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.

Endothelial Dysfunction in Patients with Advanced Heart Failure Treated with Levosimendan Periodic Infusion Compared with Optimal Medical Therapy: A Pilot Study

“…Finally, Nathaniel et al [32] analysed 10 stable HF with reduced LVEF patients starting ARNI comparing them with another 10 stable patients with the same condition but that remained on conventional treatment. FMD increased after 12 weeks of ARNI (2.2 ± 1.9 vs. 5.5 ± 2.1%; p < 0.001) but not in the controls (4.8 ± 3.8 vs. 5.4 ± 3.4%; p = 0.34).…”

Vericiguate: a new treatment for chronic heart failure

“…Существует несколько возможностей косвенного фармакологического влияния на эти процессы с помощью препаратов, которые уже успешно применяются для лечения СН (ингибиторы АПФ и блокаторы ангиотензиновых рецепторов, валсартан/сакубитрил и ингибиторы SGLT2) [58][59][60][61][62], а также атеросклероза (статины) [63]. Что касается заместительной терапии в форме применения нитратов и донаторов NO, то их положительное влияние на гемодинамику, ремоделирование, а в некоторых группах пациентов (у афроамериканцев с тяжелой СН) -на выживаемость [58,64] обычно с течением времени нивелируется в результате возникновения побочных эффектов (чаще артериальной гипотензии), толерантности и оксидативного стресса.…”