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Neurohumoral improvement and torsional dynamics in patients with heart failure after treatment with levosimendan.

ABSTRACT: Levosimendan improves clinical and hemodynamic parameters exerting an anti-inflammatory and antiapoptotic effect in decompensated heart failure. The aim of this study was to evaluate the effects of levosimendan on LV torsion, plasma levels of NT-proBNP and on the balance between pro-inflammatory (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10).We enrolled 24 patients (age 62 ± 7 years) with acute HF, NYHA class IV and severe LV dysfunction. All patients underwent transthoracic echocardiography using two-dimensional speckle tracking analysis to detect LV twist angle (LVTA), at baseline and 1 week after treatment with levosimendan infusion. Biochemical parameters (pro-BNP, IL-6, IL-10, TNF-α) were determined by enzyme-linked immunosorbent (ELISA).After one week, we observed an improvement in LV function especially in LVTA (4.15 ± 2.54 vs 2.9 ± 2.1 p < 0.01), in LV ejection fraction (27.3 ± 8.04 vs 21.6 ± 6.8 p = 0.03) and also a significant reduction in BNP levels (1844 ± 560 vs 4713 ± 1050, p = 0.03). The multiple linear regression analysis showed a significant relation between a reduction of TNF α/IL-10 ratio (Δ > 20%) and BNP (Δ > 40%), LVEF (Δ > 10%) and LVTA (Δ > 20%) (O.R. 1.77, 95% C.I. 1.11-2.83; O.R. 1.49, 95% C.I. 1.08-2.67; O.R. 1.66, 95% C.I. 1.10-2.74, respectively, confirmed p, all < 0.01 by Hosmer-Lemeshov confirmation and the formal test for interaction).Levosimendan exerts a hemodynamic effect by improving EF and LV torsion in patients with acute HF in association with a positive effect on the balance between pro and anti-inflammatory cytokines.

SUBMITTER: Navarri R

PROVIDER: S-EPMC5497181 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

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Rehospitalization after intermittent levosimendan treatment in advanced heart failure patients: a meta-analysis of randomized trials.

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| S-EPMC5695198 | biostudies-literature

Levosimendan improves exercise performance in patients with advanced chronic heart failure.

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| S-EPMC5042087 | biostudies-literature

Levosimendan in pulmonary hypertension and right heart failure.

Project description:Pulmonary hypertension is a multifactorial disease with a high morbidity and mortality. Right ventricular function is the most important predictor of morbidity and mortality in patients suffering from pulmonary hypertension, but currently there are no approved treatments directly supporting the failing right ventricle. Levosimendan is a calcium sensitizing agent with inotropic, pulmonary vasodilatory, and cardioprotective properties. Given its pharmacodynamic profile, levosimendan could be a potential novel agent for the treatment of right ventricular failure caused by pulmonary hypertension. The aim of this review is to provide an overview of the current knowledge on the effects of levosimendan in pulmonary hypertension and right heart failure.

| S-EPMC6058424 | biostudies-literature

Heart failure treatment in patients with cardiac implantable electronic devices: Opportunity for improvement.

Project description:BackgroundHeart failure and reduced ejection fraction (HFrEF) is the predominant indication for cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) implantation. The care gap and opportunity to optimize guideline-directed medical therapy (GDMT) is unclear.ObjectiveWe sought to define uptake, eligibility, dose, and adherence to GDMT in patients with CRT/ICD and HFrEF.MethodsMEDLINE was searched from 2000 to July 2021 for major randomized trials, registries, and cohort studies evaluating GDMT in this population. Thirty-eight studies focused on medical therapy in patients with CRT/ICD devices (CRT = 23, ICD = 11, and both = 4).ResultsIn the pivotal device trials, ACEI/ARB and beta-blocker use was high (mean 94%, range 41%-99%; and 83%, range 27%-97%, respectively), but mineralocorticoid receptor antagonists were modest (mean 45%, range 32%-61%), in keeping with guidelines of that era. Similar results were found in observational registries. CRT was associated with beta-blocker uptitration, while the effects on ACEI/ARB were less consistent. For beta blockers, 57%-68% of patients were uptitrated, increasing the mean percent of target dose achieved by 24% from baseline to follow-up. In one study, adherence increased, for ACEI/ARB from 37% to 55% and beta blockers 34% to 58%. Only 1 study assessed potential eligibility at implant for sacubitril-valsartan (72%) or ivabradine (28%), and no study examined sodium-glucose cotransporter-2 inhibitors. Increased uptake, titration, and dose was associated with reduced mortality, hospitalization, and device therapies.ConclusionPatients with HFrEF and ICD/CRT are undertreated with respect to GDMT, and there is opportunity to optimize therapy to improve morbidity and mortality.

| S-EPMC8710628 | biostudies-literature

Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap.

Project description:Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. It was first approved in Sweden in 2000 for the short-term treatment of acutely decompensated severe chronic heart failure when conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate. After more than 20 years, clinical applications have considerably expanded across critical care and emergency medicine, and levosimendan is now under investigation in different cardiac settings (eg, septic shock, pulmonary hypertension) and for non-cardiac applications (eg, amyotrophic lateral sclerosis). This narrative review outlines key milestones in levosimendan history, by addressing regulatory issues, pharmacological peculiarities and clinical aspects (efficacy and safety) of a drug that did not receive great attention in the heart failure guidelines. A brief outlook to the ongoing clinical trials is also offered.

| S-EPMC8350150 | biostudies-literature

Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure.

Project description:Treatment of decompensated heart failure often includes administration of levosimendan. Myeloperoxidase (MPO) is released during polymorphonuclear neutrophil (PMN) degranulation, and mediates dysregulation of vascular tone in heart failure. We evaluated the effects of levosimendan-treatment on MPO in patients with acute decompensation of chronic heart failure over a one week course. Plasma MPO levels were significantly decreased after levosimendan treatment (from 252.1 ± 31.1 pmol/l at baseline to 215.02 ± 27.96 pmol/l at 6 h, p < 0.05). Ex vivo incubation of whole blood with levosimendan decreased MPO release after PMN-stimulation (8.2 ± 1.4-fold increase at baseline vs. 6.0 ± 1.1-fold increase with levosimendan). MPO levels also significantly correlated with diastolic blood pressure over the time course. In a multivariate linear model, the main contributor to systolic, diastolic and mean blood pressure was level of PMN elastase. MPO contributed only in heparin-treated patients, suggesting a more significant role for endothelial-bound MPO than for circulating MPO or elastase with respect to blood pressure regulation. We here provide the first evidence that levosimendan treatment inhibits MPO release by PMNs in decompensated heart failure patients. This mechanism may regulate endothelial function and vascular tone in heart failure patients.

| S-EPMC4394753 | biostudies-other

Levosimendan for patients with heart failure undergoing major oncological surgery: A randomised blinded pilot study.

Project description:Background and Aims:Cardiovascular diseases and cancer are among the leading causes of mortality worldwide. The aim of this study is to evaluate the efficacy and safety of preoperative administration of levosimendan in patients with chronic heart failure (CHF) scheduled for major abdominal oncologic surgery. Methods:This study included 60 patients with abdominal malignancy, ejection fraction (EF) <35% and CHF scheduled for surgery under isoflurane-fentanyl anaesthesia and were managed in the surgical intensive care unit perioperatively. They were randomised to receive levosimendan infusion (n = 30) at a dose of 0.1 ?g/kg/min or placebo (n = 30) for 24 hours before surgery. Results:The risk of hypotension (RR: 0.40, 95% CI: 0.19-0.83) or decompensated heart failure (RR: 0.31, 95% CI: 0.12-0.76) was significantly lower in the levosimendan group. The ejection fraction, cardiac index and stroke volume index were significantly higher in the levosimendan group after surgery (P < 0.001). Duration of postoperative ventilation and hospital stay were significantly shorter in the levosimendan group (P < 0.001) while the frequency of dysrhythmia, deterioration of renal function and sepsis was comparable. Conclusion:In patients with low EF <35% and CHF, administration of levosimendan for 24 hours before major abdominal oncologic surgeries may reduce the risk of hypotension and decompensated heart failure and may improve cardiac function.

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Quality improvement initiative to optimize heart failure treatment in patients with cardiac implantable electronic devices.

Project description: Not available

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Effect of Rad knockout on heart failure improvement

Project description:To investiage the ability of positve inotropism from myocardial Rad reduction we induced Rad knockout after onset of pressure overload to reverse or compensate progression of heart failure

2024-09-01 | GSE220640 | GEO

Pulsed Levosimendan in advanced heart failure due to congenital heart disease: a case series.

Project description:Background:Levosimendan is a non-adrenergic calcium-sensitizing agent with positive inotropic and vasodilatory effects. Its use in acute decompensation of heart failure is established. Good evidence now exists for repetitive infusions of Levosimendan to improve symptoms and reduce hospitalization in advanced heart failure (AdHF) populations. Its use in heart failure resulting from congenital heart disease is not yet commonplace. Case summary:We present three cases in which pulsed Levosimendan was used in the management of AdHF secondary to underlying congenital heart disease. There was symptomatic and biomarker evidence of improvement. Discussion:Intermittent Levosimendan may represent a valuable therapy to reduce hospitalization and improve quality of life in adults with congenital heart conditions.

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