Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Perioperative use of levosimendan in patients undergoing cardiac surgery: systematic review and meta-analysis / Uso perioperatorio de levosimendán en pacientes sometidos a cirugía cardiaca: revisión sistemática de la literatura y metaanálisis

Abstract Introduction: Patients undergoing cardiac surgery frequently develop low cardiac output syndrome (LCOS). Multiple interventions including levosimendan have been used in the prevention and treatment of LCOS. Preliminary studies reported lower mortality respect to placebo or other inotropes, however, recently, 3 clinical trials found no benefit against this outcome. Objective: Our objective was to evaluate the evidence of levosimendan on mortality and secondary outcomes in patients undergoing cardiac surgery, and to determine the sources of heterogeneity. Methods: We conducted a systematic review and meta-analysis of the clinical trials that evaluated the efficacy of levosimendan in patients undergoing cardiac surgery. We obtained the odds ratio (OR) of mortality and other outcomes such as kidney injury with dialysis requirement and LCOS, using fixed and random effects models. The risk of bias was assessed and the sources of heterogeneity were explored. Results: Of 47 studies identified, 14 studies were selected (n=2752). Regarding the mortality outcome and use of levosimendan, only a decrease was found in the studies of low quality (OR 0,30; CI 95%, 0,18 to 0,51). While high-quality studies, there was no protective effect (OR 0.99,95% CI 0.70-1.40) with an I2 = 0%. The quality of the studies and ejection fraction were the main sources of heterogeneity. Conclusion: In high-quality studies, the use of levosimendan in patients undergoing cardiovascular surgery has no effect on 30-day mortality. There was a protective effect on postoperative renal failure with dialysis.

Resumen Introducción: Los pacientes llevados a cirugía cardiaca tienen riesgo de desarrollar síndrome de bajo gasto cardiaco posoperatorio (SBGC). Estudios previos han encontrado una menor mortalidad con levosimendán respecto a placebo u otros inotrópicos; sin embargo, tres experimentos clínicos no encontraron beneficio frente a este desenlace. Objetivo: Evaluar la evidencia del levosimendán sobre la mortalidad y los desenlaces secundarios en pacientes sometidos a cirugía cardiaca, y determinar las fuentes de heterogeneidad. Métodos: Mediante una revisión sistemática y metaanálisis de los experimentos clínicos que evaluaron la eficacia del levosimendán en los pacientes llevados a cirugía cardiaca, se evaluó la eficacia en la mortalidad y en otros desenlaces, como lesión renal y SBGC, utilizando los modelos de efectos fijos y aleatorios. Resultados: De 47 estudios identificados, fueron seleccionados 14 (n = 2752). Respecto al desenlace de mortalidad y el uso de levosimendán solo se encontró una disminución en los estudios de baja calidad (OR 0.30; IC 95%, 0.18-0.51), mientras que para los de alta calidad no hubo efecto protector (OR 0.99; IC 95%, 0.70-1.40) con un I2=0%. La calidad de los estudios y la fracción de eyección fueron las principales fuentes de heterogeneidad. Conclusión: el uso del levosimendán en los pacientes llevados a cirugía cardiovascular no tiene efectos sobre la mortalidad a 30 días en los estudios de alta calidad. Hubo efecto protector sobre la falla renal postoperatoria con necesidad de diálisis.

Decompensated congestive heart failure - treatment with levosimendan

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Levosimendan as a treatment for acute renal failure associated with cardiogenic shock after hip fracture / Levosimendana como tratamento para insuficiência renal aguda associada a choque cardiogênico após fratura de quadril

Abstract Inotropic drugs are part of the treatment of heart failure; however, inotropic treatment has been largely debated due to the increased incidence of adverse effects and increased mortality. Recently levosimendan, an inotropic positive agent, has been proved to be effective in acute heart failure, reducing the mortality and improving cardiac and renal performance. We report the case of a 75-year-old woman with history of heart and renal failure and hip fracture. Levosimendan was used in preoperative preparation as an adjuvant therapy, to improve cardiac and renal function and to allow surgery.

Resumo Fármacos inotrópicos fazem parte do tratamento de insuficiência cardíaca; no entanto, o tratamento com inotrópicos tem sido amplamente debatido devido ao aumento da incidência de efeitos adversos e da mortalidade. Recentemente, levosimendana, um agente inotrópico positivo, provou ser eficaz na insuficiência cardíaca aguda, reduz a mortalidade e melhora o desempenho cardíaco e renal. Relatamos o caso de uma paciente de 75 anos, com história de insuficiência cardíaca e renal e fratura de quadril. Levosimendana foi usada na preparação do pré-operatório como terapia adjuvante para melhorar a função cardíaca e renal e permitir a cirurgia.

Uso de levosimendan en enfermos con falla cardíaca aguda / Levosimendan in patients with acute cardiac failure

Objetivo: Valorar el uso de levosimendan en el contexto de la falla cardíaca aguda. Material y métodos: Se incluyeron 25 pacientes que ingresaron o desarrollaron insuficiencia cardíaca aguda, con respuesta parcial al manejo habitual definida como la presencia de bajo gasto cardíaco a pesar de tratamiento inotrópico. Se inició levosimendan administrando una dosis de carga y se continuó con una infusión durante 24 horas, monitorizándose a los pacientes con un catéter de flotación pulmonar y registrándose los parámetros hemodinámicos, así como las variables clínicas de frecuencia cardíaca (FC) y presión arterial media (PAM). Resultados: Observamos mejoría clínica en todos los pacientes. Hemodinámicamente se documentó disminución de la presión capilar pulmonar (PCP) de 18 cmH2O (11-30 cmH2O) a 14 cmH2O (8-15 cmH2O) (p = 0.3) para las 12 horas de haberse iniciado la infusión y al final de 13 cmH2O (8-12 cmH2O) (p = 0.2.) Igualmente se observó mejoría en cuanto al índice cardíaco (IC) 2.1 L/min/m² (1.8-3.5 L/min/m²), a 2.86 L/min/m² (2-4.3 L/min/m²) (p = 0.03) a las 12 h de la infusión y manteniéndose de 3.08 L/min/m² (2.4-3.9 L/min/m²) al término de la infusión (p = 0.02.). Sólo 6 pacientes mostraron como complicación taquicardia con FC mayor de 120 x min, que fue transitoria y que no requirió manejo adicional. En ningún caso requirió iniciar infusión de algún vasopresor. La mortalidad hasta el momento es de 8 pacientes. Conclusión: El uso de levosimendan en pacientes con falla cardíaca aguda mejora las variables hemodinámicas y clínicas con pocos efectos adversos en esta población de estudio.

Objective: To assess levosimendan efficacy in acute cardiac failure. Methods: We included 25 patients with acute cardiac failure and partial conventional therapy response defined as persistence of low cardiac output with inotropic support. We started levosimendan at loading dose and continuous infusion for 24 hours, recording hemodynamic data, as well as clinical variables. Results: All patients showed clinical and hemodynamic improvement. Pulmonary wedge capillary pressure (PWCP) decreased from 18 cmH2O (11 -30 cmH2O) to 14 cmH2O (8-15 cmH2O) at 12 hours (p = 0.3) and to 13 cmH2O (8-12 cmH2O) at the end of the infusion period (p = 0.2). Cardiac index increased from 2.1 L/min/m² (1.8-3.5 L/ min/m²) to 2.86 L/min/m² (2-4.3 L/min/m²) at 12 hours (p = 0.03) and to 3.08 L/min/m² at the end of the infusion period (p = 0.02). Tachycardia higherthan 120 bpm was present in six patients. No major hypotensive events were present. Mortality to the present is of eight patients. Conclusion: Levosimendan infusion improved hemodynamics and clinical variables in acute cardiac failure with few side effects in this small series of patients.