AUTHOR=Nilkant Riya , Choi Perry S. , Mullis Danielle M. , Chang Robin , Sharir Amit , Reddy Sushma , Pelletier Glenn J. , Ma Michael TITLE=Histologic changes in systemically loaded right ventricles at time of transplantation JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1640561 DOI=10.3389/fcvm.2025.1640561 ISSN=2297-055X ABSTRACT=IntroductionIn a subset of complex congenital heart disease patients, the right ventricle (RV) is connected to the higher-resistance systemic circulation, often leading to RV dysfunction. This study characterizes the systemic RV histology at time of heart transplantation in two groups — patients with hypoplastic left heart syndrome with Fontan palliation (HLHS-F) and those with dextro-transposition of the great arteries post atrial switch operation (d-TGA-AS). We sought to better understand histological differences between the systemic RV in the single ventricle vs. biventricular circulations.MethodsWe procured RV tissue samples at the mid-cavity free walls from nine explanted recipient hearts: six HLHS-F and three d-TGA-AS. RV and LV muscle samples from two organ donors whose hearts were unused for non-cardiac reasons served as controls. Tissue sections were stained with Masson's Trichrome and Hematoxylin and Eosin. Given the small cohort size and heterogeneity, analyses were descriptive. Continuous variables are reported as median (range).ResultsThe d-TGA-AS population was older than the HLHS-F population (median: 42 years; range: 38–44 vs. median: 24 years; range: 12–32, respectively). RV fibrosis in the d-TGA-AS population was greater at 28% (7–35) vs. the HLHS-F population which was 4% (2–24) and donor controls (median: 2% range: 0–4). In contrast, RV wall thickness was greater in HLHS-F (median: 12,303 µm; range: 9,976–15,745) than in d-TGA-AS (median: 9,063 µm; range: 8,316–10,322) and donors (median 7,984 µm; range: 2,582–13,386). Donor LV thickness (median: 17,056 µm; range: 16,688–17,423) exceeded all RV groups.ConclusionThe primary histologic finding for the d-TGA-AS group was fibrosis, while the HLHS-F group showed predominantly hypertrophy. The temporal presentation of the patients was different, with the HLHS-F patients presenting earlier for transplant than the d-TGA-AS. These observations suggest that different histologic changes may occur in response to longstanding systemic pressures in these two anatomic subgroups of patients with systemic RV.