Lower left ventricular ejection time in <i>MYBPC3</i> variant carriers with overt or subclinical hypertrophic cardiomyopathy
Bibliographic record
Abstract
Abstract Aims Hypertrophic cardiomyopathy (HCM) is an inherited cardiomyopathy mainly caused by pathogenic variants in MYBPC3 and MYH7, encoding myosin binding protein C3 and myosin heavy chain 7, respectively. These variants can cause increased actin-myosin crossbridge cycling resulting in ventricular hypercontractility. Little is known about genotype-specific differences. Mice lacking Mybpc3 exhibited reduced left ventricular ejection time (LVET). In this study we tested whether LVET is specifically altered in patients carrying MYBPC3 variants by retrospective echocardiographic analysis in two genotype-defined HCM cohorts. Methods and results LVET was measured by echocardiography and adjusted for heart rate (LVET index, LVETI) in 173 patients carrying MYBPC3 or MYH7 pathogenic variant. There was a discovery cohort (Hamburg; 46 MYBPC3, 31 MYH7) and a validation cohort (“Valsartan in Attenuating Disease Evolution in Early Sarcomeric HCM”; 55 MYBPC3 , 41 MYH7 ). Data were compared with 44 healthy controls from Hamburg. Variant carriers were stratified for overt (G+LVH+) or subclinical left ventricular hypertrophy (G+LVH-). LVETI was lower in MYBPC3 and higher in MYH7 G+LVH+ patients than in controls in the discovery, validation and pooled cohorts (pooled: 385 ± 23 ms MYBPC3 , 436 ± 38 ms MYH7, 411 ± 15 ms controls). Similar findings were seen in G+LVH-. Conclusion The data suggest that variants in MYBPC3 and MYH7 result in distinct biophysical consequences, which can be detected by measuring LVETI in patients. The findings may have implications for potential genotype-specific differences in response to therapies targeting sarcomere function.
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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 | 0.001 |
| 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 | 0.001 | 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".