Juan Torrado1, Chad Cain2, Adolfo G Mauro2, Francisco Romeo3, Ramzi Ockaili2, Vinh Q Chau2, John A Nestler2, Teja Devarakonda2, Siddhartha Ghosh2, Anindita Das2, Fadi N Salloum4. 1. Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia; Department of Cardiology, Clinic Hospital, School of Medicine, Republic University, Montevideo, Uruguay. 2. Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia. 3. Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia; Department of Cardiology, Hospital Italiano, Buenos Aires, Argentina. 4. Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia. Electronic address: fadi.salloum@vcuhealth.org.
Abstract
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.
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.
Authors: Amil M Shah; Brian Claggett; Narayana Prasad; Guichu Li; Mayra Volquez; Karola Jering; Maja Cikes; Attila Kovacs; Wilfried Mullens; Jose C Nicolau; Lars Køber; Peter van der Meer; Pardeep S Jhund; Ghionul Ibram; Martin Lefkowitz; Yinong Zhou; Scott D Solomon; Marc A Pfeffer Journal: Circulation Date: 2022-09-09 Impact factor: 39.918
Authors: Hui-Fang Song; Sheng He; Shu-Hong Li; Jun Wu; Wenjuan Yin; Zhengbo Shao; Guo-Qing Du; Jie Wu; Jiao Li; Richard D Weisel; Subodh Verma; Jun Xie; Ren-Ke Li Journal: J Cell Mol Med Date: 2020-07-06 Impact factor: 5.310
Authors: Zachary M Gertz; Chad Cain; Donatas Kraskauskas; Teja Devarakonda; Adolfo G Mauro; Jeremy Thompson; Arun Samidurai; Qun Chen; Sarah W Gordon; Edward J Lesnefsky; Anindita Das; Fadi N Salloum Journal: JACC CardioOncol Date: 2019-12-17