Noncardiac Predictors of Cardiac Allograft Vasculopathy following Pediatric Heart Transplantation

Background: Cardiac allograft vasculopathy (CAV) is an important predictor of outcome in patients following pediatric heart transplantation (pHTX). It is standard of care at most pediatric heart transplant centers to perform regular coronary angiograms to detect early coronary artery changes and adjust medical management accordingly. Recently, optical coherence tomography (OCT) imaging has been suggested as a more sensitive marker of CAV. It was the aim of this study to characterize systemic arterial characteristics in patients following pHTX with or without angiographic or OCT evidence of CAV.

Method: Prospective cohort study comparing pHTX patients with evidence of CAV (CAV-HTX) based on angiography (ISHLT grade ≥1) and/or OCT (grade ≥2) to pHTX patients without CAV (Control-HTX). Descriptive variables including comorbidities such as chronic kidney disease (CKD) were documented. Common carotid intima media thickness (cIMT) was analyzed with ultrasound. Central blood pressure, central augmentation index corrected to a heart rate of 75/minute (cAIx75) and carotid-femoral pulse wave velocity (PWV) were measured (SpygmoCor XCEL). Reactive hyperemia index (RHI) as a measure of endothelial function and peripheral AIx75 (pAIx75) were determined (EndoPAT). Retinal vessels were assessed by arteriolar-to-venular ratio (AVR; iMedos). Data are expressed as mean ± standard deviation; groups compared using the Student t-test, linear and logistic regression analyses.

Results: Twenty patients were included in group CAV-HTX, 19 in group Control-HTX. CAV-HTX patients were significantly older (21 ± 7 vs. 15 ± 7 years, p = 0.006) and had undergone pHTX earlier than controls (16 ± 8 vs 10±6, p=0.014), but were transplanted at similar age (7 ± 7 vs. 6 ± 6, p = 0.714). CKD was significantly associated with CAV (OR: 10, p = 0.004), and there was a trend towards an association with diabetes (p = 0.119). Following correction for age and sex, there was no significant difference in weight, heart rate, brachial and central blood pressure as well as PWV (p = 0.490), pAIx75 (p = 0.366), RHI (B = 0.4, p = 0.082), and AVR (p = 0.970). However, IMT (B = 0.03, p = 0.041) was significantly thicker in the CAV-HTX group, while cAIx75 was lower (B = −9, p = 0.026).

Conclusion: CAV following pHTX in our cohort is associated with IMT thickening and CKD. We suggest that these markers be followed closely in pHTX patients. Surprisingly, cAIx75—describing relative pulse wave reflection—was decreased in group CAV-HTX in spite of similar blood pressure. This could be related to confounders not analyzed herein.

Publication History

Article published online:
28 January 2023