What are the different groups of pulmonary hypertension?

Groups of Pulmonary Hypertension

Pulmonary hypertension (PH) is classified into five distinct clinical groups based on etiology, pathophysiology, hemodynamic characteristics, and treatment approaches, as defined by the European Society of Cardiology (ESC) and European Respiratory Society (ERS). 1

Definition of Pulmonary Hypertension

• PH is defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest as assessed by right heart catheterization 1
• PH can be categorized as pre-capillary (pulmonary arterial wedge pressure [PAWP] ≤15 mmHg) or post-capillary (PAWP >15 mmHg) based on hemodynamic measurements 1

The Five Clinical Groups of Pulmonary Hypertension

Group 1: Pulmonary Arterial Hypertension (PAH)

• Characterized by pre-capillary PH with normal PAWP ≤15 mmHg 1, 2
• Includes multiple subgroups:
  • 1.1 Idiopathic PAH 1
  • 1.2 Heritable PAH (BMPR2, ALK1, endoglin mutations) 1
  • 1.3 Drug and toxin-induced PAH 1
  • 1.4 Associated PAH (APAH) including:
    • Connective tissue diseases 1
    • HIV infection 1
    • Portal hypertension 1
    • Congenital heart disease 1
    • Schistosomiasis 1
    • Chronic hemolytic anemia 1
  • 1.5 Persistent pulmonary hypertension of the newborn (subgroup 1") 1
  • 1' Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH) 1

Group 2: PH due to Left Heart Disease

• Post-capillary PH with PAWP >15 mmHg 1, 2
• Includes:
  • 2.1 Systolic dysfunction 1
  • 2.2 Diastolic dysfunction 1
  • 2.3 Valvular disease 1
  • 2.4 Pediatric heart diseases including congenital/acquired left heart inflow or outflow tract obstruction and congenital cardiomyopathies 1, 3

Group 3: PH due to Lung Diseases and/or Hypoxia

• Pre-capillary PH associated with respiratory disorders 1
• Includes:
  • 3.1 Chronic obstructive pulmonary disease 1
  • 3.2 Interstitial lung disease 1
  • 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 1
  • 3.4 Sleep-disordered breathing 1
  • 3.5 Alveolar hypoventilation disorders 1
  • 3.6 Chronic exposure to high altitude 1
  • 3.7 Developmental abnormalities 1

Group 4: Chronic Thromboembolic PH (CTEPH) and Other Pulmonary Artery Obstructions

• Pre-capillary PH due to obstruction of pulmonary arteries 1, 4
• Includes:
  • CTEPH 1
  • Pulmonary angiosarcoma 1
  • Other intravascular tumors 1
  • Arteritis 1
  • Congenital pulmonary artery stenoses 1
  • Parasitic conditions affecting pulmonary arteries 1

Group 5: PH with Unclear and/or Multifactorial Mechanisms

• Heterogeneous group with various underlying conditions 1
• Includes:
  • 5.1 Hematological disorders (myeloproliferative disorders, splenectomy) 1
  • 5.2 Systemic disorders (sarcoidosis, pulmonary Langerhans cell histiocytosis) 1
  • 5.3 Metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders) 1
  • 5.4 Others (tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis) 1
  • Segmental PH observed in discrete lung areas perfused by aorto-pulmonary collaterals in congenital heart diseases 1

Hemodynamic Classification

• Pre-capillary PH: mPAP ≥25 mmHg with PAWP ≤15 mmHg (Groups 1,3,4, and some cases of Group 5) 1, 2
• Post-capillary PH: mPAP ≥25 mmHg with PAWP >15 mmHg (Group 2 and some cases of Group 5) 1, 2
  • Isolated post-capillary PH: Diastolic pressure gradient (DPG) <7 mmHg and/or pulmonary vascular resistance (PVR) ≤3 Wood Units 1
  • Combined post-capillary and pre-capillary PH: DPG ≥7 mmHg and/or PVR >3 Wood Units 1

Epidemiological Considerations

• The prevalence of PAH is approximately 15-60 cases per million adult population 3, 5
• Left heart disease (Group 2) is believed to be the most common cause of PH, affecting approximately 1% of the global population 1, 4
• Schistosomiasis-associated PAH and high altitude-related PH represent significant global health burdens, particularly in low and middle-income countries 1, 5

Clinical Implications

• Each group has distinct pathophysiological mechanisms, clinical presentations, and treatment approaches 3, 4
• Accurate classification is essential for appropriate management, as treatments approved for PAH may not be effective or may be harmful in other PH groups 2, 6
• Prognosis varies significantly between groups, with PAH having a poor prognosis if untreated (approximately 15% mortality in the first year) 3, 6