Evaluation Of Efficacy Of Levosimendan On Congestive Heart Failure

PrefaceCongestive heart failure(CHF) is the main cause of death in cardiovascular diseases. Since 1999s' the focus on the therapy of CHF was to interrupt the neuroendocrine system in order to decrease the adverse effect and delay ventricular remodeling. The tranditional drugs to enhance myocardial contractility include: cedilanid, sympathomimetic amines and selective phosphodiesterase-3 inhibitor. The mechanism of them was to increase the concentration of intracellular Ca. Many new drugs have been made, which can enhance myocardial contractility without increasing myocardial oxygen-consumption. We compared levosimendan with dobutamine on hemodynamic performance and clinical outcomes in patients with CHF, and evaluated the efficacy and safety of levosimendan.Materials and methods50 patients presenting with CHF( UCG revealed LVEF≤40%) caused by ischemic cardiomyopathy and dilated cardiomyopathy were enrolled in the trial, which is a randomized, open and controlled study. On the basis of tranditional therapy( including cedilanid, diuretics, ACEI, ARB and so on), the patients were designed into two groups randomizely. In the levosimendan group, 12μg/Kg of levosimendan was administrated intravenously, and then 0.1μg/Kg·min ivdrop, one hour later, increased to 0.2μg/Kg·min lasting 23 hours. In the controlled group, 2μg/Kg of dobutamine was administrated, and then 4μg/Kg·min lasting 23 hours. We collected the informations of physical examination( body temperature, BP, HR, R), ECG, UCG, blood and urine routine test, blood biochemical index, and extent of dyspnea at 30min before administration, and recorded the vital signs at 1h,2h,3h,4h,5h,6h,24h,48h after administration respectively, and recorded the extent of dyspnea at 6h, 24h, 48h after administration, and monitored blood ions at 6h after administration,and monitored blood glucose, blood cholesterol, hepatic and renal function, blood ions and blood routine test at 24h, 48h after administration, and undergone UCG on the patients to determine the LVEF and SV. We compared LVEF and SV, dyspnea, general conditions and differences of concentration of blood K and Ca before and after administration. We used SPSS 11.5 software package for statistic analysis.Results1. Comparison of LVEF and SV before and 24hs after administration between two groupsIntergroupsthe improvement of LVEF and SV had statistic difference. Intragroup: in the trial group, LVEF had statistic difference before and 24hs after administration; in the controlled group, LVEF had no statistic difference before and 24hs after administration.2. General indexIntragroup:in the controlled group, the improvement of dyspnea and general conditions had significant statistic difference before and 24hs after administration.3. Concentration of blood K, CaIntragroup:in the trial group, the Concentration of blood K had statistic difference before and 6hs after administration. In the controlled group, the Concentration of blood Ca had statistic difference before and 6hs after administration.4. Adverse effects(1) quit the drug: in the trial group, 2 cases quited the drug due to ventrical premature systole and ventrical fibrillation respectively. In the controlled group, 4 cases quit the drug due to palpitation.(2) adverse effect: hypopotassaemia occurred in 9 cases 6hrs after administration in the trial group, and turn normal 18hrs after supplying K. Ventrical fibrillation occurred in 1 case, and turn to sinus rhythm after nonsynchronous electric defibrillation. Ventrical premature systole occurred in 1 case, and improved after supplying K. In the controlled group, palpitation occurred in 6 cases, and disappeared 2-4 hours after quit the drug.DiscussionIn patients with CHF, the myocardial contractility and LVEF decreased which sympathetic nervous system(SNS), presenting HR and respiratory rate increased, and dyspnea. This study showed that Although both dobutamine and levosimendan improved the cardiac index, the increase was significantly greater with levosimendan.According to the EF and SV of 28 patients, we found that EF and SV were more significantly improved on the trial group without increasing myocardial oxgen-consumption. LIDO trial revealed that levosimendan can improve hemodynamic condition more significantly than dobutamine. This benefit can last to 180 days. And the mortality in levosimendan group decreased.Clinical trials revealed that levosimendan can combine with troponin C(cTnC) and increase the sensitivity of spectrin to Ca. It can also open the ATP-sensitive K channel on the vascular smooth muscle. The changes of heart and vessels caused by levosimendan were beneficial for blood supply of coronary artery, pulmonary circulation and cirumferential circulation. At the present time, levosimendan had been used in more than 30 countries in Europe and South America. 3 global clinical trials revealed that levosimendan can improve the symptoms and hemodynamic index, and also can decrease the mortality at 6 months in patients with HF. It may be the main drug instead of traditional drugs for the treatment of acute discompensatory heart failure.Conclusion1. Levosimendan can increase EF in CHF patients.2. Levosimendan can decrease the extent of dyspnea and improve the general conditions in CHF patients.