Coronary Flow Reserve Predicts Graft Loss in Pediatric Heart Transplant Patients

Cardiac allograft vasculopathy (CAV) is a common cause of graft loss (GL) in heart transplant (HT) patients (pt). Coronary flow reserve (CFR) quantifies coronary microcirculatory function. We aimed to determine the utility of CFR for predicting GL. We reviewed pediatric HT pt at our center with CFR measurements from 1993-2008. Normal CFR was defined as change in coronary flow with adenosine 2 times above the baseline measurement. Pt were grouped based on CFR <2X baseline (abnormal) or ≥2X baseline (normal). GL was defined as repeat-HT or death. Statistical analysis included the Mann-Whitney U and Fisher exact tests for descriptive purposes. Freedom from graft loss was analyzed using the log rank test and multivariable Cox proportional hazards modeling with time varying covariates to account for time to CFR measurement. There were 185 pediatric HT pt and 499 CFR measurements; 62% were male, 70% had a pre-HT diagnosis of congenital heart disease, and median [IQR] age at HT was 0.8 yr [IQR 0.26-7.7]. The cohort mean CFR was 2.9X ± 0.8. CFR was <2X in 21 pt and time from HT to CFR measurement was longer for CFR<2X vs CFR≥2X, 7.03 [3.18-7.69] vs 1.51 yr [1.04-5.24], respectively; p<0.001). There was no difference in the proportion of pt with biopsy proven 2R acute cellular rejection (ACR) between CFR≥2X vs CFR <2X (11 vs 14%, respectively; p=0.71); Only 3/21 pt with CFR<2X had ACR at that time. Incidence of GL was higher for CFR<2X from time of CFR measurement and from time of HT (Figure 1A and 1B, respectively). Cox modeling with time varying covariates showed higher risk of GL for CFR<2X (HR=4.36 95%CI 2.07-9.20) and older age at HT (HR=1.05, CI 1.01-1.08). Abnormal CFR is suggestive of microvascular CAV and can predict risk of GL. CFR may aid in risk stratification, assessing CAV severity, response to CAV-directed medical therapy, and in timing of re-listing for HT.