Effect of Sacubitril/Valsartan on the Right Ventricular Function and Pulmonary Hypertension in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta‐Analysis of Observational Studies

Abstract

Background Sacubitril/valsartan (S/V) demonstrated significant effects in improving left ventricular performance and remodeling in patients with heart failure with reduced ejection fraction. However, its effects on the right ventricle remain unclear. This systematic review and meta‐analysis aimed to assess the impact of S/V on right ventricular function and pulmonary hypertension. Methods and Results We searched PubMed, Embase, Cochrane Library, and Web of Science from January 2010 to April 2021 for studies reporting right ventricular and pulmonary pressure indexes following S/V treatment. The quality of included studies was assessed using the Newcastle‐Ottawa scale. Variables were pooled using a random‐effects model to estimate weighted mean differences with 95% CIs. We identified 10 eligible studies comprising 875 patients with heart failure with reduced ejection fraction (mean age, 62.2 years; 74.0% men), all of which were observational. Significant improvements on right ventricular function and pulmonary hypertension after S/V initiation were observed, including tricuspid annular plane systolic excursion (weighted mean difference, 1.26 mm; 95% CI, 0.33–2.18 mm; P =0.008), tricuspid annular peak systolic velocity (weighted mean difference, 0.85 cm/s; 95% CI, 0.25–1.45 cm/s; P =0.005), and systolic pulmonary arterial pressure (weighted mean difference, 7.21 mm Hg; 95% CI, 5.38–9.03 mm Hg; P <0.001). Besides, S/V had a significant beneficial impact on left heart function, which was consistent with previous studies. The quadratic regression model revealed a certain correlation between tricuspid annular plane systolic excursion and left ventricular ejection fraction after excluding the inappropriate data ( P =0.026). Conclusions This meta‐analysis verified that S/V could improve right ventricular performance and pulmonary hypertension in heart failure with reduced ejection fraction, which did not seem to be fully dependent on the reverse remodeling of left ventricle. Registration URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42021247970.

Long-Term Effects of Sacubitril-Valsartan on Cardiac Remodeling: A Parallel Echocardiographic Study of Left and Right Heart Adaptive Response

“…To date, only Masarone et al in 215 patients with HFrEF [ 13 ], reported improvement in RV-pulmonary arterial coupling through the measurement of TAPSE/PASP ratio after 2 years of treatment with S/V, which was independent of left ventricular remodeling parameters. Therefore, although there is still no large evidence in the literature, our data support and confirm findings of available observational studies reporting the benefits of S/V on right heart function [ 30 ].…”

Clinical and hemodynamic improvement in pulmonary hypertension after switching to sacubitril/valsartan in heart failure patients with preserved ejection fraction

“…Invasive measurement also revealed a significantly reduced mean PCW at follow-up in patients with IpcPH [18 (15-23) mm Hg vs. 21 (18)(19)(20)(21)(22)(23)(24)(25)(26) mm Hg presacubitril/ valsartan, P , 0.01] (Fig. 1), whereas the reduction in mean PCW in patients with CpcPH was only tendential but not statistically significant [16 (10-25) mm Hg vs. 21 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) mm Hg presacubitril/valsartan, P = 0.09] (Fig. 2).…”

“…[12][13][14] Other studies have shown that sacubitril/valsartan reduces pulmonary pressure and improves right ventricular function in patients with heart failure with reduced ejection fraction, which does not seem to depend on reverse of left ventricular remodeling. [15][16][17][18] More recently, 2 small case series have shown that sacubitril/ valsartan also affects PAP in patients with HFpEF, suggesting an effect of sacubitril/valsartan on pulmonary hypertension independent of left ventricular function. 19,20 Therefore, we sought to investigate whether sacubitril/ valsartan affects pulmonary hypertension in a larger cohort of symptomatic patients with HFpEF.…”

The Dysfunctional Right Ventricle in Dilated Cardiomyopathies: Looking from the Right Point of View

“…These findings support the belief that there is a connection between LV and RV reverse remodeling in patients undergoing HF therapies which have been mainly attributed to LV dysfunction [ 76 ]. A systematic review and meta-analysis on the effect of S/V on the RV function in patients with HFrEF showed that RV systolic performance, evaluated by TAPSE and S’ wave velocity, improves after S/V treatment initiation [ 77 ]. Accordingly, not only LV function parameters, but also easily obtainable indices of RV function, such as TAPSE, S’ wave velocity, and RVFWLS should be measured when evaluating the response to treatment in HFrEF patients.…”