Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap.
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ABSTRACT:
SUBMITTER: Conti N
PROVIDER: S-EPMC8350150 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:(1) Background: Heart failure (HF) is a major cause of morbidity and mortality throughout the world. Despite substantial progress in its prevention and treatment, mortality rates remain high. Device therapy for HF mainly includes cardiac resynchronization therapy (CRT) and the use of an implantable cardioverter-defibrillator (ICD). Recently, however, a new device therapy-cardiac contractility modulation (CCM)-became available. (2) Aim: The purpose of this study is to present a first case-series of patients with different clinical patterns of HF with a reduced ejection fraction (HFrEF), supported with the newest generation of CCM devices. (3) Methods and results: Five patients with a left ventricular ejection fraction (LVEF) ? 35% and a New York Heart Association (NYHA) class ? III were supported with CCM OPTIMIZER® SMART IPGCCMX10 at our clinic. The patients had a median age of 67 ± 8.03 years (47-80) and were all males-four with ischemic etiology dilated cardiomyopathy. In two cases, CCM was added on top of CRT (non-responders), and, in one patient, CCM was delivered during persistent atrial fibrillation (AF). After 6 months of follow-up, the LVEF increased from 25.4 ± 6.8% to 27 ± 9%, and the six-minute walk distance increased from 310 ± 65.1 m to 466 ± 23.6 m. One patient died 47 days after device implantation. (4) Conclusion: CCM therapy provided with the new model OPTIMIZER® SMART IPG CCMX10 is safe, feasible, and applicable to a wide range of patients with HF.
| S-EPMC6572164 | biostudies-literature
Project description:End-stage liver failure is a condition of collapsing liver function with mortality rates up to 80. Liver transplantation is the only lifesaving therapy. There is an unmet need for therapy to extend the waiting time for liver transplantation or regeneration of the native liver. Here we review the state-of-the-art of non-cell based and cell-based artificial liver support systems, cell transplantation and plasma exchange, with the first therapy relying on detoxification, while the others aim to correct also other failing liver functions and/or modulate the immune response. Meta-analyses on the effect of non-cell based systems show contradictory outcomes for different types of albumin purification devices. For bioartificial livers proof of concept has been shown in animals with liver failure. However, large clinical trials with two different systems did not show a survival benefit. Two clinical trials with plasma exchange and one with transplantation of mesenchymal stem cells showed positive outcomes on survival. Detoxification therapies lack adequacy for most patients. Correction of additional liver functions, and also modulation of the immune system hold promise for future therapy of liver failure.
| S-EPMC7228976 | biostudies-literature
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
Project description:Levosimendan is an inodilator indicated for the short-term treatment of acutely decompensated severe chronic heart failure, and in situations where conventional therapy is not considered adequate. The principal pharmacological effects of levosimendan are (a) increased cardiac contractility by calcium sensitisation of troponin C, (b) vasodilation, and (c) cardioprotection. These last two effects are related to the opening of sarcolemmal and mitochondrial potassium-ATP channels, respectively. Data from clinical trials indicate that levosimendan improves haemodynamics with no attendant significant increase in cardiac oxygen consumption and relieves symptoms of acute heart failure; these effects are not impaired or attenuated by the concomitant use of beta-blockers. Levosimendan also has favourable effects on neurohormone levels in heart failure patients. Levosimendan is generally well tolerated in acute heart failure patients: the most common adverse events encountered in this setting are hypotension, headache, atrial fibrillation, hypokalaemia and tachycardia. Levosimendan has also been studied in other therapeutic applications, particularly cardiac surgery - in which it has shown a range of beneficial haemodynamic and cardioprotective effects, and a favourable influence on clinical outcomes - and has been evaluated in repetitive dosing protocols in patients with advanced chronic heart failure. Levosimendan has shown preliminary positive effects in a range of conditions requiring inotropic support, including right ventricular failure, cardiogenic shock, septic shock, and Takotsubo cardiomyopathy.
| S-EPMC3868185 | biostudies-literature
Project description: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.
| S-EPMC5497181 | biostudies-other
Project description:Autonomic imbalance is a common finding in heart failure (HF) with reduced ejection fraction (HFrEF). Addressing different targets within the autonomic nervous systems has been evaluated in patients with HF, including renal sympathetic denervation, vagal nerve stimulation, and baroreceptor activation therapy (BAT). Although all are pathophysiologically plausible and promising, only BAT shows sufficient evidence for implementation into clinical practice in randomized controlled trials. Baroreceptor activation therapy can be used in patients with symptomatic HFrEF despite optimal guideline-directed medication and device therapy. This article reviews the current and future use of neuromodulation in HF and provides an overview on current guideline recommendations and clinical practice.
| S-EPMC9385118 | biostudies-literature
Project description:AimsIntermittent levosimendan administration has been suggested to improve survival in patients with advanced heart failure (AdHF). Quality of life is a key issue for AdHF patients and is negatively affected by frequent hospitalizations.Methods and resultsCENTRAL, Google Scholar, MEDLINE/PubMed, Scopus, and the Cochrane Central Register of clinical trials (updated 15/1/2017) were searched for randomized controlled trials investigating the effect of intermittent levosimendan administration in patients with AdHF. The primary outcome was the number of patients requiring rehospitalization 3 months after the end of treatment. A total of 319 patients from six trials were included. Overall pooled analysis showed that the use of levosimendan was associated with a significant reduction in the number of rehospitalizations at 3 months: 33/207 (16%) vs. 39/113 (35%), risk ratio 0.40, 95% confidence interval 0.27-0.59, P < 0.001, I2 = 0%. This result was confirmed by sensitivity analyses.ConclusionsWithin the limitations of this meta-analysis including also studies in which endpoints were not independently adjudicated and not clearly specified, repetitive or intermittent administration of levosimendan for patients with AdHF was associated with a reduction in the rehospitalization rate at 3 months. Large, high-quality randomized controlled trials are needed to confirm this finding.
| S-EPMC5695198 | biostudies-literature
Project description:AimsCardiopulmonary exercise test (CPET) provides parameters such as peak VO2 and ventilation/CO2 production (VE/VCO2) slope, which are strong prognostic predictors in patients with stable advanced chronic heart failure (ADHF). The study aim was to evaluate the effects of the inodilator levosimendan on CPET in patients with ADHF under stable clinical conditions.Methods and resultsWe enrolled patients with ADHF (peak VO2 < 12 mL/min/kg) in a double-blind, placebo-controlled protocol. Patients were randomly assigned to i.v. infusion of placebo (500 mL 5% glucose; n = 19) or levosimendan (in 500 mL 5% glucose; n = 23). Before and 24 h after the end of the infusion, patients underwent determination of New York Heart Association class, B-type natriuretic peptide (BNP), haemoglobin, serum creatinine, and blood urea nitrogen levels, as well as CPET, standard spirometry, and alveolar capillary gas diffusion. BNP showed no change with placebo (1042 ± 811 to 1043 ± 867 pg/mL), but it was decreased with levosimendan (1163 ± 897 to 509 ± 543 pg/mL, P < 0.001). No changes were observed for haemoglobin, creatinine, and blood urea nitrogen in either group. With levosimendan, a minor improvement was observed in spirometry measurements, but not in alveolar capillary gas diffusion. Peak VO2 showed a small, non-significant increase with placebo (9.5 ± 1.7 to 10.0 ± 2.1 mL/kg/min, P = 0.12), and a greater increase with levosimendan (9.8 ± 1.7 to 11.0 ± 1.9 mL/kg/min, P < 0.005). The VE/VCO2 slope showed no change (44.0 ± 11 vs. 43.4 ± 10.3, P = 0.44), and a decrease (41.9 ± 10 vs. 36.6 ± 6.4, P < 0.001) in the placebo and in the levosimendan group, respectively.ConclusionLevosimendan treatment significantly improves peak VO2 and reduces VE/VCO2 slope and BNP in patients with ADHF.
| S-EPMC5042087 | biostudies-literature
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.
| S-EPMC7319860 | biostudies-literature
Project description:Much work has demonstrated that speakers of verb-final languages are able to construct rich syntactic representations in advance of verb information. This may reflect general architectural properties of the language processor, or it may only reflect a language-specific adaptation to the demands of verb-finality. The present study addresses this issue by examining whether speakers of a verb-medial language (English) wait to consult verb transitivity information before constructing filler-gap dependencies, where internal arguments are fronted and hence precede the verb. This configuration makes it possible to investigate whether the parser actively makes representational commitments on the gap position before verb transitivity information becomes available. A key prediction of the view that rich pre-verbal structure building is a general architectural property is that speakers of verb-medial languages should predictively construct dependencies in advance of verb transitivity information, and therefore that disruption should be observed when the verb has intransitive subcategorization frames that are incompatible with the predicted structure. In three reading experiments (self-paced and eye-tracking) that manipulated verb transitivity, we found evidence for reading disruption when the verb was intransitive, although no such reading difficulty was observed when the critical verb was embedded inside a syntactic island structure, which blocks filler-gap dependency completion. These results are consistent with the hypothesis that in English, as in verb-final languages, information from preverbal noun phrases is sufficient to trigger active dependency completion without having access to verb transitivity information.
| S-EPMC4392588 | biostudies-literature