Author + information
- Received May 4, 2018
- Revision received July 23, 2018
- Accepted July 30, 2018
- Published online October 29, 2018.
- Juan Torrado, MD, PhDa,b,
- Chad Cain, BSa,
- Adolfo G. Mauro, MSa,
- Francisco Romeo, MDa,c,
- Ramzi Ockaili, PhDa,
- Vinh Q. Chau, MDa,
- John A. Nestler, BAa,
- Teja Devarakonda, BSa,
- Siddhartha Ghosh, PhDa,
- Anindita Das, PhDa and
- Fadi N. Salloum, PhDa,∗ (, )@VCU@HospItalBA
- aPauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia
- bDepartment of Cardiology, Clinic Hospital, School of Medicine, Republic University, Montevideo, Uruguay
- cDepartment of Cardiology, Hospital Italiano, Buenos Aires, Argentina
- ↵∗Address for correspondence:
Dr. Fadi N. Salloum, Congdon Chair in Cardiology and Associate Professor of Medicine and Physiology & Biophysics, Division of Cardiology, Box 980204, Virginia Commonwealth University, 1101 East Marshall Street, Room 7-070, Richmond, Virginia 23298.
Background Sacubitril/valsartan (SAC/VAL) is approved by the U.S. Food and Drug Administration for heart failure with reduced ejection fraction (HFrEF).
Objectives This study investigated the effects of SAC/VAL on acute myocardial infarction (MI) and cardiac remodeling in a translational rabbit model of MI.
Methods New Zealand White rabbits were sedated and underwent conscious MI (45-min ischemia) by balloon inflation (previously implanted surgically) followed by 72 h (acute protocol) or 10 weeks (chronic protocols) of reperfusion. “Infarct-sparing” protocol: SAC/VAL, VAL, or placebo were randomly allocated and administered at reperfusion. “HFrEF-treatment” protocol: rabbits were randomized, and treatment commenced after echocardiography-confirmed left ventricular ejection fraction (LVEF) ≤40%. “HFrEF-prevention” protocol: treatment started at reperfusion and continued daily throughout the study.
Results Compared with placebo, SAC/VAL and VAL significantly reduced infarct size (TTC staining) and plasma troponin levels; however, only SAC/VAL preserved LVEF at 72 h post-MI. In the HFrEF-treatment protocol, LVEF improvement was observed with SAC/VAL compared with both placebo and VAL starting 2 weeks post-treatment, a benefit that persisted throughout study duration. In the HFrEF-prevention protocol, SAC/VAL and VAL attenuated the decline in LVEF post-MI, although SAC/VAL offered better functional protection. The functional improvement observed in both treatment protocols was paralleled by significant reduction in left ventricular (LV) scar size (Picrosirius red staining) in the SAC/VAL groups.
Conclusions Reperfusion therapy with SAC/VAL or VAL offers robust acute infarct-sparing benefits; however, SAC/VAL treatment offered superior short-term and long-term benefits in preventing MI-induced LV dysfunction compared with VAL. SAC/VAL also significantly attenuated LV scar size following MI compared with placebo, whereas VAL did not reach statistical significance in scar reduction.
- adverse cardiac remodeling
- heart failure
- infarct scar size
- left ventricular ejection fraction
- myocardial infarction
This study was supported by Novartis Pharmaceuticals (LCZ696BUSNC02T to Dr. Salloum). Sacubitril/valsartan and valsartan were provided by Novartis Pharmaceuticals, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received May 4, 2018.
- Revision received July 23, 2018.
- Accepted July 30, 2018.
- 2018 American College of Cardiology Foundation
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