Wild‐type transthyretin cardiac amyloidosis and aortic stenosis: Can carpal tunnel syndrome help distinguish the chicken from the egg?
Bibliographic record
Abstract
BACKGROUND: The frequent association between transthyretin wild-type (TTRwt) cardiac amyloidosis (CA) and aortic stenosis (AS) suggests a bidirectional relationship: TTRwt-CA could induce AS and vice versa. Systemic manifestations may highlight this interaction: systemic amyloidogenesis would lead to systemic symptoms, CA, and AS, whereas the myocardial stresses induced by degenerative AS might promote local amyloidogenesis without systemic symptoms. Carpal tunnel syndrome (CTS) is the most frequently reported extracardiac symptom. Through a comparison of TTRwt-CA patients with and without CTS, we sought to determine whether CTS serves as a reliable indicator of systemic involvement and its impact on cardiac and valvular characteristics. METHODS AND RESULTS: A total of 411 consecutive patients with TTRwt-CA were included. CTS, present in 70.3%, was associated with a younger age (80 vs. 84 years, p < 0.001), more extracardiac symptoms, and advanced CA, with greater cardiac remodeling and a higher heart-to-mediastinum ratio (1.63 vs. 1.54; p = 0.012) compared to patients without CTS. AS was present in 21% and 31% of patients with and without CTS, respectively (p = 0.024). Except for AS, these associations remained significant after adjusting for confounding factors. In severe AS, patients with CTS exclusively exhibited low-flow low-gradient (LFLG) AS and less severe class of aortic valvular calcium score (5.6% vs. 60%; p = 0.006) compared to those without CTS. CONCLUSION: Our findings suggest that CTS may delineate two phenotypes in TTRwt-CA: a systemic phenotype associated with advanced CA and poorly calcified LFLG AS, and a cardiac phenotype characterized by less severe CA and a mixed pattern of highly calcified AS, suggesting disparate pathophysiologies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".