283.1 🎓 醫孞生版

283.1.0.1 📌 䞀頁重點

283.1.0.1.1 Definition + Classification
283.1.0.1.1.1 Hemodynamic Definition (2018 WSPH)
  • PH: mPAP > 20 mmHg at rest (revised from > 25)
  • Pre-capillary PH: mPAP > 20 + PCWP ≀ 15 + PVR ≥ 2 WU
  • Post-capillary PH: mPAP > 20 + PCWP > 15
  • Combined (Cpc-PH): post-capillary + PVR > 2 WU
283.1.0.1.1.2 WHO Classification

Group 1 — Pulmonary Arterial Hypertension (PAH) - Idiopathic PAH - Heritable (BMPR2, ALK1, ENG, SMAD9 mutations) - Drug/toxin-induced (anorexigens, methamphetamine, dasatinib) - Associated with: CTD (scleroderma, SLE), congenital heart disease (CHD), portal HTN, HIV, schistosomiasis - PVOD / PCH (pulmonary veno-occlusive disease / capillary hemangiomatosis) - Persistent PH of newborn

Group 2 — Due to Left Heart Disease - Most common cause overall - HFrEF, HFpEF - Valvular disease (mitral, aortic) - LV inflow/outflow obstruction - Treat underlying LH disease — DON’T use PAH-specific drugs

Group 3 — Due to Lung Disease / Hypoxia - COPD, ILD, sleep apnea, hypoventilation, high altitude - Mostly mild-moderate PH - Treat underlying disease + oxygen

Group 4 — CTEPH (Chronic Thromboembolic PH) - Post-PE; 3-5% of survivors - Surgical (PEA) curable - Riociguat, BPA for inoperable

Group 5 — Unclear / Multifactorial - Hematologic: chronic hemolytic anemia (SCD), MPN - Systemic: sarcoidosis, LAM, neurofibromatosis - Metabolic: glycogen storage, Gaucher, thyroid - Other: fibrosing mediastinitis, CKD

283.1.0.1.2 Epidemiology + Pathology
283.1.0.1.2.1 PAH
  • Prevalence ~ 15-50 per million
  • Female > male (4:1 in IPAH)
  • Mean age 50
  • 1-year survival untreated 68%; treated 90%
  • 5-year ~ 50-60%
283.1.0.1.2.2 Pathology of PAH
  • Plexiform lesions (pathognomonic)
  • Medial hypertrophy, intimal proliferation, adventitial fibrosis
  • Endothelial dysfunction (↓ NO, ↑ ET-1)
  • Smooth muscle proliferation
  • In situ thrombosis
  • Inflammation
283.1.0.1.3 Clinical Presentation
283.1.0.1.3.1 Symptoms
  • Dyspnea on exertion (most common, insidious)
  • Fatigue
  • Chest pain (angina-like)
  • Syncope (severe disease)
  • Lightheadedness
  • Lower extremity edema (RV failure)
  • Ascites (advanced)
  • Hemoptysis (rare)
283.1.0.1.3.2 Physical Examination
  • Loud P2 (palpable in 2nd ICS L)
  • RV heave (parasternal lift)
  • TR murmur (holosystolic at LSB)
  • JVD with prominent A wave
  • Hepatomegaly + pulsatile liver (severe TR)
  • Edema, ascites
  • Cyanosis, clubbing if CHD
  • Sclerodactyly, telangiectasia if scleroderma
283.1.0.1.4 Workup
283.1.0.1.4.1 Initial
  • Echocardiogram (screening + estimate PASP from TR jet)
    • PASP > 40 mmHg or RV dysfunction → workup PH
  • ECG: RAE, RVH, RAD, RBBB
  • CXR: enlarged central PA, pruning of peripheral vessels, RV prominence
  • PFTs + DLCO: rule out lung disease (Group 3)
  • High-resolution CT chest: ILD, COPD, parenchymal disease
  • V/Q scan: high sensitivity for CTEPH (always do — don’t miss group 4)
  • CT pulmonary angio: confirm CTEPH; assess parenchyma
  • 6-minute walk test (6MWT): severity + monitoring
  • BNP / NT-proBNP: severity + prognosis
  • Autoimmune workup: ANA, anti-centromere, anti-Scl-70, anti-RNP (scleroderma)
  • HIV testing, hepatitis B/C, LFTs: portal HTN, HIV-PAH
  • TSH (thyroid disorders)
  • PSG (sleep apnea)
283.1.0.1.4.2 Right Heart Catheterization (RHC) — Gold Standard
  • Definitive diagnosis
  • Measures: mPAP, PCWP (left filling), PVR, CO, mixed venous O2
  • Vasoreactivity testing (inhaled NO, IV epoprostenol):
    • Positive: ↓ mPAP ≥ 10 mmHg + final mPAP < 40 + CO unchanged/↑
    • ~ 10% of IPAH responders → CCB therapy (long-term survivors)
283.1.0.1.4.3 Risk Stratification (REVEAL 2.0, ESC/ERS 4-strata)
  • Functional class (WHO I-IV)
  • 6MWT distance (> 440, 320-440, 165-320, < 165)
  • BNP/NT-proBNP
  • RV function on echo
  • mRA pressure, cardiac index, mixed venous O2
  • Low / intermediate-low / intermediate-high / high risk
  • Goal: achieve low-risk status
283.1.0.1.5 Treatment
283.1.0.1.5.1 Group 1 PAH — Pathway-Targeted

Tier 1 (Disease-Modifying) — Three Pathways

Endothelin Pathway (↑ ET-1 in PAH) - Endothelin Receptor Antagonists (ERAs): - Bosentan: non-selective ETA/ETB; LFT monitoring (hepatotoxic) - Ambrisentan: ETA-selective; less hepatotoxic - Macitentan: dual; less LFT issues; SERAPHIN trial — primary endpoint

NO/cGMP Pathway (↓ NO in PAH) - PDE5 inhibitors: sildenafil 20 TID, tadalafil 40 QD - sGC stimulator: riociguat — for PAH AND CTEPH (CHEST-1, PATENT-1) - Do NOT combine PDE5i + riociguat (hypotension)

Prostacyclin Pathway (↓ prostacyclin in PAH) - Epoprostenol (Flolan): IV continuous infusion; severe PAH - Treprostinil: IV, SC, inhaled, oral; FREEDOM-EV - Iloprost: inhaled; AIR study - Selexipag: oral prostacyclin receptor agonist; GRIPHON study

Tier 1 (NEW 2022-2024) - Sotatercept: activin signaling inhibitor (TGFβ family modulator) - STELLAR trial 2023 — improved 6MWT, reduced clinical worsening - FDA approved 2024 for PAH

Tier 2 (Supportive) - Diuretics for RV failure - Oxygen if SaO2 < 90% - Anticoagulation (debated in IPAH; not recommended routinely 2022 ESC) - CCB only for vasoreactive responders (10% of IPAH) - Avoid: pregnancy (lethal), high altitude, decongestants

283.1.0.1.5.2 Combination Therapy
  • Initial combination preferred over sequential (AMBITION trial — ambrisentan + tadalafil > monotherapy)
  • Triple therapy for high-risk or non-responders: ERA + PDE5i + prostanoid
283.1.0.1.5.3 Lung Transplantation
  • For refractory PAH despite maximal therapy
  • 5-year survival ~ 55%
283.1.0.1.5.4 Group 2 PH (Left Heart Disease)
  • Treat underlying LH disease (HF, valve)
  • AVOID PAH-specific drugs (worsen pulmonary edema)
  • Diuretics, optimize LH disease
283.1.0.1.5.5 Group 3 PH (Lung Disease)
  • Treat underlying lung disease (COPD, ILD)
  • Oxygen if hypoxemic
  • Pulmonary rehab
  • PAH drugs NOT routinely effective; sometimes trial inhaled treprostinil in severe (INCREASE trial — for ILD-PH)
283.1.0.1.5.6 Group 4 CTEPH
  • Pulmonary endarterectomy (PEA) — surgical cure
    • Best at experienced centers
    • 5-year survival > 80% post-PEA
  • Inoperable / persistent post-PEA:
    • Riociguat (sGC stimulator) — CHEST-1
    • Balloon pulmonary angioplasty (BPA) — for distal disease
    • Macitentan (MERIT trial)
  • Anticoagulation lifelong
  • Multidisciplinary CTEPH center referral
283.1.0.1.5.7 Group 5 PH
  • Treat underlying condition
  • Limited PAH drug data
283.1.0.1.6 Special Topics
283.1.0.1.6.1 Pulmonary Veno-Occlusive Disease (PVOD)
  • Subset of group 1 PAH
  • Post-capillary obstruction
  • High pulmonary edema risk with PAH drugs
  • Lung transplant
283.1.0.1.6.2 Schistosomiasis-Associated PAH
  • Common cause globally (especially Brazil, Egypt)
  • Praziquantel + PAH therapy
283.1.0.1.6.3 Pregnancy
  • PAH carries maternal mortality 25-30%
  • Avoid pregnancy strongly
  • Contraception counseling
  • ERAs teratogenic (REMS program)
  • IUD + barrier preferred
283.1.0.1.6.4 Right Heart Failure Management
  • Diuretics (with caution — preload-dependent RV)
  • Inotropes (dobutamine, milrinone — beware vasodilation)
  • Vasopressors (norepinephrine, vasopressin — for hypotension)
  • Inhaled NO acute
  • Atrial septostomy (palliation)
  • VA-ECMO bridge

283.1.0.2 🩺 床邊速查

  • PH = mPAP > 20 (2018 revised from > 25)
  • 5 groups (PAH / LH / lung / CTEPH / multifactorial)
  • Workup: echo → V/Q scan + CT + PFT + autoimmune → RHC for diagnosis
  • PAH treatment: 3 pathways (ERA + PDE5i/riociguat + prostanoid) + sotatercept (new 2024)
  • CTEPH cure: PEA; alternatives riociguat + BPA
  • Don’t miss CTEPH: always V/Q scan (more sensitive than CTPA)