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April 5, 2022Frontiers in Cardiovascular Medicine16 citationsOpen Access

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

CPCorrado PelaiaGAGiuseppe ArmentaroMVMara Volpentesta

Key Result

Sacubitril-valsartan treatment for 6 months significantly reduced the global apnea-hypopnea index from 26.5 to 21.7 events/hour in patients with heart failure with reduced ejection fraction and sleep apnea.

Study Design

Type

Observational (n=132)

Multicenter

Yes

Structured PICO

Does sacubitril-valsartan improve sleep apnea severity and cardiorespiratory parameters in patients with HFrEF and sleep apnea?

P
Population
132 consecutive outpatients with HFrEF (LVEF ≤35%, NYHA class II–III) and sleep apnea (SA) under treatment with CPAP for at least 3 months, mean age 67 ± 9.8 years, 81.1% male, based in Italy. Key inclusion: persistence of symptoms despite optimized treatment with stable doses of ACE-Is or ARBs for at least 4 weeks.
I
Intervention
Sacubitril-valsartan (initial dose 24/26 mg or 49/51 mg bid, titrated up to maximum tolerated dose) replacing ACE-I or ARB, administered for 6 months.
O
Outcome
Changes in global apnea-hypopnea index (AHI) value after 6 months of treatment, measured by nocturnal cardio-respiratory monitoring during a temporary 24-hour CPAP interruption.surrogate

Main Result

Absolute Event Rate: 21.7% vs 26.5%

p-value: p=<0.0001

Limitations

  • Enrolled patients were not randomized, and bias selection cannot be excluded
  • Used cardio-respiratory monitoring instead of polysomnography equipped with electroencephalography channels
  • Night-to-night AHI variability can at least in part confound the effects of sac/val
  • Focused attention only on nighttime registration
  • Possible misclassification of hypopneas

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.

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Cite This Study

Pelaia et al. (2022) conducted an observational in Heart Failure with Reduced Ejection Fraction (HFrEF) and Sleep Apnea (SA) (n=132). Sacubitril-Valsartan vs. Baseline was evaluated on Global apnea-hypopnea index (AHI) events/hour (p=<0.0001). Sacubitril-valsartan treatment for 6 months significantly reduced the global apnea-hypopnea index from 26.5 to 21.7 events/hour in patients with heart failure with reduced ejection fraction and sleep apnea.

synapsesocial.com/papers/6a102016d13714ec96ff393ahttps://doi.org/10.3389/fcvm.2022.861663
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