Progression of cardiac allograft vasculopathy in heart recipients with donor-transmitted coronary atherosclerosis

Introduction: Cardiac allograft vasculopathy (CAV) significantly limits graft survival. Understanding how immune and atherogenic factors influence the timing of CAV is crucial for timely therapy adjustments and better prognosis. Currently, there are no large single-center studies examining CAV progression in recipients with different baseline coronary conditions after heart transplantation (HT).
Aim: To assess the time to development of CAV in recipients with donor-transmitted coronary atherosclerosis (DTA) compared with recipients who initially had native coronary arteries.
Materials and methods: This study analyzed 1,001 heart transplant recipients aged 10–78 years (median 49[38–57]) who underwent HT from 2009 to 2020. Excluding in-hospital deaths. The majority were male (85.6%); hypertension (46.9%), dyslipidemia (39.6%), and diabetes (21.6%) were present. All recipients underwent invasive coronary angiography (iCA) early postoperative period to assess baseline coronary status, followed by annual iCA screening. Immune and atherogenic factors, recipient and donor data were analyzed.
Results: Based on the results of the first iCA, 70.3% (n=704) of recipients had no angiographic signs of coronary artery disease (CAD), while the remaining subjects showed signs of DTA. In 17% (n=180) of recipients, angiography revealed mild signs of cardiac allograft CAD (lesions <70%). Significant CAD (lesions >70%) was detected in 11.7% (n=117) of recipients. Recipients were divided into two groups: Group I (CAV 0) n=704, consisted of recipients with no angiographic signs of CAD, and Group II (DTA) n=180 composed of patients with angiographic signs of CAD (lesions <70%). In Group I, progression of vasculopathy from grade CAV0 to grades CAV2-3 was detected in 107 (15.2%) patients; in Group II, progression from DTA (lesions <70%) to grades CAV2-3 was in 73 (40.5%) patients. The median time to CAV progression (to grades CAV2-3) in the I group was 5497 days (95% CI: 4447 – ∞), compared to 2503 days (95% CI: 2000 – ∞) in the DTA group. The log-likelihood ratio test was statistically significant (p = 0.001), with a hazard ratio (HR) of 3.469 [95% CI, 2.570 – 4.682]. Using the Cox proportional hazards model, the following predictors of CAV progression were identified in Group I: female sex of recipients (HR = 0.225, 95% CI [0.083 – 0.612], p = 0.003), episodes of decreased LV EF (HR = 2.18, 95% CI [1.278 – 3.727], p = 0.004), and a combination of acute cellular rejection (ACR) and antibody-mediated rejection (AMR) (HR = 2.74, 95% CI [1.174 – 6.392], p = 0.02). No significant predictors of CAV 2-3 progression were identified in Group II. 

Conclusion: Significant CAV (stage 2–3) progresses twice as rapidly in recipients with DTA, compared to those without it. DTA increased the risk of CAV progression 3.5-fold versus recipients with native coronary arteries. In the I group (CAV0), a history of combined ACR and AMR and reduced LV EF increased CAV progression risk by 2- and 2.7-fold, respectively, while female recipients had a >4-fold lower risk. Female donors reduced CAV risk by a factor of 1.836, and each one-year increase in donor age raised CAV risk by 2.8%.