Effects of Sacubitril-Valsartan on Clinical, Echocardiographic, and Polygraphic Parameters in Patients Affected by Heart Failure With Reduced Ejection Fraction and Sleep Apnea

Abstract

Background: Heart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril-valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity.

Methods: We recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 h before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val.

Results: After 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine, and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p < 0.0001), central AHI (p < 0.0001), obstructive AHI (p < 0.0001), oxygen desaturation index (ODI) (p < 0.0001), and percentage time of saturation below 90% (TC90) (p < 0.0001). The changes of CI, estimated glomerular filtration rate (eGFR), NT-proBNP, and tricuspid annular plane excursion (TAPSE) contributed to 23.6, 7.6, 7.3, and 4.8% of AHI variability, respectively, and the whole model accounted for a 43.3% of AHI variation.

Conclusions: Our results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA.

Keywords: apnea-hypopnea index; echocardiography; heart failure; sacubitril-valsartan; sleep apnea.

Figure 1

Changes of AHI, ODI, mean SpO₂ and TC90 after 6 months of therapy with sac/val in the subgroup with OSA. AHI, apnea hypopnea index; ODI, oxygen desaturation index; SpO₂, peripheral arterial oxyhemoglobin saturation; TC90, percentage time of saturation below 90%; OSA, obstructive sleep apnea. **p < 0.01; ***p < 0.001; ****p < 0.0001.

Figure 2

Changes of AHI, ODI, mean SpO₂, and TC90 after 6 months of therapy with sac/val in the subgroup with CSA. AHI, apnea hypopnea index; ODI, oxygen desaturation index; SpO₂, peripheral arterial oxyhemoglobin saturation; TC90, percentage time of saturation below 90%; CSA, central sleep apnea. ***p < 0.001; ****p < 0.0001.