Abstract 5675: Brugada-Type ST Segment Elevation after Sodium Channel Blockade is Caused by Right Ventricular Excitation Failure in Discontinuous Myocardium
Bibliographic record
Abstract
Introduction: Brugada-type ST segment elevation has been associated with reduced sodium channel function and structural heart disease and is a risk marker for sudden cardiac death. Depolarizing and repolarizing abnormalities in the right ventricular wall have been described in patients. The mechanism of ST segment elevation however, is still debated. We determined depolarization and repolarization characteristics in an isolated heart of a young patient carrying a sodium channel mutation previously described in a family with Brugada syndrome. Methods and Results: A 15-year old female patient with a loss-of-function mutation (G752R) in the gene encoding the cardiac sodium channel underwent cardiac transplantation for end-stage heart failure in dilated cardiomyopathy. The explanted, perfused heart was submerged in perfusion fluid. We simultaneously recorded an “Einthoven” configuration pseudo-ECG and 194 unipolar electrograms from the endo- and epicardium of both ventricles. At baseline, a single shortly coupled premature stimulus resulted in more fractionated electrograms in the right than left ventricle (38 vs 6%, p < 0.001, Z-test). After sodium channel blockade by ajmaline, ST segment elevation of 0.3 mV was observed in pseudo-aVR which coincided with the virtual disappearance of the QRS complex in unipolar electrograms at the basal epicardium of the right ventricle followed by monophasic ST segment elevation. The local origin of this phenomenon was demonstrated by Laplacian electrograms. Neither early repolarization nor late activation correlated with the ST-change. Marked epicardial fatty infiltration was present at sites of local ST segment elevation, but not elsewhere. Simulations in a bidomain whole-heart computer model showed that either sodium current reduction or random replacement of 50% of the right ventricular epicardium by fat alone does not cause ST segment elevation. In combination however, part of the epicardial myocardium was not excited throughout the cardiac cycle by current-to-load mismatch resulting in Brugada-type ST segment elevation. Conclusions: Brugada-type ST segment elevation after sodium channel blockade is caused by excitation failure in discontinuous myocardium at the right ventricular epicardium.
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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) | 0.000 | 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) | 0.005 | 0.001 |
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".