How would I classify this patient's pulmonary hypertension into a WHO group?

Classification of Pulmonary Hypertension into WHO Groups

To classify pulmonary hypertension into a WHO group, you must first confirm PH with right heart catheterization showing mean pulmonary arterial pressure ≥25 mmHg, then systematically evaluate for specific etiologies according to the 2018 updated WHO classification system. 1

Diagnostic Confirmation of PH

First, confirm the presence of pulmonary hypertension:

• Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest measured by right heart catheterization 1
• Note: The 2018 redefinition lowered the threshold to >20 mmHg 1

WHO Classification System

The 2018 updated clinical classification divides PH into 5 groups 1:

Group 1: Pulmonary Arterial Hypertension (PAH)

• Hemodynamic criteria: Pre-capillary PH with mPAP >20 mmHg, PAWP ≤15 mmHg, PVR ≥3 Wood units 1
• Includes:
  • Idiopathic PAH
  • Heritable PAH (BMPR2, ALK1, ENG, SMAD9, CAV1, KCNK3 mutations)
  • Drug and toxin-induced
  • Associated with connective tissue disease, HIV, portal hypertension, congenital heart disease
  • PAH with long-term response to calcium channel blockers
  • PAH with overt features of venous/capillary involvement

Group 2: PH due to Left Heart Disease

• Hemodynamic criteria: Post-capillary PH with mPAP >20 mmHg, PAWP >15 mmHg 1
• Includes:
  • Left ventricular systolic/diastolic dysfunction
  • Valvular disease
  • Congenital/acquired left heart inflow/outflow tract obstruction
  • Congenital cardiomyopathies

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

• Pre-capillary PH associated with:
  • Chronic obstructive pulmonary disease
  • Interstitial lung disease
  • Mixed restrictive and obstructive pattern
  • Sleep-disordered breathing
  • Alveolar hypoventilation disorders
  • Chronic exposure to high altitude
  • Developmental lung diseases

Group 4: PH due to Pulmonary Artery Obstructions

• Pre-capillary PH due to:
  • Chronic thromboembolic pulmonary hypertension (CTEPH)
  • Other pulmonary artery obstructions (tumors, arteritis, congenital stenoses, parasites)

Group 5: PH with Unclear and/or Multifactorial Mechanisms

• Includes:
  • Hematological disorders (chronic hemolytic anemia, myeloproliferative disorders)
  • Systemic disorders (sarcoidosis, pulmonary Langerhans cell histiocytosis)
  • Metabolic disorders (glycogen storage disease, Gaucher disease)
  • Others (segmental PH, chronic renal failure with/without dialysis)

Systematic Approach to Classification

1. Confirm PH with right heart catheterization 1

   • Measure mPAP, PAWP, PVR

2. Determine if pre-capillary or post-capillary PH 1

   • Pre-capillary: PAWP ≤15 mmHg (Groups 1,3,4,5)
   • Post-capillary: PAWP >15 mmHg (Group 2, some Group 5)

3. Systematic evaluation for specific etiologies:

   a. For suspected Group 1 (PAH):

   • Rule out Groups 2-5 first (diagnosis of exclusion)
   • Check for associated conditions (connective tissue disease, HIV, portal hypertension)
   • Consider genetic testing for BMPR2 mutations 2
   • Evaluate for drug/toxin exposure history

   b. For suspected Group 2 (left heart disease):

   • Echocardiography to assess left ventricular function and valvular disease
   • Consider left heart catheterization if needed

   c. For suspected Group 3 (lung disease):

   • Pulmonary function tests
   • High-resolution CT of chest
   • Sleep studies if indicated

   d. For suspected Group 4 (CTEPH):

   • Ventilation/perfusion (V/Q) scan (recommended as first-line test) 1
   • CT pulmonary angiography if V/Q scan positive or indeterminate

   e. For suspected Group 5:

   • Evaluate for hematologic disorders, systemic conditions, metabolic disorders

Important Diagnostic Tests

• Ventilation/perfusion scan: Essential to rule out CTEPH (Group 4) 1
• High-resolution CT: Evaluate for lung parenchymal disease (Group 3) 1
• Pulmonary function tests: Identify underlying respiratory conditions 3
• Echocardiography: Assess cardiac function and structure 3
• Abdominal ultrasound: Screen for portal hypertension 1
• Laboratory tests: CBC, renal/liver function, thyroid function, immunology 1

Clinical Pitfalls to Avoid

1. Failure to confirm PH with right heart catheterization

   • Echocardiography alone is insufficient for definitive diagnosis 3

2. Overlooking CTEPH (Group 4)

   • Always perform V/Q scan in unexplained PH; CT angiography alone may miss CTEPH 1

3. Missing mixed etiologies

   • Patients may have features of multiple groups (e.g., combined pre- and post-capillary PH) 1

4. Incomplete workup for Group 1 PAH

   • PAH is a diagnosis of exclusion after ruling out Groups 2-5 1

5. Neglecting treatment implications of classification

   • PAH-specific therapies (e.g., sildenafil, epoprostenol) are indicated only for Group 1 4, 5
   • Misclassification can lead to inappropriate treatment and worse outcomes

By systematically following this approach, you can accurately classify pulmonary hypertension into the appropriate WHO group, which is essential for determining proper treatment and prognosis.