Comparison of ischemic side effects of levosimendan and dobutamine with integrated backscatter analysis.
ABSTRACT Levosimendan improves cardiac contractility without increasing oxygen consumption. However, its effects on ischemia were not supported with the utilization of a noninvasive parameter of myocardial characterization.
The changes observed in integrated backscatter (IBS) may be reflective of change in myocardial ischemia. In this study, the effect of levosimendan on ischemia detected by IBS was evaluated in patients with ischemic heart failure (HF).
Patients who had LVEF < 40% and NYHA III-IV symptoms of HF were included in this study. Patients were randomized to levosimendan (n = 21), or to dobutamine (n = 25) groups. The cyclic variation of integrated backscatter (CVIBS) was determined as the difference between the maximal and minimal values in a cardiac cycle, average of three consecutive beats. CVIBS was taken from the mid-anteroseptal, mid-inferior, and mid-posterolateral areas of the parasternal short axis images before the drug administration and at the end of the 24-hour infusion period.
Baseline characteristics and concomitant medications were similar in both groups. A significant reduction in CVIBS was detected in anteroseptal (7.6 +/- 1.4 dB versus 5.9 +/- 0.8 dB, p = 0.01), inferior wall (7.4 +/- 0.8 dB versus 6.7 +/- 1.5 dB, p = 0.03), and posterolateral wall (9.0 +/- 1.2 dB versus 8.2 +/- 0.6 dB, p = 0.04) after dobutamine administration, while no significant changes were observed in the levosimendan group in all walls.
Unlike dobutamine, levosimendan may not induce myocardial ischemia as shown by CVIBS at commonly used dosages in the setting of decompensated HF without active ischemia.
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ABSTRACT: Agents that increase cardiac contractility (positive inotropes) have beneficial hemodynamic effects in patients with acute and chronic heart failure but have frequently led to increased mortality when given on a long-term basis. Despite this fact, inotropes remain commonly used in the management of heart failure. We reviewed the available data on short- and long-term inotrope use in heart failure, emphasizing high-quality evidence on the basis of randomized trials that were powered to address clinical end points. Available data suggest that long-term inotropic therapy has a negative impact on survival in patients with heart failure, regardless of the agent used. The data that inotropic therapy improves quality of life are mixed. High-quality randomized evidence is lacking for the use of inotropes for other heart failure indications, such as for acute decompensations or as a "bridge to transplant." On the basis of the available evidence, the routine use of inotropes as heart failure therapy is not indicated in either the acute or chronic setting. Potentially appropriate uses of inotropes include as temporary treatment of diuretic-refractory acute heart failure decompensations or as a bridge to definitive treatment such as revascularization or cardiac transplantation. Inotropes also may be appropriate as a palliative measure in patients with truly end-stage heart failure. A model of heart failure pathophysiologic features that combines an understanding of both hemodynamic and neurohormonal factors will be required to best develop and evaluate novel treatments for advanced heart failure.American Heart Journal 10/2001; 142(3):393-401. · 4.50 Impact Factor
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ABSTRACT: To review systematically the use of intravenous (IV) inotropic agents acting through the adrenergic signalling pathway, compared with placebo or an active agent, in patients with heart failure. Studies investigating the use of intravenous inotropes in patients with heart failure published between 1966 and 2000 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. In total, 21 trials, that included 632 patients receiving IV inotropic drugs, placebo or non-treatment control, were identified. Drugs of the following classes were included, the beta-agonists; dobutamine, high-dose (>2.5 microg/kg/min) dopamine, dopexamine and the phosphodiesterase (PDE) inhibitors; amrinone, milrinone, enoximone and toborinone. Sixteen trials (474 patients) contributed data from acute invasive haemodynamic studies of symptomatically severe heart failure. Five trials (158 patients) were based on intermittent inotropic therapy in an outpatient context. With few exceptions, trials of intravenous inotropic agents were small and often failed to report clinically important outcomes. Compared to placebo, intravenous inotropic agents acting through the adrenergic system tended to increase mortality (odds ratio 1.50 (95% CI=0.51 to 3.92) but this did not reach significance and insufficient data were available to determine whether symptoms improved. There appeared to be little difference in the effect of beta-agonists compared to PDE inhibitors on patient outcomes but this could be attributed to the paucity of data. Intravenous inotropic agents acting through the adrenergic pathway are often used in patients with worsening heart failure to achieve arbitrary haemodynamic targets. Our analyses show that there is very little evidence that such treatment improves symptoms or patient outcomes and may not be safe. This highlights the need for further well designed randomised clinical trials.European Journal of Heart Failure 08/2002; 4(4):515-29. · 5.25 Impact Factor
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ABSTRACT: We have previously shown that cardiac cycle-dependent variation of integrated backscatter occurs in normal myocardium. To determine whether myocardial ischemia and reperfusion can be distinguished by real-time integrated backscatter imaging we performed 10 min balloon occlusion of the Left Anterior Descending (LAD) coronary artery followed by reperfusion in 10 closed-chest anesthetized dogs. Images were obtained at baseline, during occlusion, and up to 120 min after reperfusion. We measured the magnitude and delay of cyclic variation of integrated backscatter in segments with and without asynergy. Radiolabeled microspheres were used to verify both ischemia and reperfusion. Ischemic segments exhibited decreased magnitude and increased normalized delay of cyclic variation of integrated backscatter (from 3.3 +/- 0.3 dB to 1.4 +/- 0.2 dB, mean +/- SE; and from 0.95 +/- 0.03 to 1.67 +/- 0.15, respectively, all p less than or equal to 0.001). Reperfusion promptly restored the magnitude of cyclic variation toward normal. However, the delay of the cyclic variation was restored only partially. Wall motion analysis of the ischemic sites revealed persistent abnormalities throughout the reperfusion interval despite return to normal of the magnitude and delay of cyclic variation. Thus, real-time integrated backscatter imaging permits detection and differentiation of changes in myocardial acoustic properties indicative of ischemia and of subsequent reperfusion.Ultrasound in Medicine & Biology 02/1990; 16(4):391-8. · 2.46 Impact Factor