Abstract 4138528: Clinical Characteristics of Five Different Endotypes from Coronary Reactivity Testing, and the Emergence of Sex Patterns in Coronary Microvascular Dysfunction
Bibliographic record
Abstract
Background: The common preconception is that non-obstructive coronary artery disease(NOCAD) predominantly affects females with little to no cardiac risk factors. However, it is unclear whether there is a significant difference in baseline characteristics between those with a positive vs negative coronary reactivity testing(CRT) result. Furthermore, CRT explores multiple pathophysiological mechanisms which make a positive result nuanced. This study identifies 5 different endotypes based on CRT results, aiming to identify phenotypic characteristics that correlate with these endotypes. METHODS: 409 patients were included in a cohort study, representing all patients referred for CRT to a tertiary referral centre for NOCAD, between 2016-2024. Patients underwent protocol CRT of coronary flow reserve(CFR) and index of microvascular resistance(IMR) measurements following adenosine infusion(140mcg/kg/min) and bolus acetylcholine(100mcg). Results were compared by positive vs negative CRT, normal vs abnormal CFR/IMR, and by 5 different endotypes identified from CRT result combinations. RESULTS: There was no significant difference in clinical characteristics between the positive vs negative CRT result groups. However, with further stratification, there were significant sex differences and cardiac risk profile differences in CFR and IMR results. There was a greater proportion of females in the abnormal (low) CFR group(p<0.001), and higher burden of cardiac risk factors in the abnormal (high) IMR group(p<0.001). The highest burden of cardiac risk factors was seen in the 'Traditional Coronary Microvascular Dysfunction (CMD)' endotype, defined as those with abnormal(low) CFR and abnormal(high) IMR. The 'Functional CMD' endotype was characterised by younger females, whilst the 'Compensated CMD' and 'Coronary spasm' endotype showed no sex difference. The normal CFR and normal IMR endotype reflected the referred population(Figure 1). CONCLUSION: There is an emergence of clinical phenotypes according to the five coronary reactivity testing endotypes. Lower CFR appears to be a more “female pattern” of microvascular dysfunction. Endotypes reflect underlying pathology and may provide mechanistic explanations for sex differences in the microvascular dysfunction types of NOCAD, whilst explaining the lack of sex differences in other types. Further detailed understanding of CRT endotypes will allow us to understand the mechanistic differences in cardiovascular outcomes between males and females.
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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) | 0.003 | 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".