Efficacy Analysis Of Single-dose Versus Repeated Levosimendan Infusion In Patients With Decompensated Heart Failure

Objective:Heart failure is the end stage of various heart diseases,for example,acute myocardial infarction,hypertensive heart disease,rheumatic valvular heart disease,dilated cardiomyopathy,congenital heart disease and pulmonary heart disease.In Europe and America,more than 10%elderly people over 70 were diagnosed as heart failure,while the prevalence rate reached 1.3%in China,which was showed in a meta-analysis in 2013.Furthermore,the 5-year mortality rate of patients with chronic heart failure was almost 50%.Heart failure has become a global health burden.As a novel medication treatment of heart failure used in recent years,levosimendan(LS)has the function of increasing cardiac function and dialating blood vessels mainly as a calcium sensitization agent.Several clinical studies indicated that the treatment effect of levosimendan was superior to milrinone and sodium nitroprusside on acute heart failure.And European heart failure guidelines recommend the use of levosimendan in treating acute heart failure.Previous studies have also fully confirmed the curative effect and safety of levosimendan in patients with decompensated heart failure,however,the optimum dosage and dosing frequency remained disagreed.The present study aimed to compare the curative effect of single and repeated dose of intravenous injection of levosimendan in patients with decompensated heart failure(DHF),further exploring the optimum dosage and dosing frequency.Methods:The present prospective study included consecutive patients with decompensated heart failure in the Cixi Municipal People's Hospital from January 2012 to October 2014.All patients enrolled were assessed to be grade III to IV according to the NYHA cardiac functional class,with left ventricular ejection fraction(LVEF)lower than 40%judged by echocardiography Doppler examination using the modified Simpson method.A total of 89 patients were included in this study,and they were randomly divided into the single dose group(n=44 cases)or the repeated group(n=45 cases)by random digit grouping method.On the basis of conventional heart failure medication treatment including individual rational use of renin angiotensin aldosterone system inhibitor[RASI],beta blockers,diuretics and digitalis,levosimendan was injected according to the treatment standard,with initial loading dose 12?g/kg for 10 minutes of intravenous injection,followed by 0.2?g/kg/min continuous intravenous injection for 24 hours using micro-pump.Patients in the repeated group were treated with the above dose of levosimendan again one month later.The differences of NYHA cardiac functional class assessment,echocardiography and plasma NT-proBNP level were compared between the two groups 3 months after the first treatment.All statistical analyses were performed using SPSS 19.0 statistical analysis software.Continuous variables were expressed as mean±standard deviation,while categorical data were summarized as proportions.Student's t test and ?2 tests were conducted as appropriate.A P value<0.05 was considered statistically significant.Results:The general information assessment shows that there was no significant difference of gender,average age,and the component ratio of NYHA functional class III level and IV level between the single dose group of 44 patients(male 33 cases,75.0%)and the repeated dose group of 45 patients(male 29 cases,64.4%);the proportion of patients with concomitant diseases and risk factors such as diabetes,hypertension,coronary heart disease,dilated cardiomyopathy and smoking showed no significant difference;conventional medication treatment of heart failure,including RASI,beta blockers,diuretics,statins,digoxin and amiodarone,was also statistically the same,which made it comparable between these two groups.(P>0.05).In the aspect of cardiac function improvement,baseline characteristics including the NYHA cardiac functional class,LVEF,myocardial performance index(MPI)value and NT-proBNP levels showed no significant difference and were comparable between these two groups before using levosimendan(LS)(P>0.05).However,after 3 months of follow-up,the NYHA cardiac functional class,(-1.02±0.79 vs.-1.51±0.66,P<0.01),LVEF(2.9±7.1%vs.improved 6.7±8.1%,P<0.05)as well as MPI value were all significantly improved(-0.05±0.14 vs.-0.22±0.13,P<0.01)in the repeated dose group compared with the single dose group.And the levels of plasma NT-proBNP were also significantly decreased in the repeated dose group(-882.6 + 454.2pg/ml vs.-1188.0 +422.6,P<0.01).As the result of adverse events analyses,during the injection process of levosimendan(LS)there were totally 5 cases of transient hypotension(5.6%;3 in the single dose group,and 2 in the repeated group),which all could spontaneously alleviate after slowing down or suspend the injection.There was 1 case of hypokalemia in the single dose group,recovered after potassium supplement.Moreover,during the 3 months of follow-up,there were no new onset of arrhythmias such as atrial fibrillation,ventricular tachycardia and ventricular fibrillation in all subjects,as well as other serious adverse events including death.Conclusion:1.Levosimendan(LS)is effective in improving the cardiac function of patients with decompensated heart failure(DHF),both using the single dose and repeated doses of intravenous injection treatment.2.In patients with decompensated heart failure(DHF),the treatment of repeated Levosimendan(LS)injection one month after a single dose usage could further improve cardiac function.3.Levosimendan(LS)is safe and effective in patients with decompensated heart failure(DHF),and there was no serious adverse events occurred during the treatment.