Skip to content

Pulmonary Arterial Hypertension (PAH)

BASICS

  • Definition: Disease of small pulmonary arteries (precapillary PH) causing increased pulmonary arterial pressure (PAP) and vascular resistance → right-sided heart failure.
  • Diagnosis (Right Heart Catheterization):
  • Mean PAP ≥20 mm Hg at rest
  • Pulmonary vascular resistance ≥3 Wood units
  • Pulmonary capillary wedge pressure ≤15 mm Hg
  • Excludes left heart, lung, thromboembolic, or systemic/metabolic causes
  • WHO Group 1 PH: PAH (idiopathic, heritable, drug/toxin-induced, connective tissue disease, HIV, portal HTN, congenital heart disease, schistosomiasis)
  • Related but distinct: PVOD and PCH (pulmonary venous/capillary diseases)

EPIDEMIOLOGY

  • Any age; mean age 37 yrs
  • Sex: Female > Male (ratio 1.7–4.8:1 in idiopathic PAH)
  • Incidence/Prevalence:
  • PAH: 5–52/million; IPAH: 2–6/million
  • PAH prevalence: 15–50/million
  • Drug-induced: 1/25,000 for >3 months anorectic use
  • High risk: scleroderma (6–60%), portal HTN, HIV

ETIOLOGY & PATHOPHYSIOLOGY

  • Vascular: Inflammation, vasoconstriction, endothelial dysfunction, intimal proliferation, increased cell proliferation, reduced apoptosis → vascular remodeling & obstruction.
  • Cardiac: Right ventricular hypertrophy/remodeling → RV failure, ischemia.
  • Idiopathic (IPAH): Unknown cause, often sporadic, sometimes familial.
  • Genetic: 75% heritable PAH & 25% IPAH have BMPR2 mutations (autosomal dominant).

RISK FACTORS

  • Female sex
  • Illicit anorectic drug use
  • Recent pulmonary embolism
  • Family history (first-degree relatives of familial PAH)

DIAGNOSIS

History

  • Symptoms: Dyspnea, weakness, syncope, dizziness, chest pain, palpitations, LE edema

Physical Exam

  • Loud P2, early pulmonary valve click, tricuspid regurgitation murmur, pulmonic insufficiency murmur (Graham Steell), JVD, ascites, hepatomegaly, peripheral edema

Differential Diagnosis

  • Other causes of dyspnea (lung parenchymal disease, thromboembolism, cardiac disease)

Diagnostic Tests

  • ECG: RVH, right axis deviation, RV strain, R/S >1 in V1
  • PFT: ↓DLCO
  • ABG: Hypoxemia, hypocapnia
  • V/Q scan: Rule out CTEPH (group 4)
  • 6MWD: Reduced max O2 consumption; correlates with severity
  • BNP/NT-proBNP: Early marker, prognosis
  • CXR: Prominent central PAs, peripheral pruning, RV enlargement (late)
  • Echo Doppler: Screening; suggests RV/RA enlargement, tricuspid regurgitation
  • Right heart catheterization: Gold standard
  • Other: LFTs (portal HTN), HIV, ANA, TSH, sickle cell, genetic screening (BMPR2) if indicated

TREATMENT

Goals

  • NYHA/WHO functional class I or II
  • Normal/near-normal RV size/function, hemodynamics (RAP <8 mm Hg, CI >2.5–3 L/min/m²)
  • 6MWD >380–440 m, normal BNP

General Measures

  • Supervised exercise (avoid strenuous activity), psychosocial support, avoid pregnancy, influenza/pneumococcal vaccination, oxygenation (PaO₂ >60 mm Hg)

Medication

  • Acute vasodilator test (during cath): Inhaled NO, IV epoprostenol, IV adenosine
  • If positive: (fall in mean PAP ≥10 mm Hg and <40 mm Hg, CO unchanged/increased)
    • CCBs (nifedipine LA, diltiazem, amlodipine)
    • Avoid verapamil; avoid CCBs if low cardiac index or high RA pressure
  • If negative/WHO-FC II–IV:
  • Oral therapy: ambrisentan, bosentan, macitentan, riociguat, sildenafil, tadalafil
  • Advanced (FC III–IV): IV epoprostenol (first-line FC IV), treprostinil (IV/SC/inhaled), inhaled iloprost, selexipag, combination regimens as needed
  • Endothelin receptor antagonists (ERA): bosentan, ambrisentan, macitentan
  • PDE5 inhibitors: sildenafil, tadalafil, vardenafil
  • Guanylate cyclase stimulator: riociguat
  • Prostacyclin analogs: epoprostenol, treprostinil, iloprost, beraprost
  • Anticoagulation: Consider in IPAH/HPAH (warfarin INR 1.5–2.5) unless contraindicated
  • Diuretics: For RV overload (edema, ascites)
  • Digoxin: For RV failure/atrial arrhythmia

REFERRAL / SURGERY

  • Specialist referral: Pulmonology/cardiology for PAH suspicion/management
  • Atrial septostomy: For severe, refractory PAH as bridge/option before transplant
  • Lung/heart-lung transplant: Advanced, refractory cases

ADMISSION, INPATIENT, NURSING

  • Most therapy is palliative; focus on symptom management and optimizing quality of life

ONGOING CARE

  • Exercise (low level, as tolerated), respiratory training
  • Diet: Fluid/salt restriction (esp. RV failure)

PATIENT EDUCATION

  • Discuss prognosis, need for lifestyle changes, potential for transplant

PROGNOSIS

  • Median survival: 2–3 yrs from diagnosis (older data), now 5-yr survival ~70% with modern therapy
  • Most common cause of death: Right heart failure
  • Poor prognostic markers: Rapid progression, RV failure, NYHA/WHO FC III–IV, 6MWD <300 m, peak VO₂ <10.4 mL/kg/min, pericardial effusion, RV enlargement, RAP >20 mm Hg, CI <2 L/min/m², high BNP/NT-proBNP, scleroderma

COMPLICATIONS

  • Thromboembolism, heart failure, pleural effusion, sudden death, high maternal/fetal risk in pregnancy

ICD-10 Codes

  • I27.0 Primary pulmonary hypertension
  • I27.2 Other secondary pulmonary hypertension

CLINICAL PEARLS

  • PAH is a precapillary form of PH—diagnosis by right heart catheterization.
  • Positive vasodilator test: CCBs are first-line in IPAH.
  • Refer early to specialists; prognosis improved with modern therapies but disease remains serious.