Biomarker profiles of favorable ventricular remodeling in heart failure patients with reduced ejection fraction: Insights from the echocardiographic substudy of the VICTORIA trial
Bibliographic record
Abstract
Abstract Background Favorable ventricular remodeling, defined as a decrease in left ventricular end-systolic volume indexed (LVESVI) to body surface area or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Because the underlying biomarker correlates remain unclear, we investigated circulating biomarker profiles and their relationship to ventricular remodeling. Methods We studied 419 high-risk patients with worsening HFrEF from the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial with core-lab assessed echocardiograms and measurements of 92 biomarkers (Olink CVD III panel). Biomarkers were measured in plasma using proximity extension assays and conventional ELISAs. Paired biomarkers (in 306 patients) and echocardiographic measurements (in 419 patients) were available at baseline and 8 months post-randomization. We evaluated the association of biomarkers at baseline and their temporal changes with favorable cardiac remodeling. Favorable remodeling was prespecified as a 5% LVEF absolute increase or 15% LVESVI relative decrease between baseline and 8 months. Reported p-values for protein changes are adjusted for the false discovery rate (FDR) at 0.05 to account for multiple comparisons. Results Of 419 patients (median age 66 [interquartile range 57-74] years, 27.4% women), 206 (49.2%) had favorable remodeling and 213 (50.8%) did not. Patients with favorable remodeling had a lower median body mass index (26.5 vs 28.3 kg/m2, P = 0.010), lower prevalence of diabetes (36.4% vs 47.4%, P = 0.022) and coronary artery disease (39.3% vs 62.0%, P<0.001). After correcting for multiple testing, no baseline biomarker levels differed between patients with and without favorable remodeling. Between baseline and 8 months, however, there was a significant decrease in biomarkers relating to inflammation and cardiac metabolism with favorable remodeling compared with those without (Figure). Particularly NT-proBNP (ratio 0.46, 95%confidence interval [CI] 0.38-0.57), TNF Superfamily Member 13b (ratio 0.85, 95%CI 0.80-0.91), growth differentiation factor-15 (ratio 0.76, 95%CI 0.68-0.84), cathepsin D (ratio 0.88, 95%CI 0.82-0.94), and insulin growth factor binding protein 7 (ratio 0.81, 95%CI 0.74-0.88) showed a significantly larger decrease in those with than those without favorable remodeling (Figure and Table). Conclusion Our results suggest favorable cardiac remodeling occurs in half of high-risk HFrEF with recent worsening. We provide new insights into the clinical phenoype and associated inflammatory and cardiac metabolism changes. These findings may help identify potential treatment targets for future drug discovery.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".