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April 8, 2019Scientific ReportsOpen Access

Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure

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Key result

Sacubitril/valsartan significantly improved left ventricular ejection fraction (39% vs 34%, P<0.05) and attenuated progressive left ventricular dilation compared to vehicle in rats with heart failure post-myocardial infarction.

Why the study?

ARNi therapy improves prognosis in heart failure patients, but the underlying mechanisms remain unclear.

Does sacubitril/valsartan improve myocardial remodeling and cardiac perfusion in a rat model of heart failure post-MI compared to valsartan or vehicle?

Population

10-weeks old male Lewis rats with confirmed HF after MI

Comparison

Sacubitril/valsartan vs valsartan vs vehicle

Design

Randomized preclinical study

Follow-up

1 or 5 weeks

Authors

DPDaniel PfauCornell UniversitySTStephanie ThornUniversity of Illinois Urbana-ChampaignJZJiasheng ZhangFujian Medical University

Discussion

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Overview

Preclinical rat data should not yet change practice; leaves open whether sacubitril/valsartan benefits exceed valsartan in human post-MI remodeling.

Structured PICO

Does sacubitril/valsartan improve myocardial remodeling and cardiac perfusion in a rat model of heart failure post-MI compared to valsartan or vehicle?

P
Population
90 male Lewis rats (10-weeks old) with confirmed heart failure post-myocardial infarction, randomized to sacubitril/valsartan, valsartan, or vehicle for 1 or 5 weeks.
I
Intervention
Sacubitril/valsartan 68 mg/kg/day administered daily by oral gavage for 1 or 5 weeks.
C
Comparator
Valsartan 31 mg/kg/day or vehicle (water) administered daily by oral gavage for 1 or 5 weeks.
O
Outcome
Myocardial remodeling (LVEF, LV volumes, fibrosis, hypertrophy) and cardiac perfusion (angiogenesis tracer uptake, dobutamine-stimulated flow).surrogate

Main Result

Absolute Event Rate: 39% vs 34%

p-value: p=<0.05

In a rat model of heart failure post-MI, sacubitril/valsartan improved global LV function, limited remodeling, and increased infarct perfusion more consistently than valsartan alone.

Limitations

  • Did not perform hemodynamic measurements
  • Did not assess ventricular arrhythmia occurrence or inducibility
  • Did not define the specific mechanism through which SAC/VAL increases blood flow reserve in the infarct
  • Did not use enalapril as a comparator
  • Study was not adequately powered to demonstrate statistical differences between the SAC/VAL and VAL groups

Cite This Study

Pfau et al. (2019) studied Heart failure post-myocardial infarction (n=90). Sacubitril/valsartan vs. Vehicle (water) and Valsartan (31 mg/kg/day) was evaluated on Left ventricular ejection fraction (LVEF) at 1 week after treatment (p=<0.05). Sacubitril/valsartan significantly improved left ventricular ejection fraction (39% vs 34%, P<0.05) and attenuated progressive left ventricular dilation compared to vehicle in rats with heart failure post-myocardial infarction.

synapsesocial.com/papers/6a9832e7ce42e14121e19201https://doi.org/10.1038/s41598-019-42113-0
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