Genetic variants of HIF1α are associated with right ventricular fibrotic load in repaired tetralogy of Fallot patients: A cardiovascular magnetic resonance study

Thanh T. Hoang, Paulo Henrique Manso, Sharon Edman, Laura Mercer-Rosa, Laura E. Mitchell, Anshuman Sewda, Michael D. Swartz, Mark A. Fogel, A. J. Agopian, Elizabeth Goldmuntz

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Studies suggest that right ventricular (RV) fibrosis is associated with RV remodeling and long-term outcomes in patients with tetralogy of Fallot (TOF). Pre-operative hypoxia may increase expression of hypoxia inducible factor-1-alpha (HIF1α) and promote transforming growth factor β1 (TGFβ1)-mediated fibrosis. We hypothesized that there would be associations between: (1) RV fibrosis and RV function, (2) HIF1α variants and RV fibrosis, and (3) HIF1α variants and RV function among post-surgical TOF cases. Methods: We retrospectively measured post-surgical fibrotic load (indexed volume and fibrotic score) from 237 TOF cases who had existing cardiovascular magnetic resonance imaging using late gadolinium enhancement (LGE), and indicators of RV remodeling (i.e., ejection fraction [RVEF] and end-diastolic volume indexed [RVEDVI]). Genetic data were available in 125 cases. Analyses were conducted using multivariable linear mixed-effects regression with a random intercept and multivariable generalized Poisson regression with a random intercept. Results: Indexed fibrotic volume and fibrotic score significantly decreased RVEF by 1.6% (p = 0.04) and 0.9% (p = 0.03), respectively. Indexed fibrotic volume and score were not associated with RVEDVI. After adjusting for multiple comparisons, 6 of the 48 HIF1α polymorphisms (representing two unique signals) were associated with fibrotic score. None of the HIF1α polymorphisms were associated with indexed fibrotic volume, RVEDVI, or RVEF. Conclusion: The association of some HIF1α polymorphisms and fibrotic score suggests that HIF1α may modulate the fibrotic response in TOF.

Original languageEnglish
Article number51
JournalJournal of Cardiovascular Magnetic Resonance
Volume21
Issue number1
DOIs
StatePublished - 19 Aug 2019

Keywords

  • Cardiovascular magnetic resonance imaging
  • Fibrosis
  • HIF1α
  • Right ventricular ejection fraction
  • Right ventricular end-diastolic volume
  • Tetralogy of Fallot

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