Microcirculatory Dysfunction and Its Role in Diagnosing Acute Rejection in Pediatric Heart Transplantation: A Pilot...

Background/Objectives: Acute rejection remains a major challenge in pediatric heart transplantation (HT), with limited tools for early diagnosis. In adult HT recipients, microcirculatory dysfunction, as measured by the index of microcirculatory resistance (IMR), has been identified as a potential biomarker of rejection. However, its role in pediatric populations is largely unexplored. This pilot study aimed to evaluate the association between coronary microcirculatory dysfunction and acute rejection in pediatric heart transplant recipients, as well as its relationship with echocardiographic alterations. Methods: This prospective, single-center study included 10 pediatric HT recipients who underwent routine coronary angiography and endomyocardial biopsy. The IMR, coronary flow reserve (CFR), and fractional flow reserve (FFR) were assessed. Acute rejection was classified as either acute cellular rejection (ACR) or antibody-mediated rejection (AMR) based on ISHLT criteria. Echocardiographic parameters included left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), right ventricular (RV) dysfunction, and diastolic function. Patients were followed for a median of 9.7 months [IQR: 7.0-11.7]. Results: Patients with a history of acute rejection (40%, n = 4) were exclusively found in the IMR ≥ 15 group (66.7%), while no cases were observed in the IMR < 15 group (0%; p = 0.04). During follow-up, only one patient experienced acute rejection, occurring in the IMR ≥ 15 group, although the difference between groups was not statistically significant (p = 0.39). Both LVEF and GLS were worse in patients with IMR ≥ 15 compared to IMR < 15 (62.5% vs. 76.3% and -17.3% vs. -18.8%, respectively), although these differences did not reach statistical significance. No complications were reported during coronary physiology assessment. Conclusions: Microcirculatory dysfunction, as measured by IMR, was significantly associated with a history of acute cellular rejection in pediatric heart transplant recipients. While its predictive value for acute rejection during follow-up remains unclear due to the small sample size, this pilot study highlights the safety and feasibility of coronary physiology assessment in this population. Larger studies are needed to validate these findings and establish pediatric-specific diagnostic thresholds.