Abstract 4367634: Genetic Variants and Prognosis in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-analysis
Bibliographic record
Abstract
Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, frequently associated with sarcomere gene variants. While genetic testing is key for diagnosis and family screening, the prognostic relevance of sarcomere-positive versus sarcomere-negative status remains unclear. Clarifying this relationship is increasingly important with the emergence of genotype-informed therapies. Hypothesis: We hypothesized that HCM patients with pathogenic sarcomere variants have a higher risk of major adverse cardiac events (MACE), including sudden cardiac death (SCD), heart failure hospitalization, appropriate ICD therapy, and need for heart transplantation or LVAD. Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines, searching PubMed, Embase, and Cochrane through May 2025. Eligible studies included adult HCM patients with genetic testing and defined clinical outcomes. Two reviewers independently screened and extracted data. Risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled hazard ratios (HRs) or risk ratios (RRs) were calculated using random-effects models. Subgroup analyses were performed by mutation type (e.g., MYH7, MYBPC3), age group, and endpoint category (arrhythmic vs HF-related). Results: Seventeen studies comprising 7,860 HCM patients were included. Of these, 4,180 (53%) were genotype-positive. Sarcomere-positive patients had significantly higher risks of SCD or appropriate ICD therapy (HR 2.12, 95% CI 1.48–3.02, p<0.001) and HF hospitalization (HR 1.67, 95% CI 1.21–2.34, p=0.002). Among mutation carriers, MYH7 variants were associated with higher likelihood of progression to transplant or LVAD compared to MYBPC3 or genotype-negative cases. Heterogeneity was moderate and resolved in subgroup analyses. Sensitivity analyses confirmed result stability. Conclusions: Pathogenic sarcomere gene variants in HCM are associated with increased arrhythmic and HF-related risks. These findings support the role of genetic testing in prognostic stratification and clinical management. Genotype may inform timing of therapy and guide future personalized approaches.
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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 | 0.010 | 0.024 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.030 |
| Bibliometrics | 0.006 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 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".