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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.

Sec. Heart Failure and Transplantation

Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1640561

Histologic changes in systemically loaded right ventricles at time of transplantation

Provisionally accepted
  • 1Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, School of Medicine, Stanford University, Stanford, California, United States
  • 2Division of Cardiology, Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, California, United States
  • 3Division of Adult Cardiac Surgery, Department of Cardiothoracic Surgery, School of Medicine, Stanford University, Stanford, California, United States

The final, formatted version of the article will be published soon.

Introduction In 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. Methods We 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). Results The 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) versus 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: 12303 µm; range: 9976-15745) than in d-TGA-AS (median: 9063 µm; range: 8316-10322) and donors (median 7984 µm; range: 2582-13386). Donor LV thickness (median: 17056 µm; range: 16688–17423) exceeded all RV groups. Conclusion The 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.

Keywords: Systemic right ventricle, Ventricular failure, Heart Transplantation, Histology, Ventricular tissue, Fibrosis

Received: 03 Jun 2025; Accepted: 02 Oct 2025.

Copyright: © 2025 Nilkant, Choi, Mullis, Chang, Sharir, Reddy, Pelletier and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Michael Ma, mma@stanford.edu

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