William T Abraham1, Karl-Heinz Kuck2, Rochelle L Goldsmith3, JoAnn Lindenfeld4, Vivek Y Reddy5, Peter E Carson6, Douglas L Mann7, Benjamin Saville8, Helen Parise9, Rodrigo Chan10, Phi Wiegn11, Jeffrey L Hastings11, Andrew J Kaplan12, Frank Edelmann13, Lars Luthje13, Rami Kahwash14, Gery F Tomassoni15, David D Gutterman16, Angela Stagg17, Daniel Burkhoff18, Gerd Hasenfuß19. 1. Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio. Electronic address: William.Abraham@osumc.edu. 2. Department of Cardiology, ASKLEPIOS Klinik St. Georg, Hamburg, Germany. 3. Exercise Physiology Laboratory, Columbia University Medical Center, New York, New York. 4. Department of Heart Failure and Transplant, Vanderbilt Heart, Nashville, Tennessee. 5. Department of Cardiac Arrhythmia Services, The Mount Sinai Hospital, New York, New York. 6. Medical Intensive Care Unit, Washington VA Medical Center, Washington, DC. 7. Cardiovascular Division, Medicine, Washington University School of Medicine, St. Louis, Missouri. 8. Berry Consultants, Austin, Texas. 9. R. P. Chiacchierini Consulting, Gaithersburg, Maryland. 10. Chan Heart Rhythm Institute, Mesa, Arizona. 11. Department of Clinical Cardiac Electrophysiology, Dallas VA Medical Center, Dallas, Texas. 12. Department of Clinical Cardiac Electrophysiology, Cardiovascular Associates of Mesa, Mesa, Arizona. 13. Department of Cardiology and Pneumology, Universität Göttingen, Göttingen, Germany. 14. Department of Heart Failure & Transplantation, The Ohio State University Heart and Vascular Center, Columbus, Ohio. 15. Department of Clinical Cardiac Electrophysiology, Baptist Health Lexington, Lexington, Kentucky. 16. Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin. 17. Clinical Trials, Impulse Dynamics, Orangeburg, New York. 18. Cardiovascular Research Foundation, New York, New York. 19. Heart Center of Göttingen, University Medical Center Göttingen, Göttingen, Germany.
Abstract
OBJECTIVES: This study 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).
RCT Entities:
OBJECTIVES: This study 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).
Authors: Albert K Feeny; John Rickard; Kevin M Trulock; Divyang Patel; Saleem Toro; Laurie Ann Moennich; Niraj Varma; Mark J Niebauer; Eiran Z Gorodeski; Richard A Grimm; John Barnard; Anant Madabhushi; Mina K Chung Journal: Circ Arrhythm Electrophysiol Date: 2020-06-14