What is the definition of pulmonary hypertension?

Definition of Pulmonary Hypertension

Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest as assessed by right heart catheterization. 1, 2

Current Definition and Classification

• PH is a hemodynamic and pathophysiological condition characterized by elevated pressure in the pulmonary arteries, with a diagnostic threshold of mPAP ≥25 mmHg at rest measured via right heart catheterization 2, 1
• The most recent evidence from 2024 has updated this definition to mPAP >20 mmHg, representing an evolution in our understanding of the condition 3, 4
• The definition of PH on exercise (previously defined as mPAP >30 mmHg) is not supported by sufficient published data and is no longer recommended 2, 1

Hemodynamic Classifications

• Pre-capillary PH: mPAP ≥25 mmHg with pulmonary wedge pressure (PWP) ≤15 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units 2
• Post-capillary PH: mPAP ≥25 mmHg with PWP >15 mmHg 2
  • Passive: Transpulmonary pressure gradient (TPG) ≤12 mmHg 2
  • Reactive (out of proportion): TPG >12 mmHg 2

Clinical Classification

PH is categorized into five major groups based on etiology, pathophysiology, and therapeutic approaches 1, 2:

1. Group 1: Pulmonary Arterial Hypertension (PAH)

   • Idiopathic PAH
   • Heritable PAH (BMPR2, ALK1, endoglin mutations)
   • Drug and toxin-induced
   • Associated with other conditions (connective tissue diseases, HIV, portal hypertension, congenital heart disease) 2, 1

2. Group 2: PH Due to Left Heart Disease

   • Left ventricular systolic dysfunction
   • Left ventricular diastolic dysfunction
   • Valvular disease 2, 1

3. 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 2, 1

4. Group 4: Chronic Thromboembolic PH (CTEPH)

   • Thromboembolic obstruction of proximal pulmonary arteries
   • Thromboembolic obstruction of distal pulmonary arteries
   • Non-thrombotic pulmonary embolism 2, 1

5. Group 5: PH with Unclear and/or Multifactorial Mechanisms

   • Hematological disorders
   • Systemic disorders
   • Metabolic disorders
   • Other 2, 1

Clinical Impact

• PH affects approximately 1% of the global population, with a higher burden likely in low-income and middle-income countries 3
• Without appropriate management, PH leads to right ventricular hypertrophy, right heart failure, and ultimately death 3, 5
• The median life expectancy from diagnosis in patients with idiopathic PAH, before the availability of disease-specific therapy, was 2.8 years 2

Diagnostic Considerations

• Right heart catheterization remains the gold standard for confirming PH diagnosis 1, 2
• The 2022 ACR Appropriateness Criteria update acknowledges the redefinition of PH as mPAP >20 mmHg at rest 2
• Precapillary PH is characterized by mPAP >20 mmHg, PAWP ≤15 mmHg, and PVR ≥3 Wood units (groups 1,3,4, and 5) 2
• Combined pre- and postcapillary PH is characterized by mPAP >20 mmHg, PAWP >15 mmHg, and PVR ≥3 Wood units (groups 2 and 5) 2

Important Caveats

• The definition of PH has evolved over time, with the threshold being lowered from 25 mmHg to 20 mmHg in more recent guidelines 2, 3, 4
• Despite this evolution, most established clinical trials and registries have used the ≥25 mmHg threshold 2
• The significance of a mean PAP between 21 and 24 mmHg remains unclear and requires further evaluation in epidemiological studies 2
• Exercise-induced PH definitions remain controversial and are not currently supported by sufficient evidence 2, 1