Sex-dependent Pathophysiology and Therapeutic Considerations in Right Heart Disease
Bibliographic record
Abstract
Right ventricular (RV) adaptation to the increased afterload in the setting of pulmonary hypertension (PH) and other cardiac and pulmonary vascular conditions is a major determinant of survival. Although the RV remains understudied and less well understood than the left ventricle, recent advances have been made in understanding the function and biology of the RV in health and in disease, particularly in PH. RV adaptation in PH exhibits significant sexual dimorphisms in pathophysiology, adaptation, and outcomes. Despite a higher incidence of PH, women consistently demonstrate better RV adaptation and survival rates in the setting of increased RV afterload compared with men. Sexual dimorphisms extend to therapy responsiveness, with women benefiting more from certain pulmonary vasodilators and exhibiting superior RV recovery. In this review we discuss the current literature on sexual dimorphisms in RV structure, function, and molecular pathways in health and disease, as well as in RV-specific clinical manifestations, treatments, and outcomes in PH. Sex steroid-mediated effects as well as emerging studies on sex steroid-independent effects are reviewed. In general, sex steroids such as 17β-estradiol and dehydroepiandrosterone exert RV-protective effects. In contrast, testosterone negatively impacts RV structure and function. Emerging evidence highlights the influence of nonhormonal genetic determinants, such as BMPR1A and DMRT2 loci, which are associated with better RV function in women. A better understanding of the interplay between sex hormones, genetic factors, and RV biology is crucial for advancing and developing RV-directed therapies for patients of either sex.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".