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A dvanced heart failure (AdHF) is characterized by a progressive worsening of disabling symptoms, which are (or become) refractory to all therapies, and by a high rehospitalization rate and mortality (Fig. 1). These patients may be candidates for life-prolonging therapies, such as heart transplantation or long-term mechanical circulatory support, or must just require palliative therapies. 1 Inotropic therapy has been considered for the long-term treatment of such patients to preserve hemodynamic and symptomatic balance, to prevent their frequent rehospitalization, and to support their overall quality of life (QoL). 2 After all, AdHF represents the extreme end of the spectrum of heart failure and has the worst prognosis. 3 In this context, I read with interest the article by Zhang X et al 4 "Comparative effectiveness and safety of intermittent or repeated use of levosimendan, milrinone, or dobutamine in patients with advanced heart failure: a network meta-analysis" published in this issue of J Cardiovasc Pharmacol. I commend the authors for their contribution in a field characterized by the absence of large clinical studies: Meta-analyses of the existing evidence can ignite the spark for further research.Zhang et al focus on the safety and efficacy of intermittent or repeated infusion or oral use of levosimendan, milrinone, and dobutamine in patients with AdHF. These patients often have difficulty tolerating guideline-directed pharmacologic therapy for heart failure and may require inotropic therapy to maintain a reasonable QoL.The authors compared levosimendan, milrinone, dobutamine, and respective control groups for intermittent or prolonged therapy in patients with AdHF with different outcomes by a network and single-arm meta-analysis of relevant clinical data extracted from the literature in a systematic review.Levosimendan was found to be the only 1 of the 3 selected inotropes that did not significantly increase mortality compared with the control treatments and was more effective in improving brain natriuretic peptide levels and left ventricular ejection fraction (LVEF). Conversely, more hypotension events were observed in the levosimendan group. In a nutshell, the results suggest that compared with milrinone and dobutamine, the intermittent use of levosimendan with close monitoring of blood pressure is relatively safe in patients with AdHF and is associated with better prognosis.The authors of this valuable work acknowledge that exercise has some important limitations that merit enumeration here.
A dvanced heart failure (AdHF) is characterized by a progressive worsening of disabling symptoms, which are (or become) refractory to all therapies, and by a high rehospitalization rate and mortality (Fig. 1). These patients may be candidates for life-prolonging therapies, such as heart transplantation or long-term mechanical circulatory support, or must just require palliative therapies. 1 Inotropic therapy has been considered for the long-term treatment of such patients to preserve hemodynamic and symptomatic balance, to prevent their frequent rehospitalization, and to support their overall quality of life (QoL). 2 After all, AdHF represents the extreme end of the spectrum of heart failure and has the worst prognosis. 3 In this context, I read with interest the article by Zhang X et al 4 "Comparative effectiveness and safety of intermittent or repeated use of levosimendan, milrinone, or dobutamine in patients with advanced heart failure: a network meta-analysis" published in this issue of J Cardiovasc Pharmacol. I commend the authors for their contribution in a field characterized by the absence of large clinical studies: Meta-analyses of the existing evidence can ignite the spark for further research.Zhang et al focus on the safety and efficacy of intermittent or repeated infusion or oral use of levosimendan, milrinone, and dobutamine in patients with AdHF. These patients often have difficulty tolerating guideline-directed pharmacologic therapy for heart failure and may require inotropic therapy to maintain a reasonable QoL.The authors compared levosimendan, milrinone, dobutamine, and respective control groups for intermittent or prolonged therapy in patients with AdHF with different outcomes by a network and single-arm meta-analysis of relevant clinical data extracted from the literature in a systematic review.Levosimendan was found to be the only 1 of the 3 selected inotropes that did not significantly increase mortality compared with the control treatments and was more effective in improving brain natriuretic peptide levels and left ventricular ejection fraction (LVEF). Conversely, more hypotension events were observed in the levosimendan group. In a nutshell, the results suggest that compared with milrinone and dobutamine, the intermittent use of levosimendan with close monitoring of blood pressure is relatively safe in patients with AdHF and is associated with better prognosis.The authors of this valuable work acknowledge that exercise has some important limitations that merit enumeration here.
Background: The potential harm and clinical benefits of inotropic therapy in patients with decompensated heart failure with reduced ejection fraction or advanced heart failure were debated for three decades. Nonetheless, confronted with a dismal quality of life in the last months to years of life, continuous home inotropic therapy has recently gained traction for palliative therapy in patients who are not candidates for left ventricular mechanical circulatory support or heart transplantation. Methods: As continuous inotropic therapy is only considered for patients who experience symptomatic relief and display objective evidence of improvement, clinical equipoise is no longer present, and randomized controlled trials are hard to conduct. Results: We first outline the transient use of inotropic therapy in patients with decompensated heart failure with reduced ejection fraction and emphasize the hemodynamic requisite for inotropic therapy, which is a demonstration of a low cardiac output through a low mixed venous oxygen saturation. Lastly, we review the current experience with the use of home inotropic therapy in patients who are not candidates or are awaiting mechanical circulatory support or heart transplantation. Conclusions: Evidence-based clinical data are needed to guide inotropic therapy for refractory decompensated heart failure with reduced ejection fraction in patients who are ineligible or awaiting mechanical circulatory support or heart transplantation.
Review Breaking Boundaries: Novel Effects of Levosimendan in Various Diseases Hongyuan Zhang 1, Minxing Zhao 2, and Yanrong Liu 1,3,* 1 Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, M139PT Manchester, UK. 2 Loreto High School, Chorlt on, M217SW Manchester, UK. 3 The Department of Cardiology, the 1st Affiliated Nanjing Medical University, 300 Guangzhou Road, Nanjing, China. * Correspondence: yanrong.liu@manchester.ac.uk Received: 6 February 2024 Accepted: 23 February 2024 Published: 18 March 2024 Abstract: Levosimendan, an inodilator that has been applied in clinical use for over two decades, has transcended its initial indication in the management of acutely decompensated chronic heart failure. Over the years, it has been adopted in septic shock, perioperative use of cardiac surgery, advanced end-stage heart failure, and has shown potential for inhaled administration, highlighting its versatility. Levosimendan has diverse mechanisms of action which mediate its non-traditional uses. Ongoing research aims to expand our understanding and develop personalized treatment strategies for the use of levosimendan. The significance of levosimendan in acute decompensated heart failure and cardiogenic shock, highlights its evolving role in contemporary cardiovascular medicine. This comprehensive review explores its pharmacodynamics, effects, and the challenges and opportunities it presents in various clinical settings. We describe levosimedan’s expanding usage, ranging from septic shock, intermittent intravenous in advanced heart failure, perioperative cardiac surgery and pulmonary hypertension management by inhaled levosimendan as well as its future prospects.
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