Predictive Modeling of Endocardial Fibroelastosis Recurrence in Patients with Congenital Heart Disease.

OBJECTIVE: Endocardial 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.

HYPOTHESIS: This study aimed to identify hemodynamic predictors and genetic links to epithelial/endothelial-to-mesenchymal transition (EMT/EndMT) alterations for preoperative risk assessment.

METHODS: We 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 genes (HHE) related to cardiac EMT/EndMT and congenital heart disease.

RESULTS: EFE recurred in 55.4% of patients, within a medium 2.2 years post-surgery. 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 AUC of 0.782. Furthermore, 89% of the patients exhibited damaging variants in HHE, with 38% linked to cardiac EMT/EndMT GO processes and 22% associated with known CHD genes. Notably, HHE genes associated with cardiac EMT/EndMT were significantly associated with faster EFE recurrence in multivariate analysis (HR 3.56, 95% CI 1.24-10.17, p=0.018).

CONCLUSIONS: These 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.