The relationship between cold ischemic time and graft failure in heart transplantation:multicenter prospective study
M Ju, Y J RheeAbstract
Background
Cold ischemic time (CIT) is traditionally regarded as a critical determinant of outcomes after heart transplantation, with prolonged CIT associated with graft dysfunction. Most prior studies, however, have relied on arbitrary threshold-based comparisons, typically using 3 hours as a cutoff, and data examining outcomes across a wide spectrum of CIT remain limited. Notably, recent large-scale analyses have suggested that extremely short CIT may also be associated with adverse outcomes, challenging conventional assumptions.
Methods
Adult recipients (≥18 years) undergoing isolated heart transplantation were prospectively enrolled in a multicenter registry between January 2014 and February 2023. Patients receiving multi-organ transplantation or with missing key data were excluded. The study population was stratified into four groups according to CIT: ≤60 minutes, 61–120 minutes, 121–180 minutes, and >180 minutes. The primary endpoint was graft failure, defined as the requirement for early postoperative extracorporeal membrane oxygenation during intensive care unit management. Secondary endpoints included early mortality and long-term survival. Multivariable regression analysis was performed to identify independent predictors of graft failure.
Results
A total of 989 patients were included in the final analysis. Approximately 80% of recipients had a CIT of less than 3 hours, and 17% underwent transplantation with a CIT of ≤60 minutes. Increasing CIT was associated with a significant increase in total ischemic time; however, no significant differences were observed among groups with respect to postoperative extracorporeal support, early mortality, or long-term survival. In multivariable analysis, preoperative extracorporeal support, elevated C-reactive protein levels, and prolonged warm ischemic time were independently associated with graft failure, whereas dilated cardiomyopathy was associated with a reduced risk. CIT was not independently associated with graft failure or mortality within the observed range.
Conclusions
In this prospective multicenter cohort, variation in cold ischemic time within commonly encountered clinical ranges was not associated with increased graft failure, early mortality, or impaired long-term survival after heart transplantation. Instead, recipient condition and perioperative factors, particularly systemic inflammation and warm ischemic time, were the dominant determinants of early graft failure. These findings suggest that moderate prolongation of cold ischemic time may be clinically acceptable, although caution is warranted when extrapolating results across different transplantation systems and geographic settings.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.