• Daniel Diaz-Gil, Natalia Silva-Gomez, Sarah U Morton, Jonathan G Seidman, Christine E Seidman, David Zurakowski, Steven J Staffa, Gerald R Marx, Sitaram M Emani, Pedro J Del Nido, and Ingeborg Friehs.
• Department of Cardiac Surgery, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass; Department of Pediatrics, Boston University Chobanian & Avedisian School of Medicine, Boston, Mass; Department of Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
• J. Thorac. Cardiovasc. Surg. 2024 Aug 27.

BackgroundEndocardial fibroelastosis (EFE) is a major effector in the maldevelopment of the heart in patients with congenital heart disease. Despite successful surgical removal, EFE can redevelop, but the underlying cause of EFE recurrence remains unknown. This study aimed to identify hemodynamic predictors and genetic links to epithelial/endothelial-to-mesenchymal transition (EMT/EndMT) alterations for preoperative risk assessment.MethodsWe assessed the impact of preoperative hemodynamic parameters on EFE recurrence in a cohort of 92 patients with congenital heart disease who underwent left ventricular (LV) EFE resection between January 2010 and March 2021. Additionally, whole-exome sequencing in 18 patients was used to identify rare variants (minor allele frequency <10-5) in high-expression heart (HHE) genes related to cardiac EMT/EndMT and congenital heart disease.ResultsEFE recurred in 55.4% of patients, within a median of 2.2 years postsurgery. Multivariable analysis revealed specific hemodynamic parameters (mitral valve inflow and area, LV filling pressure, and aortic valve gradient and diameter) as predictors, forming a predictive model with an area under the receiver operating characteristic curve of 0.782. Furthermore, 89% of the patients exhibited damaging variants in HHE genes, with 38% linked to cardiac EMT/EndMT Gene Ontology processes and 22% associated with known congenital heart disease genes. Notably, HHE genes associated with cardiac EMT/EndMT were significantly associated with faster EFE recurrence in a multivariate analysis (hazard ratio, 3.56; 95% confidence interval, 1.24-10.17; P = .018).ConclusionsThese findings established a predictive scoring system using preoperative hemodynamic parameters for EFE recurrence risk assessment. Alterations in HHE genes, particularly those linked to cardiac EMT/EndMT, exacerbate the risk of recurrence.Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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