Levosimendan for Treatment of Primary Graft Dysfunction After Heart Transplantation: Optimal Timing of Application

Immohr, Moritz Benjamin; Akhyari, Payam; Boettger, Charlotte; Erbel, Sophia; Westenfeld, Ralf; Scheiber, Daniel; Tudorache, I.; Aubin, Hug; Lichtenberg, Artur; Boeken, Udo

doi:10.6002/ect.2020.0342

Cited by 11 publications

(9 citation statements)

References 45 publications

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“…Immohr and colleagues [ 10 ] retrospectively examined data from 150 patients who underwent heart transplantation between 2010 and 2020 and identified 41 patients who were treated postoperatively with levosimendan, 36 of whom had postoperative primary graft dysfunction. Stratification of patients according to whether levosimendan was commenced early (≤ 48 h post-transplant [ n = 23]) or late (> 48 h post-transplant [ n = 18]) revealed that early commencement was associated with a range of statistically significant outcome advantages, which included decreased duration of VA-ECMO support (5.1 ± 3.5 vs 12.6 ± 9.3 days; p < 0.01) and decreased mortality (0.0% vs 33.3%; p < 0.01).…”

Section: Postoperative Settingsmentioning

confidence: 99%

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Girardis

Béttex

Bojan

et al. 2022

J Anesth Analg Crit Care

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The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a “should be considered” recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.

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Section: Postoperative Settingsmentioning

confidence: 99%

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Girardis

Béttex

Bojan

et al. 2022

J Anesth Analg Crit Care

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“…This delay could influence weaning. Immohr et al [ 45 ] found that, for heart transplant patients, early administration (< 48 h) was associated with faster weaning and a lower mortality in univariable analysis, with a trend toward reduced mortality in multivariable analysis. In our study, we did not find any effect modification related to the time between ECMO initiation and levosimendan administration in subgroup analysis.…”

Section: Discussionmentioning

confidence: 99%

Levosimendan in patients undergoing extracorporeal membrane oxygenation after cardiac surgery: an emulated target trial using observational data

et al. 2023

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Background Retrospective cohorts have suggested that levosimendan may facilitate the weaning of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We therefore studied this clinical question by emulating a randomized trial with observational data. Methods All patients with refractory postcardiotomy cardiogenic shock and assisted with VA-ECMO, admitted to a surgical intensive care unit at La Pitié-Salpêtrière Hospital between 2016 and 2019, were eligible. To avoid immortal-time bias, we emulated a target trial sequentially comparing levosimendan administration versus no levosimendan administration in patients treated with VA-ECMO. The primary outcome was time to successful ECMO weaning. The secondary outcomes were 30-day and 1-year mortality. We performed a multivariable analysis to adjust for confounding at baseline. Results Two hundred and thirty-nine patients were included in the study allowing building a nested trials cohort of 1434 copies of patients. No association of levosimendan treatment and VA-ECMO weaning was found (HR = 0.91, [0.57; 1.45], p = 0.659 in multivariable analysis), or 30-day mortality (OR = 1.03, [0.52; 2.03], p = 0.940) and 1-year mortality (OR = 1.00, [0.53; 1.89], p = 0.999). Conclusions Using the emulated target trial framework, this study did not find any association of levosimendan treatment and ECMO weaning success after postcardiotomy cardiogenic shock. However, the population of interest remains heterogeneous and subgroups might benefit from levosimendan.

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“…In addition to commonly used inodilators such as milrinone, inhaled nitric oxide can be used. Recent data identified levosimendan as a potential therapy, with a retrospective analysis suggesting early application may improve survival and aid weaning from MCS [41].…”

Section: Treatment Of Primary Graft Dysfunctionmentioning

confidence: 99%

Acute complication posttransplant: primary allograft dysfunction

Brahmbhatt

Blitzer

Billia

et al. 2023

Current Opinion in Organ Transplantation

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Purpose of review Heart transplant is the gold standard treatment for patients with end-stage heart failure, improving both quality of life and survival. Despite advances in donor and recipient management, primary graft dysfunction (PGD) remains the most common cause of morbidity and mortality in the early posttransplant period. This review summarizes recent discoveries in the underlying pathophysiology, risk prediction and management of PGD. Recent findings The incidence of PGD appears to be rising and it is not clear whether this is due to better recognition or secular changes in transplant practice. The utilization of donation after circulatory death organs for transplant is a further consideration for the development of PGD. Organ transport systems and preservation techniques may help to prevent PGD. As some of the risk factors for developing PGD remain modifiable, we summarize the current evidence for prevention and management of PGD. Summary A better understanding will allow us to appropriately manage donors and recipients to reduce the complex interactions that lead to PGD. The development of an international consortium provides the opportunity for deep phenotyping and development of contemporary risk prediction models for PGD, which may reduce the incidence and consequent early mortality associated with heart transplantation.

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Levosimendan for Treatment of Primary Graft Dysfunction After Heart Transplantation: Optimal Timing of Application

Cited by 11 publications

References 45 publications

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

Levosimendan in patients undergoing extracorporeal membrane oxygenation after cardiac surgery: an emulated target trial using observational data

Acute complication posttransplant: primary allograft dysfunction

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