What is pre-capillary pulmonary hypertension (PH)?

Pre-Capillary Pulmonary Hypertension: Definition and Classification

Pre-capillary pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (mPAP) >20 mmHg at rest, with a pulmonary arterial wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units, as measured by right heart catheterization. 1, 2

Hemodynamic Parameters

Pre-capillary PH is characterized by specific hemodynamic criteria:

• mPAP >20 mmHg at rest
• PAWP ≤15 mmHg (normal left atrial pressure)
• PVR ≥3 Wood units

These parameters are essential for distinguishing pre-capillary PH from other forms of pulmonary hypertension, particularly post-capillary PH, which has a PAWP >15 mmHg. 1, 2

Clinical Classification

Pre-capillary PH encompasses several clinical groups in the World Health Organization (WHO) classification:

1. Group 1: Pulmonary Arterial Hypertension (PAH)

   • Idiopathic PAH
   • Heritable PAH (BMPR2, ALK1, EIF2AK4 mutations)
   • Drug and toxin-induced PAH
   • Associated PAH (connective tissue diseases, HIV, portal hypertension, congenital heart disease, schistosomiasis)

2. Group 3: PH due to lung diseases and/or hypoxia

   • Chronic obstructive pulmonary disease
   • Interstitial lung disease
   • Sleep-disordered breathing
   • Alveolar hypoventilation disorders
   • Chronic exposure to high altitude
   • Developmental lung diseases

3. Group 4: Chronic thromboembolic PH (CTEPH) and other pulmonary artery obstructions

   • CTEPH
   • Other pulmonary artery obstructions (tumors, arteritis, congenital stenoses, parasites)

4. Group 5: PH with unclear and/or multifactorial mechanisms

   • Hematological disorders
   • Systemic disorders (sarcoidosis, pulmonary histiocytosis)
   • Metabolic disorders
   • Others (fibrosing mediastinitis, chronic renal failure) 1

Diagnostic Approach

Right heart catheterization is mandatory for the definitive diagnosis of pre-capillary PH, as it provides direct measurement of the key hemodynamic parameters. 2

The diagnostic algorithm includes:

1. Initial suspicion: Based on symptoms (dyspnea, fatigue, syncope) and risk factors
2. Non-invasive assessment: Echocardiography showing elevated systolic pulmonary artery pressure
3. Exclusion of left heart disease: Normal PAWP ≤15 mmHg
4. Determination of PVR: Value ≥3 Wood units confirms significant pulmonary vascular disease
5. Etiological workup: To identify the specific cause and classify according to WHO groups

Clinical Significance

The distinction between pre-capillary and post-capillary PH is crucial for:

• Treatment decisions: Pre-capillary PH may benefit from pulmonary vasodilator therapies, while post-capillary PH requires treatment of the underlying left heart disease 2
• Prognosis: Different forms of pre-capillary PH have varying prognoses
• Therapeutic targets: The pathophysiological mechanisms differ between pre-capillary and post-capillary PH

Important Considerations

• In some cases, a fluid challenge (500 mL saline over 10 minutes) during right heart catheterization may unmask occult left heart disease in patients with borderline PAWP values 2
• Combined pre- and post-capillary PH can occur when both pulmonary vascular disease and left heart disease are present (mPAP >20 mmHg, PAWP >15 mmHg, PVR ≥3 Wood units) 1
• The definition of PH has evolved over time, with the threshold for mPAP being lowered from ≥25 mmHg to >20 mmHg in the most recent guidelines 1, 3

Understanding the hemodynamic definition and classification of pre-capillary PH is essential for appropriate diagnosis, risk stratification, and management of affected patients.