Efficacy And Safety Of Levosimendan In Patients With Acute Decompensated Heart Failure

Objective: To evaluate the efficacy and safety of levosimendan inpatients with acute decompensated heart failure.Methods: Total of74patients were enrolled into this study from thecardiology department of The Second Hospital of Hebei Medical Universityfrom September2011to December2012. The inclusion criteria were asfollows:1. Patients with chronic systolic heart failure who had acceptedstandard treatment----angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor antagonists (ARB), aldosterone receptor antagonists(MRA) and β-blockers;2. Patients were on admission for acute left ventriculardysfunction;3. New York Heart Association (NYHA) Class was Ⅲ-Ⅳ andechocardiography showed left ventricular ejection fraction (LVEF)≤40%.Exclusion criteria:1. Patients with atrial fibrillation or other malignantarrhythmias;2. Patients with cardiac shock, hypotension (systolic bloodpressure <90mmHg, mean blood pressure <65mmHg) or hypovolemia;3.Allergic constitution and patients were allergic to anti-heart failure medicine;4. Patients with severe electrolyte disturbance, severe liver dysfunction orrenal insufficiency, hemoglobin <90g/L;5. Patients with acute myocardialinfarction within one month, valvular heart disease, pericardial disease,restrictive or hypertrophic cardiomyopathy, autoimmunity disease,uncontrolled thyroid gland disease, pulmonary disease that need to be curedby glucocorticoids or theophylline drugs and patients with tumor;6. Age>80years;7. Patients themselves or their families refused to participate in thisstudy. These patients were randomly divided into two groups according to therandom digital table: In the levosimendan group (n=34, average age61.61±7.37), patients were treated by intravenous levosimendan and otherroutine drugs. An initial loading dose of12μg/kg was infused over10minutes followed by a continuous infusion of0.05-0.2μg/kg/min for24h, and doseadjustment was under close monitoring by the physician. In the control group(n=36, average age60.36±7.35), patients were treated only with routine drugs.We collected information as follows:1. Heart rate (HR), respiratory rate (R),systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and6,12,24,48hours after administration;2. B-type natriuretic peptide (BNP)before and7days after administration;3. LVEF, stroke volume (SV), leftventricular end diastolic volume (LVEDV) and left ventricular end systolicvolume (LVESV) before and7days after administration;4. Liver function,renal function, electrolyte, hemoglobin (HGB) and hematocrit (HCT) beforeand24hours,7days after administration;5. NYHA class before and7daysafter administration. Observe the incidence of major adverse cardiac events(MACE) including hypotension, malignant arrhythmia, worsening heartfailure and sudden death. SPSS13.0software was used to analyze thecollected data，and P-value <0.05was considered with statistically significantdifference.Results:1Concerning the baseline clinical characteristics, there were no statisticaldifferences in age, gender, weight, smoking, drinking and incidences ofischemic and dilated cardiomyopathy, diabetes mellitus and hypertension. Wealso didn’t find any statistical differences in HR, R, SBP, DBP, LVEF, SV,LVEDV, LVESV, BNP, serum creatinine (Scr), serum cystatin C (CYSC),serum β2-microglobulin (β2MG), serum urea nitrogen (BUN), HGB, HCT,serum glutamic-pyruvic transaminase (ALT), serum glutamic-oxaloacetictransaminase (AST), electrolytes (K+, Na+), NYHA class and concomitantdrugs.2Before administration, BNP was1236.24±255.26pg/ml in thelevosimendan group and1297.63±298.60pg/ml in the control group. Sevendays later, the average BNP reduced to668.35±239.69pg/ml in thelevosimendan group and1198.00±232.98pg/ml in the control group. BNPdecreased significantly in the two groups (t=76.356, P=0.000; t=6.350, P=0.000), but compared with the control group, the level of BNP was lower inthe levosimendan group (t=9.373, P=0.000).The baseline values of LVEF, SV, LVEDV and LVESV in thelevosimendan group were33.52±2.35%,63.75±4.76ml,191.10±19.36ml and127.35±16.40ml; while33.09±2.49%,62.83±5.25ml,190.75±19.89ml and127.92±16.64ml respectively in the control group. Seven days afteradministration, the values of LVEF, SV, LVEDV and LVESV in thelevosimendan group were38.04±2.10%,66.04±5.06ml,174.13±16.40ml and108.08±12.63ml; while36.14±2.27%,62.26±5.60ml,173.09±20.23ml and110.83±15.89ml respectively in the control group. Compared to the baselinevalues, LVEF, SV, LVEDV and LVESV were significantly improved in thelevosimendan group, while LVEF, LVEDV and LVESV were foundsignificantly different in the control group. Compared with the control group,levosimendan induced a notable improvement in LVEF and SV (t=3.591,P=0.001; t=2.986, P=0.004).When patients were admitted in our department, the numbers withNYHA Ⅲ and Ⅳ were17and17respectively in the levosimendan groupwhile19and17in the control group (χ~2=0.054, P=0.816). Seven days afteradministration, NYHA classes were significantly improved in thelevosimendan group compared with the control group:12,18and3cases vs.5,20and10cases individually in NYHA Ⅱ, Ⅲ and Ⅳ (χ~2=6.704, P=0.035).3SBP and DBP before and6,12,24,48hours after administrationshowed no significant differences within and between the two groupsrespectively.Forty-eight hours after administration, HR decreased in both two groups,especially significant in the levosimendan group. Twenty-four and forty-eighthours after administration, R decreased in both two groups, especiallysignificant at48hours in the levosimendan group.The levels of Scr, CYSC, β2MG, BUN, HGB, HCT, ALT, AST, Na+showed no statistical differences before and after administration in both twogroups. In the levosimendan group, K+decreased slightly at24hours after administration, which was not found in the control group.Three MACEs (one paroxysmal ventricular tachycardia, one worseningheart failure, one sudden death) happened in the control group, while one(sudden death) in the levosimendan group. There was no hypotension in bothtwo groups. The incidence of MACE was not statistically different betweenthe two groups (P=0.615). One sinus tachycardia and one hypokalemiahappened in the levosimendan group.Conclusion：Additional levosimendan under the routine anti-heart failure treatmentcan further improve cardiac function with safety in patients with acutedecompensated heart failure.