Early Incidence of Cardiac Allograft Vasculopathy in Donation After Circulatory Death Heart Transplantation in the United States

S. Bakhtiyar¹, S. Sakowitz², S. Mallick³, P. Benharash^4
1University of Colorado, Aurora, Colorado ²UCLA David Geffen School of Medicine, Los Angeles, California ³UCLA, Los Angeles, California ⁴UCLA Division of Cardiac Surgery, Los Angeles, California

Purpose: Utilization of donation after circulatory death(DCD) heart transplantation(HT) has dramatically expanded, with survival comparable to donation after brain death/standard recovery(DBD/SR). Importantly, cardiac allograft vasculopathy(CAV) remains a leading cause of post-HT morbidity. Therefore, as the US experience with DCD HT increases, it is crucial to analyze its incidence among DCD recipients[1-3].

Methods: We utilized the Organ Procurement and Transplantation Network to tabulate adult (≥18years) HT recipients between December 2019 and April 2024, who received either DCD or DBD/SR allografts. Using the time duration from circulatory death to cross-clamp, we further stratified DCD recipients by procurement approach, into the Direct Procurement (DCD/DP) and Thoracoabdominal Normothermic Regional Perfusion (DCD/TA-NRP) subgroups.

The primary outcome of interest was the incidence of CAV within three-years following transplantation. Records with any evidence of angiographic coronary disease, as reported by individual transplant centers, were considered to have CAV. We secondarily considered whether transplantation and associated care at high-volume HT centers (HVC) (N=38/150, ≥27 transplants/year) may influence likelihood of CAV.

Kaplan-Meier estimates and Cox proportional hazard models were utilized to assess CAV-free survival, with outcomes reported as Hazard Ratios[HR] with 95% Confidence Intervals[CI]. To create balanced groups for comparison, we used entropy balancing.

Results: Of 17,462 transplants, 16,240 (93%) utilized DBD/SR allografts, 804 (5%) DCD/DP, and 418 (2%) DCD/TA-NRP. The overall incidence of CAV was 10% for the DBD/SR group, 11% for DCD/DP, and 12% for DCD/TA-NRP.

Following comprehensive risk-adjustment, DCD allografts demonstrated greater hazard of CAV over three-years of follow-up, relative to DBD/SR (HR 1.53, CI 1.15-2.03). Upon stratification by procurement approach, DCD/TA-NRP was linked with greater likelihood of CAV (HR 1.79, CI 1.18-2.74). However, DCD/DP was associated with comparable CAV hazard as DBD/SR (HR 1.38, CI 0.96-1.98).

A sensitivity analysis using entropy balancing demonstrated comparable findings, such that DCD/TA-NRP was associated with increased relative risk of CAV (HR 1.84, CI 1.19-2.86), but DCD/DP faced similar likelihood as DBD/SR (HR 1.15, CI 0.76-1.74). Upon conditional analysis of recipients who survived the first post-transplant year, DCD/TA-NRP remained independently linked with greater CAV hazard (HR 1.84, CI 1.20-2.80). Finally, considering only recipients at HVC, DCD/TA-NRP was significantly associated with increased CAV (HR 2.01, CI 1.31-3.10; Reference: DBD/SR).

Other factors linked with increased CAV risk including recipient male sex (HR 1.41, CI 1.19-1.67), Hispanic ethnicity (HR 1.33, CI 1.11-1.60), pre-transplant intra-aortic balloon pump dependence (HR 1.31, CI 1.11-1.55), and donor male sex (HR 1.36, CI 1.16-1.60).

Conclusion: In this first national analysis of CAV among DCD HT recipients, we found greater CAV risk among DCD/TA-NRP, but not DCD/DP-procured allografts. As the DCD landscape continues to evolve, our findings call for further study of factors within DCD/TA-NRP procurement that contribute to this added chronic vasculopathy and rejection risk.

Identify the source of the funding for this research project: None