Impact of pre-heart transplant levosimendan administration on post-transplant vasoplegia and primary graft dysfunction

Abstract

[Abstract]

Introduction: Levosimendan, a calcium-sensitizing inotropic agent, is used in patients with advanced heart failure (HF) awaiting heart transplantation (HT). Its prolonged effects, due to an active metabolite, may influence post-transplant vasodilation, particularly when administered shortly before HT. However, its impact on post-HT complications such as vasoplegia and primary graft dysfunction (PGD) remains unclear. This study aimed to evaluate whether preoperative levosimendan affects these outcomes.

Methods: This retrospective, multicenter observational study included adult HT recipients from 2010 to 2022 across three Spanish centers. Patients were grouped based on whether they received levosimendan within 1 month prior to HT. Main outcomes were post-HT vasoplegia (defined as cardiac index ≥2.5 L/min/m2, systemic vascular resistance <1000 dyn·s·cm-5, and either a vasoactive-inotropic score (VIS) > 20 or norepinephrine administration >0.1 µg/kg/min at 24 h post-HT) and severe PGD, as defined by the 2014 ISHLT criteria. Secondary outcomes included all-cause mortality. Subgroup analyses were performed for patients receiving levosimendan within 1 week of HT and by sex. Statistical analyses included propensity score (PS) matching, Kaplan-Meier curves, and multivariate Cox regression models.

Results: Among 598 HT recipients, 94 (15.7%) received levosimendan preoperatively. After PS adjustment, no significant differences were found in the incidence of vasoplegia (40.0% vs. 39.2%, OR 0.99, p = 0.98) or severe PGD (10.6% vs. 10.3%, OR 1.25, p = 0.63) between groups. Post-HT mortality was also not different (HR 0.78, p = 0.37). Vasoplegia did not affect mortality, while severe PGD was linked to higher mortality. Subgroup and sex-based analyses revealed no significant outcome differences.

Conclusions: Pre-HT levosimendan use was not associated with increased early post-transplant complications and appears to be a safe strategy.

Summary: This study evaluated whether giving levosimendan before HT affects early post-transplant complications. Among 598 patients, 94 received levosimendan within a month before surgery. Results showed no significant differences in rates of vasoplegia, severe primary graft dysfunction, or mortality. Levosimendan use appears safe in the immediate pre-transplant setting.