Relationship Between Genotype Status and Clinical Outcome in Hypertrophic Cardiomyopathy
Bibliographic record
Abstract
Background The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved. Methods and Results We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease‐causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G−). Patients were followed up for a median of 7.8 years (interquartile range, 3.5–13.4 years); HCM end points were examined by cumulative event incidence. Over follow‐up, 135 (9%) patients died, 33 from a variety of HCM‐related causes. After adjusting for age, all‐cause and HCM‐related mortality did not differ between G− versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46–1.31]; P =0.37; HR, 0.93 [95% CI, 0.38–2.30]; P =0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G− versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63–2.26]; P =0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88–2.21]; P =0.16). In multivariable analysis, age was the only independent predictor of all‐cause and HCM‐related mortality, heart failure progression, and sudden death events. Conclusions In this large consecutive cohort of patients with HCM, genotype (G+ or G−) was not a predictor of clinical course, including all‐cause and HCM‐related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.
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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 | 0.001 | 0.004 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".