Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol.

OBJECTIVE: To compare the efficacy of milrinone and dobutamine in patients chronically treated with carvedilol. BACKGROUND: Milrinone and dobutamine are used to manage decompensated heart failure, but their efficacy in patients on beta-blocker therapy was unknown. METHODS: Twenty patients with decompensated heart failure were prospectively enrolled. Inotropic responses to milrinone (12.5, 25 or 50 microg/kg bolus infusions) or dobutamine (5, 10, 15 or 20 microg/kg/min infusions) were evaluated by right-heart catheterization. RESULTS: Milrinone increased cardiac index (2.0-2.6 l/min/m2, P=0.0001) without significantly altering heart rate (70-75 bpm, P=0.19). Milrinone decreased mean pulmonary artery pressure (36-29 mm Hg, P=0.0001), pulmonary capillary wedge pressure (24-18 mm Hg, P=0.0001) and mean arterial blood pressure (78-75 mm Hg, P=0.0002). Left ventricular stroke volume index increased in the milrinone group (31-35 ml/beat/m2, P=0.0001). Dobutamine produced an increase in cardiac index (2.4-3.3 l/min/m2, P=0.0001) only at doses that are not typically used to treat heart failure (15-20 microg/kg/min). At these doses, dobutamine increased heart rate (68-82 bpm, P=0.008), mean systemic pressure (90-117 mm Hg, P=0.0001) and mean pulmonary artery pressure (21-30 mm Hg, P=0.001). Dobutamine did not alter left ventricular stroke volume index or pulmonary capillary wedge pressure. Conclusions: Dobutamine and milrinone have different hemodynamic effects in patients treated chronically with carvedilol. These differences should be considered when selecting inotropic therapy for decompensated heart failure.     

Clinical outcomes of levosimendan versus dobutamine in patients with acute decompensated heart failure with reduced ejection fraction and impaired renal function

To assess the clinical outcomes of levosimendan and dobutamine in patients with acute decompensated heart failure with reduced ejection fraction and impaired renal function in Indian scenario. Cardiac, renal, electrolytes and hepatic parameters as well as the clinical outcomes were assessed. Levosimendan and dobutamine improved ejection fraction significantly. Levosimendan in comparison to dobutamine, increased cardiac output (0.76 vs. ?0.38 at 48 h, 1.15 vs. ?0.31 day 7, -2.02 vs. ?1.51 day 30), cardiac index (0.89 vs.-0.13 at 48 h, 1.16 vs. ?0.07 at day 7 and 1.05 vs. ?0.25 at day 30) and eGFR (?1.4 vs. ?0.75 at day 30) significantly. Levosimendan reduced ICU stay (p = 0.038) significantly whereas dobutamine decreased the hospital stay duration (p = 0.015). There was no major difference in re-hospitalization and mortality between groups. Ventricular tachyarrhythmia was the main adverse event noted in Levosimendan arm. Levosimendan showed improved cardiac as well as renal outcomes within a month when compared to dobutamine and it is the first study to determine the renal parameters of Levosimendan in an Indian setting.     

Effects of levosimendan versus dobutamine on left atrial function in decompensated heart failure

BACKGROUND:

Although the effects of levosimendan on the left ventricle (LV) have been studied, its effect on left atrial (LA) function is poorly understood, despite its key role in optimizing LV function.

OBJECTIVE:

To compare the effects of levosimendan and dobutamine on LA and LV function in patients with decompensated heart failure (DHF).

METHODS:

Seventy-four patients (mean [± SD] age 64±10 years) with DHF and an LV ejection fraction of 35% or lower were randomly assigned to receive levosimendan (n=37) or dobutamine (n=37). LA active emptying fraction, LA passive emptying fraction (PEF) and the ratio of mitral inflow early diastolic velocity to annulus velocity (E/e) were evaluated with pulsed wave and tissue Doppler imaging along with plasma B-type natriuretic peptide (BNP) level measurements before and after drug infusion.

RESULTS:

The ejection fraction was significantly increased in both groups. The levosimendan group had a greater decrease in BNP and a greater increase in active emptying fraction at 24 h compared with the dobutamine group. The PEF, E/e and deceleration time of the E wave were significantly improved in the levosimendan group, but not in the dobutamine group. Levosimendan-induced percentage change of BNP was significantly correlated with the percentage change of E/e and PEF (r=0.48 [P<0.005] and r=−0.38 [P<0.05], respectively).

CONCLUSIONS:

In patients with DHF, levosimendan and dobutamine both improve LV systolic function. However, levosimendan also improves LV diastolic function and LA performance in parallel with a greater improvement in neurohormonal activation compared with dobutamine.     

Comparative effects of levosimendan and dobutamine on right ventricular function in patients with biventricular heart failure

Severe heart failure represents a major source of morbidity and mortality. Poor right ventricular function is an independent prognostic marker for mortality in patients with chronic heart failure. In this study, levosimendan (L) and dobutamine (D) in patients with severe chronic biventricular failure were compared. Forty consecutive patients, who were judged for inotropic therapy by their primary physicians, with acutely decompensated systolic heart failure and having moderate-to-severe right ventricular dysfunction with right ventricular fractional area change of ≤24%m were randomized to L and D in a 2:1 fashion. Echocardiographic parameters including tricuspid annular motion and clinical issues were considered. Mean age and sex distribution were not different between the two groups. After the infusion, ejection fraction improved and systolic pulmonary artery pressure decreased significantly in both arms. Longitudinal systolic function of tricuspid annulus improved significantly better in patients with L compared to patients with D (15% ± 12% vs. 2% ± 6% improvement, P < 0.001). Furthermore, L improved both 24-h urine output and creatinine, whereas D showed only a small, but significant improvement in urine output without any improvement in the creatinine levels. Levosimendan seems to offer more beneficial effects compared to dobutamine in a specific group of patients with biventricular failure.     

Levosimendan may provide a better neurohormonal response in heart failure patients receiving beta blocker therapy — Reply

The hemodynamic effects of levosimendan have been shown to be maintained or even enhanced by beta blockers. Furthermore, levosimendan has recently been reported to represent mortality benefit in patients receiving beta blockers. However, it is not clear whether these favorable effects of levosimendan under beta blockade are also suggested by a better neurohormonal response. We evaluated neurohormonal response to levosimendan in patients receiving beta blocker in our study population on the basis of the comments of Giamouzis and colleagues on previously published article, in which both levosimendan and dobutamine were found to be very effective inotropic agents in achieving favorable neurohormonal response but levosimendan had a better and prolonged effect. The findings of recent subgroup analysis suggested that levosimendan treatment trended toward a greater reduction in NT-proBNP levels and therefore may provide a better neurohormonal response in patients receiving beta blockers as compared with those patients not receiving beta blocker.     

卡维地洛对慢性心力衰竭心功能和ANP及BNP的影响

目的观察卡维地洛(达利全)对慢性心力衰竭(CHF)患者心功能和ANP/BNP的影响。方法60例CHF患者,在常规治疗病情基本稳定的基础上,增加服用卡维地洛,从每次3.125mg开始,2次/d,缓慢递增。治疗前后分别进行心率、血压、心功能分期评估和血清ANP/BNP测定。结果与治疗前相比,治疗5个月后,心率明显下降(P<0.01),心功能分级明显改善,血清ANP/BNP明显下降(P<0.01)。66.7%患者服用卡维地洛剂量可达到目标剂量25mg,2次/d;33.3%患者使用中等剂量12.5mg,2次/d,维持治疗。结论长期服用卡维地洛能改善心功能,降低血清ANP和BNP水平。     

卡维地络对充血性心力衰竭患者促炎细胞因子的影响

目的：观察卡维地络对充血性心力衰竭（CHF）患者促炎细胞因子浓度的影响。方法：选择66例CHF患者，随机分为常规治疗组和卡维地络治疗组，32例健康体检者为正常对照组。用双抗体夹心ELISA法测定血浆肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）和IL-1β的浓度，分析其与CHF程度的关系。结果：（1）CHF患者三种细胞因子浓度均明显高于正常对照组（P〈0．05或〈0．01），CHF程度越重细胞因子浓度越高（P〈0．01）；（2）治疗后卡维地络组心功能分级左室收缩末内径较治疗前显著降低（P均〈0．05），左室短轴缩短率（LVFS）、每搏量（SV）、左室射血分数（LVEF）较治疗前显著升高（P〈0．05～〈0．01）；常规治疗组仅LVEF显著升高（P〈0．05）；治疗后卡维地络组LVEF、LVFS较常规治疗组显著升高（P〈0．05）；（3）治疗后卡维地络组三种细胞因子浓度显著降低（P〈0．01或〈0．05）；常规治疗组TNF—α、IL-6降低（P〈0．05），而IL-1β水平降低不显著。结论：CHF患者促炎细胞因子浓度升高，可作为判断心衰严重程度的指标。卡维地络能有效抑制促炎细胞因子的产生，改善心功能和心室重构。     

卡维地洛治疗扩张型心肌病心力衰竭疗效观察

目的　评价第三代 β受体阻滞剂卡维地洛治疗扩张型心肌病 (DCM)心力衰竭的临床疗效。方法　 6 2例 DCM心力衰竭患者在接受常规治疗 (洋地黄、利尿剂、血管紧张素转换酶抑制剂 )病情稳定后 ,随机分为卡维地洛组和美多心安组。均从小剂量 (卡维地洛组 ,2 .5 m g bid;美多心安组 ,6 .2 5 m g bid)缓慢递增。检测治疗前后 DCM患者左心室功能和结构的变化以及血液中内皮素 - 1(ET- 1)、心钠素 (ANP)和血管紧张素 (Ang )的改变。结果　治疗 6个月后 ,两组心脏功能分级均明显改善 ,左心室射血分数 (L VEF)、短轴缩短率 (FS)、左心室射血前期与射血时间比(PEP/ L VET)、舒张早期峰值血流速度 (PFVE)、舒张早期峰值血流速度与舒张晚期峰值血流速度比 (PFVE/ PF-VA)均明显增加 ,卡维地洛组较美多心安组 L VEF增加更为明显。两组左心房内径 (L AD)、左心室收缩末期内径(L VSD)、左心室舒张末期内径 (L VDD)明显减小 ,卡维地洛组 L VSD减小较美多心安组更明显。治疗后血浆中ET- 1、ANP和 Ang 均明显降低。结论　卡维地洛和美多心安都能够改善 DCM心力衰竭患者左心室收缩和舒张功能 ,逆转左心室重构 ,卡维地洛较美多心安疗效更佳。     

Effect of dobutamine on pulmonary gas exchange in patients with severe heart failure.

Twenty patients (two female, 18 male, mean age 57 +/- 11 years) with severe heart failure NYHA IV (7 coronary artery disease, 13 congestive cardiomyopathy) were treated with 8.8 +/- 1.7 micrograms.kg-1 x min-1 of dobutamine. Pulmonary gas exchange was analysed by withdrawal of blood samples from a central venous catheter and a radial artery cannula. Dobutamine increased SvO2 from 58.7 +/- 11.2% to 72.2 +/- 6.3% (P = 0.0001) and decreased avDO2 from 7.7 +/- 2.45 Vol% to 4.97 +/- 1.34 Vol% (P = 0.0001). PaO2 and PaCO2 were not changed. Qs/Qt increased slightly from 9.1 +/- 8.3% to 11.3 +/- 6.4% (P = 0.035). Cardiac index increased by 51% (P = 0.0001), pulmonary capillary wedge pressure decreased by 28% (P = 0.0001). In patients with severe heart failure, dobutamine improved haemodynamics without detrimental effects on arterial oxygen concentration.     

Combination therapy with carvedilol and amiodarone in patients with severe heart failure

BACKGROUND: Carvedilol and at least in some studies, amiodarone have been shown to improve symptoms and prognosis of patients with heart failure. There are no reports on the outcome of combined treatment with both drugs on top of angiotensin-converting enzyme inhibitors (ACEI), diuretics and digitalis. METHODS AND RESULTS: In 109 patients with severe heart failure submitted for heart transplantation at one single center between the years 1996 and 1998 [left ventricular ejection fraction (LVEF) 24.6+/-11%, 85% males, 52% idiopathic dilated cardiomyopathy (DCM), mean observation time 1. 9+/-0.4 years] a therapy with low-dose amiodarone (1000 mg/week) plus titrated doses of carvedilol (target 50 mg/day) was instituted. In addition, patients received a prophylactic dual chamber pacemaker (PM) in order to protect from bradycardia and for continuous holter monitoring. The devices were programmed in back-up mode with a basal rate of 40 i.p.m. with a hysteresis of 25%. Significantly, more patients were in sinus rhythm after 1 year than at study entry (85% vs. 63%, P<0.01). In 47 patients, under therapy over at least 1 year, the resting heart rate fell from 90+/-19 to 59+/-5 b.p.m. (P<0.001). Ventricular premature contractions in 24-h holter ECGs were suppressed from 1.0+/-3 to 0.1+/-0.3%/24 h (P167 b.p.m. detected by the pacemaker (1.2+/-2.8 episodes/patient/3 months vs. 0.3+/-0.8 episodes/patient/3 months after 1 year (P<0.01). The LVEF increased from 26+/-10 to 39+/-13% (P<0.001). NYHA class improved from 3. 17+/-0.3 to 1.8+/-0.6 (P<0.001) as well as right heart catheterization data. From the total cohort, seven patients (6%) developed symptomatic documented bradycardic rhythm disturbances requiring reprogramming of their pacemakers to DDD(R)/VVI(R) mode with higher basic rates. Two of these patients developed AV block, four sinu-atrial blocks or sinus bradycardia and one patient had bradycardic atrial fibrillation. During the observation period five patients died (3 sudden, 1 due to heart failure and 1 due to mesenteric infarction). Two patients had undergone heart transplants. The 1-year survival rate (Kaplan-Meier) without transplantation was 89%. Compared to historic control patients with amiodarone only (n=154) or without either agent (n=283) this rate was 64 and 57% (P<0.01). CONCLUSIONS: Heart failure patients benefit from a combined therapy with carvedilol and amiodarone resulting in a markedly improved NYHA stage, an increase in LV ejection fraction, a stabilization of sinus rhythm, a significant reduction in heart rate, a delay of electrical signal conduction and a suppression of ventricular ectopies. Approximately 6% of patients under such a regime became pacemaker-dependent in the first year. Compared to historic controls prognosis was better and the need for heart transplantation was lower. The exact role of either agent in combination or alone should be clarified in larger randomized studies.     

卡维地洛治疗慢性充血性心力衰竭的临床观察

目的：探讨卡维地洛疗慢性充血性心力衰竭的有效性及安全性。方法：选择40例缺血性心肌病患者，随机分为卡维地洛治疗组和对照组，治疗12个月。治疗前、后分别应用超声心动图测量左室射血分数（LVEF）左室收缩末直经（LVESd）和左室舒张末直径（LVEDd）。结果：所有病例治疗后，LVEF升高，LVESd、LVEDd降低，与治疗前相比差异显著（P〈0．01）。与对照组相比，卡维地洛治疗组治疗后各参数明显改善，差异显著（P〈0．05）。结论：卡维地洛治疗慢性充血性心力衰竭安全有效。     

卡维地洛改善充慢性心力衰竭患者心功能的临床研究

目的:观察卡维地洛(Carvedilol)治疗慢性心力衰竭(CHF)的临床疗效.方法:将80例NYHA心功能Ⅱ～Ⅳ级CHF患者随机分为两组:Carvedilol组40例,采用常规治疗(ACEI、利尿剂、血管扩张剂、有或无洋地黄) Carvedilol;Betaloc组40例,常规治疗 Betaloc.随访1～2年,观察两组治疗前后血流动力学、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)、6 min步行距离(6-MWD)及心功能变化. 结果:两组治疗后心率(HR)、收缩压(SBP)、心肌耗氧量(HR×SBP)、LVEDD、LVESD、LVEF、左室短轴缩短分数(LVFS)、NYHA心功能分级均较治疗前显著改善(P＜0.01),而Carvedilol组在血流动力学及心功能改善上较Betaloc组更明显(P＜0.05);但治疗后组间HR降低无显著差异(P＞0.05).两组治疗后6-MWD也均较治疗前显著增加(P＜0.01),尤其Carvedilol组(P＜0.05).Carvedilol组无不良反应出现. 结论:联用Carvedilol治疗CHF安全有效.     

The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine

AIM: To investigate the effect of a new inotropic drug, levosimendan compared with dobutamine on levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and malondialdehyde (MDA) in patients with severe decompensated heart failure. METHODS AND RESULTS: Twenty-nine consecutive patients (22 males and 7 females), mean age 70.5+/-9.9 years, with decompensated heart failure on standard medical therapy, were randomised to receive either a 24 h infusion of levosimendan (n=15) or dobutamine (n=14). Blood samples were drawn at baseline, 48 h and 5 days post infusion. Levosimendan produced a significant reduction in BNP compared to baseline, at both 48 h (744.1+/-100 vs 1136.3+/-93.7 pg/ml, p=0.04) and 5 days (446+/-119.3 vs 1136.3+/-93.7 pg/ml, p=0.03), while IL-6 values decreased after 5 days (4.8+/-1.3 vs 8.6+/-1.5 pg/ml, p=0.01). MDA levels were significantly lower 5 days after levosimendan compared to baseline (2.3+/-0.2 vs 3+/-0.3 microM, p=0.01). TNF-alpha levels did not differ between the groups. The comparison of percentage alteration compared to baseline showed that BNP (-44.5+/-7.6% vs 4.8+/-18.7%, p=0.025), MDA (-21.8+/-5.1% vs 14.9+/-8.5%, p=0.001) and IL-6 (-38.8+/-12.5% vs 70.2+/-24%, p=0.001) levels were significantly lower in the levosimendan group 5 days after treatment compared to the dobutamine group. CONCLUSIONS: Treatment with levosimendan in advanced decompensated heart failure exerts a beneficial hemodynamic, anti-inflammatory and antioxidant effect. These findings may give an insight into the favourable impact on mortality that levosimendan appears to have in published multicenter trials.     

卡维地洛改善充慢性心力衰竭患者心功能的临床研究

目的：观察卡维地洛(Carvedilol)治疗慢性心力衰竭(CHF)的临床疗效。方法：将80例NYHA心功能Ⅱ～Ⅳ级CHF患者随机分为两组：Carvedilol组40例,采用常规治疗(ACEI、利尿剂、血管扩张剂、有或无洋地黄)+Carvedilol；Betaloc组40例,常规治疗+Betaloc。随访1～2年,观察两组治疗前后血流动力学、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)、6min步行距离(6-MWD)及心功能变化。结果：两组治疗后心率(HR)、收缩压(SBP)、心肌耗氧量(HR×SBP)、LVEDD、LVESD、LVEF、左室短轴缩短分数(LVFS)、NYHA心功能分级均较治疗前显著改善(P＜0．01),而Carvedilol组在血流动力学及心功能改善上较Betaloc组更明显(P＜0．05)；但治疗后组间HR降低无显著差异(P＞0．05)。两组治疗后6-MWD也均较治疗前显著增加(P＜0．01),尤其Carvedilol组(P＜0．05)。Carvedilol组无不良反应出现。结论：联用Carvedilol治疗CHF安全有效。     

卡维地洛治疗扩张型心肌病心力衰竭患者的疗效

目的：观察卡维地洛治疗扩张型心肌病心力衰竭患者的临床疗效。方法：选择扩张型心肌病心力衰竭患者82例,采用随机分组的方法分为卡维地洛组（42例）和常规治疗组（40例）,卡维地洛组在常规治疗基础上加用卡维地洛3．125～25mg2次／d。比较两组左室舒张期末内径（LVEDd）、左室收缩期末内径（LVEsd）、左房内径（LAD）、左室射血分数（LVEF）、6min步行距离（6MWD）等指标变化情况。结果：治疗6个月后,两组患者心功能均有改善,卡维地洛组总有效率显著高于常规治疗组（90．5％比72．5％,P〈0．05）;两组治疗后患者的LVEDd、LVESd、LVEF及6MWD均有显著改善（P〈0．05）,且与常规治疗组比较,卡维地洛组治疗后患者的LVEDd[（59．1±9．6）mm比（54．2±10．2）mm]、LVESd[（46．1±8．7）mm比（41．4±12．2）mm]显著缩小,LVEF[（42．1±10．5）％比（48．4±9．6）％]及6MWD[（264．52±51．23）m比（309．26±45．24）m]显著增加（P均〈0．05）。结论：在常规治疗基础上加用卡维地洛可明显改善扩张型心肌病心力衰竭患者的疗效。     

卡维地洛对心力衰竭的治疗作用

目的　明确新型肾上腺素受体阻滞剂卡维地洛在心力衰竭治疗中的价值。方法　 3 0只 Wistar大鼠随机分为3组 ,分别进行空白处理 ( A组 ,对照组 )、过度游泳训练 8周 ( B组 ,心力衰竭组 )、过度游泳训练 8周后服卡维地洛3 m g· kg- 1 · d- 1 8周 ( C组 ,卡维地洛组 ) ,经 16周后 ,测血流动力学指标、心肌细胞凋亡率、左心室质量指数、心肌间质纤维化程度等。结果　各项指标比较 ,A、B组各项指标均有显著差异 ;B、C组间血流动力学指标无显著差异而心肌细胞凋亡率有显著差异。结论　卡维地洛对心肌细胞有保护作用 ,可改善心力衰竭的长期预后     

卡维地洛治疗国人慢性心力衰竭的疗效观察

目的:评价卡维地洛治疗慢性心力衰竭的有效性和安全性。方法:46例慢性心力衰竭(NYHA心功能Ⅱ-Ⅲ级)病人常规应用利尿剂、ACEI、或地高辛等药物,病情稳定后随机分两组:治疗组23例加用卡维地洛,从3.125mg,1次/d开始,2周后加量至6.25mg,1次/d,再2周后加量至目标剂量12.5mg,1次/d;对照组23例接受安慰剂治疗。结果:卡维地洛治疗组有效18例,有效率78.3％;对照组有效11例,有效率47.8％,两组比较有显著性差异(P<0.05)。两组死亡率、再次入院率无显著性差别(P>0.05)。卡维地洛治疗组平均心率比基线值分别下降了8.2次/min。结论:目标剂量的卡维地洛治疗国人慢性心力衰竭有效,且安全。