Use of Levosimendan in Patients with Pulmonary Hypertension: What is the Current Evidence?

Masarone, Daniele; Kittleson, M.; Pollesello, Piero; Tedford, Ryan J.; Pacileo, Giuseppe

doi:10.1007/s40265-022-01833-w

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…Milrinone, a phosphodiesterase III inhibitor, can be administered intravenously to act as a nonselective inodilator (111) or nebulized and administered via the respiratory circuit to act as a selective pulmonary vasodilator (112,113). Another inodilator is levosimendan, which increases the systolic and diastolic function of both ventricles after intravenous administration and modulates various potassium channels in smooth muscle cells, leading to non-selective pulmonary vasodilation (114). Lastly, systemic endothelin antagonists (bosentan, ambrisentan, tezosentan) are another group of effective non-selective pulmonary vasodilators to treat PAH (115).…”

Section: Alternative Inhaled No Delivery Systems Besides Mechanical V...mentioning

confidence: 99%

Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence

Muenster,

Zarragoikoetxea,

Moscatelli

et al. 2024

Front. Cardiovasc. Med.

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Inhaled nitric oxide (NO) has been used in pediatric and adult perioperative cardiac intensive care for over three decades. NO is a cellular signaling molecule that induces smooth muscle relaxation in the mammalian vasculature. Inhaled NO has the unique ability to exert its vasodilatory effects in the pulmonary vasculature without any hypotensive side-effects in the systemic circulation. In patients undergoing cardiac surgery, NO has been reported in numerous studies to exert beneficial effects on acutely lowering pulmonary artery pressure and reversing right ventricular dysfunction and/or failure. Yet, various investigations failed to demonstrate significant differences in long-term clinical outcomes. The authors, serving as an advisory board of international experts in the field of inhaled NO within pediatric and adult cardiac surgery, will discuss how the existing scientific evidence can be further improved. We will summarize the basic mechanisms underlying the clinical applications of inhaled NO and how this translates into the mandate for inhaled NO in cardiac surgery. We will move on to the popular use of inhaled NO and will talk about the evidence base of the use of this selective pulmonary vasodilator. This review will elucidate what kind of clinical and biological barriers and gaps in knowledge need to be solved and how this has impacted in the development of clinical trials. The authors will elaborate on how the optimization of inhaled NO therapy, the development of biomarkers to identify the target population and the definition of response can improve the design of future large clinical trials. We will explain why it is mandatory to gain an international consensus for the state of the art of NO therapy far beyond this expert advisory board by including the different major players in the field, such as the different medical societies and the pharma industry to improve our understanding of the real-life effects of inhaled NO in large scale observational studies. The design for future innovative randomized controlled trials on inhaled NO therapy in cardiac surgery, adequately powered and based on enhanced biological phenotyping, will be crucial to eventually provide scientific evidence of its clinical efficacy beyond its beneficial hemodynamic properties.

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Section: Alternative Inhaled No Delivery Systems Besides Mechanical V...mentioning

confidence: 99%

Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence

Muenster,

Zarragoikoetxea,

Moscatelli

et al. 2024

Front. Cardiovasc. Med.

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“…The monitoring of blood electrolytes for patients treated with diuretics is essential because hypomagnesemia and hypokalemia augment the inhibitory effect of digoxin on the sodium–potassium pump, resulting in proarrhythmic consequences [ 25 ]. Levosimendan is a calcium sensitizer with inotropic, pulmonary vasodilatory, and cardioprotective features that has been shown to be an effective and safe treatment strategy for PAH and PH associated with left heart disease [ 26 ]. Levosimendan treatment improved cardiac output, decreased right ventricular afterload, and alleviated pulmonary vascular remodeling in SU5416/hypoxia-induced PAH rat models [ 27 ].…”

Section: Pharmacological Therapy For Pahmentioning

confidence: 99%

Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs

et al. 2023

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Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully understood, pulmonary vasoconstriction, vascular remodeling, immune and inflammatory responses, and thrombosis are thought to be involved in the development and progression of PAH. In the era of non-targeted agents, PAH had a very dismal prognosis with a median survival time of only 2.8 years. With the deep understanding of the pathophysiological mechanism of PAH as well as advances in drug research, PAH-specific therapeutic drugs have developed rapidly in the past 30 years, but they primarily focus on the three classical signaling pathways, namely the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. These drugs dramatically improved pulmonary hemodynamics, cardiac function, exercise tolerance, quality of life, and prognosis in PAH patients, but could only reduce pulmonary arterial pressure and right ventricular afterload to a limited extent. Current targeted agents delay the progression of PAH but cannot fundamentally reverse pulmonary vascular remodeling. Through unremitting efforts, new therapeutic drugs such as sotatercept have emerged, injecting new vitality into this field. This review comprehensively summarizes the general treatments for PAH, including inotropes and vasopressors, diuretics, anticoagulants, general vasodilators, and anemia management. Additionally, this review elaborates the pharmacological properties and recent research progress of twelve specific drugs targeting three classical signaling pathways, as well as dual-, sequential triple-, and initial triple-therapy strategies based on the aforementioned targeted agents. More crucially, the search for novel therapeutic targets for PAH has never stopped, with great progress in recent years, and this review outlines the potential PAH therapeutic agents currently in the exploratory stage to provide new directions for the treatment of PAH and improve the long-term prognosis of PAH patients.

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“…Авторы неда вних обзоров экспериментальных и клинических исследований сделали вывод, что левосимендан может быть компонентом возможной схемы лечения различных форм ЛГ (пациенты с истинной ЛГ или ЛГ, обусловленной заболеванием левых отделов сердца) [57], а также правожелудочковой недо статочности вследствие ЛГ, заболеваний левых отделов сердца и врожденных пороков сердца [58]. На сегодняшний день в литературе отсутствуют убедительные доказательства, чтобы рекомендовать использование левосимендана при ЛГ и связанной с ней дисфункции ПЖ.…”

Section: легочная гипертензия правожелудочковая недо статочностьunclassified

Levosimendan: current and possible areas of clinical application: A review

Boboshko,

Zibareva,

Lomivorotov

2023

Annals of Critical Care

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Levosimendan belongs to the class of calcium sensitizers, which exhibits its positive inotropic effects by increasing the affinity of troponin from the myocardium to calcium without additional myocardial oxygen demand, what favorably distinguishes it from catecholamines and their negative effects (myocardial ischemia, arrhythmias, vasoconstriction, hyperglycemia). In 2000, the drug was first used for the short-term treatment of decompensated chronic heart failure. After more than 20 years, the clinical use of levosimendan has covered a wide area among patients with pathology of the cardiovascular system and its use has gone far beyond the primary indications. To date, the drug has been studied in more than 200 randomized trials in patients with various clinical profiles: acute decompensation of chronic heart failure, progressive heart failure, acute myocardial infarction, cardiogenic shock, therapy of low cardiac output syndrome in cardiac surgery, perioperative use in pediatric cardiac surgery, septic shock, pulmonary hypertension, right ventricular failure, Takotsubo cardiomyopathy, patients with mechanical circulatory support devices. This review highlights the pharmacological features of the drug and key randomized clinical trials on the use of levosimendan in various categories of patients, in addition to officially recommended indications. The article also provides a brief overview of current and planned randomized trials.

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Use of Levosimendan in Patients with Pulmonary Hypertension: What is the Current Evidence?

Cited by 7 publications

References 44 publications

Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence

Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence

Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs

Levosimendan: current and possible areas of clinical application: A review

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