Pre-Capillary Pulmonary Hypertension: Definition and Clinical Significance
Pre-capillary pulmonary hypertension is defined hemodynamically by a mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, pulmonary artery wedge pressure (PAWP) ≤15 mmHg, and pulmonary vascular resistance (PVR) >3 Wood units, measured by right heart catheterization. 1
Hemodynamic Criteria
The defining hemodynamic parameters that distinguish pre-capillary PH from other forms are:
- mPAP ≥25 mmHg at rest (though recent data suggests normal mPAP is 14±3 mmHg with upper limit ~20 mmHg) 1, 2
- PAWP ≤15 mmHg (distinguishes from post-capillary PH where PAWP >15 mmHg) 1
- PVR >3 Wood units (critical threshold separating pre-capillary from other forms) 1
- Cardiac output normal or reduced 1
The low wedge pressure is the key distinguishing feature—it indicates the problem originates before the pulmonary capillaries (in the pulmonary arteries themselves), rather than being caused by backup from left heart disease. 1
Clinical Groups with Pre-Capillary PH
Pre-capillary PH encompasses four of the five clinical classification groups: 1, 3
Group 1: Pulmonary Arterial Hypertension (PAH)
- Idiopathic PAH 1
- Heritable PAH (BMPR2 mutations and other genetic mutations) 1
- Drug and toxin-induced PAH 1
- Associated PAH: connective tissue disease, portal hypertension, congenital heart disease, HIV, schistosomiasis 1
- Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) 1
Group 3: PH Due to Lung Diseases and/or Hypoxia
- Chronic obstructive pulmonary disease (COPD) 1
- Interstitial lung disease 1
- Sleep-disordered breathing 1
- Alveolar hypoventilation disorders 1
- Chronic high altitude exposure 1
Group 4: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
- Persistent pulmonary artery obstruction following pulmonary embolism 1
- Other pulmonary artery obstructions (angiosarcoma, arteritis, congenital stenoses) 1
Group 5: PH with Unclear/Multifactorial Mechanisms
- Hematological disorders, systemic diseases, metabolic disorders 1
Pathophysiological Distinction
The fundamental difference between pre-capillary and post-capillary PH lies in the site of vascular resistance: 3
Pre-capillary PH: The pathology is in the pulmonary arteries and arterioles before the capillary bed, causing increased resistance to blood flow from intrinsic vascular remodeling, vasoconstriction, or obstruction 1, 4, 3
Post-capillary PH (Group 2): Elevated pressure results from backward transmission of elevated left atrial pressure due to left heart disease, with PAWP >15 mmHg 1, 3
Clinical Implications
The distinction between pre-capillary and post-capillary PH is critical because treatment strategies differ fundamentally: 4
- PAH-specific therapies (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclin analogs) are indicated for Group 1 PAH 4
- These same therapies are NOT recommended for Groups 2,3, or 5 PH, where treatment focuses on the underlying disease 4
- Group 4 CTEPH requires pulmonary endarterectomy if eligible, or balloon pulmonary angioplasty and/or medical therapy 4
Important Caveats
Combined pre- and post-capillary PH exists when patients have mPAP >20 mmHg, PAWP >15 mmHg, AND PVR ≥3 Wood units—this represents overlap pathophysiology often seen in patients with multiple cardiovascular comorbidities. 2, 5, 6
Right heart catheterization remains the gold standard for diagnosis and classification—echocardiography can suggest PH but cannot definitively distinguish pre-capillary from post-capillary forms. 1, 2
Prognosis without treatment is poor: Historical data showed median survival of only 2.8 years for idiopathic PAH before disease-specific therapies became available. 2, 7