| Domain | Current finding | Quantitative detail | Evidence type/source/year |
|---|---|---|---|
| Hemodynamic definition | IPAH is a subgroup of precapillary pulmonary arterial hypertension defined by elevated pulmonary pressures with normal left-sided filling pressure and increased pulmonary vascular resistance. | PH: mPAP >20 mmHg; precapillary PH: PAWP ≤15 mmHg and PVR >2 Wood units. Updated threshold reflected in 2022 ESC/ERS and 2024 WSPH-aligned sources. | Human clinical/guideline review, ERJ 2024; consensus statement 2023 (pqac-00000004) |
| Epidemiology | IPAH/PAH remains a rare disease with low incidence and prevalence, but registries show persistent global burden. | Incidence 2.5–7.5 cases per million/year; prevalence 15–50 per million. Female predominance reported; one review cites PAH female:male ratio 4.3:1 and IPAH 4.1:1. | Human registry/review, ERJ 2023; J Transl Med 2023 (pqac-00000004, pqac-00000008) |
| Genetics | BMPR2 is the leading causal gene; current gene curation supports a broader panel for heritable/idiopathic disease. | 12 genes with definitive evidence: BMPR2, ACVRL1, ATP13A3, CAV1, EIF2AK4, ENG, GDF2, KCNK3, KDR, SMAD9, SOX17, TBX4; 3 moderate: ABCC8, GGCX, TET2; 6 limited including AQP1, BMP10, FBLN2, KLF2, KLK1, PDGFD. | Human genetics review/consensus, ERJ 2024 and 2023 (pqac-00000001, pqac-00000004, pqac-00000000) |
| Symptoms / diagnostic delay | Clinical presentation is nonspecific and commonly delayed, contributing to advanced disease at diagnosis. | Common symptoms: fatigue, dyspnea on exertion, chest pain, syncope; mean diagnostic delay ~2.8 years. | Human clinical consensus/review, ERJ 2023 (pqac-00000004) |
| Survival / prognosis | Outcomes have improved with therapy but long-term prognosis remains poor and heterogeneous. | Historical median survival without treatment ~2.8 years; current era median survival >7 years in one review. Population-based adult PAH survival ranges: 1-year 85–99%, 3-year 65–95%, 5-year 50–86%; Europe pooled 1-year 90%, 3-year 78%, 5-year 61%. | Human observational review/systematic review, 2023–2024 (pqac-00000008, pqac-00000003) |
| Risk assessment | Low-risk status remains the therapeutic goal; noninvasive markers anchor current models, with hemodynamics/imaging adding value. | Core predictors across tools: WHO functional class, 6MWD, natriuretic peptides; additional prognostic variables include PVR, CI, RAP/right atrial area, and RV imaging parameters. | Human prognostic review, ERJ 2024 (pqac-00000003) |
| Sotatercept | First-in-class activin-signaling inhibitor adds disease-modifying therapy beyond vasodilator pathways. | In STELLAR post hoc analysis at 24 weeks vs placebo: mPAP −13.9 mmHg, PVR −254.8 dyn·s·cm⁻⁵, mean RAP −2.7 mmHg, mixed venous O2 saturation +3.84%, PA compliance +0.58 mL·mmHg⁻¹, RV end-diastolic area −5.31 cm². PULSAR showed ~18% PVR reduction. | Human phase 2/3 trial evidence, ERJ 2023; review 2023 (pqac-00000009) |
| 2024 single-cell immune findings | IPAH inflammatory signaling includes adaptive immune–vascular crosstalk, especially T/NK-cell mediated communication. | Hub genes identified: CXCL9, CCL5, GZMA, GZMK; scRNA-seq localized CCL5/GZMA mainly to T and NK cells interacting with endothelial cells, smooth muscle cells, and fibroblasts. | Human transcriptomic + scRNA-seq with animal validation, J Transl Med 2024 (pqac-00000010) |
| 2024 ferroptosis findings | Ferroptosis is implicated as a pathogenic upstream inflammatory mechanism linking endothelial injury to remodeling. | In MCT rats, ferrostatin-1 1 mg/kg/day mitigated PAH severity; model used MCT 60 mg/kg. Mechanistic data linked ferroptotic PAEC DAMPs to complement activation, macrophage recruitment, PASMC proliferation, and inflammatory monocyte phenotypes. | Human multiomics + animal + in vitro mechanistic study, Circ Res 2024 (pqac-00000011) |


*Table: This table compiles compact, high-yield evidence for idiopathic pulmonary arterial hypertension across core knowledge-base domains. It highlights current definitions, burden, genetics, prognosis, treatment advances, and 2024 mechanistic discoveries using only previously gathered sources.*