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.     

Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure

In this randomized, placebo-controlled study, it was found that a 24-hour levosimendan infusion improves echocardiographic markers of abnormal left ventricular diastolic function (transmitral flow patterns and mitral annulus velocities, as assessed by transthoracic pulse-wave Doppler and tissue Doppler imaging, respectively) and reduces substances of excessive neurohormonal activation (plasma B-type natriuretic peptide and interleukin-6) in patients with advanced heart failure. Moreover, levosimendan-treated patients had fewer events and longer progression-free survival during a 5-month follow-up compared with those who received placebo. Thus, levosimendan seems to be effective in improving left ventricular diastolic function and reducing neurohormonal activation in patients with severe heart failure.     

Pulmonary hypertension and right ventricular function in advanced heart failure

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequently encountered in patients with advanced heart failure (HF). Both conditions aggravate prognosis and influence clinical decisions. Echocardiography is the screening tool of choice for pulmonary pressures and RV function, although invasive assessment of PH is necessary when advanced therapies are considered. Reversibility of PH in response to short-term pharmacologic treatment or even to long-term unloading after left ventricular assist device (LVAD) implantation is a favorable prognostic sign for both medically treated patients and heart transplant candidates. Although patients with severe PH secondary to HF have not derived benefit from pulmonary arterial hypertension therapies thus far, agents that modulate the cyclic guanosine monophosphate pathway, including phosphodiesterase 5A inhibitors, hold promise and are being actively investigated in advanced HF. Therapies that lead to reduction in left-sided pressures, including cardiac resynchronization and LVAD placement, also have a favorable effect on pulmonary pressures and RV function. However, no specific medical treatment for RV dysfunction exists to date, highlighting an important gap in the management of patients with advanced HF.     

Effects of levosimendan on coronary artery flow and cardiac performance in patients with advanced heart failure

BACKGROUND: Levosimendan has inotropic and vasodilatory effects. We investigated the effects of levosimendan on coronary flow and associated changes in neurohormonal activation and cardiac performance in patients with advanced heart failure. METHODS: Forty-two patients with NYHA III-IV and a left ventricular ejection fraction (EF) 25+/-6%, were randomised to levosimendan 0.1 microg/kg/min (n=21) or placebo for 24 h. Before and 24 h after each treatment, we assessed: the maximal velocity (Vmax), time integral (VTI) and deceleration time (DT) of the diastolic coronary flow wave (CF) in LAD using transthoracic Doppler echocardiography, pulmonary artery systolic pressure by Doppler echocardiography, E/E' ratio using Doppler imaging of mitral inflow velocity, tissue Doppler imaging of the mitral annulus and B-type natriuretic peptide (BNP) levels. RESULTS: By ANOVA, there was a greater increase in CF-Vmax (43+/-23 vs.25+/-8 cm/s), CF-DT (904+/-250 vs. 667+/-151 ms), and EF and a greater decrease in BNP, pulmonary artery systolic pressure and E/E? after levosimendan than after placebo (p<0.05). Compared to baseline, the percent changes in CF-VTI were related to the concomitant changes in EF, E/E?, and BNP after treatment with levosimendan (r=0.69, r=?0.51 and r=?0.80, p<0.05 respectively). CONCLUSION: Treatment with levosimendan improves coronary flow and microcirculation in parallel with an improvement in cardiac performance and neurohormonal activation in patients with advanced heart failure.     

Assessment of right ventricular function by echocardiography in patients with chronic heart failure

Background

The main focus of most of the studies in heart failure (HF) is the assessment of the left ventricular functions, while the right ventricle was much less studied. Much of this neglect is due to the complexity of anatomy and physiology of the right ventricle which are considered challenges during assessment of RV.

Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure

This randomized, placebo-controlled trial showed that levosimendan administration causes a significant reduction of circulating proinflammatory cytokine interleukin-6 and soluble apoptosis mediators, such as soluble Fas and Fas ligand in patients with decompensated heart failure. These immunomodulatory effects may lead to improvement of symptoms and echocardiographic markers of cardiac contractile performance in these patients.     

Importance of right ventricular function in congestive heart failure

Failure of the right ventricle may be due to a congenital anomaly, intrinsic disease, pulmonary stenosis or pulmonary hypertension. Left ventricular failure may also lead to right ventricular failure if the heart fails totally or secondary to pulmonary hypertension, or if filling of the right ventricle is decreased due to left ventricular dilation or hypertrophy. Treatment of right ventricular failure has yielded disappointing results, except when caused by left ventricular failure that responds to therapy. Digitalis and diuretics may have more adverse than beneficial effects. In patients with both left and right ventricular failure, survival is usually less than 2 years.     

Effect of bisoprolol on right ventricular function and brain natriuretic peptide in patients with heart failure

Beta-blocker use improves left ventricular ejection fraction (LVEF) in patients with heart failure. A similar effect of b blockers on right ventricular function has been proposed, although the effect of bisoprolol, a highly selective b-1 blocker, on right ventricular function has not been assessed. This study investigated the short-term effect of bisoprolol on right ventricular function in chronic heart failure patients. A cohort of 30 heart failure patients who were not taking b blockers at baseline was studied prospectively. Right ventricular ejection fraction (RVEF) and LVEF were measured at both baseline and 4 months by radionuclide angiography. Bisoprolol was up-titrated during four monthly visits by a preestablished protocol to a target dose of 10 mg/d. The dose of vasodilators was not changed. Quality of life and brain natriuretic peptide level were assessed. Mean age was 62.7+/-14.3 years. Baseline RVEF was 30.7%+/-6.3% and baseline LVEF was 21.7%+/-9.4%. Mean bisoprolol dose reached was 5.3+/-3.9 mg daily. At 4 months, RVEF significantly increased by 7.1% (95% confidence interval, 3.9-10.2; p=0.0001) and LVEF also increased significantly by 7.9% (95% confidence interval, 4.0%-11.9%; p=0.0003). Quality-of-life score improved from 42.8 to 30.8 (p=0.047). No correlation was found between brain natriuretic peptide levels and RVEF. Bisoprolol treatment for 4 months resulted in a significant improvement of RVEF, which paralleled the improvement of LVEF.     

Effects of ventricular ectopy on sinus R-R intervals in patients with advanced heart failure.

OBJECTIVE: To determine the effect of ventricular ectopy on subsequent sinus R-R intervals. DESIGN: Comparative, repeated-measures design. SETTING: University medical center. SUBJECTS: Ten consecutive sinus R-R intervals and their standard deviations before and after ventricular ectopy from 24-hour ambulatory electrocardiogram recordings were obtained from 25 patients with heart failure (left ventricular ejection fraction 0.18 +/- 0.08; New York Heart Association Functional Class III-IV) and three healthy subjects. RESULTS: The effects of 7564 single ventricular ectopic beats, 272 ventricular couplets, and 49 episodes of ventricular tachycardia in the patients with heart failure and 1369 single ventricular ectopic beats in the three healthy subjects were evaluated. Repeated-measures ANOVA indicated no significant differences in sinus R-R intervals immediately before or after ventricular ectopy. Standard deviation of sinus R-R intervals before and after ventricular ectopy did not differ significantly. CONCLUSIONS: Ventricular ectopy does not significantly alter subsequent sinus R-R intervals and is unlikely to affect measurement of heart rate variability, particularly by techniques that use standard deviation methods.     

Right ventricular longitudinal strain correlates well with right ventricular stroke work index in patients with advanced heart failure referred for heart transplantation

BackgroundRight ventricular (RV) systolic function has a critical role in determining the clinical outcome and success of using left ventricular assist devices (LVADs) in patients with refractory heart failure. Tissue Doppler and M-mode measurements of tricuspid systolic motion (tricuspid S′ and tricuspid annular plane systolic excursion [TAPSE]) are the most currently used methods for the quantification of RV longitudinal function; RV deformation analysis by speckle-tracking echocardiography (STE) has recently allowed the analysis of global RV longitudinal function. Using cardiac catheterization as the reference standard, this study aimed at exploring the correlation between RV longitudinal function by STE and RV stroke work index (RVSWI) in patients referred for cardiac transplantation.Methods and ResultsRight-side heart catheterization and transthoracic echo Doppler were simultaneously performed in 41 patients referred for cardiac transplantation evaluation for advanced systolic heart failure. Thermodilution RV stroke volume and invasive pulmonary pressures were used to obtain RVSWI. RV longitudinal strain (RVLS) by STE was assessed averaging all segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall segments (free-wall RVLS). Tricuspid S′ and TAPSE were also calculated. No significant correlations were found for TAPSE or tricuspid S′ with RVSWI (r = 0.14; r = 0.06; respectively). Close negative correlations between global RVLS and free-wall RVLS with the RVSWI were found (r = ?0.75; r = ?0.82; respectively; both P < .0001). Furthermore, free-wall RVLS demonstrated the highest diagnostic accuracy (area under the receiver operating characteristic (ROC) curve 0.90) and good sensitivity and specificity of 92% and 86%, respectively, to predict depressed RVSWI using a cutoff value of less than ?11.8%.ConclusionsIn a group of patients referred for heart transplantation, TAPSE and tricuspid S′ did not correlate with invasively obtained RVSWI. RV longitudinal deformation analysis by STE correlated well with RVSWI, providing a better estimation of RV systolic performance.     

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.     

Determinants of right ventricular failure in patients admitted with acute left heart failure

Pulmonary hypertension, which may lead to right ventricular (RV) failure, increases with left ventricular (LV) diastolic dysfunction severity. The prevalence and determinants of RV failure were analyzed in 120 patients admitted with acute left heart (LH) failure. Patients were divided into RV failure (n=50) and non-RV failure (n=70) groups. The prevalence of RV failure was found to be 42%. In both groups, two thirds of the patients had isolated LV diastolic dysfunction and the rest had combined LV systolic and diastolic dysfunction. Patients in the RV failure group were characterized by higher LV diastolic grade (2.2 ± 0.6 vs 1.84 ± 0.7; P=.0070), pulmonary artery systolic pressure (PASP; 57.8 ± 15.3 vs 50.14 ± 12.1 mm Hg; P=.0028), right atrial enlargement (92% vs 25.7%; P=.000001), and more-than-moderate tricuspid regurgitation (58% vs 27.1%; P=.0006). RV failure is a frequent finding in patients with advanced LH failure. It is strongly associated with the severity of LV diastolic dysfunction and the severity of PASP.     

左西孟旦治疗难治性心衰患者的疗效观察

目的：本研究通过对左西孟旦和传统临床治疗心衰药物的心衰疗效观察,评价其临床疗效及安全性。方法：选择难治性心衰患者64例,随机分成左西孟旦组和常规治疗组各32例,两组均给予常规抗心衰药物治疗,左西孟旦组在此基础上给予左西孟旦治疗,常规治疗组给予多巴酚丁胺治疗,对比治疗前后两组的心功能分级、左室射血分数（LVEF）、每搏量（SV）及血浆N末端B型利钠肽前体（NT-proBNP）水平的变化,同时观察药物不良事件的发生率。结果：左西孟旦组心功能改善总有效率明显高于常规治疗组（90.6%比71.9%,P〈0.05）;治疗后与常规治疗组比较,左西孟旦组LVEF[（35.5±7.8）%比（39.2±6.9）%]、SV[（72.0±1.8）ml比（77.6±1.2）ml]明显提高（P〈0.05）,NT-proBNP[（1562±836）μg/L比（865±310）μg/L]水平显著降低（P〈0.01）。左西孟旦组的不良反应发生率明显低于常规治疗组（6.3%比25%,P〈0.01）。结论：左西孟旦对于难治性心衰患者,可显著改善心功能,降低N末端B型利钠肽前体,安全性好。     

Effects of carvedilol on left ventricular diastolic function and chamber volumes in advanced heart failure

AIM: Carvedilol treatment in chronic heart failure (CHF) demonstrated to reduce mortality and rehospitalisation, and improvement of cardiac systolic function with reduction of left ventricular volumes and remodelling. The effects of the drug on left ventricular (LV) filling are less studied. Systolic dysfunction is often associated to diastolic alteration, pseudonormal and restrictive filling pattern are related with poor prognosis. In this study we evaluated diastolic cardiac modifications during carvedilol therapy at early and long term in patients with advanced CHF and pseudonormal or restrictive filling pattern by echo Doppler method. METHODS: We studied 59 patients with severe but stable CHF (40 in class NYHA III and 19 in class NYHA IV) with both systolic and diastolic dysfunction due to idiopathic or ischemic cardiomyopathy. Group I (n=32) received preceding treatment plus carvedilol and Group II (n=27) continued standard therapy with ACE-inhibitors, diuretics, digossin and vasodilators. In all subjects were evaluated LV volumes mass and ejection fraction (EF). Therefore, we studied transmitral filling parameters: Early filling wave (E), atrial filling wave (A), E/A ratio, deceleration time of E (DT) and isovolumetric releasing time (IVRT) by echo Doppler method. RESULTS: After 4 months of therapy carvedilol group showed a significant increase of A wave (p<0.001) DT (p<0.0001) and IVRT (p<0.0001), and significant reduction of E/A ratio (p<0.0005) respect to Group II. Any significant changes were observed for volumes mass and EF. Transmitral Doppler measurements remained unchanged or further ameliorated at 12 months (A p<0.0005; DT p<0.00002; IVRT p<0.000004; E/A p<0.0008), we also observed E wave reduction (p<0.001) in Group I respect to controls. Besides, after 1 year of follow-up we observed a reduction of systolic volume (p<0.001) pulmonary pressure (p<0.0001) and consequent increase of EF (p<0.001) in group treated with beta-blockers. Multivariate analysis demonstrated that Doppler modification were minimally related to heart rate and blood pressure reduction. CONCLUSIONS: Carvedilol treatment improve diastolic function in CHF with severe diastolic impairment driving restrictive or pseudonormal filling pattern towards altered pattern at early time. These changes remained also after 1 year of therapy and appeared to precede increase of systolic function and improvement of emodynamic status.