Levosimendan in acute heart failure following primary percutaneous coronary intervention‐treated acute ST‐elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo‐controlled study

Husebye, Trygve; Eritsland, Jan; Müller, Carl; Sandvik, Leiv; Arnesen, Harald; Seljeflot, Ingebjørg; Mangschau, Arild; Bjørnerheim, Reidar; Andersen, Geir Øystein

doi:10.1093/eurjhf/hfs215

Cited by 83 publications

(97 citation statements)

References 34 publications

(63 reference statements)

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“…This study also found that levosimendan reduced the risk of worsening heart failure and death in patients with LV failure complicated by AMI. In the LEAF study [23], more episodes of hypotension occurred during the levosimendan infusion when compared to placebo treatment, but there was no significant difference in blood pressure at the end of the infusion when comparing the 2 groups. These small studies [11,12,13,14,23] indicate that levosimendan is a safe drug for use in AMI and does not increase the incidence of myocardial ischemia, mortality or serious arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Intravenous Levosimendan in Patients with Heart Failure Complicated by Acute Myocardial Infarction

Jia

Guo²,

Zhang³

et al. 2014

Cardiology

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Objectives: To evaluate the efficacy of a short-term intravenous infusion of levosimendan in patients with heart failure due to acute myocardial infarction (AMI). Methods: This was a randomized, single-center, single-blind study that included 160 patients. Patients were randomly divided into 2 groups: 1 received levosimendan (n = 80) and the other received placebo (n = 80). The study included multiple primary end points (death, myocardial ischemia or worsening heart at the 6 month follow-up) and used a composite outcome. Results: The primary end point rate in the levosimendan group was lower than that in placebo group (43.7 vs. 62.5%, HR 0.636, 95% CI 0.413-0.981, p = 0.041). Moreover, the mortality rate at 6 months was similar between the 2 groups (17.5 vs. 22.5%, HR 0.786, 95% CI 0.382-1.543, p = 0.458). There was a higher incidence of myocardial ischemia in the levosimendan group at 14 days than in the placebo group (11.2 vs. 7.5%, HR 1.510, p = 0.435), but between 15 and 180 days, it was significantly lower in the levosimendan group than in the placebo group (3.8 vs. 13.8%, HR 0.261, p = 0.036). Conclusion: Short-term intravenous infusion of levosimendan appears to be more effective than placebo for treating patients with heart failure complicated by AMI.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Intravenous Levosimendan in Patients with Heart Failure Complicated by Acute Myocardial Infarction

Jia

Guo²,

Zhang³

et al. 2014

Cardiology

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“…The patient population and study design in the LEAF trial have previously been described in detail 19. Briefly, 61 patients with PCI‐treated STEMI who (i) had successful opening of the occluded coronary artery, (ii) had decreased wall motion in at least 3 of 16 segments of the left ventricle evaluated by echocardiography, and (iii) developed clinical signs of HF within 48 h (range: 14–33 h) following PCI were randomized to treatment with the calcium sensitizer levosimendan or placebo 19.…”

Section: Methodsmentioning

confidence: 99%

“…The present study is a post hoc study of the LEAF (LEvosimendan in Acute heart Failure following myocardial infarction) trial,19 an interventional study on patients developing HF within 48 h following PCI‐treated STEMI. We hypothesized that enhanced complement activation could be a hallmark of acute HF in this patient group and may discriminate between HF with or without cardiogenic shock.…”

Section: Introductionmentioning

confidence: 99%

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

et al. 2018

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AimsHeart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction.Methods and resultsThe LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention‐treated ST‐elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow‐up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non‐shock group (n = 52). Controls (n = 44) were age‐matched and sex‐matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b‐9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non‐shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b‐9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b‐9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM‐1 and sVCAM‐1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b‐9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively).ConclusionsComplement activation discriminated cardiogenic shock from non‐shock in acute ST‐elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.

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“…Several clinical trials and their meta-analyses have reported its clinical efficacy, including improved cardiac performance, rapid symptom relief, reduced hospital stays and better survival in patients with ADHF [28,29]. It also increases renal blood flow and glomerular filtration rate as other positive inotropes do [30].…”

Section: Established Treatment Strategiesmentioning

confidence: 99%

Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome

et al. 2015

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Background: Cardiorenal syndrome (CRS) encompasses conditions in which cardiac and renal disorders co-exist and are pathophysiologically related. The newest classification of CRS into seven etiologically and clinically distinct types for direct patient management purposes includes hemodynamic, uremic, vascular, neurohumoral, anemia- and/or iron metabolism-related, mineral metabolism-related and protein-energy wasting-related CRS. This classification also emphasizes the pathophysiologic pathways. The leading CRS category remains hemodynamic CRS, which is the most commonly encountered type in patient care settings and in which acute or chronic heart failure leads to renal impairment. Summary: This review focuses on selected therapeutic strategies for the clinical management of hemodynamic CRS. This is often characterized by an exceptionally high ratio of serum urea to creatinine concentrations. Loop diuretics, positive inotropic agents including dopamine and dobutamine, vasopressin antagonists including vasopressin receptor antagonists such as tolvaptan, nesiritide and angiotensin-neprilysin inhibitors are among the pharmacologic agents used. Additional therapies include ultrafiltration (UF) via hemofiltration or dialysis. The beneficial versus unfavorable effects of these therapies on cardiac decongestion versus renal blood flow may act in opposite directions. Some of the most interesting options for the outpatient setting that deserve revisiting include portable continuous dobutamine infusion, peritoneal dialysis and outpatient UF via hemodialysis or hemofiltration. Key Messages: The new clinically oriented CRS classification system is helpful in identifying therapeutic targets and offers a systematic approach to an optimal management algorithm with better understanding of etiologies. Most interventions including UF have not shown a favorable impact on outcomes. Outpatient portable dobutamine infusion is underutilized and not well studied. Revisiting traditional and novel strategies for outpatient management of CRS warrants clinical trials.

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Levosimendan in acute heart failure following primary percutaneous coronary intervention‐treated acute ST‐elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo‐controlled study

Cited by 83 publications

References 34 publications

Efficacy of Intravenous Levosimendan in Patients with Heart Failure Complicated by Acute Myocardial Infarction

Efficacy of Intravenous Levosimendan in Patients with Heart Failure Complicated by Acute Myocardial Infarction

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome

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