OPTIMIZING MYOCARDIAL PROTECTION IN CIRCULATORY DEATH DONORS: INSIGHTS FROM A TERTIARY CARE CENTER EXPERIENCE

BACKGROUND. The use of controlled donors after circulatory death (cDCD) for heart transplantation has long been debated in Italy, largely given to the longest in the world no-touch period after death declaration (20 minutes of asystolia), that leads to very prolonged inadequate organ perfusion after withdrawal of life-sustaining therapy (WLST). However, in April 2023, the National Transplant Centre (CNT) approved heart donation in cDCD. Following this, the first cDCD heart donation was successfully performed at Treviso Hospital in May 2023. To minimize ischemic and ischemia-reperfusion injury a standardized preconditioning protocol is applied for every cDCD case in Treviso Hospital. This protocol is administered before and during WLST and after NRP (normothermic regional perfusion). It includes a combination of pharmacological treatments to reduce oxidative stress (melatonin, N-acetylcysteine, and ascorbic acid), improve microcirculation (statins), and mitigate organ’s ischemic injury (steroids) as well as organ ischemia/reperfusion injury (remifentanil and sevoflurane when the heart is available for transplantation). AIM OF THE STUDY. This study evaluates the efficacy of the preconditioning protocol in protecting the heart from ischemic and ischemia-reperfusion injury during cDCD, describing the elevation of biomarkers of myocardial injury (troponin T and CK-MB). METHODS. The study retrospectively analyzed cDCD cases performed at Treviso Regional Hospital from May 2023 to December 2024. The inclusion criteria were: cDCD following WLST, application of the preconditioning protocol, and availability of serial troponin T and CK-MB measurements. The study involved both heart donors and non-heart donors who experienced unintentional myocardial reperfusion with a resumption of cardiac activity during NRP. Serial measurements of troponin T, CK-MB, liver and renal biomarkers, and hemogasanalysis parameters were collected and analyzed, together with intraprocedural echocardiographic features. RESULTS. The study included 11 patients (5 heart donors and 6 non-heart donors). The median functional warm ischemia time (fWIT) was 47 minutes, and the median pure warm ischemia time during acirculatory phase (WITap) was 35 minutes. Myocardial damage during the cDCD procedure was limited, as indicated by a median troponin T peak of 195 ng/L within the first 4 hours, representing a threefold increase compared to baseline across all donors. Echocardiographic evaluation in heart donors demonstrated excellent myocardial recovery, with no persistent ventricular dysfunction that contraindicated transplantation. Parameters such as pH, lactate, and hemoglobin were consistently maintained within optimal ranges during NRP. CONCLUSIONS. These preliminary data suggest that the preconditioning protocol developed in Treviso optimizes myocardial protection during cDCD, limiting ischemic and ischemia-reperfusion injury despite extended warm ischemia times. This protocol could represent a promising strategy to enhance cDCD heart transplantation outcomes. Further studies are needed to validate its efficacy and explore broader applications.