Differential Effects of Brain Death and Circulatory Death on Myocardial Integrity and Transplant Outcomes.

Abstract

Heart transplantation is the definitive treatment for end-stage heart failure, yet the persistent scarcity of donor organs has necessitated expanded criteria for donor selection, particularly the inclusion of donors after brain death (DBD) and circulatory death (DCD). These two mechanisms of donor death result in distinct pathophysiological alterations that impact myocardial viability, inflammatory activation, and immune recognition. DBD is characterized by a catecholamine surge, hormonal collapse, and systemic inflammation, contributing to endothelial dysfunction and immunologic priming. In contrast, DCD grafts are subjected to warm ischemia and reperfusion injury, elevating the risk of primary graft dysfunction and delayed recovery. These physiological differences may differentially influence graft performance, immunologic rejection, infection risk, and long-term survival. This review presents a detailed analysis of how the cause of donor death influences clinical outcomes in heart transplantation. It explores the mechanistic underpinnings of DBD- and DCD-associated injury, assesses their impact on post-transplant complications, and evaluates emerging strategies such as ex vivo perfusion, donor-derived cell-free DNA monitoring, and gene expression profiling. Additionally, it discusses how donor physiology intersects with recipient characteristics, the selective use of heterotopic transplantation, and evolving approaches in immunosuppression and risk stratification. These insights support the development of precision-guided protocols that integrate donor and recipient profiles to optimize graft utilization and improve outcomes.