Hypoxia inducible factor (HIF1A) is associated with increased right ventricular fibrosis by T1 mapping cardiac magnetic resonance in patients with repaired tetralogy of Fallot
Bibliographic record
Abstract
Abstract Background Right ventricular fibrotic remodeling has been identified pre- and postoperatively in patients with tetralogy of Fallot (ToF) and linked to adverse outcomes. Polymorphisms of hypoxia inducible factor-1-alpha (HIF1α) have been associated with fibrotic burden by cardiac magnetic resonance (CMR) late gadolinium enhancement imaging. Their association with diffuse fibrotic myocardial remodeling is unknown. Purpose We sought to determine whether polymorphisms in hypoxia inducible factor (HIF1α) are related to CMR markers of diffuse myocardial fibrosis in pediatric patients with repaired ToF. Methods Patients with repaired ToF who had undergone CMR with T1 mapping as well as whole genome sequencing were included. Myocardial native T1 was quantified using a modified Look-Locker inversion recovery sequence and measured in the left ventricular free wall, the interventricular septum, and the right ventricular free wall. Patients who had at least one functioning allele of HIF1α were compared to those who did not using Mann Whitney U test for continuous variables and chi-square or Fischer test for discrete variables. Data are displayed in Table 1 as median (IQR) for continuous variables and frequency (percentage) for discrete variables. Results 46 patients had both CMR and whole genome sequencing. Only one HIF1α variant was identified in the cohort and present in 13 patients. There were no significant differences in demographics, surgical variables, right or left ventricular volumes or function between the groups (Table 1). Despite a trend towards a lower age at the time of CMR (11.3 vs 13.7 years; p=0.07), patients with HIF1α had higher native T1 values (1094 vs. 1050; p=0.027; Table 1) in the right ventricular outflow tract myocardium, reflecting increased diffuse interstitial ventricular fibrosis in patients with the HIF1α variant. Conclusion Hypoxia-inducible factor is associated with imaging markers of increased diffuse right ventricular fibrosis late after repair of tetralogy of Fallot. Funding Acknowledgement Type of funding sources: None. Table 1
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".