Flow disturbances and the development of endocardial fibroelastosis

J Thorac Cardiovasc Surg. 2020 Feb;159(2):637-646. doi: 10.1016/j.jtcvs.2019.08.101. Epub 2019 Sep 26.


Objectives: Endothelial-to-mesenchymal transition (EndMT) has been identified as the underlying mechanism of endocardial fibroelastosis (EFE) formation. The purpose of this study was to determine whether hemodynamic alterations due to valvar defects promote EndMT and whether age-specific structural changes affect ventricular diastolic compliance despite extensive surgical resection of EFE tissue.

Material and methods: We analyzed EFE tissue from 24 patients with hypoplastic left heart syndrome (HLHS) who underwent left ventricular (LV) rehabilitation surgery at Boston Children's Hospital between December 2011 and March 2018. Six patients with flow disturbances across the aortic valve and/or mitral valve but no HLHS diagnosis and macroscopic appearance of "EFE-like tissue" in the LV were included for comparison. All samples were examined for amount of collagen/elastin production and degradation, and presence of active EndMT by histologic analysis.

Results: EFE tissue from patients with and without HLHS consisted predominantly of elastin and collagen fibers. There was no alteration in degradation activity for collagen or elastin as shown by in situ zymography. Active EndMT was found in all patients with and without HLHS with flow disturbances ("EFE-like"). In patients with HLHS, EFE infiltrated into the underlying myocardium with increasing age.

Conclusions: Patients with and without HLHS with flow disturbances due to stenotic or incompetent valves develop EndMT-derived fibrotic tissue covering the LV. When EFE recurs, it is directly associated with flow disturbances and switches to an infiltrative growth pattern with increasing age, leading to increased diastolic stiffness of the LV.

Keywords: endocardial fibroelastosis; endothelial-to-mesenchymal transition; hypoplastic left heart syndrome.

MeSH terms

  • Cardiac Surgical Procedures
  • Child
  • Child, Preschool
  • Cohort Studies
  • Collagen / metabolism
  • Elastin / metabolism
  • Endocardial Fibroelastosis* / etiology
  • Endocardial Fibroelastosis* / pathology
  • Endocardial Fibroelastosis* / physiopathology
  • Heart Ventricles / chemistry
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Heart Ventricles / surgery
  • Hemodynamics / physiology
  • Humans
  • Hypoplastic Left Heart Syndrome* / complications
  • Hypoplastic Left Heart Syndrome* / physiopathology
  • Hypoplastic Left Heart Syndrome* / surgery
  • Infant


  • Collagen
  • Elastin