Association of clonal hematopoesis and autonomic dysfunction with cardiovacular outcomes in atrial fibrillation
Bibliographic record
Abstract
Abstract Introduction Individuals carrying clonal hematopoiesis of indeterminate potential (CHIP) mutations have an increased risk of cardiovascular disease. Similarly, cardiac autonomic dysfunction is strongly associated with poor prognosis. Purpose This study aimed to investigate the association between CHIP, autonomic dysfunction, and major adverse cardiovascular events (MACE) in patients with atrial fibrillation (AF). Methods We included patients from the ongoing Swiss-AF cohort study with targeted sequencing for CHIP-related mutations and a digital high-resolution 16-lead resting ECG recording (5-minute duration) for cardiac autonomic function assessment. Deep-targeted sequencing of a panel of 96 CHIP mutations was performed at baseline. Cardiac autonomic function was quantified using periodic repolarization dynamics and dichotomized at 7.5 deg, as previously validated. Multivariable adjusted Cox proportional hazard models were used to investigate the association between CHIP status and autonomic dysfunction with MACE (composite of death, myocardial infarction, stroke/TIA, heart failure or major bleeding). Results A total of 1,511 patients (mean age 73±8.5 years, 28% women) were included, with a mean follow-up of 6.1 years. MACE rate was 52.5% in CHIP carriers, 54.1% in patients with autonomic dysfunction, 64% in CHIP carriers with autonomic dysfunction and 36.2% in patients without CHIP and without autonomic dysfunction. In the age- and sex-adjusted model, patients with CHIP had an increased risk of MACE (hazard ratio [HR] 1.11 (95% CI 0.93–1.32, p=0.257), as well as patients with autonomic dysfunction (HR 1.40 (95% CI 1.19–1.65, p<0.001) and CHIP carriers with autonomic dysfunction (HR 1.40 (95% CI 1.06–1.85, p=0.002). After multivariable adjustment, only autonomic dysfunction remained significantly associated with MACE (HR 1.28, 95% CI 1.09–1.51, p=0.003). Conclusion In this prospective cohort of patients with AF, CHIP carriers with autonomic dysfunction had the worst prognosis. These findings underscore the prognostic relevance of autonomic function and CHIP mutations in cardiovascular risk assessment in AF.
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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 | 0.001 |
| 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) | 0.002 | 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".