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cardio.idiopathic-pulmonary-arterial-hypertension.v1PRODUCTION
cardio.idiopathic-pulmonary-arterial-hypertension.v1

Idiopathic pulmonary arterial hypertension (Group 1 PAH)

cardiologychronicadult
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm Group 1 PAH per 2022 ESC/ERS — mPAP ≥20 + PVR >2 WU + PCWP ≤15 + exclusion of Groups 2–5

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Advance rule
Set
Advance when

Group 1 confirmed; CTEPH and Groups 2/3/5 excluded

Patient inputs (23)

Mandatory to exclude CTEPH (Group 4) before labelling Group 1 (ESC/ERS 2022 Class I)

Exclude Group 3 (lung disease) (ESC/ERS 2022)

Age + sex shapes risk score; women 4:1 in IPAH (ESC/ERS 2022)

Systemic SBP <100 + tachycardia = REVEAL high-risk (Benza CHEST 2012)

HR >=90 = high-risk (REVEAL Lite 2.0)

Resting SpO2 + 6MWT desaturation; supplemental O2 if <90% (ESC/ERS 2022)

eGFR for diuretic + drug clearance (ESC/ERS 2022)

ERA hepatotoxicity baseline + monthly monitoring (bosentan REMS; macitentan less) per ESC/ERS 2022

PAH + pregnancy = ~30% maternal mortality; ERAs teratogenic; mandatory monthly during ERA (ESC/ERS 2022)

Detect existing PAH therapy + nitrates / PDE5 contraindications + ERA-induced LFT changes (ESC/ERS 2022)

GOLD STANDARD diagnosis: mPAP >=20, PVR >2 WU, PCWP <=15; vasoreactivity test in IPAH only (ESC/ERS 2022 Humbert)

NT-proBNP <300 = low-risk; >1100 = high-risk; tracks RV strain (ESC/ERS 2022 4-strata)

Initial screening; RVSP, TAPSE, RV/LV ratio, septal flattening, pericardial effusion (ESC/ERS 2022)

6MWD <165 m = high-risk; >440 m = low-risk per 4-strata score

WHO FC I-IV — primary driver of treatment intensity + risk (ESC/ERS 2022 4-strata)

CTD-PAH workup — ANA, anti-Scl70, anti-centromere, anti-RNP for SSc/MCTD; APS (ESC/ERS 2022)

HIV-PAH is Group 1 subtype (ESC/ERS 2022)

Portal HTN + Hep B/C -> portopulmonary HTN (Group 1) (ESC/ERS 2022)

Drug- and toxin-induced PAH (Group 1.3) (ESC/ERS 2022)

Heritable PAH (BMPR2/ACVRL1/ENG/SMAD9/CAV1/KCNK3) (ESC/ERS 2022)

RVH, RAD, RBBB, RV strain — supportive (ESC/ERS 2022)

RV mass, function, LGE — prognostic adjunct (ESC/ERS 2022)

Serial BNP for monitoring response (ESC/ERS 2022)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningwho_fc_iv_or_syncope
    WHO FC IV (symptoms at rest) OR exertional syncope
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningrv_failure_signs
    RV failure — JVD elevated, ascites, hepatic congestion, hypotension, oliguria, lactate elevation (ESC/ERS 2022 Humbert)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpregnancy_in_PAH
    Positive pregnancy test in PAH patient (ESC/ERS 2022 — Class III contraindication)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpump_failure_iv_prostacyclin
    IV prostacyclin pump failure or line disconnection
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverelft_3x_uln_on_era
    AST/ALT ≥3× ULN on bosentan / macitentan / ambrisentan
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepericardial_effusion_progression
    New or enlarging pericardial effusion on echo
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesix_min_walk_drop_50m_or_ntprobnp_double
    6MWD drop >50 m OR NT-proBNP doubling at follow-up
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

TREATMENTrequiredDrives dose adjustment
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Recommended regimen

PAH-specific therapy by ESC/ERS 4-strata risk score
axis: pah_risk_stratified_therapystep 1 - Low-risk — ERA + PDE5i dual therapy upfront (AMBITION)
Selected step "Low-risk — ERA + PDE5i dual therapy upfront (AMBITION)" — Low-risk on ESC/ERS 4-strata: WHO FC I–II, 6MWD >440 m, NT-proBNP <300, RAP <8, CI ≥2.5, SvO2 >65%
  • macitentan
    first line
    ERA
    10 mg • PO • once daily
    triggers: low_risk_PAH
    SERAPHIN — reduced morbidity/mortality endpoint; once-daily; less hepatotoxic than bosentan
    rxcui 1442132
  • ambrisentan
    first line
    ERA
    5 mg • PO • once daily (max: 10 mg/day)
    triggers: low_risk_PAH
    AMBITION dual upfront with tadalafil
    rxcui 358274
  • tadalafil
    first line
    PDE5_inhibitor
    20 mg • PO • once daily (max: 40 mg/day)
    triggers: low_risk_PAH
    PHIRST + AMBITION; once-daily; no nitrate use
    rxcui 358263
  • sildenafil
    first line
    PDE5_inhibitor
    20 mg • PO • TID (max: 80 mg TID)
    triggers: low_risk_PAH, tadalafil_unavailable
    SUPER-1; less convenient than tadalafil; no nitrate use
    rxcui 136411

outpatient playbook — drug actions (6)

  1. 1. ERA + PDE5i
    macitentan 10 mg + tadalafil 40 mg (or ambrisentan 10 mg + tadalafil 40 mg) • PO • once daily
    trigger: Low-risk Group 1 PAH
    AMBITION + SERAPHIN
  2. 2. add prostacyclin (oral selexipag, inhaled treprostinil, or SC treprostinil)
    selexipag 200 mcg → 1600 mcg BID; treprostinil inhaled 3 → 12 breaths QID; treprostinil SC 1.25 ng/kg/min → titrate • PO/inhaled/SC • BID/QID/continuous
    trigger: Intermediate-risk on dual
    GRIPHON / TRIUMPH
  3. 3. sotatercept
    0.3 → 0.7 mg/kg SC q3 wks • SC • q3 wks
    trigger: Intermediate-high or high-risk on background therapy
    STELLAR / ZENITH
  4. 4. IV epoprostenol or IV treprostinil
    epoprostenol 2 ng/kg/min → titrate; treprostinil IV 1.25 ng/kg/min → titrate • IV continuous • continuous via central line
    trigger: High-risk / WHO FC IV
    Only therapy with mortality benefit in high-risk
  5. 5. high-dose CCB — vasoreactivity-positive IPAH only
    amlodipine 5 -> 20 mg or diltiazem 120 -> 720 mg/day • PO • daily/TID
    trigger: Acute vasoreactivity test positive (mPAP fall >=10 to <40 + preserved CO)
    ~10% of IPAH; reassess at 3-6 mo (ESC/ERS 2022)
  6. 6. supportive — diuretic + O2 + iron repletion
    furosemide 20–40 mg PO daily; O2 titrated to SpO2 ≥92%; iron sucrose 200 mg IV per protocol • PO/inhaled/IV • daily/continuous/protocol
    trigger: RV failure / hypoxemia / iron deficiency
    2022 ESC/ERS

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Progressive exertional dyspnea unexplained by left HD or lung disease (ESC/ERS 2022); Exertional syncope / presyncope — high-risk PAH presentation (ESC/ERS 2022); Right HF signs — JVD, peripheral edema, ascites, hepatic congestion (ESC/ERS 2022).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Idiopathic pulmonary arterial hypertension (Group 1 PAH)** (cardio.idiopathic-pulmonary-arterial-hypertension.v1).
Phenotype framing: Confirm Group 1 subtype per ESC/ERS 2022: 1.1 idiopathic, 1.2 heritable, 1.3 drug/toxin, 1.4 CTD/HIV/portopulm/CHD/schistosomiasis, 1.5 PVOD/PCH
Scope: Confirm Group 1 PAH per 2022 ESC/ERS — mPAP ≥20 + PVR >2 WU + PCWP ≤15 + exclusion of Groups 2–5

No severity triggers fired against current inputs.

Plan

Regimen axis: **PAH-specific therapy by ESC/ERS 4-strata risk score** — step "Low-risk — ERA + PDE5i dual therapy upfront (AMBITION)".
1. macitentan 10 mg PO once daily (ERA, first line) — SERAPHIN — reduced morbidity/mortality endpoint; once-daily; less hepatotoxic than bosentan
2. ambrisentan 5 mg PO once daily (ERA, first line) — AMBITION dual upfront with tadalafil
3. tadalafil 20 mg PO once daily (PDE5_inhibitor, first line) — PHIRST + AMBITION; once-daily; no nitrate use
4. sildenafil 20 mg PO TID (PDE5_inhibitor, first line) — SUPER-1; less convenient than tadalafil; no nitrate use

Setting playbook (outpatient) — Confirm diagnosis at PAH expert centre, exclude CTEPH/Group 2/3/5, risk-stratify, initiate risk-matched therapy, achieve low-risk profile
5. ERA + PDE5i macitentan 10 mg + tadalafil 40 mg (or ambrisentan 10 mg + tadalafil 40 mg) PO once daily — Low-risk Group 1 PAH (AMBITION + SERAPHIN)
6. add prostacyclin (oral selexipag, inhaled treprostinil, or SC treprostinil) selexipag 200 mcg → 1600 mcg BID; treprostinil inhaled 3 → 12 breaths QID; treprostinil SC 1.25 ng/kg/min → titrate PO/inhaled/SC BID/QID/continuous — Intermediate-risk on dual (GRIPHON / TRIUMPH)
7. sotatercept 0.3 → 0.7 mg/kg SC q3 wks SC q3 wks — Intermediate-high or high-risk on background therapy (STELLAR / ZENITH)
8. IV epoprostenol or IV treprostinil epoprostenol 2 ng/kg/min → titrate; treprostinil IV 1.25 ng/kg/min → titrate IV continuous continuous via central line — High-risk / WHO FC IV (Only therapy with mortality benefit in high-risk)
9. high-dose CCB — vasoreactivity-positive IPAH only amlodipine 5 -> 20 mg or diltiazem 120 -> 720 mg/day PO daily/TID — Acute vasoreactivity test positive (mPAP fall >=10 to <40 + preserved CO) (~10% of IPAH; reassess at 3-6 mo (ESC/ERS 2022))
10. supportive — diuretic + O2 + iron repletion furosemide 20–40 mg PO daily; O2 titrated to SpO2 ≥92%; iron sucrose 200 mg IV per protocol PO/inhaled/IV daily/continuous/protocol — RV failure / hypoxemia / iron deficiency (2022 ESC/ERS)

Non-pharmacologic actions:
- Refer to PAH expert centre (Class I) (ESC/ERS 2022)
- Lung transplant evaluation if intermediate-high/high after triple therapy (ESC/ERS 2022)
- PAH-specific exercise rehab (ESC/ERS 2022)
- Pneumococcal + annual influenza + COVID + RSV vaccinations (ESC/ERS 2022)
- Contraception counselling (pregnancy contraindicated) (ESC/ERS 2022)
- Avoid pregnancy, high altitude, decongestants, NSAIDs (preload-dependent RV) (ESC/ERS 2022)
- Mental-health support — depression and anxiety prevalent (ESC/ERS 2022)

AVOID / contraindication checks:
- ERA block in pregnancy mandatory contraception (ESC/ERS 2022)
- Bosentan monthly LFT stop if 3xULN (BREATHE 1; ESC/ERS 2022)
- PDE5i block if on nitrates (ESC/ERS 2022)
- Riociguat NEVER combine with PDE5i (PATENT PLUS; ESC/ERS 2022)
- High dose CCB only if vasoreactivity positive (ESC/ERS 2022)
- Epoprostenol never stop abruptly (ESC/ERS 2022)
- Sotatercept monitor CBC for erythrocytosis (STELLAR NEJM 2023)

Monitoring

Regimen monitoring:
- 6MWD q3m (ESC/ERS 2022)
- NT-proBNP q3m (ESC/ERS 2022)
- WHO FC q3m (ESC/ERS 2022)
- echo q6m (ESC/ERS 2022)
- RHC at baseline then after escalation or q3-5y (ESC/ERS 2022)
- LFT monthly on bosentan (BREATHE-1 REMS)
- LFT q3m on macitentan/ambrisentan (SERAPHIN, Pulido NEJM 2013)
- pregnancy test monthly on ERA (ESC/ERS 2022)
- CBC q3m on sotatercept (STELLAR NEJM 2023)

Setting (outpatient) monitoring:
- q3 mo follow-up: WHO FC + 6MWD + NT-proBNP + echo (ESC/ERS 2022)
- RHC at baseline, after escalation, then q3-5 y or earlier if deteriorating (ESC/ERS 2022)
- LFT monthly on bosentan; q3 mo on macitentan/ambrisentan (ESC/ERS 2022; SERAPHIN)
- Pregnancy test monthly on ERA (ESC/ERS 2022)
- CBC q3 mo on sotatercept (erythrocytosis monitoring) (STELLAR NEJM 2023)

Follow-up plan: PAH-specific exercise rehab; pneumococcal/influenza/COVID vaccinations; contraception counselling; mental-health support
- Close-out criterion: follow-up scheduled with PAH expert center

Monitoring phase: q3 mo follow-up with WHO FC + 6MWD + NT-proBNP + echo; q6 mo RHC if intermediate/high or after escalation; LFT monthly on bosentan; pregnancy test monthly on ERA

Disposition

Current setting: outpatient — Confirm diagnosis at PAH expert centre, exclude CTEPH/Group 2/3/5, risk-stratify, initiate risk-matched therapy, achieve low-risk profile

Disposition criteria:
- Continue chronic management at PAH expert centre (ESC/ERS 2022)
- Lung transplant referral if intermediate-high/high after triple therapy + sotatercept (ESC/ERS 2022)
- Palliative care if not transplant candidate (ESC/ERS 2022)

Escalation triggers (move to higher acuity):
- WHO FC IV / syncope / RV failure -> admit + IV prostacyclin + transplant referral (ESC/ERS 2022)
- New pericardial effusion / RV dilation worsening -> escalate therapy (ESC/ERS 2022)
- 6MWD drop >50 m or NT-proBNP doubling -> reassess + escalate (ESC/ERS 2022)

Patient Action Plan

**PAH home action plan (RV-failure zones)**
Personalised values: baseline_6MWD, baseline_NTproBNP, home_diuretic, O2_baseline_LPM, PAH_centre_phone.

**Stable — at baseline 6MWD, no new dyspnea, weight steady** (green):
Triggers:
- No new shortness of breath at rest or on usual activity (ESC/ERS 2022)
- No new ankle / leg swelling, abdominal fullness, or weight gain (ESC/ERS 2022)
- Daily home weight within 1 kg of baseline (ESC/ERS 2022)
- SpO2 >=92% on baseline O2 (ESC/ERS 2022)
Actions:
- Take all PAH meds exactly as prescribed (NEVER stop IV/SC prostacyclin abruptly — life-threatening rebound) (ESC/ERS 2022)
- Sodium <2 g/day; fluids per plan (ESC/ERS 2022)
- Daily weight at the same time, after voiding (ESC/ERS 2022)
- Continue prescribed exercise plan (ESC/ERS 2022)
- Keep all PAH centre appointments (ESC/ERS 2022)

**Caution — new RV strain or congestion** (yellow):
Triggers:
- Weight gain >2 kg in 3 days (ESC/ERS 2022)
- New ankle / leg swelling, abdominal fullness, or RUQ discomfort (ESC/ERS 2022)
- New shortness of breath on lower-than-usual activity (ESC/ERS 2022)
- New palpitations or dizziness (ESC/ERS 2022)
- Pump alarms or site pain (SC) (ESC/ERS 2022)
Actions:
- Take prescribed rescue diuretic dose (ESC/ERS 2022)
- Tighten sodium intake (ESC/ERS 2022)
- Check pump function, site, and infusion line if applicable (ESC/ERS 2022)
- Call PAH centre within 24 h (ESC/ERS 2022)
Contact provider when:
- No improvement after 24-48 h of rescue diuretic (ESC/ERS 2022)
- Pump malfunction or line concern (any time) (ESC/ERS 2022)
- New oxygen requirement above baseline (ESC/ERS 2022)

**Medical alert — RV failure or pump failure** (red):
Triggers:
- Severe shortness of breath at rest, cannot lie flat (ESC/ERS 2022)
- Fainting, near-fainting, or chest pain (ESC/ERS 2022)
- New confusion or extreme drowsiness (ESC/ERS 2022)
- Pump stopped / line disconnected (IV/SC prostacyclin) (ESC/ERS 2022)
- Hemoptysis (ESC/ERS 2022)
- BP <90 systolic with cool extremities (ESC/ERS 2022)
Actions:
- Call 911 / emergency services immediately (ESC/ERS 2022)
- For IV prostacyclin pump failure establish backup line/pump or send EMS to PAH centre directly (ESC/ERS 2022)
- Sit upright (ESC/ERS 2022)
- Do NOT lie flat (ESC/ERS 2022)
- Bring medication list and PAH centre contact (ESC/ERS 2022)
Contact provider when:
- Any red zone symptom — ED + page PAH centre on the way (ESC/ERS 2022)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] WHO FC IV (symptoms at rest) OR exertional syncope
- [LIFE_THREATENING] RV failure — JVD elevated, ascites, hepatic congestion, hypotension, oliguria, lactate elevation (ESC/ERS 2022 Humbert)
- [LIFE_THREATENING] Positive pregnancy test in PAH patient (ESC/ERS 2022 — Class III contraindication)

Citations

- 2022 ESC/ERS Pulmonary Hypertension Guidelines + 2026 ATS/CHEST/PHA PAH Update [PMID:36017548](https://pubmed.ncbi.nlm.nih.gov/36017548/)
- Cited evidence (PMID 23984728) [PMID:23984728](https://pubmed.ncbi.nlm.nih.gov/23984728/)
- Cited evidence (PMID 26308684) [PMID:26308684](https://pubmed.ncbi.nlm.nih.gov/26308684/)
- Cited evidence (PMID 26699168) [PMID:26699168](https://pubmed.ncbi.nlm.nih.gov/26699168/)
- Cited evidence (PMID 23883378) [PMID:23883378](https://pubmed.ncbi.nlm.nih.gov/23883378/)

Last reconciled with current guidelines: 2026-04-28.
References