Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction

Abstract

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.

The Impact of Cardiac Rehabilitation on Activities of Daily Life in Elderly Patients With Heart Failure

“…A relevant question is whether these improvements had to be ascribed to the exercise training alone or whether other components of the rehabilitation intervention also concurred to the observed benefits. Theoretically, according to literature data showing an improvement in functional capacity and cardiopulmonary parameters in patients with HF (Giallauria et al, 2020;Malfatto et al, 2020;Dos Santos et al, 2021), we cannot dismiss the possibility that the optimization of pharmacological treatment might also have played a role. However, we have to underscore that, in our study, changes in therapy concerned a very limited number of patients over a limited number of days.…”

Effects of sacubitril-valsartan on heart failure patients with mid-range ejection fractions: A systematic review and meta-analysis

“…A study assessing the early effects of ARNI on exercise tolerance in patients with HFmHF found that ARNI improved exercise tolerance, peak VO₂, and ventilatory efficiency at 6.2 months of follow-up ( Vitale et al, 2019 ). Giallauria et al found that ARNI therapy improves autonomic function, functional capacity, and ventilation ( Giallauria et al, 2020 ). In clinical practice, ARNI can be considered a drug for HFmrEF patients, however, further studies are needed to better elucidate the underlying mechanisms of this functional improvement.…”

Benefits of a Supervised Ambulatory Outpatient Program in a Cardiovascular Rehabilitation Unit Prior to a Heart Transplant: A Case Study

“…The measurement of HR recovery could be an alternative solution. Defined as the difference between peak HR and HR obtained 1 min after exercise cessation ( 51 ), the HR recovery is however, dependent on post-exercise recovery modalities ( 52 , 53 ). In the present study, HR recovery was probably affected by the 3-min unloaded pedaling of post-exercise recovery.…”