Impact of sacubitril/valsartan on cardiac and systemic hypoxia in chronic heart failure

Hélène Nougué; François Picard; Alain Cohen-Solal; Damien Logeart; Jean-Marie Launay; Nicolas Vodovar

doi:10.1016/j.isci.2023.108520

Impact of sacubitril/valsartan on cardiac and systemic hypoxia in chronic heart failure

iScience. 2023 Nov 23;27(1):108520. doi: 10.1016/j.isci.2023.108520. eCollection 2024 Jan 19.

Authors

Hélène Nougué^{1

2}, François Picard³, Alain Cohen-Solal^{1

4}, Damien Logeart^{1

4}, Jean-Marie Launay¹, Nicolas Vodovar¹

Affiliations

¹ Université de Paris and Inserm UMR-S 942, Paris, France.
² Department of Anaesthesiology and Intensive Care, Saint Louis - Lariboisière - Fernand Vidal University Hospital, Paris, France.
³ Service d'insuffisance cardiaque, Hôpital Cardiologique du Haut-Lévêque, Pessac, France.
⁴ Department of Cardiology, Lariboisière Hospital, Paris, France.

Abstract

In heart failure patients with reduced ejection fraction, Sacubitril/valsartan (S/V) increased proBNP T71 glycosylation, which is regulated negatively by hypoxia via miR-30a in vitro. Using a cohort of 73 HFrEF patients who were transitioned from standard HF medication to S/V, we found that the increase in proBNP T71 glycosylation after S/V was associated with a decrease in cardiac hypoxia. We further found that plasma levels of K709-acteylated HIF1α, HIF-regulated and HIF-independent biomarkers also evolved consistently with a decrease in hypoxia. We further confirmed that biomarker changes were related to hypoxia, in a rat model subjected to isobaric hypoxia. We measured them in rats subjected to isobaric hypoxia. Overall, these data strongly suggest that optimally treated HFrEF patients exhibited subclinical hypoxia that is improved by S/V. The data also posit proBNP T71 glycosylation as a biomarker of cardiac hypoxia.

Keywords: Health sciences; Medicine; Pharmacology.