Impact of angiotensin receptor–neprilysin inhibition on vascular function in heart failure with reduced ejection fraction: A pilot study

Abstract
The mechanisms for the benefits of Angiotensin Receptor Neprilysin Inhibition (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure reduction. Measures of vascular function such as arterial stiffness and endothelial function are strong prognostic markers of cardiovascular outcomes in HFrEF, yet the impact of ARNi on vascular health remains to be explored. We hypothesized that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. We tested 10 stable HFrEF patients at baseline and following 12 weeks of ARNi [64 ± 9 years, Men/Women: 9/1, left ventricular ejection fraction (EF): 28 ± 6%] as well as 10 stable HFrEF patients that remained on conventional treatment (CON: 60 ± 7 years, Men/Women: 6/4, EF: 31 ± 5%; all p = NS). Arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV) and endothelial function was assessed via brachial artery flow-mediated dilation (FMD). PWV decreased after 12 weeks of ARNi (9.0 ± 2.1 vs. 7.1 ± 1.2 m/s; p < 0.01) but not in CON (7.0 ± 2.4 vs. 7.5 ± 2.3 m/s; p = 0.35), an effect that remained when controlling for reductions in mean arterial pressure (p < 0.01). FMD increased after 12 weeks of ARNi (2.2 ± 1.9 vs. 5.5 ± 2.1%; p < 0.001) but not in CON (4.8 ± 3.8 vs. 5.4 ± 3.4%; p = 0.34). Baseline PWV (p = 0.06) and FMD (p = 0.07) were not different between groups. These preliminary data suggest that 12 weeks of ARNi therapy may reduce arterial stiffness and improve endothelial function in HFrEF. Thus, the findings from this pilot study suggest that the benefits of ARNi are beyond blood pressure reduction and include improvements in vascular function. New & Noteworthy: Twelve weeks of ARNi therapy may reduce arterial stiffness (assessed by carotid-femoral PWV) and improve endothelial function (assessed by brachial artery FMD) in HFrEF when compared to conventional treatment. Improvement in vascular function may be a physiological mechanism for the clinical benefit seen with ARNi in HFrEF. Moreover, these pleiotropic benefits of ARNi beyond BP lowering may be vital for the treatment of HFrEF and possibly other cardiovascular diseases.
Description
This article was originally published in Physiological Reports. The version of record is available at: https://doi.org/10.14814/phy2.15209
Keywords
ARNi, arterial stiffness, endothelial function, flow- mediated dilation, pulse wave velocity
Citation
Nathaniel, S., McGinty, S., Witman, M. A. H., Edwards, D. G., Farquhar, W. B., Hosmane, V., & Wenner, M. M. (2022). Impact of angiotensin receptor–neprilysin inhibition on vascular function in heart failure with reduced ejection fraction: A pilot study. Physiological Reports, 10, e15209. https://doi.org/10.14814/phy2.15209