Elevated Filling Pressures and Graft Loss after Pediatric Heart Transplantation

Background: Coronary allograft vasculopathy (CAV) is a leading cause of late graft loss after pediatric heart transplantation (HTx). Even in the absence of epicardial CAV, pathological changes in the microvasculature characterized by restrictive physiology (RP) are present. We aim to assess whether RP is associated with a higher risk of graft loss and future cardiovascular (CV) adverse outcomes after pediatric HTx.

Methods: We screened 193 patients under the age of 18 years who underwent initial or re-transplantation (ReHTx) at DHZC (1986–2020). We included 153 patients with 159 grafts with at least one cardiac catheterization (baseline) with measured filling pressures and coronary angiography performed at least 6 months after initial and ReHTx. RP was defined as the presence of pulmonary capillary wedge pressure (PCWP) of ≥15 mm Hg and/or right atrial pressure (RAP) of >12 mm Hg. ReHTx-free survival was compared between RP and non-RP grafts using Kaplan–Meier curves and Cox regression analysis. CV outcomes were also assessed between the two groups. Epicardial CAV and acute rejection were classified according to ISHLT 2010 and 2004 guidelines, respectively.

Results: The median age was 9 years (IQR: 3–14) in 159 grafts (152 initial + 7 ReHTx). The median follow-up time was 12 years (IQR: 7–18). At baseline, cardiac catheterization RP was present in 13% (20/159) of grafts and it was associated with poorer ReHTx-free survival compared with the non-RP grafts (log-rank p = 0.004). This poorer survival of RP grafts compared with non-RP grafts is verified based on a Cox proportional hazards model adjusted for age at HTx, transplantation era, and CAV2–3, indicating grafts with moderate or severe CAV (hazard ratio 2.2; 95% CI 1.04–4.1; p = 0.018). In addition, CV adverse outcomes such as CAV2–3 and cardiac arrhythmias occurred in 45% (9/20) of grafts with RP at baseline cardiac catheterization versus 36% (50/139) of non-RP grafts.

Conclusion: The presence of restrictive physiology is associated with poorer graft survival after pediatric HTx. These findings highlight the importance of frequent invasive filling pressure surveillance to assess graft function, which may improve long-term graft survival after pediatric HTx.

Publication History

Article published online:
11 February 2025