Abstract 13327: Mechanistic Basis of Sinoatrial Node Pacemaker Failure in Atrial Cardiomyopathy
Bibliographic record
Abstract
Introduction: Sinoatrial node (SAN) dysfunction commonly occurs in atrial cardiomyopathy (ACM: “tachy-brady syndrome”), often requiring pacemaker implantation, but mechanisms are unknown. Atrial-selective myosin light chain-4 (MYL-4) mutations cause familial ACM with a high rate of early SAN dysfunction and pacemaker requirement. We studied rats engineered with a knock-in MYL-4 clinical E11K mutation and addressed mechanisms of SAN dysfunction. Methods: Atrial electrical properties were assessed with in vivo electrophysiology (EPS), ex vivo optical mapping, SAN single-cell voltage and current clamp, Ca 2+ -handling with Ca 2+ -sensitive dye microscopy. Gene expression was assessed by qPCR and fibrosis with Masson-Trichrome stain. Results: E11K rats showed progressive SAN recovery-time increases (Fig. A) and conduction-slowing (Fig. B). SAN cells showed slowed phase-4 depolarization (Fig. C) and reduced pacemaker “funny” current (I f ) (Fig. D). Ca 2+ homeostasis was also affected, showing decreased Ca 2+ -transients (Fig. E). SAN also displayed remodeling with increased collagen deposition (Fig. F). Conclusions: ACM resulting from E11K mutation induces multimodal electrical and structural remodeling of the SAN region, worsening with age. These observations provide new insights into mechanisms of the clinically important tachy-brady syndrome associated with ACM.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".