Improved heart function and cardiac remodelling following sacubitril/valsartan in acute coronary syndrome with HF

Abstract

Aims: This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI).

Methods and results: We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6 months after treatment when a clinical follow-up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non-ST-elevation myocardial infarction (NSTEMI) group, and ST-elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT-proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT-proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P < 0.05), NT-proBNP, LVMI, and LVESVI decreased significantly in both groups after 6 months (P < 0.05), and LVEDVI decreased significantly in the S/V group (P = 0.001). In the S/V group, ΔLVEF (t = -2.745, P = 0.006), ΔNT-proBNP (P = 0.009), ΔLVEDVI (t = 4.203, P = 0.001), and ΔLVESVI (t = 3.907, P = 0.001) were significantly improved than those in the routine group. In the S/V group, ΔLVEF was negatively correlated with ΔNT-proBNP (r = -0.244, P = 0.004), ΔLVMI (r = -0.190, P = 0.028), ΔLVEDVI (r = -0.173, P = 0.045), and ΔLVESVI (r = -0.261, P = 0.002). In Cox regression model analysis, ΔLVEF {hazard ratio [HR] = 0.87 [95% confidence interval (CI) 0.80-0.95], P = 0.003}, ΔLVEDVI [HR = 1.04 (95% CI 1.01-1.06), P = 0.013], and ΔLVESVI [HR = 1.04 (95% CI 1.01-1.08), P = 0.026] were independent risk factors for MACE. Subgroup analysis showed that ΔLVEF (t = 6.290, P = 0.001), ΔLVEDVI (t = 2.581, P = 0.011), and ΔNT-proBNP (P = 0.019) in the NSTEMI group were significantly improved than those in the UA group, ΔLVEDVI in the NSTEMI group was significantly better than that in the STEMI group (t = -3.365, P = 0.001), and ΔLVEF in the STEMI group was significantly better than that in the UA group (t = -3.928, P = 0.001). There was a significant difference in the survival probability without MACE among the three groups in the analysis of the Kaplan-Meier curve (P = 0.042). The incidence of MACE in the UA group was significantly higher than that in the NSTEMI group (32.4% vs. 6.3%, P = 0.004).

Conclusions: The cardiac function is improved and cardiac remodelling is reversed significantly after treatment of S/V in ACS patients with reduced left ventricular ejection fraction after PCI, and the improvement is more obvious than the routine group. There is a significant negative correlation between the change in LVEF and the changes in NT-proBNP, LVMI, LVEDVI, and LVESVI. The increase of LVEF and the decrease of LVEDVI and LVESVI are protective factors to improve the prognosis. Patients with myocardial infarction and reduced left ventricular ejection fraction might benefit more from the initiation of S/V as first-line heart failure treatment after PCI.

Keywords: Acute coronary syndrome; Heart failure with reduced ejection fraction; Percutaneous coronary intervention; Sacubitril/valsartan.

Figure 1

Correlations between ΔLVEF and contemporaneous ΔNT‐proBNP, ΔLVMI, ΔLVEDVI, and ΔLVESVI in the sacubitril/valsartan (S/V) group. Scatterplots detailed the significant negative correlations between ΔLVEF and ΔNT‐proBNP, ΔLVMI, ΔLVEDVI, and ΔLVESVI in the S/V group. LVEDVI, left ventricular end‐diastolic volume index; LVEF, left ventricular ejection fraction; LVESVI, left ventricular end‐systolic volume index; LVMI, left ventricular mass index; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide.

Figure 2

Association between the changes in parameters and major adverse cardiac event (MACE) in the sacubitril/valsartan (S/V) group. Forest plot investigated the association between the changes in cardiac function and remodelling parameters and MACE of the S/V group in the fully adjusted regression model, which indicated that ΔLVEF, ΔLVEDVI, and ΔLVESVI were independent risk factors for MACE. CI, confidence interval; EF, ejection fraction; HR, hazard ratio; LVEDVI, left ventricular end‐diastolic volume index; LVEF, left ventricular ejection fraction; LVESVI, left ventricular end‐systolic volume index; LVMI, left ventricular mass index; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide.

Figure 3

Changes in left ventricular ejection fraction (LVEF), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), left ventricular end‐diastolic volume index (LVEDVI), and left ventricular end‐systolic volume index (LVESVI) in subgroups of the sacubitril/valsartan (S/V) group. Subgroup analyses showed that ΔLVEF, ΔLVEDVI, and ΔNT‐proBNP in the non‐ST‐elevation myocardial infarction (NSTEMI) group were significantly improved than those in the unstable angina (UA) group, ΔLVEDVI in the NSTEMI group was significantly better than that in the ST‐elevation myocardial infarction (STEMI) group, and ΔLVEF in the STEMI group was significantly better than that in the UA group.