EARLY DETECTION OF CORONARY ARTERY THICKENING IN PEDIATRIC HEART TRANSPLANT RECIPIENTS USING OPTICAL COHERENCE TOMOGRAPHY

Abstract

Cardiac allograft vasculopathy (CAV) is the leading cause of graft failure and mortality in pediatric heart transplant recipients, characterized by diffuse and concentric coronary intimal thickening. CAV is most successfully treated at mild stages. Thus, early CAV detection is critical because it permits earlier intervention, ultimately prolonging graft and patient longevity. Coronary angiography is the standard for CAV screening and diagnosis; however, it can underestimate disease extent, severity, and prevalence in pediatric patients, and lacks the sensitivity to detect early thickening because early vascular remodeling does not necessarily restrict luminal diameter. In addition, because of cardiac denervation during transplantation, CAV disease progression often occurs silently and may not be discovered until advanced stages. Thus, higher definition imaging modalities are required to identify early vascular changes. Coronary optical coherence tomography (OCT) is a high-definition intravascular imaging technique that may aid early diagnosis. We used OCT to investigate coronary intimal thickening in pediatric transplant recipients and examined its: 1) location (i.e. vessel type and location), and 2) nature (i.e. characteristics of cross-sectional and longitudinal thickening). Coronary angiography and OCT images from pediatric cardiac transplant recipients were collected (N=152 from 73 individuals; median age: 11.5 y (8.4-15.3); 54.1% male). OCT images were collected from the left anterior descending, left circumflex, and right coronary arteries, and classified by location (i.e. proximal, medial, and distal) using coronary angiography. OCT identified significant intimal thickening (intimal thickness >0.25 mm) in 31 pullbacks, 88% of which were angiographically silent. 88% of longitudinal thickening was segmental rather than global. 50% of cross-sectional thickening was eccentric rather than concentric (Figure 1). Thickness severity did not differ between coronary artery type, but intimal thickness was increased proximally (P=0.004). Increased age at transplant was associated with increased intimal thickness (P=0.036), and left circumflex artery thickening (P=0.004). Our study supports the efficacy and feasibility of OCT in detecting otherwise angiographically-silent intimal thickening in pediatric heart transplant patients. Early CAV detection optimizes patient outcomes. Our study also highlights the restricted description of CAV thickening as being strictly global and concentric. We postulate that the eccentric and segmental thickening detectable by OCT may represent pathophysiological processes earlier in the natural history of CAV, though further study is needed to test this hypothesis. In conclusion, OCT offers a safe, high-definition means of detecting coronary vascular changes in pediatric heart transplant recipients that may otherwise be angiographically silent.