Impact of Sacubitril/Valsartan on surfactant binding proteins, central sleep apneas, lung function tests and heart failure biomarkers: Hemodynamic or pleiotropism?

Massimo Mapelli; Irene Mattavelli; Elisabetta Salvioni; Cristina Banfi; Stefania Ghilardi; Fabiana De Martino; Paola Gugliandolo; Valentina Mantegazza; Valentina Volpato; Christian Basile; Maria Inês Fiuza Branco Pires; Valentina Sassi; Benedetta Nusca; Carlo Vignati; Mauro Contini; Chiarella Sforza; Maria Luisa Biondi; Pasquale Perrone Filardi; Piergiuseppe Agostoni

doi:10.3389/fcvm.2022.971108

Impact of Sacubitril/Valsartan on surfactant binding proteins, central sleep apneas, lung function tests and heart failure biomarkers: Hemodynamic or pleiotropism?

Front Cardiovasc Med. 2022 Sep 15:9:971108. doi: 10.3389/fcvm.2022.971108. eCollection 2022.

Authors

Massimo Mapelli^{1

2}, Irene Mattavelli¹, Elisabetta Salvioni¹, Cristina Banfi¹, Stefania Ghilardi¹, Fabiana De Martino¹, Paola Gugliandolo¹, Valentina Mantegazza¹, Valentina Volpato¹, Christian Basile³, Maria Inês Fiuza Branco Pires⁴, Valentina Sassi¹, Benedetta Nusca⁵, Carlo Vignati^{1

2}, Mauro Contini¹, Chiarella Sforza², Maria Luisa Biondi¹, Pasquale Perrone Filardi³, Piergiuseppe Agostoni^{1

2}

Affiliations

¹ Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
² Cardiovascular Section, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
³ Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy.
⁴ Centro Hospitalar Tondela-Viseu, Viseu, Portugal.
⁵ UOC Cardiologia e UTIC, Ausl Imola, Imola, Italy.

Abstract

Purpose: Little is known about the mechanism underlying Sacubitril/Valsartan effects in patients with heart failure (HFrEF). Aim of the study is to assess hemodynamic vs. non-hemodynamic Sacubitril/Valsartan effects by analyzing several biological and functional parameters.

Methods: Seventy-nine patients (86% males, age 66 ± 10 years) were enrolled. At baseline and 6 months after reaching the maximum Sacubitril/Valsartan tolerated dose, we assessed biomarkers, transthoracic echocardiography, polysomnography, spirometry, and carbon monoxide diffusing capacity of the lung (DLCO).

Results: Mean follow-up was 8.7 ± 1.4 months with 83% of patients reaching Sacubitril/Valsartan maximum dose (97/103 mg b.i.d). Significant improvements were observed in cardiac performance and biomarkers: left ventricular ejection fraction increased (31 ± 5 vs. 37 ± 9 %; p < 0.001), end-diastolic and end-systolic volumes decreased; NT-proBNP decreased (1,196 [IQR 648-2891] vs. 958 [IQR 424-1,663] pg/ml; p < 0.001) in parallel with interleukin ST-2 (28.4 [IQR 19.4-36.6] vs. 20.4 [IQR 15.1-29.2] ng/ml; p < 0.001) and circulating surfactant binding proteins (proSP-B: 58.43 [IQR 40.42-84.23] vs. 50.36 [IQR 37.16-69.54] AU; p = 0.014 and SP-D: 102.17 [IQR 62.85-175.34] vs. 77.64 [IQR 53.55-144.70] AU; p < 0.001). Forced expiratory volume in 1 second and forced vital capacity improved. DLCO increased in the patients' subgroup (n = 39) with impaired baseline values (from 65.3 ± 10.8 to 70.3 ± 15.9 %predicted; p = 0.013). We also observed a significant reduction in central sleep apneas (CSA).

Conclusion: Sacubitril/Valsartan effects share a double pathway: hemodynamic and systemic. The first is evidenced by NT-proBNP, proSP-B, lung mechanics, and CSA improvement. The latter is confirmed by an amelioration of DLCO, ST-2, SP-D as well as by reverse remodeling echocardiographic parameters.

Keywords: Sacubitril/Valsartan; biomarkers; heart failure; hemodynamics; pleiotropic; surfactant binding proteins.

Copyright © 2022 Mapelli, Mattavelli, Salvioni, Banfi, Ghilardi, De Martino, Gugliandolo, Mantegazza, Volpato, Basile, Branco Pires, Sassi, Nusca, Vignati, Contini, Sforza, Biondi, Perrone Filardi and Agostoni.