Author + information
- Received September 25, 2019
- Revision received January 24, 2020
- Accepted January 27, 2020
- Published online March 23, 2020.
- Petra Nijst, MD, PhDa,b@petra_nijst,
- Pieter Martens, MD, PhDa,
- Jeroen Dauw, MDa,b,
- W.H. Wilson Tang, MDc,
- Philippe B. Bertrand, MD, PhDa,
- Joris Penders, MD, PhDd,
- Liesbeth Bruckers, MSce,
- Gabor Voros, MD, PhDf,g,
- Rik Willems, MD, PhDf,g,
- Pieter M. Vandervoort, MDa,b,
- Matthias Dupont, MDa and
- Wilfried Mullens, MD, PhDa,h,∗ ()
- aDepartment of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium
- bDoctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
- cDepartment of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
- dDepartment of Laboratory Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium
- eInteruniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium
- fDepartment of Cardiology, University Hospitals Leuven, Leuven, Belgium
- gDepartment of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
- hBiomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
- ↵∗Address for correspondence:
Dr. Wilfried Mullens, Ziekenhuis Oost-Limburg, Department of Cardiology, Schiepse Bos 6, 3600 Genk, Belgium.
Background The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear.
ObjectiveS The aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy.
Methods In this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure–related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months.
Results Eighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias.
Conclusions The incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822)
- cardiac resynchronization therapy
- heart failure with recovered ejection fraction
- left bundle branch block
- myocardial recovery
- neurohumoral blockers
This work was supported by a research grant from Biotronik (research grant number FF023). Drs. Nijst, Martens, and Mullens are researchers for the Limburg Clinical Research Program Uhasselt – ZOL – Jessa, supported by the foundation Limburg Sterk Merk, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Dr. Nijst is supported by a research grant from the Frans Van de Werf Fund for Clinical Cardiovascular Research. Dr. Willems has received research funding from Biotronik, Boston Scientific, and Medtronic; has received speaking and consultancy fees from Biotronik, Boston Scientific, Medtronic, Abbott, and Sorin; and is supported as a postdoctoral clinical researcher by the Fund for Scientific Research Flanders. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 25, 2019.
- Revision received January 24, 2020.
- Accepted January 27, 2020.
- 2020 American College of Cardiology Foundation
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