Key result
Sacubitril/Valsartan significantly improved left ventricular ejection fraction from 31% to 37% and reduced NT-proBNP, surfactant binding proteins, and central sleep apneas in patients with HFrEF.
Why the study?
Little was known about the mechanisms underlying Sacubitril/Valsartan effects in patients with HFrEF, motivating an assessment of its hemodynamic versus non-hemodynamic effects.
Does sacubitril/valsartan improve surrogate markers of hemodynamic and pleiotropic function (biomarkers, lung function, sleep apneas) in patients with HFrEF?
Observational (n=79)
No
Does sacubitril/valsartan improve surrogate markers of hemodynamic and pleiotropic function (biomarkers, lung function, sleep apneas) in patients with HFrEF?
Sacubitril/valsartan exerts both hemodynamic and pleiotropic benefits in HFrEF, evidenced by favorable reverse remodeling, improved lung diffusion capacity, reduced central sleep apneas, and decreased levels of novel biomarkers like proSP-B and ST-2.
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.
No takes yet. Share an insight, caveat, or question.
Mapelli et al. (2022) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=79). Sacubitril/Valsartan vs. Baseline (pre-treatment) was evaluated on Left ventricular ejection fraction (LVEF) (p=<0.001). Sacubitril/Valsartan significantly improved left ventricular ejection fraction from 31% to 37% and reduced NT-proBNP, surfactant binding proteins, and central sleep apneas in patients with HFrEF.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: