Long-Term Effects of Angiotensin Receptor–Neprilysin Inhibitors on Myocardial Function in Chronic Heart Failure Patients with Reduced Ejection Fraction

Abstract

Background. We sought to evaluate the long-term effects of angiotensin receptor blocker–neprilysin inhibitor (ARNI) therapy on reverse remodeling of the failing myocardium in HFrEF patients. Methods. We performed a prospective non-randomized longitudinal study on 228 HFrEF patients treated with ARNI at our center. Prior to ARNI introduction all patients received stable doses of ACEI/ARB for at least six months. Clinical, biochemical and echocardiography data were obtained at ARNI introduction and 12-month follow-up. Results At follow-up, we found significant improvements in LVEF (29.7% ± 8% vs. 36.5% ± 9%; p < 0.001), LVOT-VTI (14.8 ± 4.2 cm vs. 17.2 ± 4.2 cm; p < 0.001), TAPSE (1.7 ± 0.5 cm vs. 2.1 ± 0.6 cm; p < 0.001) and LV-EDD (6.5 ± 0.8 cm vs. 6.3 ± 0.9 cm; p = 0.001). NT-proBNP serum levels also decreased significantly (1324 (605, 3281) pg/mL vs. 792 (329, 2022) pg/mL; p = 0.001). A total of 102 (45%) of patients responded favorably to ARNI (ΔLVEF < +5%; Group A) and 126 (55%) patients achieved ΔLVEF ≥ +5% (Group B). The two groups differed significantly in age, heart failure etiology, baseline LVEF and baseline NT-proBNP. On multivariable analysis, nonischemic heart failure, LVEF < 30% and NT-proBNP < 1500 pg/mL emerged as independent correlates of favorable response to ARNI therapy. Conclusion. ARNI therapy appears to improve echocardiographic parameters of left and right ventricular function in HFrEF patients above the effect of pre-existing optimal medical management. These effects may be particularly pronounced in patients with nonischemic heart failure, LVEF < 30% and lower degree of neurohumoral activation.

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

“…The pooled data from 8 studies 13 , 14 , 15 , 22 , 23 , 24 , 25 , 28 (732 patients) showed increases in TAPSE (WMD, 1.26 mm; 95% CI, 0.33 to 2.18 mm; I 2 =78.3%; Figure 1 and Table S2 ). Two studies 14 , 24 (186 patients) reported data on S’, which was improved after the treatment with S/V (WMD, 0.85 cm/s; 95% CI, 0.25–1.45 cm/s; I 2 =0.0%; Figure 1 and Table S2 ).…”

“…The mean follow‐up duration ranged from 3 to 17.1 months. Of the 10 included studies, 6 13 , 15 , 22 , 23 , 24 , 25 were prospective, and 4 14 , 26 , 27 , 28 were retrospective. One study 24 had a control group that received angiotensin‐converting enzyme inhibitor, whereas the others had no control group.…”

“…Because it was not meaningful to analyze the only study 24 with a control group separately, we decided to extract the experimental group data from it. Six studies 13 , 14 , 22 , 23 , 26 , 27 were from Italy, one 28 was from Turkey, one 15 was from France, one 24 was from Greece, and one 25 was from Slovenia.…”

“…The Newcastle‐Ottawa scale scores of the included studies are shown in Table S1 , ranging from 6 to 9. Most included studies 13 , 14 , 15 , 22 , 23 , 25 , 26 , 27 , 28 had a moderate risk of bias because of the lack of a control group, 4 14 , 26 , 27 , 28 of which had a higher risk of bias because of the nature of the retrospective studies. The risk of bias was shown to be low in only one study.…”

“…The pooled data from 10 studies 13 , 14 , 15 , 22 , 23 , 24 , 25 , 26 , 27 , 28 (850 patients) showed increases in LVEF (WMD, 4.40%; 95% CI, 2.21%–6.60%; I 2 =93.0%; Figure 2 and Table S3 ). Five studies 13 , 14 , 15 , 23 , 26 (313 patients) reported data on LVEDV.…”