Levosimendan improves renal function in acute decompensated heart failure: possible underlying mechanisms (original) (raw)
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Haemodynamic effects of levosimendan in advanced but stable chronic heart failure
ESC Heart Failure, 2018
Aims Levosimendan improves haemodynamics in acute decompensated heart failure (HF). However, it is increasingly used for repetitive or intermittent infusions in advanced but stable chronic HF, without clear indication, selection criteria, or effect. We tested the hypotheses that (1) levosimendan improves haemodynamics in stable chronic HF and (2) that the response is dependent on baseline clinical and haemodynamic factors. Methods and results Twenty-three patients [median age 56 (49-64) years, four (17%) women] with stable New York Heart Association (NYHA) III and IV HF received a single 24 h levosimendan infusion. Non-invasive haemodynamics (inert gas re-breathing technique), estimated glomerular filtration rate, and N-terminal pro-brain natriuretic peptide were assessed before and after infusion. Levosimendan had the following effects (median change): a significant increase in cardiac output (+9.8 ± 21.6%; P = 0.026) and decrease in N-terminal pro-brain natriuretic peptide (À28.1 ± 16.3%, P < 0.001), estimated total peripheral resistance (À16.9 ± 18.3%, P = 0.005), and mean arterial pressure (À5.9 ± 8.2%, P = 0.007), but no change in estimated glomerular filtration rate (+0.89 ± 14.0%, P = 0.955). There were no significant associations between baseline clinical and/or haemodynamic factors and the levosimendan effect on cardiac output. Conclusions Levosimendan was associated with improved haemodynamics in patients with stable chronic HF, but we could not identify any predictors of the magnitude of haemodynamic response.
Levosimendan in acute and advanced heart failure
Journal of Cardiovascular Pharmacology
Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has been inconsistent or inconclusive but, in contrast to conventional inotropes, there have been no indications of worsened survival and some signals of improved heart failure-related quality of life. For this reason, levosimendan has been proposed as a safer inodilator option than traditional agents in settings, such as advanced heart failure. Positive effects of levosimendan on renal function have also been described. At the HEART FAILURE 2018 congress of the Heart Failure Association of the European Society of Cardiology, safe and effective use levosimendan in acute and advanced heart failure was examined in a series of expert tutorials. The proceedings of those tutorials are summarized in this review, with special reference to advanced heart failure and heart failure with concomitant renal dysfunction. Meta-analysis of clinical trials data is supportive of a renal-protective effect of levosimendan, while physiological observations suggest that this effect is exerted at least in part via organ-specific effects that may include selective vasodilation of glomerular afferent arterioles and increased renal blood flow, with no compromise of renal oxygenation. These lines of evidence require further investigation and their clinical significance needs to be evaluated in specifically designed prospective trials.
Cardiovascular Drugs and Therapy, 2007
Background Levosimendan is a relatively new cardiac inotropic agent with calcium sensitizing activity. This study was conducted to investigate the effects of levosimendan (L) and dobutamine (D) on renal function in patients hospitalized with decompensated heart failure (HF). Method The present study included 88 consecutive patients hospitalized with acutely decompensated HF (New York Heart Association (NYHA) Class 3-4) requiring inotropic therapy. Patients were randomized 2:1 to either L or D for intravenous inotropic support. Diuretic therapy was kept constant during infusions. Renal function values, including serum creatinine (CR), blood urea nitrogen, 24-h urinary output levels and calculated glomerular filtration rate (GFR) were measured just prior to and 24 h after the infusions in all patients, and 48 and 72 h after the infusions in every second patient in both groups. The pre and post-infusion values of renal function and left ventricular ejection fraction (LVEF) were evaluated. Results LVEF increased significantly in both groups. Those in L showed a significant improvement in calculated GFR after 24 h, whereas those in D showed no significant change (median in change in L:+15.3%, median change in D: −1.33%). Furthermore, in the L group a significant improvement was observed in calculated GFR after 72 h compared to baseline levels, whereas in D no significant change (median change in L:+45.45%, median change in D: +0.09%) was seen. Both agents improved 24-h urinary output.
Cardiovascular Drugs and Therapy
Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has been inconsistent or inconclusive but, in contrast to conventional inotropes, there have been no indications of worsened survival and some signals of improved heart failure-related quality of life. For this reason, levosimendan has been proposed as a safer inodilator option than traditional agents in settings, such as advanced heart failure. Positive effects of levosimendan on renal function have also been described. At the HEART FAILURE 2018 congress of the Heart Failure Association of the European Society of Cardiology, safe and effective use levosimendan in acute and advanced heart failure was examined in a series of expert tutorials. The proceedings of those tutorials are summarized in this review, with special reference to advanced heart failure and heart failure with concomitant renal dysfunction. Meta-analysis of clinical trials data is supportive of a renal-protective effect of levosimendan, while physiological observations suggest that this effect is exerted at least in part via organ-specific effects that may include selective vasodilation of glomerular afferent arterioles and increased renal blood flow, with no compromise of renal oxygenation. These lines of evidence require further investigation and their clinical significance needs to be evaluated in specifically designed prospective trials.
Pharmacological approaches to cardio-renal syndrome: a role for the inodilator levosimendan
European Heart Journal Supplements, 2017
Pathological interplay between the heart and kidneys-also known as cardio-renal syndrome (CRS)-is frequently encountered in heart failure and is linked to worse prognosis and quality of life. Drug therapies for this complex situation may include nitroprusside or the recombinant B-type natriuretic peptide nesiritide for patients with acute CRS with normal or high blood pressure, and inotropes or inodilators for patients with acute CRS with low blood pressure. Clinical data for a renal-protective action of levosimendan are suggestive, and meta-analysis data obtained in a range of low-output states are consistent with a levosimendan-induced benefit. Evidence of favourable organ-specific effects of levosimendan, including pre-glomerular vasodilation and increased renal artery diameter and renal blood flow, were collected both in preclinical and clinical studies. Larger randomized controlled trials are however needed to confirm the renal effects of levosimendan in various clinical settings.
Pediatric Cardiology, 2011
The clinical and hemodynamic effects of compassionate therapy with levosimendan were evaluated in a 14-year-old patient with end-stage renal disease and arterial hypertension secondary to glycogenosis type Ia. The patient previously had normal heart function but experienced acute development of severe myocardial dysfunction resistant to diuretic therapy and inotropic support. Levosimendan administration was followed by a marked clinical and echocardiographic improvement. The authors believe that levosimendan may be useful for cases of resistant acute heart failure with arterial hypertension. Although administration of levosimendan is not recommended for patients with chronic renal disease, no adverse effect was observed. Therapeutic action for these patients seems to last longer than for patients with a normal kidney.
Advances in Clinical and Experimental Medicine, 2020
Background. Advanced heart failure (AdvHF) is associated with high morbidity and mortality. Patients with this clinical condition are potential candidates for heart transplantation or mechanical circulatory support. Initially, however, they are usually supported with inotropic drugs. Recent studies have suggested that levosimendan, independently of hemodynamic improvements, may lead to outcome benefits. Objectives. To present clinical experiences concerning the indications, effectiveness, tolerance, and safety of levosimendan in the real-life therapy of patients with decompensated AdvHF in 3 cardiac centers in Poland. Material and methods. This is a prospective, observational, three-center study. Forty-nine patients with AdvHF admitted with decompensation were included (88% men, mean age 58 years, 65% ischemic etiology, left ventricular ejection fraction (LVEF) in median 20%) and followed up for an early (3 months) and prolonged period (1 year) after infusion of levosimendan. Patients were analyzed in relation to death. Results. Levosimendan therapy was associated with reduced HF symptoms and signs, New York Heart Association (NYHA) class and level of B-type natriuretic peptide (BNP) at discharge. Five patients died during hospitalization, a further 10 during the three-month follow-up and 3 died during the next nine-month follow-up. During the three-month follow-up, 22 patients were re-hospitalized due to HF and in the next nine-month follow-up 8 were re-hospitalized. A multivariate analysis indicated the QRS duration at discharge (hazard ratio (HR) = 1.02; 95% confidence interval (95% CI) = 1.003-1.03; p = 0.018), high-sensitivity C-reactive protein (hsCRP) (HR = 1.01; 95% CI = 1.004-1.02; p = 0.002), and simultaneous dobutamine infusion (HR = 6.54; 95% CI = 1.4-30.5; p = 0.017) were independent risk factors for death in the one-year follow-up. There were no side effects leading to the interruption of the levosimendan infusion. Conclusions. The use of levosimendan was safe and associated with clinical improvement and reduction in BNP level in AdvHF patients hospitalized due to HF decompensation, although the mortality and rehospitalization rate during the one-year follow-up remains high.
Renal Effects of Levosimendan: A Consensus Report
Cardiovascular Drugs and Therapy, 2013
Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure.