| Domain | Item | Quantitative data (frequency, thresholds, cohort values) | Ontology term suggestions | Key sources with URL and year |
|---|---|---|---|---|
| Phenotype | Pulmonary arterial hypertension / elevated pulmonary artery pressure | PH defined as **mPAP >20 mmHg**; precapillary PH defined by **mPAP >20 mmHg, PAWP ≤15 mmHg, PVR >2 WU** | HPO: Pulmonary hypertension [HP:0002092]; UBERON: pulmonary artery [UBERON:0002012] | Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024; Lechartier et al. 2023, https://doi.org/10.1055/s-0043-1770115 (pqac-00000009, pqac-00000013) |
| Phenotype | Right ventricular hypertrophy / right-sided heart failure | Core disease consequence; PAH leads to RV hypertrophy and progressive right heart failure; in Taiwanese PAH cohort, mean **mPAP 41 ± 16 mmHg**, **PVR 8 ± 7 WU**, **CI 2.7 ± 1.1 L/min/m²** | HPO: Right ventricular hypertrophy [HP:0006682], Right-sided heart failure [HP:0001678]; UBERON: right ventricle [UBERON:0002084] | Li & Quigley 2024, https://doi.org/10.1042/BST20231547; Wang et al. 2024, https://doi.org/10.3390/ijms25052734 (pqac-00000015, pqac-00000018) |
| Phenotype | Pulmonary vascular remodeling / neointimal and plexiform lesions | Qualitative hallmark; BMPR2-related disease associated with proliferation, reduced apoptosis, neointimal lesions, complex plexiform lesions | HPO: Pulmonary hypertension [HP:0002092]; GO: blood vessel remodeling [GO:0001974], regulation of apoptotic process [GO:0042981]; CL: endothelial cell [CL:0000115], smooth muscle cell [CL:0000192] | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022 (pqac-00000017) |
| Phenotype | Female predominance | Across registries **70–80%** of PAH patients are female; younger adult prevalence about **2:1 female:male**; female predominance varies by subgroup | HPO: not disease-specific; use clinical demographic annotation rather than HPO | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022 (pqac-00000017) |
| Phenotype | Worse hemodynamics in BMPR2/GDF2 variant carriers | In 69-patient cohort, BMPR2 and GDF2 variant subgroups had worse hemodynamics; GDF2 carriers had lower plasma **GDF2 135.6 ± 36.2 pg/mL vs 267.8 ± 185.8 pg/mL**, **p=0.002** | HPO: Pulmonary hypertension [HP:0002092]; GO: BMP signaling pathway [GO:0030509] | Wang et al. 2024, https://doi.org/10.3390/ijms25052734 (pqac-00000018) |
| Phenotype | Reduced diffusing capacity / CT abnormalities in specific genetic subgroups | PVOD/PCH and KDR-related disease may present with **low DLCO** and CT abnormalities; SOX17 subset may show dilated/tortuous pulmonary vessels, ground-glass opacities, haemoptysis | HPO: Decreased diffusing capacity of the lungs for carbon monoxide [HP:0045051], Hemoptysis [HP:0031964], Ground-glass opacification on pulmonary HRCT [HP:0025179] | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022 (pqac-00000016) |
| Diagnostic test | Right heart catheterization (RHC) | Required for definitive diagnosis; updated precapillary PH criteria: **mPAP >20 mmHg, PAWP ≤15 mmHg, PVR >2 WU** | LOINC: not specified in current evidence; UBERON: pulmonary artery [UBERON:0002012] | Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024; Lechartier et al. 2023, https://doi.org/10.1055/s-0043-1770115 (pqac-00000009, pqac-00000013) |
| Diagnostic test | Echocardiography | Principal screening tool but cannot confirm mPAP; recommended annually in asymptomatic high-risk groups | HPO support term if abnormal: Abnormal echocardiogram [HP:0031862]; UBERON: heart [UBERON:0000948] | Lechartier et al. 2023, https://doi.org/10.1055/s-0043-1770115; Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024 (pqac-00000013, pqac-00000019) |
| Diagnostic test | ECG | Recommended annually for asymptomatic high-risk groups (e.g., BMPR2 carriers, first-degree relatives of HPAH patients) | HPO: Abnormal electrocardiogram [HP:0003115] | Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024 (pqac-00000019) |
| Diagnostic test | NT-proBNP / BNP | Recommended annually for screening asymptomatic high-risk groups; in Taiwanese cohort mean **NT-proBNP 1869 ± 2988 ng/L** | LOINC suggestion: NT-proBNP [33762-6]; HPO: Abnormal circulating natriuretic peptide concentration [HP:0034375] | Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024; Wang et al. 2024, https://doi.org/10.3390/ijms25052734 (pqac-00000019, pqac-00000018) |
| Diagnostic test | DETECT screening tool | Can be applied to appropriate patients with systemic sclerosis spectrum disorders meeting inclusion/exclusion criteria | Ontology: screening tool; no direct HPO term | Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024 (pqac-00000019) |
| Diagnostic test | Vasoreactivity testing | About **10%** of PAH patients are acute responders; response defined as **mPAP decrease ≥10 mmHg to ≤40 mmHg with increased/unchanged CO** | HPO: Response to vasodilator challenge abnormality not standardized; clinical test annotation preferred | Treatment/biomarker summary excerpt 2024 (pqac-00000020) |
| Diagnostic test | Genetic testing / gene panel | Recommended for idiopathic PAH, suspected HPAH/family history, anorexigen-associated PAH, PAH-CHD, and suspected PVOD/PCH; international expert panel lists **12 genes with definitive evidence** | SO: sequence variant; MONDO: heritable pulmonary arterial hypertension [MONDO:0017148] | Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024; Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022 (pqac-00000019, pqac-00000001) |
| Epidemiology | PAH incidence | **2.5–7.5 cases per million per year** | MONDO/EFO disease annotation rather than HPO | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022 (pqac-00000017) |
| Epidemiology | PAH prevalence | **15–50 per million** in registry data; another review cites **15–26 per million** in western countries | MONDO/EFO disease annotation rather than HPO | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022; Li & Quigley 2024, https://doi.org/10.1042/BST20231547 (pqac-00000017, pqac-00000015) |
| Epidemiology | Proportion of PAH classified as HPAH | About **3%** of all PAH patients are classified as HPAH | MONDO: heritable pulmonary arterial hypertension [MONDO:0017148] | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022; Kovacs et al. 2024, https://doi.org/10.1183/13993003.01324-2024 (pqac-00000017, pqac-00000010) |
| Epidemiology | Genetic contribution among familial and idiopathic PAH | Genetic cause identifiable in **70–87% of familial PAH** and **12–20% of idiopathic PAH**; another cohort/review notes **25–30%** of idiopathic PAH have an underlying genetic cause | MONDO: heritable pulmonary arterial hypertension [MONDO:0017148] | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022; Wang et al. 2024, https://doi.org/10.3390/ijms25052734 (pqac-00000017, pqac-00000018) |
| Epidemiology | BMPR2 contribution and penetrance | BMPR2 variants in **>80% familial/heritable cases**, **~17% idiopathic PAH**; penetrance **42% in heterozygous women** and **14% in heterozygous men** | HGNC: BMPR2; GO: BMP signaling pathway [GO:0030509] | Li & Quigley 2024, https://doi.org/10.1042/BST20231547; Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022 (pqac-00000015, pqac-00000016) |
| Epidemiology | Diagnostic delay | Mean delay to diagnosis about **2.8 years** | Clinical course annotation rather than HPO | Eichstaedt et al. 2023, https://doi.org/10.1183/13993003.01471-2022 (pqac-00000001) |
| Epidemiology | Cohort characteristics from Taiwanese idiopathic/heritable PAH study | **n=69**; age at diagnosis **50 ± 20 years**; **6MWD 332 ± 127 m**; **PAWP 14 ± 4 mmHg**; **WHO FC III 63.8%**; pulmonary artery saturation **66 ± 12%** | HPO: Reduced exercise tolerance [HP:0003546]; UBERON: pulmonary artery [UBERON:0002012] | Wang et al. 2024, https://doi.org/10.3390/ijms25052734 (pqac-00000018) |


*Table: This table compiles evidence-backed clinical phenotypes, diagnostic criteria, screening tools, and epidemiology relevant to heritable pulmonary arterial hypertension. It is useful for rapid disease knowledge-base population because it pairs quantitative findings with ontology suggestions and direct evidence sources.*