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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

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Use of Levosimendan in Patients with Advanced Heart Failure: An Update.

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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.

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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.

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

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Project description: Not available

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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

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