| Objective:To investigate the prognostic value of soluble growth stimulating expression factor 2(sST2)and N terminal pro B type natriuretic peptide(NT-proBNP)on cardiovascular death and heart failure rehospitalization in heart failure patients with mid-range ejection fraction(HFmrEF)with angiotensin receptor-neprilysin inhibitors(ARNI)intervention at real world scenarios and provide more clinical evidence for stratified comprehensive management of HFmrEF patients.Methods:We identified 74 patients from the department of cardiovascular medicine of affiliated hospital of HeBei university with a primary diagnosis of heart failure(HF)between October 2018 and January 2020.Echocardiography showed patients with enlarged left heart,ejection fraction less than or equal to 50%,and no contraindications to ARNI treatment.The enrolled HF patients were re-classified into two groups on the basis of baseline echocardiography: HF with mid-range ejection fraction(HFmrEF,40%≤EF≤49%)and HF with reduced ejection fraction(HFrEF,EF<40%),and were treated with oral intervention of sacurbatrovalsartan(ARNI)after hemodynamic stabilization.All patients were given sST2,NT-proBNP and echocardiography immediately after admission and 6 months after discharge.Patients were followed up for 6 months to record cardiovascular death and rehospitalization of heart failure.The enrolled HF patients were re-classified into different groups on the basis of baseline and 6 months follow-up echocardiography: HFmrEF: unchanged group(40% ≤EF≤49%),reduced group(EF <40%),and elevated group(EF≥50 %);HFrEF: unchanged(EF <40%)and increased(EF≥40%).HFmrEF and HFrEF patients with clinical endpoint events(cardiovascular death and rehospitalization of heart failure)were classified as event group A,and those without clinical events were classified as non-event group A.Patients with a clinical endpoint event in HFmrEF were classified as event group B,and those without clinical events were classified as non-event group B.Statistical analysis was performed using changes in sST2,NT-proBNP,ejection fraction(EF),cardiovascular cause mortality,and heart failure rehospitalization rates as observation indicators.To investigate the prognostic value of sST2 and NT-proBNP on end point(cardiovascular death and heart failure rehospitalization)in HFmrEF with ARNI intervention at real world scenarios.Results:(1)Seventy-four patients who met the initial conditions were strictly followed up for 6 months after discharge.Ten of them were withdrawn and lost to follow-up.HFmrEF group: n = 20,and HFrEF group: n = 44.Six months later,22 patients reached the primary end point was re-admission of heart failure in 22 patients(HFmrEF:n=5(25%),HFrEF:n=15(34%))and death in 2 patients(HFmrEF:n=1,HFrEF:n=1).At admission,the serum of sST2 and NT-proBNP in HFmrEF and HFrEF patients: event group A: 364.52±103.42,5632.00±1677.70,higher than non-event group A(286.30±108.14,3907.24±2000.00),and there were significant differences in the two groups(t=2.789,P=0.007;t=3.455,P=0.001).According to 6 mouths follow-up,the serum of sST2 and NT-proBNP in HFmrEF and HFrEF patients: event group A: 335.42(200.85,501.10),5130.00(2787.00,10490.00),higher than non-event group A(154.00(116.90,223.02),876.00(500.00,2172.50)),and there were significant differences in the two groups(U=120.00,P=0.000;U =40.00,P=0.000).At admission,the serum of sST2 and NT-proBNP in HFmrEF patients: event group B: 375.09(170.18,502.93),4860.00±3054.86,higher than nonevent group B(150.23(134.76,175.83),2171.43 ± 1020.44),and there were significant differences in the two groups(U=40.00,P=0.047;t=1.502,P=0.015).According to 6 mouths follow-up,the serum of sST2 and NT-proBNP in HFmrEF patients: event group B:(208.07±108.37,2562.67±339.05),higher than non-event group B(106.63.31±29.63,1343.29±903.20),and there were significant differences in the two groups(t=2.465,P=0.045;t=4.382,P=0.000).(2)Univariable Cox analysis showed that the serum of sST2,NT-proBNP,heart rate,somking and creatinine were independent risk factors for patients with HFmrEF and HFrEF at admission(RR 1.006,95%CI:1.001-1.011,P=0.036;RR1.002,95%CI:1.000-1.005,P=0.045;RR 1.068,95%CI:1.017-1.123,P=0.008;RR5.857,95%CI:1.039-1.330,P=0.045;RR 0.829,95%CI:0.697-0.986,P=0.012).Univariable Cox analysis showed that the serum of sST2 and NT-proBNP were independent risk factors for patients with HFmrEF at admission(RR 1.006,95%CI:1.001-1.011,P=0.036;RR 1.002,95%CI:1.000-1.005,P=0.045;RR 1.068,95%CI:1.017-1.123,P=0.008).(3)After Cox multivariate regression model,excluding confounders,the surm of NT-proBNP at admission(RR 1.000,95%CI:0.951-1.051,P=0.044)were independent risk factors for cardiovascular death and heart failure rehospitalization of HFmrEF and HFrHF.After Cox multivariate regression model,excluding confounders,the surm of NT-proBNP at admission(RR 1.287,95%CI:0.950-1.553,P=0.043)were independent risk factors for cardiovascular death and heart failure rehospitalization of HFmrEF.(4)The area under the ROC curve of serum sST2 at admission in predicting the cardiovascular death and heart failure rehospitalization of HFmrEF and HFrEF was 0.714(95%CI:0.578-0.850,P=0.005),the optimal boundary value was 302.56 pg/ml,the sensitivity was 90.9%,and the specificity was 61.9%.The area under the ROC curve of serum NT-proBNP at admission in predicting the cardiovascular death and heart failure rehospitalization of HFmrEF was 0.732(95%CI:0.606-0.857,P=0.002),the optimal threshold was 4733.00 pg/ml,the sensitivity was 81.8%,and the specificity was 66.7%.The area under the ROC curve of serum ST2 combined with serum NT-proBNP at admission in predicting cardiovascular death and heart failure rehospitalization of HFmrEF was 0.887(95%CI:0.777-0.998,P=0.000),the secitivity was 90.9%,and the specificity was 85.7%.The area under the ROC curve of serum sST2 at admission in predicting the cardiovascular death and heart failure rehospitalization of HFmrEF was 0.821(95%CI: 0.576-1.000,P=0.026),the optimal boundary value was 248.05 pg/ml,the sensitivity was 66.7%,and the specificity was 100.0%.The area under the ROC curve of serum NT-proBNP at admission in predicting the cardiovascular death and heart failure rehospitalization of HFmrEF was 0.905(95%CI: 0.764-1.000,P=0.005),the optimal threshold was 3051.50 pg/ml,the sensitivity was 100.0%,and the specificity was 71.4%.The area under the ROC curve of serum ST2 combined with serum NT-proBNP at admission in predicting cardiovascular death and heart failure rehospitalization of HFmrEF was 1.000(95%CI:1.000-1.000,P=0.000),the secitivity was 100%,and the specificity was 100%.(5)There is a dynamic change in LVEF between HFmrEF and HFrEF.According to 6 mouths follow-up,HFmrEF changed to HFpEF by 70% and HFrEF by 20%,and HFrEF changed to HFmrEF by 27% and HFpEF by 18%.According to 6 months follow-up echocardiography,14(70%)were diagnosed as LVEF elevated group,4(20%)as LVEF reduction group,and 2(10%)as LVEF unchanged group in HFmrEF group and 20(45%)were diagnosed as LVEF elevated group,and 24(55%)as LVEF unchanged group in HFrEF.Regardless of ejection fraction,patients with elevated LVEF had a lower incidence of clinical endpoint events than patients with decreased LVEF or unchanged LVEF(HFmrEF:0 vs.4,0 vs.2,All P<0.05;HFrEF:2 vs.14,P<0.05).Conclusion:(1)The surm of sST2 and NT-proBNP can be used as predictors of the clinical endpoint event of HFmrEF.Combineding detection of sST2 and NT-proBNP levels can improve the diagnostic value of HFmrEF patients after ARNI treatment.It is a supplement to the prognosis study of HFmrEF patients and has important reference value in clinical practice.(2)The heart failure patients with elevated LVEF have better clinical outcomes. |
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