What is pulmonary hypertension?

Pulmonary Hypertension: Definition, Classification, and Clinical Implications

Pulmonary hypertension (PH) is a hemodynamic and pathophysiological condition defined as an increase in mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest as assessed by right heart catheterization. 1 This condition can lead to right heart failure and ultimately death if untreated, affecting approximately 1% of the global population with potentially higher prevalence in low and middle-income countries. 2

Definition and Diagnosis

• PH is diagnosed through right heart catheterization, which remains the gold standard for confirming elevated pulmonary pressures. 1
• The most recent guidelines define PH as mPAP ≥25 mmHg at rest, with normal pulmonary capillary wedge pressure (PCWP) ≤15 mmHg in pre-capillary forms. 1
• The definition of PH on exercise (mPAP >30 mmHg) is not supported by sufficient published data. 1
• Dyspnea on exertion is the most common presenting symptom, particularly in older individuals. 3, 2

Classification

PH is classified into five main groups based on etiology, pathophysiology, and therapeutic approaches:

Group 1: Pulmonary Arterial Hypertension (PAH)

• Characterized by pre-capillary PH with pulmonary vascular resistance >3 Wood units 1
• Includes:
  • Idiopathic PAH
  • Heritable PAH (BMPR2, ALK1, and other mutations)
  • Drug and toxin-induced PAH
  • Associated PAH (connective tissue diseases, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, chronic hemolytic anemia) 1
• PAH associated with congenital heart disease is further subclassified into:
  • Eisenmenger's syndrome
  • PAH with prevalent systemic-to-pulmonary shunts
  • PAH with small defects
  • PAH after defect correction 1

Group 2: PH Due to Left Heart Disease

• Post-capillary PH with PCWP >15 mmHg 1
• Includes:
  • Left ventricular systolic dysfunction
  • Left ventricular diastolic dysfunction
  • Valvular disease
  • Congenital/acquired left heart inflow/outflow tract obstruction 1

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

• Includes:
  • Chronic obstructive pulmonary disease (COPD)
  • Interstitial lung disease
  • Sleep-disordered breathing
  • Alveolar hypoventilation disorders
  • Chronic exposure to high altitude 1

Group 4: Chronic Thromboembolic PH (CTEPH)

• Results from persistent obstruction of pulmonary arteries following pulmonary embolism 1
• Also includes other pulmonary artery obstructions such as angiosarcoma, arteritis, and congenital pulmonary artery stenoses 1

Group 5: PH with Unclear and/or Multifactorial Mechanisms

• Includes:
  • Hematological disorders (chronic hemolytic anemia, myeloproliferative disorders)
  • Systemic disorders (sarcoidosis, pulmonary histiocytosis)
  • Metabolic disorders (glycogen storage disease, Gaucher disease)
  • Others (tumoral obstruction, fibrosing mediastinitis, chronic renal failure) 1

Pathophysiology

• PH involves adverse vascular remodeling with obstruction, stiffening, and vasoconstriction of pulmonary vasculature. 2
• The disease progression leads to right ventricular hypertrophy and eventually right heart failure, which is the main cause of death. 3, 2
• In PAH specifically, there is evidence of Rho-kinase activation in pulmonary arteries and dysfunction in three key endothelial pathways: nitric oxide pathway, endothelin-1 pathway, and prostacyclin pathway. 4, 5

Clinical Implications and Management

• PH significantly impacts all aspects of patient care, particularly in emergency settings where careful volume management is crucial. 3

• In right ventricular failure, vasopressors and inotropes are often required instead of fluid boluses to prevent exacerbating right ventricular ischemia. 3

• Intubation should be avoided when possible as hypoxemia and hypercapnia can worsen right heart function. 3

• Treatment approaches vary by PH classification:

  • For PAH (Group 1): Specific therapies targeting the three dysfunctional endothelial pathways are available, including prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors like sildenafil. 6, 4, 7
  • For Groups 2,3, and 5: Treatment focuses on the underlying cause. 4
  • For Group 4 (CTEPH): Pulmonary endarterectomy is the preferred treatment if patients are eligible; otherwise, balloon pulmonary angioplasty and/or medical therapy may be considered. 4

• Despite advances in treatment, PAH remains a fatal disease with a 3-year survival rate of approximately 58%. 4

Special Considerations

• Patients with PH may require specialized interventions not readily available in all settings, such as pulmonary artery catheterization, inhaled pulmonary vasodilators, and mechanical support. 3
• Early consultation with PH specialists and transfer to tertiary care centers with appropriate monitoring and support capabilities is advised for acute management. 3
• Genetic screening should be systematically considered in PAH patients for mutations in BMPR2, ACVRL1, ENG, or Smad8 genes. 7