical Center, Dallas, Texas
- lDepartment of Clinical Cardiac Electrophysiology, Cardiovascular Associates of Mesa, Mesa, Arizona
- mDepartment of Cardiology and Pneumology, Universität Göttingen, Göttingen, Germany
- nDepartment of Heart Failure & Transplantation, The Ohio State University Heart and Vascular Center, Columbus, Ohio
- oDepartment of Clinical Cardiac Electrophysiology, Baptist Health Lexington, Lexington, Kentucky
- pCardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin
- qClinical Trials, Impulse Dynamics, Orangeburg, New York
- rCardiovascular Research Foundation, New York, New York
- sHeart Center of Göttingen, University Medical Center Göttingen, Göttingen, Germany
- ↵∗Address for correspondence:
Dr. William Abraham, Division of Cardiovascular Medicine, The Ohio State University, 473 West 12th Avenue, Room 110P DHLRI, Columbus, Ohio 43210-1252.
Objectives The authors sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%.
Background CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period.
Methods A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration <130 ms, and ejection fraction ≥25% and ≤45% were randomized to continued medical therapy (control, n = 86) or CCM (treatment, n = 74, unblinded) for 24 weeks. Peak VO2 (primary endpoint), Minnesota Living With Heart Failure questionnaire, NYHA functional class, and 6-min hall walk were measured at baseline and at 12 and 24 weeks. Bayesian repeated measures linear modeling was used for the primary endpoint analysis with 30% borrowing from the FIX-HF-5 subgroup. Safety was assessed by the percentage of patients free of device-related adverse events with a pre-specified lower bound of 70%.
Results The difference in peak VO2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O2/kg/min, satisfying the primary endpoint. Minnesota Living With Heart Failure questionnaire (p < 0.001), NYHA functional class (p < 0.001), and 6-min hall walk (p = 0.02) were all better in the treatment versus control group. There were 7 device-related events, yielding a lower bound of 80% of patients free of events, satisfying the primary safety endpoint. The composite of cardiovascular death and HF hospitalizations was reduced from 10.8% to 2.9% (p = 0.048).
Conclusions CCM is safe, improves exercise tolerance and quality of life in the specified group of HF patients, and leads to fewer HF hospitalizations. (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure; NCT01381172)
This study was supported by research grants from Impulse Dynamics. Ms. Stagg is an employee of Impulse Dynamics. Drs. Abraham, Parise, Gutterman, Burkhoff, and Hasenfuß have served as consultants to Impulse Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 13, 2018.
- Revision received April 24, 2018.
- Accepted April 24, 2018.
- 2018 The Authors