Endotypes of angina with non-obstructive coronary arteries: a prospective multicentre study
Bibliographic record
Abstract
BACKGROUND AND AIMS: Angina with non-obstructive coronary arteries (ANOCA) is a prevalent myocardial ischaemic syndrome, and women are disproportionately affected. Mechanisms of ischaemia are challenging to diagnose and treatment is empirical. METHODS: Consecutive patients with angina (or equivalent symptoms), no angiographically severe stenosis and fractional flow reserve > 0.80 undergoing coronary functional testing were prospectively enrolled in nine centres in Europe and North America. Haemodynamic endotypes were assessed measuring coronary flow reserve and resistance using an intracoronary pressure- and temperature-sensitive sensor and bolus thermodilution. Measurements were obtained during resting conditions and following adenosine and acetylcholine. Chest pain and electrocardiographic ischaemic changes were recorded. The participant characteristics of each haemodynamic endotype were investigated using regression analysis. A three-step Delphi consensus method was applied to identify endotype-specific therapies. RESULTS: Overall, 1001 participants (mean age 62 ± 11years, 56% female) were enrolled and eight distinct endotypes were defined by adenosine testing (n = 3) and acetylcholine testing (n = 5), respectively: high resting coronary blood flow (n = 195, 19%); high resistance (n = 125, 13%); compensated high resistance (n = 112, 11%); epicardial coronary spasm (n = 162, 17%); microvascular spasm (n = 75, 8%); endothelial dysfunction (n = 96, 10%); ischaemia w/o haemodynamic changes (n = 68, 7%); and enhanced cardiac nociception (n = 79, 8%). More than one endotype occurred in 119 (12%) individuals and normal responses occurred in 234 (23%) individuals. Each endotype was associated with distinct clinical correlates. The Delphi consensus (100% 'agree' or 'strongly agree') identified endotype-specific medical therapy with a Likert scale score ≥ 6 for all endotypes. CONCLUSIONS: In patients with suspected ANOCA, assessment of the symptomatic, electrocardiographic, and haemodynamic responses to adenosine and acetylcholine identifies distinct endotypes and enables mechanism-guided stratified medicine.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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".