IMPACT OF SACUBITRIL/VALSARTAN ON SURFACTANT BINDING PROTEIN, CENTRAL SLEEP APNEA, LUNG FUNCTION TESTS AND HEART FAILURE BIOMARKERS: HEMODYNAMIC OR PLEIOTROPISM?

Aims: Little is known about the mechanism underlying Sacubitril/Valsartan effects in patients with heart failure (HFrEF). Aim of the study is to assess its impact on circulating surfactant binding proteins (proSP-B and SP-D), biomarkers, lung and cardiac function and sleep apneas. Methods and results: Seventy-nine patients (86% males, age 66±10 years) were enrolled. At baseline and 6-8 months after reaching the maximum Sacubitril/Valsartan tolerated dose, we assessed biomarkers, transthoracic echocardiography, polysomnography, spirometry, and carbon monoxyde diffusing capacity of the lung (DLCO). At a mean follow-up of 261±41 days, 83% of patients reached the maximum dose. 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 (1196 IQR 648-2891 vs. 958 IQR 424-1663 pg/ml; p<0.001) along with interleukin ST-2 (28.4 IQR 19.4-36.6 ng/ml; p<0.001), paralleled by a reduction of 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.