Pulmonary Hypertension — Overview

Definition

Hemodynamic Classification (6th WSPH)

WHO Clinical Classification (5 Groups)

Left heart disease (Group 2) is the most common form of PH in community studies; idiopathic PAH is the rarest.

Pathophysiology

1. Vasoconstriction

• Hypoxia triggers intrinsic pulmonary arterial smooth muscle cell (PASMC) contraction — even without endothelium.
• Reduced shear stress → ↓ nitric oxide (NO) production → impaired vasodilation → enhanced vasoconstriction.
• Serotonin and thromboxane from activated platelets amplify vasoconstriction.

2. Vascular Remodeling

• Medial thickening: PASMC proliferation and hypertrophy in small pulmonary arteries and arterioles.
• Intimal proliferation: Fibrosis and concentric laminar thickening, narrowing/obliterating the vessel lumen.
• Plexiform lesions: Aneurysmatic dilations of small arteries filled with proliferating endothelial cells, SMCs, and myofibroblasts — hallmark of severe PAH. Found in IPAH, CHD-associated PAH, HIV, liver cirrhosis, and scleroderma.
• Increased arterial stiffness: Accelerated extracellular matrix turnover (e.g., tenascin-C upregulation) raises PVR independently of smooth muscle tone.
• Growth factors driving remodeling include PDGF, TGF-β, and VEGF from platelets and endothelial cells.

3. In Situ Thrombosis

• Monoclonal endothelial proliferation + platelet activation → local pro-coagulant shift within small vessels.
• Occurs without a remote embolic source, distinguishing it from thromboembolic PH (Group 4).
• Shear stress from elevated pressure further activates endothelium toward a procoagulant phenotype.

Downstream consequence

Epidemiology

• Affects all ages and races; women > men (most pronounced in PAH).
• PAH prevalence: ~15–50 per million persons.
• Overall PH prevalence: ~100–127 per 100,000 (Canada data); rising due to increasing HFpEF and sleep apnea.

Diagnostic Tests for Pulmonary Hypertension

Diagnostic Pathway

1. Echocardiography — First-Line Screen

Quantitative estimation of PAP

• Tricuspid regurgitant (TR) jet velocity measured by Doppler
• Modified Bernoulli equation: RVSP = 4v² + RAP (v = TR jet velocity in m/s)
• RVSP is assumed equal to PASP when the pulmonic valve is normal
• Normal RVSP: 28 ± 5 mm Hg; screening echo suggests PH when PASP > 40 mm Hg (Goldman-Cecil) or peak TRv > 2.8 m/s (echocardiography textbook)

Echocardiographic PH thresholds (6th WSPH–aligned):

Qualitative 2D features of elevated PAP

• Right atrial (RA) enlargement
• Right ventricular (RV) enlargement
• Flattening of the interventricular septum ("D-sign")
• Underfilled left ventricle
• Pericardial effusion (marker of high risk; RA area >26 cm² = high-risk)

Etiological clues on echo

Limitation: Echo is unreliable in parenchymal lung disease/hyperinflation; correlation with RHC is imperfect. In ~25% of patients with severe PAH, a patent foramen ovale can shunt right→left, worsening hypoxia.

2. Right Heart Catheterization — Gold Standard

1. Confirm the diagnosis of PH (mPAP >20 mm Hg)
2. Classify hemodynamic subtype (pre- vs. postcapillary)
3. Assess severity (PVR, cardiac index, RAP, SvO₂)
4. Guide therapy

Key hemodynamic parameters measured at RHC

Acute Vasoreactivity Testing (during RHC)

• Who: Indicated at initial RHC for idiopathic, hereditable, or drug-induced PAH only
• Agents: Inhaled nitric oxide, IV adenosine, or IV epoprostenol (short-acting)
• Positive response: ↓mPAP by ≥10 mm Hg to an absolute mPAP ≤40 mm Hg, with stable or improved cardiac output
• Significance: ~10% of IPAH patients are acute responders; ~50% of these sustain long-term benefit with oral calcium channel blockers (CCBs) — with 5-year survival ~94%
• ⚠️ CCBs must NOT be given without documented vasoreactivity — can cause hypotension, ↓ CO, arrhythmia, and death in non-responders

3. Laboratory Tests

Biomarkers

Connective tissue disease / etiology workup

4. Additional Non-Invasive Tests

ECG

• Right axis deviation
• RV hypertrophy (R > S in V1)
• Right atrial enlargement ("P pulmonale" — peaked P in lead II)
• ST/T changes in anterior precordium (RV strain pattern)
• ⚠️ Normal ECG does NOT exclude PH

Chest X-ray

• Enlarged proximal pulmonary arteries
• Peripheral vascular "pruning" (reduced peripheral vasculature)
• Right ventricular enlargement (reduced retrosternal air space on lateral view)
• ⚠️ Normal CXR does NOT exclude PH

V/Q Scan

• Study of choice to exclude CTEPH (Group 4)
• Shows mismatched perfusion defects (perfusion deficit without corresponding ventilation deficit)
• CT-PA may miss chronic thromboembolic disease — V/Q is preferred for CTEPH screening

Pulmonary Function Tests (PFTs)

• PAH: mild restrictive pattern or mild ↓ DLCO
• Group 3 PH: obstructive (COPD) or restrictive (ILD) pattern
• Helps differentiate lung disease–related PH

CT Chest / HRCT

• Identifies parenchymal lung disease (Group 3)
• Can show dilated central PAs, RV enlargement
• CT-PA: useful for acute PE but less sensitive for chronic CTEPH than V/Q

Cardiopulmonary Exercise Testing (CPET)

• ↓ Peak VO₂ and elevated VE/VCO₂ slope reflect impaired RV reserve
• Used in risk stratification: PeakVO₂ <11 mL/min/kg = high risk

Risk Stratification Summary (ESC/ERS, at RHC)