Comparison of single-dose and repeated levosimendan infusion in patients with acute exacerbation of advanced heart failure (original) (raw)
Related papers
Heart, 2006
Background: Levosimendan is a novel inodilator that improves central haemodynamics and symptoms of patients with decompensated chronic heart failure. The role, however, of repeated levosimendan infusions in the management of these patients has not yet been properly assessed. Purpose: This randomised placebo-controlled trial investigated the effects of serial levosimendan infusions on cardiac geometry and function, and on biomarkers of myocardial injury and neurohormonal and immune activation (troponin T, N-terminal B-type natriuretic pro-peptide (NT-proBNP), C reactive protein (CRP) and interleukin (IL) 6) in patients with advanced heart failure. Methods: 25 patients with decompensated chronic heart failure were randomised (2:1) to receive five serial 24-h infusions (every 3 weeks) of either levosimendan (n = 17) or placebo (n = 8), and were evaluated echocardiographically and biochemically before and after each drug infusion and 30 days after the final infusion. Results: Following treatment, cardiac end-systolic and end-diastolic dimension and volume indices were significantly reduced only in the levosimendan-treated patients (p,0.01). A significant decrease in NT-proBNP (p,0.01), high-sensitivity CRP (p,0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion. Although the number of patients with a positive troponin T (>0.01 ng/ml) was not different between the two groups at baseline, it was significantly higher in the placebo-treated group during the final evaluation (p,0.05). Conclusion: Serial levosimendan treatments improved left ventricular performance and modulated neurohormonal and immune activation beneficially in patients with advanced heart failure, without increasing myocardial injury.
Intermittent levosimendan treatment in patients with severe congestive heart failure
Clinical Research in Cardiology, 2013
Objective Levosimendan (LS) is a novel inodilator for the treatment of severe congestive heart failure (CHF). In this study, we investigated the potential long-term effects of intermittent LS treatment on the pathophysiology of heart failure. Methods Thirteen patients with modest to severe CHF received three 24-h intravenous infusions of LS at 3-week intervals. Exercise capacity was determined by bicycle ergospirometry, well-being assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ) and laboratory parameters of interest measured before and after each treatment. Results One patient experienced non-sustained periods of ventricular tachycardia (VT) during the first infusion and had to discontinue the study. Otherwise the LS infusions were well tolerated. Exercise capacity (VO 2max) did not improve significantly during the study although symptoms decreased (P \ 0.0001). Levels of plasma NT-proANP, NT-proBNP and NT-proXNP decreased 30-50 % during each infusion (P \ 0.001 for all), but the changes disappeared within 3 weeks. Although norepinephrine (NE) appeared to increase during the first treatment (P = 0.019), no long-term changes were observed. Conclusion Intermittent LS treatments decreased effectively and repetitively plasma vasoactive peptide levels, but no carryover effects were observed. Patients' symptoms decreased for the whole study period although there was no objective improvement of their exercise capacity. The prognostic significance of these effects needs to be further studied.
Journal of Cardiac Failure, 2007
Background: Levosimendan (LS) improves cardiac contractility without increasing myocardial oxygen demand. We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a randomized, open, prospective study. Methods and Results: Fifty patients (age 45e65 years) with LV systolic dysfunction and New York Heart Association (NYHA) III or IV were randomized in 2 groups. LS group (n 5 25) was compared with a control group (n 5 25) matched for sex, age, and NYHA class. LS was given monthly on a 24-hour intravenous protocol for 6 months. Patients were evaluated by specific activity questionnaire (SAQ) and echocardiography (ECHO) before and 3 to 5 days after last drug administration, whereas 24-hour Holter recording was performed before and during last drug administration. Patients in LS and control group had same baseline SAQ, ECHO, and Holter parameters. At the end of the study, a larger proportion of patients in the levosimendan group reported improvement in symptoms (dyspnea and fatigue) (65% versus 20% in controls, P ! .01). After 6 months, the LS group had a significant increase in LV ejection fraction versus controls (28 6 7 versus 21 6 4 %, P 5 .003), LV shortening fraction (15 6 3 versus 11 6 3 %, P 5 .006) and a decrease in mitral regurgitation (1.5 6 0.8 versus 2.7 6 0.6, P 5 .0001). There was no increase in supraventricular or ventricular beats or supraventricular tachycardia and VT episodes in LS group, compared with controls. Two patients from the LS group died in the 6-month follow-up period, compared with 8 patients in the control group (8% versus 32%, P ! .05). Conclusions: A 6-month intermittent LS treatment in patients with decompensated advanced heart failure improved symptoms and LV systolic function. (J Cardiac Fail 2007;13:556e559)
International journal of cardiology, 2017
Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the liter...
ESC Heart Failure
Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time-averaged proportional change in N-terminal pro-brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks.
Efficiency and safety of prolonged levosimendan infusion in patients with acute heart failure
European Journal of Heart Failure Supplements, 2008
Background. Levosimendan is an inotropic drug with unique pharmacological advantages in patients with acute heart failure. Scope of this study is to determine whether longer infusion patterns without the hypotension-inducing loading dose could justify an effective and safe alternative approach. Methods. 70 patients admitted to the emergencies with decompensated chronic heart failure received intravenously levosimendan without a loading dose up to 72 hours. Clinical parameters, BNP (Brain Natriuretic Peptide) and signal-averaged-ECG data (SAECG) were recorded up to 72 hours. Results. The 48-hour group demonstrated a statistically significant BNP decrease (P < .001) after 48 hours, which also maintained after 72 hours. The 72-hour group demonstrated a bordeline decrease of BNP after 48 hours (P = .039), necessitating an additional 24-hour infusion to achieve significant reduction after 72 hours (P < .004). SAECG data demonstrated a statistically significant decrease after 72 hours (P < .04). Apart from two deaths due to advanced heart failure, no major complications were observed. Conclusion. Prolonged infusion of levosimendan without a loading dose is associated with an acceptable clinical and neurohumoral response.
International Journal of Cardiology, 2014
Background: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. Methods and results: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience.
Cardiology Journal, 2011
Background: Levosimendan (L) is used in clinical practice for the treatment of severe heart failure (HF); it has inotropic and vasodilatory effects, without increasing myocardial oxygen consumption. In acute HF, levosimendan improves hemodynamic parameters; previous studies have demonstrated that it has favorable effects on left ventricular (LV) diastolic function. The aim of our study was to evaluate the effect of on LV long-axis function that represents the earlier marker of diastolic dysfunction. Methods: We enrolled 41 patients (age 62 ± 12 years) admitted to our Department for acute HF, NYHA class IV and severe LV dysfunction. Twenty-six patients were treated with L (0.1 µg/kg/min ev for 24 h without loading dose) and 15 patients were treated with standard therapy (C). We evaluated clinical, blood exams and echocardiographic parameters at baseline and one week after L or C treatment. Results: Baseline demographic, clinical and biochemical data were similar in both groups. After one week, the L group had shown a significant improvement in NYHA class and a reduction of pro-B-type natriuretic peptide (pro-BNP). In echocardiographic study, we observed an improvement in LV longitudinal function (p < 0.05) and LV ejection fraction (p < 0.05) with a reduction of E/E ' (p < 0.05) in the L group. We divided the L group into ischemic and non-ischemic patients and we demonstrated a significant increase in systolic function in the former. No differences were found between subgroups in diastolic function. Conclusions: L therapy, without loading dose, improves NYHA class and ventricular function in patients with acute HF; we believe that these prolonged hemodynamic effects are due to active metabolities of L.
Intermittent levosimendan infusions in advanced heart failure: a real world experience
Journal of International Medical Research, 2017
Objective: To analyse the effects of levosimendan infusions in advanced heart failure. Methods: Patients with advanced heart failure treated with repeated levosimendan infusions were retrospectively compared with controls. Clinical, blood and echocardiographic parameters were obtained at baseline and after 12 months, and before and after each levosimendan infusion. Hospitalizations for heart failure and in-hospital length of stay in the 6 months before enrolment and after 6 and 12 months were recorded, along with 1-year mortality. Results: Twenty-five patients treated with levosimendan and 25 controls were studied. After each levosimendan infusion, ventricular function and various clinical and metabolic parameters were improved. After 12 months, left ventricular ejection fraction (LVEF) had improved compared with baseline in the levosimendan group. The 1-year mortality rate was similar in both groups. During the 6 months before enrolment, hospitalizations were fewer in controls compared with the levosimendan group; after 6 and 12 months they increased in controls and decreased in the levosimendan group. Seven patients were super-responders to levosimendan, with LVEF improving more than 20% and hospitalizations being reduced at 12 months compared with the rest of the levosimendan group. Conclusion: Intermittent levosimendan improved LVEF and decreased hospitalizations in advanced heart failure and represents a therapeutic option for patients whose disease is worsening.