Cold ischemia >4 hours increases heart transplantation mortality. An analysis of the Spanish heart transplantation registry

Abstract

Background: Cold ischemia time (CIT) has been associated to heart transplantation (HT) prognosis. However, there is still uncertainty regarding the CIT cutoff value that might have relevant clinical implications. Methods: We analyzed all adults that received a first HT during the period 2008-2018. CITwas defined as the time between the cross-clamp of the donor aorta and the reperfusion of the heart. Primary outcome was 1month mortality. Results: We included 2629 patients, mean agewas 53.3±12.1 years and 655 (24.9%) were female. Mean CIT was 202 ± 67 min (minimum 20 min, maximum 600 min). One-month mortality per CIT quartile was 9, 12, 13, and 19%. One-year mortality per CIT quartile was 16, 19, 21, and 28%. CIT was an independent predictor of 1-month mortality, but only in the last quartile of CIT >246 min (odds ratio 2.1, 95% confidence interval 1.49-3.08, p < .001). We found no relevant differences in CIT during the study period. However, the impact of CIT in 1-month and 1-year mortality decreased with time (p value for the distribution of ischemic time by year 0.01), particularly during the last 5 years. Conclusions: Although the impact of CIT in HT prognosis seems to be decreasing in the last years, CIT in the last quartile (> 246 min) is associated with 1-month and 1-year mortality. Our findings suggest the need to limit HT with CIT N> 246 min or to use different myocardial preservation systems if the expected CIT is> 4 h.

Determining optimal donor heart ischemic times in adult cardiac transplantation

“…Clinical experience and supporting observational studies have designated an IT of less than approximately 4 h as the threshold for optimizing donor heart function and outcomes. [5][6][7][8] Extending beyond 4 h IT is notable for increased risk for PGD, an important driver for post-transplant mortality. 1,2 The increased magnitude of inflammation, cell death, and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation beyond the 4 h preservation threshold was also supported by previous studies in human donor hearts by our group.…”

“…4 Based on surgical experience and impressions from decades of heart transplant experience, an IT of less than 4 h is widely accepted as a threshold for optimal transplant outcomes. [5][6][7][8] Based on this time-honored 4-h threshold, we previously reported that O blood type donor hearts were associated with poorer survival when ITs are prolonged. 9 Jawitz et al 10 also found that donor O blood type was associated with decreased graft survival when compared with other blood types.…”

Risk factors for heart transplant survival with greater than 5 h of donor heart ischemic time

“…However, the large majority of donor hearts are currently preserved with traditional hypothermic mechanical arrest. Achieving donor heart perfusion within 4–5 h following cold preservation is recommended guideline by multiple prior studies 7 . Therefore a 5 h storage time cutoff for this study would be generally accepted to be prolonged.…”

“…Achieving donor heart perfusion within 4-5 h following cold preservation is recommended guideline by multiple prior studies. 7 Therefore a 5 h storage time cutoff for this study would be generally accepted to be prolonged. Despite this, there are likely factors that further modulate this risk when considering the use of donor hearts exposed to more prolonged preservation times.…”

The right time for ischemic time?

“…2,3 Through clinical experience and analysis, the general convention has been that up to 4 h of ischemia time can be tolerated. [4][5][6][7] Ischemic times beyond this threshold have largely been associated with worsened clinical outcomes. 8,9 In that regard, Tang et al are to be commended on this analysis and for being willing to report an outcome that would go against the established norm.…”