Determining optimal donor heart ischemic times in adult cardiac transplantation

Abstract

Objectives: Unsupervised statistical determination of optimal allograft ischemic time (IT) on heart transplant outcomes among ABO donor heart types. Methods:We identified 36,145 heart transplants (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) from the United Network for Organ Sharing database. Continuous and categorical variables were analyzed with parametric and nonparametric testing. Determination of IT cutoffs for survival analysis was performed using Contal and O'Quigley univariable method and Vito Muggeo multivariable segmented modeling.Results: Univariable and multivariable IT threshold determination revealed a cutoff at about 3 h. The hourly increase in survival risk with ≥3 h IT is asymmetrically experienced at the early 90 days (hazard ratio [HR] = 1.29, p < .001) and up to 1-year time point (HR = 1.16, p < .001). Beyond 1 year the risk of prolonged IT is less impactful (HR = 1.04, p = .022). Longer IT was associated with more postoperative complications such as stroke (2.7% vs. 2.3, p = .042), dialysis (11.6% vs. 9.1%, p < .001) and death from primary graft dysfunction (1.8% vs. 1.2%, p < .001). O blood type donor hearts with IT ≥ 3 h has significantly increased hourly mortality risk at 90 days (HR = 1.27, p < .001), 90 days to 1 year (HR = 1.22, p < .001) and >1 year (HR = 1.05, p = .041). For non-O blood types with ≥3 h IT hourly mortality risk was increased at 90 days (HR = 1.33, p < .001), but not at 90 days to 1 year (HR = 1.09, p = .146) nor ≥1 year (HR = 1.08, p = .237). Conclusions:The donor heart IT threshold for survival determined from unbiased statistical modeling occurs at 3 h. With longer preservation times, transplantation with O donor hearts was associated with worse survival.

Extracorporeal Membrane Oxygenation (ECMO) Use in Heart Transplantation

“…PGD which may result from myocardial stunning, leading to inadequate cardiac output which is beyond the capacity of the initial vasoconstrictive response to maintain cardiac afterload. The report of increase in PGD with longer ischemic time supports the second theory [57,58]. A third possibility is autonomic dyssynergia between the denervated cardioaccelerator beta 1 supply to the heart and the vasoconstrictive alpha supply to the vascular system.…”

Left Ventricular Assist Device Outcomes and Strategy 5 Years from Heart Transplant Allocation Score Change

“…14 While an ischemic time of less than four hours is generally accepted as a threshold for optimal heart transplant outcomes, there is data to suggest that survival may be compromised at lower thresholds. 15 Likewise, our multivariate analysis demonstrated increased mortality due to longer ischemic time (Table 4).…”

Heart Transplantation

“…Additionally, in another study, it was observed that grafts from older patients exposed to an ischemic time of less than 120 min had better results compared to younger ones for the same time period [15], and another reported that ischemic time beyond 3 h is associated with increased mortality. Interestingly, there appeared to be greater vulnerability for grafts from blood group O donors compared to the others [16]. Finally, there is preliminary data on the use of special devices where ex vivo non-ischemic heart preservation is carried out to reduce the negative effects of the heart outside the body with very encouraging results [17].…”