Pulmonary Hypertension is defined as a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg at rest (per older definitions) or >20 mmHg based on newer guidelines confirmed by right heart catheterization .
- Normal mPAP : 10–20 mmHg
- PH Threshold : >20 mmHg (at rest)
- PH with clinical significance : Often with pulmonary vascular resistance (PVR) ≥ 3 Wood units
High-Yield : Right heart catheterization is the gold standard for diagnosis.
Pathophysiology
PH results from increased pulmonary vascular resistance (PVR) or elevated left heart pressures , leading to right ventricular strain and failure over time.
Key Mechanisms:
- Vasoconstriction
- Vascular remodeling – due to endothelial dysfunction, proliferation, and fibrosis
- Thrombosis in situ
- Inflammation
Histological Features:
- Intimal fibrosis
- Medial hypertrophy
- Plexiform lesions in advanced disease
- Thrombotic arteriopathy
High-Yield Mnemonic : “ V-R-I-T ”
V asoconstriction, R emodeling, I nflammation, T hrombosis
Classification (WHO Groups)
| Group | Cause |
|---|---|
| Group 1 | Pulmonary Arterial Hypertension (PAH): idiopathic, heritable, drugs (e.g., fenfluramine), connective tissue disease |
| Group 2 | Left heart disease (e.g., LV dysfunction, mitral valve disease) |
| Group 3 | Lung diseases/hypoxia (e.g., COPD, ILD, sleep apnea) |
| Group 4 | Chronic thromboembolic pulmonary hypertension (CTEPH) |
| Group 5 | Multifactorial or unclear causes (e.g., sarcoidosis, metabolic disorders) |
New York Heart Association (NYHA)/WHO Functional Classification
| Class | Symptoms |
|---|---|
| I | No limitation; ordinary physical activity does not cause symptoms |
| II | Slight limitation; comfortable at rest; ordinary activity causes symptoms |
| III | Marked limitation; less-than-ordinary activity causes symptoms |
| IV | Inability to perform any activity without symptoms; signs of right heart failure present |
Clinical Features
Symptoms:
- Exertional dyspnea (most common)
- Fatigue
- Chest pain (angina)
- Syncope
- Non-productive cough
- Hemoptysis (rare)
- Palpitations
Physical Examination:
- Loud P2 (accentuated pulmonary component of S2)
- Right ventricular heave
- Jugular venous distension (JVD)
- Right-sided S3 gallop
- Tricuspid regurgitation murmur
- Hepatomegaly
- Peripheral edema
- Cyanosis (advanced disease)
Diagnosis
Gold Standard:
- Right Heart Catheterization – confirms mPAP >20 mmHg
Supporting Investigations:
| Test | Findings |
|---|---|
| Echocardiography with Doppler | RV hypertrophy/dilatation, elevated PAP |
| CT Chest | Enlarged pulmonary arteries |
| Chest X-ray | Prominent pulmonary arteries, RV enlargement |
| ECG | Right axis deviation, right atrial enlargement, RBBB |
| ABG | Respiratory alkalosis (low PaCO₂) due to hyperventilation |
| V/Q Scan | Used to detect CTEPH |
| Pulmonary Function Test (PFT) | Rule out obstructive/restrictive diseases |
| MRI | RV structure/function analysis |
| Laboratory | ANA, HIV serology to assess for secondary causes |
Treatment
General Measures:
- Oxygen therapy (especially if hypoxemic)
- Diuretics for volume overload
- Salt restriction
- Vaccination (influenza, pneumococcal)
- Anticoagulation (especially in CTEPH)
Targeted Therapies for PAH (Group 1):
| Drug Class | Examples | Indication |
|---|---|---|
| Calcium Channel Blockers | Amlodipine, Nifedipine | Only if vasoreactivity testing is positive |
| Endothelin Receptor Antagonists | Bosentan, Ambrisentan | WHO Class II or III |
| PDE-5 Inhibitors | Sildenafil, Tadalafil | WHO Class II or III |
| Prostacyclin Analogs | Epoprostenol (IV), Treprostinil | Severe cases, Class III-IV |
| Soluble Guanylate Cyclase Stimulators | Riociguat | PAH and CTEPH |
| Inhaled Nitric Oxide (iNO) | ICU use for refractory hypoxemia | Reduces PVR |
High-Yield : Epoprostenol (continuous IV infusion) is the only treatment shown to improve survival in advanced PAH.
Treatment by WHO Group:
- Group 1 (PAH) – Targeted therapies + supportive care
- Group 2 (Left heart disease) – Treat underlying cardiac condition
- Group 3 (Lung disease) – Oxygen therapy, treat primary lung disorder
- Group 4 (CTEPH) – Anticoagulation , pulmonary thromboendarterectomy , riociguat
- Group 5 – Treat underlying multifactorial cause
Surgical Options:
- Atrial septostomy (palliative)
- Lung transplantation
- Heart-lung transplantation in selected cases
Prognosis
Prognosis depends on:
- Underlying cause
- Response to treatment
- Functional class
- RV function (most important determinant of survival)
Formula to Remember
mPAP = LAP + (PVR × CO)
- LAP = Left Atrial Pressure
- CO = Cardiac Output
- PVR = Pulmonary Vascular Resistance
Clinical Pearls:
- Women (ages 20–40) are more commonly affected in idiopathic PAH.
- Exercise intolerance is often the earliest symptom.
- Always assess for connective tissue disease, HIV, and chronic thromboembolic disease.
- In patients with COPD and PH, oxygen therapy improves survival.
- Use V/Q scan over CT angiography to evaluate CTEPH.
