Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Level of copeptin for early prediction of cardiorenal syndrome in rats / 中国病理生理杂志

AIM:To study the value of copeptin(CPP)level for the prediction of cardiorenal syndrome (CRS)in the rats with subtotal nephrectomy(SNX)combined with myocardial infarction(MI).METHODS: Male SD rats(n=60)were divided into blank control group(Con group), renal failure group(SNX group), heart failure group (MI group)and heart failure+renal failure group(CRS group).The concentrations of CPP in the serum and urine,hemo-dynamic indexes,blood pressure and renal function indexes were measured 1~5 weeks after modeling.The predictive val-ue of CPP for CRS in the rats was evaluated by the receiver operating characteristic(ROC)curve.RESULTS:Compared with Con group,left ventricular systolic pressure(LVSP)at 9 d in CRS group was significantly decreased(P<0.05),left ventricular end-diastolic pressure(LVEDP)at 9 d in CRS group was significantly increased(P<0.05), and the differ-ence of blood pressure at each time point was not statistically significant.The levels of blood urea nitrogen(BUN)and uri-nary creatinine(Ucr)in CRS group were significantly increased at 1 and 3 weeks(P<0.05).Compared with Con group, serum CPP level was significantly increased at 1,3 and 5 weeks(P<0.05), and urine CPP level was significantly in-creased at 3 weeks in CRS group.Serum brain natriuretic peptide(BNP)level was significantly increased at 1 and 3 weeks,while urine BNP level was significantly increased at 5 weeks after modeling in CRS group(P<0.05).No correla-tion between serum or urine CPP and BNP or BUN levels at 1 week in CRS group was observed.The results of ROC curve analysis indicated that the area under the curve(AUC)of serum CPP was 0.908(95%CI:0.789~1.028),and the cut-off value was 56.59 ng/L(sensitivity 0.875,specificity 0.800).CONCLUSION:The combination of SNX and MI estab-lishes a CRS rat model with both heart and kidney injury,and serum CPP can be used as a sensitive and specific biomarker for early prediction of CRS.