Gene expression analysis of primary graft dysfunction in adult heart transplant recipients: A cohort study

Gene expression analysis of primary graft dysfunction in adult heart transplant recipients: A cohort study

Background: Cardiac transplantation remains the primary treatment for advanced heart failure, with primary graft dysfunction (PGD) being the leading cause of early mortality. While PGD’s exact pathogenesis is unclear, ischemia/reperfusion injury is a key factor. Donor hearts undergo multiple stresse...

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Main Authors: Samuel Padovani Steffen, MD, Alvaro Monteiro Perazzo, MD, MSc, Shirlyne Fabianni Dias Gaspar, MD, Ronaldo Honorato Barros Santos, MD, Domingos Dias Lourenço Filho, MD, PhD, Alexandre da Costa Pereira, MD, PhD, Luis Fernando B. da Costa Seguro, MD, PhD, Fabiana G. Marcondes-Braga, MD, PhD, Fernando Bacal, MD, PhD, Jose Eduardo Krieger, MD, PhD, Fabio Antonio Gaiotto, MD, PhD, Fabio Biscegli Jatene, MD, PhD
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:JHLT Open
Subjects:
heart transplantation
primary graft dysfunction
gene expression
transcriptomics
MYL4
Online Access:http://www.sciencedirect.com/science/article/pii/S2950133425000102
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Summary:Background: Cardiac transplantation remains the primary treatment for advanced heart failure, with primary graft dysfunction (PGD) being the leading cause of early mortality. While PGD’s exact pathogenesis is unclear, ischemia/reperfusion injury is a key factor. Donor hearts undergo multiple stresses, such as brain death, hypothermia, and ischemia, contributing to PGD and reduced graft survival. Many centers are studying PGD’s pathophysiology through epidemiological, biomarker, and transcriptome analyses. This study aims to evaluate, via transcriptomic analysis of myocardial biopsies, the gene expression profile of patients with PGD and compare it with those without PGD. Methods: Adult heart transplant patients were included in the study after signing the Informed Consent. The diagnosis of PGD followed the International Society for Heart and Lung Transplant criteria. Clinical and laboratory data from donors and recipients were evaluated. We included 20 consecutive heart transplant patients in the protocol. Gene expression analysis was performed via biopsies at donor heart implantation. Results: Eleven genes had their expression significantly different in patients with PGD, with MYL4 the less expressed gene, and related to the myosin function and the gene B3GALT 5 the most expressed one and associated with the inflammatory response. Conclusions: The gene expression in patients with PGD is different when compared to patients without PGD. MYL4 gene was much less expressed in these patients and B3GALT5 was overexpressed. Future studies regarding gene expression on PGD may clarify the pathophysiology and provide possible biomarkers of the disease.
ISSN:2950-1334

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