Efficacy Of Levosimendan And Sildenafil On Patients With Chronic Heart Failure And Pulmonary Hypertension

Background:Congestive heart failure and pulmonary hypertension increased the right ve ntricular afterload, leading to right heart dysfunction and myocardial injury. Ex ercise tolerance was lower and mortality was higher in the patients with pulmo nary hypertension than that in the patients without PH. However there was n o efficacious specific agents on pulmonary hypertension associated with chronic heart failure. The treatment of the pharmacotherapy of angiocardiophy (such a s diuretics, angiotension-converting enzyme inhibitor,beta-blockers) or specific i ntervention measures (left ventricular assist device, valve surgery, cardiac resyn chronization therapy and heart transplantation),may reduce PH and restore the PCWP(pulmonary capillary wedge pressure) by reducing the left ventricular fil ling pressure. However, the mPAP(mean pulmonary artery pressure) was still hi gher in some patients with PH associated with HF, although the PCWP was re duced after the treatment. In such patients, measures reducing PH was still nee ded.The traditional therapy of PH are CCBs(calcium channel blockers), oxygen therapy, anticoagulation and treating right heart dysfunction, but their effects are limited. In recent years, according to the pathogenesis of pulmonary hypertension,(pulmonary vascular smooth muscle cell proliferation and endothelial dysfunction), the targeted therapy drugs, including prostacyclin, endothelin receptor antagonist and phosphodiesterase type5inhibitor, are effective. But the first two drugs are too expensive, patients cannot bear in our country, which limited clinical promotion. NO (nitric oxide) treatment of pulmonary hypertension has rapid curative effects, but it’s action time is short, so long-term clinical application still has a lot of difficulties. However PDEI-5is relatively cheap and easy to use in clinic. Sildenafil is a kind of selective PDEI-5,by decreasing the cGMP, increasing the intrinsic NO production to relax pulmonary artery, which shows sidenafil may have beneficial effects in patients with PH associated with CHF. Levosimendan is a new kind of calcium sensitizer, enhancing myocardial contractility. It is confirmed that levosimendan can relax coronary artery, pulmonary artery, and peripheral vein by opening smooth muscle cell ATP sensitive potassium channel, then it can reduce the cardiac preload and afterload.Using levosimendan and sildenafil for the treatment of chronic heart failure and PH may has better curative effect, but few study in this field at home and abroad.20cases were reported in this paper for the treatment of pulmonary hypertension associated with chronic heart failure.Object:Evaluate the effect of levosimendan and sildenafil on the pulmonary hypertension associated with chronic heart failure.Data and Methods:20patients with HF and pulmonary hypertension were divided into contronl group(lOcases) and treatment group(10cases).Assess the left ventricular systolic fuction (LVEF), the pulmonary artery systolic pressure(PASP),the left ventricular fraction shortening (LVFS),the left atrium diameter (LAD) and the left ventricular end-diastolic diameter(LVD) by echocardiography and calculate the left ventricular mass index(LVMI). Detect N-terminal probrain natriuretic peptide(NT-proBNP) by chemiluminscence immunoassay and high sensitivity C-reactive protein(hsCRP) by immune transmission method. Measure the walking distance in6-minute walk test(6-MWT).On the basis of tranditional therapy(including cardiac glycosides, diuretics, angiotensin-converting enzyme inhibitor/angiotensin Ⅱ receptor blocker, beta-blockers).In the trearment group,an initial dose of levosimendan of12μg/Kg infused over10min, followed by a continuous infusion of0.1μg·Kg-1·min-1for24h, and oral dose of sildenafil75mg daily for4w.Use SPSS18.0software to carry on the statistic analysis. Result:1.Before treatment, there were no significant diference in LVEF,LVFS, NT-proBNP, hsCRP, between the treatment group and control group. There were diference in6-WMT,LVD,LAD,LVMI between the treatment group and control group, but removing the impact by the paired design.2. After1week treatment, comparing with the control group LVEF, LVFS,6-WMT were higher, and NT-proBNP, hsCRP,6-MWT were lower. LAD,LVD,LVMI were lower, but there were no significant difference(p>0.05).3. After4weeks, comparing with the control group LVEF, LVFS,6-WMT were higher, and NT-proBNP, hsCRP,6-MWT were lower. LAD,LVD,LVMI were lower, and there were significant difference(p<0.05).Conclusion:1. Levosimendan and sildenafil can improve cardiac function and reduce pulmonary artery pressure.2. Levosimendan and sildenafil could improve myocardial remodeling by anti-inflammatory.