Search Results (66)

Background: Low cardiac output syndrome (LCOS) is a significant cause of postoperative morbidity and mortality in children with congenital heart disease. Prophylactic levosimendan is increasingly used to prevent LCOS, but its superiority to other strategies remains unproven. Based on the pharmacokinetics of levosimendan, we hypothesize that preoperative administration is beneficial for preventing LCOS in a specifically at-risk population. Methods: This is a retrospective single-center cohort study in a tertiary pediatric intensive care unit. All patients under one year of age undergoing surgery for congenital heart disease using cardiopulmonary bypass and receiving levosimendan within 24 h before or after surgery were included and classified into two groups: preoperative and postoperative administration. Results: Overall, 107 patients were included. Fifty-three patients (49.5%) received levosimendan before surgery, with significantly lower mortality, fewer LCOS markers, and lower LCOS scores compared to patients receiving levosimendan after surgery. Although not significant, the use of extracorporeal membrane oxygenation, renal replacement therapy, and temperature control was also lower in the preoperative group. There was no difference in mechanical ventilation duration and length of stay. Conclusions: Preoperative administration of levosimendan seems associated with a lower incidence of LCOS and reduced mortality in high-risk children with congenital heart surgery. Full article

Background: Peripartum cardiomyopathy (PPCM) is a rare form of heart failure occurring during the last month of pregnancy or within five months postpartum. While levosimendan is considered beneficial in heart failure and cardiogenic shock, evidence supporting its use in PPCM is limited. This study investigated the prevalence of PPCM in Germany and evaluated outcomes associated with levosimendan use. Methods: Using national data from the German Statistical Office, all pregnant women diagnosed with PPCM and hospitalized between 2009 and 2022 were included. Patients were categorized into groups based on levosimendan treatment. Demographics, treatment modalities, peripartum complications, and transfusion rates were analyzed. Results: The prevalence of PPCM in Germany is 0.01%; 3.60% of patients received levosimendan, mostly after childbirth (61.76%). Peripartum complications and the use of mechanical circulatory support devices were significantly higher in the levosimendan group (p < 0.0001). Women in the levosimendan group suffered significantly more often from intrapartum bleeding and increased rates of blood transfusion compared to women in the non-levosimendan group. Conclusions: PPCM is a rare disease in Germany with a prevalence of 0.01%. Despite higher complication rates in women with levosimendan treatment, further studies are necessary to help determine the role and timing of levosimendan in the treatment of women with PPCM. Full article

Severe mitral regurgitation (MR) is one of the most common valvular heart diseases and is frequently associated with advanced left ventricular (LV) systolic dysfunction. Transcatheter edge-to-edge repair (TEER) offers effective symptom relief but may induce abrupt hemodynamic changes leading to afterload mismatch and acute LV failure. Levosimendan may help mitigate this complication by improving contractility, yet evidence supporting its use in this setting is scarce. Therefore, the aim of this study was to systematically evaluate the evidence on the effects of Levosimendan in patients with severe MR and LV dysfunction undergoing TEER. We performed a comprehensive search of PubMed, Embase, Scopus, and Google Scholar. Primary outcomes were postprocedural LV ejection fraction (LVEF) and systolic pulmonary artery pressure (sPAP). Secondary outcomes included procedural success, procedure duration, and in-hospital complications. Five studies comprising 315 patients (n = 141 Levosimendan, n = 174 controls) met the inclusion criteria. Pooled analysis showed no significant difference in postprocedural LVEF between Levosimendan-treated patients and controls (mean difference 0.45%, 95% CI [−1.46–2.35] p = 0.65) and no significant change from baseline. Similarly, postprocedural sPAP did not differ significantly. Procedural success was higher with Levosimendan, and procedure duration was shorter. These hypothesis-generating findings highlight the need for larger, prospective randomized trials to clarify the role of Levosimendan in this setting. Full article

Levosimendan, a calcium-sensitizing inodilator, has emerged as a promising adjunctive therapy in patients undergoing veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Its pharmacodynamic profile, combining positive inotropy with vasodilation and mitochondrial protective effects, offers a unique therapeutic potential in the context of mechanical circulatory support. Despite growing interest, the clinical impact of Levosimendan in ECMO remains debated, with heterogeneous evidence regarding its efficacy in improving weaning success, reducing vasopressor requirements or mitigating ischemia-reperfusion injury. This narrative review aims to critically appraise the current literature on Levosimendan use in ECMO settings, exploring its mechanistic rationale, pharmacologic behavior under extracorporeal circulation and potential role in various clinical scenarios including post-cardiotomy shock and refractory cardiogenic failure. The limitations of existing studies are critically examined, underscoring the need for high-quality clinical trials to define appropriate patient selection, optimal timing of administration and dosing strategies. This review synthesizes current evidence to determine whether Levosimendan constitutes a true therapeutic asset or remains merely an adjunctive agent in the complex management of ECMO supported patients. Full article

Background/Objectives: Advanced heart failure (AdvHF) characterizes patients with impaired functional capacity, severe systolic or diastolic cardiac function, unplanned visits or hospitalizations, raised natriuretic peptides, and increased mortality. Methods: Ninety-five consecutive AdvHF patients followed in a tertiary academic center in Northwestern Greece (2nd Department of Cardiology, University Hospital of Ioannina) were enrolled over a 30-month period. Three distinctive patterns of management were recognized and assessed: intermittent levosimendan administration to 33 patients, intermittent intravenous furosemide administration to 17 patients, and 45 patients were followed up exclusively on an outpatient basis with frequent visits. MAGGIC, SHFM, and BCN-Bio scores were assessed in all patients and mortality was also assessed. Results: Mean age was 73 (±10) years, and 38% were females, 41% had diabetes mellitus, 41% had chronic obstructive pulmonary disease, 59% had coronary artery disease (CAD), 73% had a history of atrial fibrillation, and 82.1% had a cardiac device implanted. The median duration of follow-up was 24 months (IQ range 14, 30). The 12-month and 30-month mortality rates were 19% and 49%, respectively. Higher rates of 1-year mortality were observed in the levosimendan group (30%). The median 12-month mortality of the three scores was comparable to the actual mortality, but their prognostic value was not satisfactory (AUC < 0.540 and p > 0.05 for all), while they performed better for 30-month mortality (AUC < 0.756 and p > 0.05 for all). In the current study, mortality at 12 months was associated with decreasing diastolic blood pressure (DBP) and sodium levels; the presence of CAD (p < 0.05 for all) and mortality at 30 months was associated with decreasing systolic blood pressure, as well as DBP and left ventricle ejection fraction, but also with the presence of CAD and the use of renin–angiotensin–aldosterone system blockers. Logistic regression-based models incorporating these factors have a greater diagnostic accuracy (AUC = 0.824 and 0.817 for 12 and 30 months, respectively; p < 0.001 for both). Conclusions: AdvHF patients represent a complex population requiring close follow-up and novel strategies to improve survival. Larger studies are needed to refine and update predictive scores in this population. Full article

Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant outcomes remain uncertain. Within a personalized-medicine framework, we targeted a low-output/INTERMACS 3 phenotype and operationalized an adaptable, protocolized levosimendan pathway focused on perfusion/congestion stabilization to preserve transplant candidacy. Methods: We conducted a single-center, retrospective cohort study of 25 consecutive adults actively listed for HT between 2019 and 2024, treated with a standardized outpatient program of a 14-day interval of 6 h intravenous levosimendan infusions (target 0.2 μg/kg/min infusions) continued until transplant. Personalization in this program was operationalized through (i) phenotype-based eligibility (low CI and elevated filling pressures despite GDMT), (ii) predefined titration and safety rules for blood pressure, arrhythmias, and renal function, and (iii) individualized continuation until transplant with nurse-supervised monitoring and review of patient trajectories. Baseline characteristics, treatment exposure and safety, changes in hospitalizations and biomarkers, and peri-transplant outcomes were analyzed. Results: Patients were predominantly male (68%), with a mean age of 47.9 ± 17.5 years and severe LV dysfunction (LVEF 30.6 ± 9.8%). Median treatment duration was 131 days (IQR 60–241). No infusions required discontinuation for hypotension or arrhythmia, and no adverse events were directly attributed to levosimendan. Two patients (8%) died on the waiting list, both unrelated to therapy. During treatment, HF hospitalizations decreased significantly compared with the previous 6 months (48% vs. 20%, p = 0.033), renal function remained stable, and NT-proBNP trended downward. Of the 23 patients transplanted, two (9%) underwent urgent HT during decompensation. Post-transplant, vasoplegia occurred in 26% (n = 6 of 23), and 30-day mortality was 9% (n = 2 of 23). Conclusions: By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement. Full article

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of hospitalization and functional decline in older adults, accounting for over 80% of all heart failure cases. Given the narrow therapeutic window of currently available inotropes and the vulnerability of this population, levosimendan has been proposed as a potential alternative. This systematic review aimed to evaluate the clinical efficacy and safety of levosimendan in older adults with decompensated HFrEF. Methods: A systematic search of PubMed, Embase, Scopus, and the Cochrane Library was conducted between January and May 2025, following PRISMA 2020 guidelines. The review was registered in PROSPERO (CRD420251032329). Of 379 articles initially identified, 8 studies (randomized, observational, and single-arm designs) enrolling patients aged ≥65 years with decompensated HFrEF met the inclusion criteria. Study quality was assessed using the Cochrane RoB-2 tool and JBI Critical Appraisal Checklists. No meta-analysis was performed due to heterogeneity in study designs, populations, and interventions. Results: A total of 2838 patients were analyzed. Levosimendan was associated with short-term improvements in hemodynamic parameters, including an increase in cardiac index (from 1.65 to 2.37 L/min/m²) and a reduction in pulmonary capillary wedge pressure (from 31 to 16 mmHg) within 24–72 h (p < 0.002). However, no statistically significant differences were observed in 30-, 90-, or 180-day mortality (p > 0.05), and findings on rehospitalization were inconsistent. Reported adverse events included hypotension (36–57%) and atrial arrhythmias (9–50%), with low treatment discontinuation rates (5–8%). Conclusions: Levosimendan may improve short-term hemodynamic parameters in older adults with decompensated HFrEF, but the available evidence is limited and heterogeneous. Its effects on mortality and rehospitalization remain inconclusive. Clinical use should be individualized and closely monitored, particularly in frail patients. Full article

Acute mesenteric ischemia (AMI) is a life-threatening condition characterised by oxidative stress, inflammation, apoptosis, and necrosis of intestinal epithelial cells. Different drugs with vasoactive, antioxidant, and anti-inflammatory properties have been used to treat AMI. Levosimendan is a drug with proven anti-ischemic effects used in the management of acute congestive heart failure. This study evaluated the protective effects of levosimendan pretreatment on intestinal, as well as lung, heart, and kidney tissue in a rat model of mesenteric artery ischemia/reperfusion (I/R) injury. Male Wistar rats (N = 24) were divided into four groups: control, I/R, levosimendan (LS) 1 mg/kg i.p, and LS + I/R (1 mg/kg i.p. 30 min before injury). I/R by itself caused elevation of oxidative markers (thyobarbituric acid reactive species (TBARS), hydrogen peroxide (H₂O₂), super oxide anjon radical (O₂⁻), and nitrogen dioxide (NO₂⁻)), induced inflammation (macrophage infiltration and Interleukin-6 (IL-6) production), and apoptosis (nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), cleaved caspase-3 (CC3), and terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL)). Levosimendan pretreatment significantly reduced oxidative stress markers and enhanced antioxidant defences (catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)). Histological analysis revealed reduced mucosal damage and preserved goblet cells in intestinal tissue. Similar protective effects of levosimendan were observed in other organs such as lung, heart, and kidney. Immunohistochemistry showed reduced epithelial apoptosis and upregulation of antioxidant and anti-inflammatory proteins. These findings highlight levosimendan’s ability to protect mesenteric I/R tissue injury and multi-organ damage by suppressing oxidative stress, inflammation, and apoptosis, emphasising its therapeutic potential in clinical settings. Full article

Background: Beyond its established inotropic effects, levosimendan has been reported to enhance renal function in patients with chronic heart failure. In this study, we investigated whether changes in renal function following levosimendan administration in patients listed for heart transplantation were associated with early post-transplant renal outcomes. Methods: We retrospectively analyzed data from 99 patients with advanced heart failure and renal insufficiency (eGFR < 90 mL/min/1.73 m²) who were listed for heart transplantation and received levosimendan therapy within 1 to 6 months prior to transplantation. Renal function was assessed immediately before and 24 h after levosimendan administration. A favorable renal response was defined as any increase in eGFR at 24 h. Post-transplant renal function was evaluated on postoperative days 1 and 7 using standard renal function parameters. Results: Favorable renal response to levosimendan prior to heart transplantation was present in 73 of 99 patients (74%, Group A), and 26 patients (26%) displayed no increase in eGFR (Group B). In the first week after heart transplantation, we found a significant improvement in renal function in Group A (ΔeGFR: +14 ± 3 mL/min/1.73 m², p < 0.001), and worsening of renal function in Group B (ΔeGFR: −4 ± 3 mL/min/1.73 m², p < 0.01). Favorable response to levosimendan prior to heart transplantation was an independent correlate of improved renal function after heart transplantation (p = 0.01). Conclusion: In patients awaiting heart transplantation, improvement in renal function after levosimendan therapy was associated with better early post-transplant renal outcomes. Levosimendan response may thus help identify reversible renal dysfunction and serve as a simple tool for transplant evaluation. Full article

Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This meta-analysis aims to determine which inotropic agent may be more effective in this clinical scenario. Methods: A systematic review and meta-analysis were conducted, including data from randomized clinical trials (RCTs) comparing levosimendan and dobutamine in patients with septic shock and persistent hypoperfusion. Summary effect estimates, including odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs), were calculated using a random-effects model. Trial sequential analysis (TSA) was also performed. Results: Of 244 studies screened, 11 RCTs were included. Levosimendan was associated with a reduction in in-hospital mortality (OR 0.64; 95% CI: 0.47; 0.88) and ICU length of stay (SMD 5.87; 95% CI: –8.37; 20.11) compared with dobutamine. Treatment with levosimendan also resulted in significant reductions in BNP (SMD –1.87; 95% CI: –2.45; −1.2) and serum lactate levels (SMD –1.63; 95% CI: –3.13; −0.12). However, TSA indicated that the current evidence is insufficient to definitively confirm or exclude effects on in-hospital and 28-day mortality. Conclusions: Levosimendan may improve hemodynamics, tissue perfusion, and biomarkers, and may reduce in-hospital mortality and ICU length of stay in patients with SICM compared with dobutamine. However, TSA highlights the need for further studies to inform clinical practice and optimize inotrope selection. Full article

Sepsis is a life-threatening condition driven by a dysregulated host immune response to infection, with cytokine overproduction contributing to organ dysfunction and high mortality. Levosimendan, a calcium sensitizer used in acute heart failure, has been proposed to exert anti-inflammatory effects, but information on its immunomodulatory effects in early sepsis remains scarce. This study aimed to investigate the dose- and time-dependent effects of levosimendan on cytokine profiles in a rat model of lipopolysaccharide (LPS)-induced sepsis. Thirty-two male Wistar albino rats were randomly assigned to four groups: sham, sepsis control, low-dose levosimendan (1 mg/kg), and high-dose levosimendan (2 mg/kg). Cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, MCP-1) were measured at 5 and 10 h post-LPS administration. High-dose levosimendan significantly reduced TNF-α, IL-1β, IL-6, and MCP-1 levels by the 10th hour, accompanied by improved Murine Sepsis Scores. IL-17 and IL-6 showed biphasic responses, increasing initially and decreasing significantly later, particularly with high-dose treatment. IL-8 reduction was observed only in the high-dose group. These findings support levosimendan’s dose and time-dependent anti-inflammatory effects and suggest it may modulate both early and late-phase cytokines in sepsis. Further studies are warranted to clarify its potential role in clinical sepsis management. Full article

Septic patients can show multiorgan failure even after an apparent recovery of hemodynamic stability. The underlying mechanism is unclear, but the main pathological element is microcirculation impairment, leading to insufficient oxygen delivery. This study aimed to assess the effects of levosimendan administration on peripheral perfusion in the prodromic phases of sepsis and compare them with the variations in microcirculation perfusion occurring with conventional dobutamine therapy. Sixteen patients with sepsis were enrolled, eight of whom were treated with norepinephrine and levosimendan and the other eight with norepinephrine and dobutamine. We observed a trend of reduction in the hematic lactate concentration and an increase in peripheral perfusion in the patients treated with levosimendan. The latter also occurred in the dobutamine group, although to a lower degree. Hematic lactate was significantly reduced in the levosimendan group, probably because of the enhanced aerobic metabolism, due to both the action on mitochondrial K_ATP channels and the better oxygen delivery to cells. The lactate values varied from T₀ (2.28 ± 0.25 mmol/L) to T₂ (1.45 ± 0.31 mmol/L) in the levosimendan group vs. from T₀ (2.79 ± 0.91 mmol/L) to T₂ (2.92 ± 0.76 mmol/) L in the dobutamine group. Hence, levosimendan may be indicated in septic patients with impaired microcirculation and tissue oxygenation and, consequently, high lactate levels. Further studies are needed to draw a profile of levosimendan as a possible treatment to restore microcirculation in septic patients. Full article

Background/Objectives: Current evidence suggests that levosimendan may have a beneficial effect in the treatment of acute heart failure (AHF) or cardiogenic shock following primary percutaneous coronary intervention (PCI). However, there is a paucity of data on the use of levosimendan prior to PCI. Therefore, our pilot study aimed to assess the short-term prognosis of a new therapeutic protocol involving preprocedural infusion of levosimendan in patients with reduced left ventricular ejection fraction undergoing high-risk PCI for acute coronary syndrome (ACS). Methods: The study is a retrospective observational study, and the population includes all subjects who received levosimendan infusion prior to high-risk PCI for ACS. Subjects requiring urgent revascularization (cardiogenic shock, cardiac arrest) or with mechanical complications of ACS were excluded. Results: The study cohort consisted of 90 subjects, predominantly men (91.1%) with significantly reduced left ventricular function (28.7% (12)) and advanced coronary artery disease, mean SYNTAX Score 25.8 (19.3–33). During in-hospital follow-up, we observed 2 primary outcomes—death. The major adverse cardiac and cerebrovascular events (MACCE) rate was 7.8%. Two clinical adverse events that did not lead to discontinuation were observed during the in-hospital period. Both were related to hypotension. Conclusions: In short-term observation, novel therapeutic approach in the management of high-risk PCI in ACS patients—pre-procedural levosimendan—was a relatively safe approach. No significant adverse events were reported. Full article

Background: Survivors of out-of-hospital cardiac arrest (OHCA) after external cardiopulmonary resuscitation (ECPR) have a mortality rate as high as 50–70%. The use of vasoactive inotropes worsen the mortality rate at admission. The administration of levosimendan within 72 h of ECPR facilitates extracorporeal membrane oxygenation (ECMO) weaning, so it is important to determine whether levosimendan improves mortality. Methods: This retrospective cohort study included 158 patients with OHCA of cardiac origin who had undergone ECPR and were hospitalized between January 2015 and December 2024. This study was conducted in the intensive care unit of China Medical University Hospital, Taichung, Taiwan. Twenty-three patients received levosimendan within 72 h, whereas the others did not receive levosimendan. Primary endpoints included ECMO weaning failure rate and 90-day all-cause mortality rate. Kaplan–Meier survival curve analysis was also performed. Covariates for all-cause mortality were estimated and adjusted by using Cox regression modeling. Results: The levosimendan group exhibited lower rates of ECMO weaning failure and 90-day all-cause mortality than the control group (13.0% vs. 52.6% and 17.4% vs. 57.0%, respectively; both p < 0.001). The 90-day survival curve analysis revealed that the levosimendan and control groups had survival rates of 82.6% and 43.0%, respectively (log-rank p < 0.001). Administration of levosimendan within 72 h resulted in a odds ratio of 0.36 (95% confidence interval: 0.18−0.79, p = 0.01). Conclusions: Administering levosimendan within 72 h of ECPR could be a protective factor in improving all-cause mortality. Full article

Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap in critical care medicine. It is an often-underdiagnosed complication of sepsis. The only widely accepted aspect of its definition is that SCM is a transient myocardial dysfunction occurring in patients with sepsis, which cannot be attributed to ischemia or pre-existing cardiac disease. The pathogenesis of SCM appears to be multifactorial, involving inflammatory cytokines, overproduction of nitric oxide, mitochondrial dysfunction, calcium homeostasis dysregulation, autonomic imbalance, and myocardial edema. Diagnosis primarily relies on echocardiography, with advanced tools such as tissue Doppler imaging (TDI) and global longitudinal strain (GLS) providing greater sensitivity for detecting subclinical dysfunction and guiding therapeutic decisions. Traditional echocardiographic findings, such as left ventricular ejection fraction measured by 2D echocardiography, often reflect systemic vasoplegia rather than intrinsic myocardial dysfunction, complicating accurate diagnosis. Right ventricular (RV) dysfunction, identified as a critical component of SCM in many studies, has multifactorial pathophysiology. Factors including septic cardiomyopathy itself, mechanical ventilation, hypoxemia, and hypercapnia—particularly in cases complicated by acute respiratory distress syndrome (ARDS)—increase RV afterload and exacerbate RV dysfunction. The prognostic value of cardiac biomarkers, such as troponins and natriuretic peptides, remains uncertain, as these markers primarily reflect illness severity rather than being specific to SCM. Treatment focuses on the early recognition of sepsis, hemodynamic optimization, and etiological interventions, as no targeted therapies currently exist. Emerging therapies, such as levosimendan and VA-ECMO, show potential in severe SCM cases, though further validation is needed. The lack of standardized diagnostic criteria, combined with the heterogeneity of sepsis presentations, poses significant challenges to the effective management of SCM. Future research should focus on developing cluster-based classification systems for septic shock patients by integrating biomarkers, echocardiographic findings, and clinical parameters. These advancements could clarify the underlying pathophysiology and enable tailored therapeutic strategies to improve outcomes for SCM patients. Full article