What are the different types of pulmonary hypertension and their management strategies?

Types of Pulmonary Hypertension and Their Management Strategies

Pulmonary hypertension (PH) is classified into five distinct clinical groups based on underlying pathophysiology, with specific management approaches required for each type to reduce morbidity and mortality. 1

Definition and Diagnosis

Pulmonary hypertension is defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest measured by right heart catheterization 2. Recent guidelines have updated this threshold to >20 mmHg 3.

Right heart catheterization is essential for:

• Confirming diagnosis
• Determining specific classification
• Guiding appropriate therapy
• Assessing prognosis

The Five Clinical Groups of Pulmonary Hypertension

Group 1: Pulmonary Arterial Hypertension (PAH)

• Pathophysiology: Pre-capillary PH with pulmonary vascular resistance >3 Wood units and normal pulmonary wedge pressure ≤15 mmHg 1
• Subtypes:
  • Idiopathic PAH
  • Heritable PAH (BMPR2 mutations and others)
  • Drug and toxin-induced PAH
  • Associated PAH (connective tissue disease, HIV, portal hypertension, congenital heart disease, schistosomiasis)
  • Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis
  • Persistent pulmonary hypertension of the newborn
• Management:
  • Initial combination therapy targeting multiple pathways is recommended 2
  • First-line options include:
    • Phosphodiesterase-5 inhibitors (sildenafil) 4
    • Endothelin receptor antagonists
    • Prostacyclin analogs (epoprostenol) for high-risk patients 5
  • Risk stratification guides therapy intensity
  • Lung transplantation for refractory cases

Group 2: PH due to Left Heart Disease

• Pathophysiology: Post-capillary PH with elevated pulmonary wedge pressure >15 mmHg 1
• Subtypes:
  • Left ventricular systolic dysfunction
  • Left ventricular diastolic dysfunction
  • Valvular heart disease
  • Congenital/acquired left heart inflow/outflow tract obstruction
  • Congenital/acquired pulmonary vein stenosis
• Prevalence: Up to 60% of patients with severe LV systolic dysfunction and 70% with preserved ejection fraction 1
• Management:
  • Focus on treating the underlying cardiac condition 2
  • Optimize volume status
  • PAH-specific therapies are not recommended and may worsen outcomes

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

• Subtypes:
  • Chronic obstructive pulmonary disease
  • Interstitial lung disease
  • Mixed restrictive/obstructive patterns
  • Sleep-disordered breathing
  • Alveolar hypoventilation disorders
  • Chronic high-altitude exposure
  • Developmental lung diseases
• Management:
  • Treat underlying pulmonary condition 2
  • Long-term oxygen therapy for hypoxemia
  • PAH-specific therapies generally not recommended
  • Consider lung transplantation for advanced disease

Group 4: Chronic Thromboembolic PH (CTEPH)

• Subtypes:
  • Chronic thromboembolic pulmonary hypertension
  • Other pulmonary artery obstructions (tumors, arteritis, congenital stenoses, parasites)
• Management:
  • Pulmonary endarterectomy is first-line for eligible patients 2
  • Balloon pulmonary angioplasty for inoperable cases
  • Riociguat (soluble guanylate cyclase stimulator) for inoperable or persistent/recurrent CTEPH 6
  • Lifelong anticoagulation (INR 2-3) 2

Group 5: PH with Unclear/Multifactorial Mechanisms

• Subtypes:
  • Hematological disorders (chronic hemolytic anemia, myeloproliferative disorders)
  • Systemic disorders (sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis)
  • Metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders)
  • Others (tumoral thrombotic microangiopathy, fibrosing mediastinitis, chronic renal failure)
• Management:
  • Treat underlying condition
  • Limited evidence for PAH-specific therapies
  • Individualized approach based on hemodynamic profile

Diagnostic Approach

1. Initial screening:

   • Transthoracic echocardiography (first-line non-invasive test) 2
   • ECG, chest radiograph, pulmonary function tests with DLCO
   • Basic laboratory tests

2. Specialized testing:

   • Ventilation/perfusion (V/Q) scan to rule out CTEPH 2
   • High-resolution CT to evaluate lung parenchyma
   • Right heart catheterization for definitive diagnosis and classification

Follow-up and Monitoring

• Regular clinical assessment every 3-6 months 2
• Exercise capacity (6-minute walk test) every 3-6 months
• Echocardiography every 6-12 months
• Repeat right heart catheterization when clinical worsening occurs or after therapy changes

Common Pitfalls and Caveats

1. Misclassification: Failure to identify the correct PH group can lead to inappropriate therapy and worse outcomes.

2. Delayed diagnosis: PH is often diagnosed late in its course when right ventricular failure has already developed.

3. Inappropriate use of PAH-specific therapies: These medications can worsen outcomes in Group 2 PH.

4. Missing CTEPH: Always perform V/Q scanning in unexplained PH, as CT angiography alone may miss chronic thromboembolic disease.

5. Inadequate right heart catheterization: Hemodynamic confirmation is essential for proper diagnosis and classification.

6. Volume management challenges: Patients with right ventricular failure require careful volume management, especially during acute decompensation.

7. Medication interruptions: Abrupt discontinuation of PAH therapies can lead to rebound pulmonary hypertension and death.