Levosimendan in heart transplantation: a systemic review and meta-analysis
R Kaddoura, A Ahmed, M Altermanini, A Chapra, F Al-Kindi, F Al-Maraghi, A OmarAbstract
Background
Levosimendan (LEVO) has been used in patients with advanced heart failure awaiting heart transplantation (HTx) to improve outcomes and in those experiencing primary graft dysfunction or failure (PGD/F) post-transplantation. However, the overall efficacy and safety of LEVO in the HTx setting remains uncertain.
Purpose
We performed a systematic review and meta-analysis to evaluate the impact of LEVO on survival and post-transplantation outcomes.
Methods
A systematic review and meta-analysis were conducted in accordance with the Cochrane Handbook and the PRISMA statement. EMBASE, MEDLINE, and Scopus databases were searched from inception to February 18, 2026. Observational studies evaluating LEVO use before or after HTx were included. RStudio software was used to pool the clinical outcomes as either descriptive in a single proportion meta-analysis for single-arm studies or comparative as an odds ratio (OR) or a mean difference (MD) with 95% confidence intervals (95% CI). A random-effects model was applied to allow for a more conservative assessment of the pooled effect size. Statistical significance was defined as p<0.05.
Results
Twenty-one single-arm (n=13) and cohort (n=8) observational studies met the eligibility criteria. Out of which 12 studies were included in the analysis. Studies were categorized into 3 groups: LEVO use as a bridge to HTx (n=12), LEVO use for PGD/F (n=6), and LEVO use after HTx (n=3). The latter group did not have enough variables to be pooled. Among patients awaiting HTx who received repeated LEVO dosing as a bridge-to-transplant therapy, mortality while on the waiting list was 8.0% (95% CI: 4.0; 19.0), whereas 15.0% (95% CI: 3.0; 52.0) of patients required left ventricular assist device support. Of the enrolled patients, 84.0% (95 CI: 51.0; 06.0) had successful HTx, with 24.0% (95 CI: 9.0; 49.0) requiring urgent HTx. The pooled post-transplantation survival was 89.0% (95 CI: 85.0; 91.0). However, LEVO use was not associated with an improved survival (OR 0.75, 95% CI: 0.26; 2.19, p=0.6000). In patients experiencing PGD/F who received LEVO, the pooled 30-day and 1-year mortality were 22.0% (95% CI: 7.0; 53.0) and 53.0% (95% CI: 40.0; 66.0), respectively. LEVO use was associated with a longer duration of extracorporeal membrane oxygenation (ECMO) support (MD 3.38 days, 95% CI: 1.77; 4.98, p<0.0001) and higher odds of 30-day mortality (OR 2.42, 95% CI: 1.01; 5.82, p=0.0480) (Figure 1). Overall, LEVO use was generally well-tolerated in terms of adverse effects, with no consistent signal for increased risk of arrhythmias, symptomatic hypotension, or renal impairment.
Conclusion
LEVO use in the HTx setting was associated with a higher mortality rate in bridge-to-transplant patients, a longer requirement of ECMO support, and a higher short-term mortality in PGD/F. These findings do not support the routine use of LEVO in this population and highlight the need for robust prospective studies.