Abstract 12698: Myocardial Infiltration of the Epicardial Adipose Tissue in Human Heart Failure
Bibliographic record
Abstract
Introduction: The epicardial adipose tissue (EAT) is adipose tissue that is contiguous with the myocardium without barrier. However, there is a fundamental gap in knowledge for the EAT’s role in health and disease. Methods: We employed single-nucleus RNA sequencing (snRNAseq) and molecular techniques to phenotype human EAT procured from patients with heart failure (HF) secondary to dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). EAT was harvested from the right and left ventricles (RV and LV) of 10 healthy control (CTRL) donors ((median age: 54.0 (interquartile range [IQR]: 49.0-57.9) years; 5 [50.0%] males; median BMI: 25.0 ([IQR]: 24.5-28.2) kg/m 2 ), 32 DCM patients ((median age: 55.0 (interquartile range [IQR]: 48.0-60.7) years; 16 [50.0%] males; median BMI: 26.1 ([IQR]: 23.0-30.3) kg/m 2 ) and 22 IHD patients ((median age: 57.5 (interquartile range [IQR]: 52.5-64.5) years; 13 [59.1%] males; median BMI: 27.2 ([IQR]: 25.1-30.7) kg/m 2 ). HF patients were age (p=0.668 (DCM); p=0.172 (IHD)), sex (p>0.999 (DCM); p=0.712 (IHD)), and BMI (p=0.711 (DCM); p=0.515 (IHD)) matched to CTRL. Results: There was a significant expansion of EAT over the LV (mean EAT thickness in CTRL: 1.11mm, DCM: 2.75mm (p=0.002) and IHD: 3.31mm (p<0.001)) and the RV (mean EAT thickness in CTRL: 2.24mm, DCM: 5.57mm (p=0.029) and IHD: 5.11mm (p=0.065)) in HF. There was only a regional expansion of EAT over the LV of IHD patients. Data were analyzed using one-way ANOVA with Tukey’s post hoc test. Histological staining revealed myocardial EAT infiltration in HF, which was absent in CTRL. Nuclei isolated from EAT and adjacent myocardium were then subjected to snRNAseq. The transcriptional signature of HF intramyocardial adipocytes closely resembled unique cell states and gene expression identified in the EAT, suggesting infiltration by the EAT. By contrast, myocardial adipocytes in CTRL tissue were distinct from the EAT. The adipocytes in the interventricular septum, which lacks contiguous EAT, were similar in HF and CTRL. Conclusion: The proximity of the EAT confers a unique position to directly modulate the myocardium. As such, targeting pathogenic EAT expansion and infiltration may be critical to the development of novel therapeutic strategies in HF patients.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.003 | 0.001 |
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".