What is the diagnostic workup for pulmonary hypertension?

Diagnostic Workup for Pulmonary Hypertension

The diagnostic workup for pulmonary hypertension requires a systematic approach starting with echocardiography as the first-line non-invasive screening test, followed by additional testing to determine etiology, with right heart catheterization being mandatory for definitive diagnosis and classification.

Definition and Initial Suspicion

Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (PAP) ≥25 mmHg at rest measured by right heart catheterization 1, 2. Early symptoms are often nonspecific, including:

• Breathlessness on exertion (most common)
• Fatigue
• Syncope (especially in children)
• Angina pectoris
• Palpitations
• Dry cough
• Exertional nausea and vomiting 3

Diagnostic Algorithm

Step 1: Initial Screening Tests

When PH is suspected, the following initial tests should be performed:

• Transthoracic echocardiography (recommended as first-line screening) 1
• Electrocardiogram
• Chest radiograph
• Basic laboratory tests:
  • Complete blood count
  • Renal and liver function tests
  • Thyroid function tests 3

Step 2: Assessment Based on Echocardiographic Probability

If echocardiography shows high or intermediate probability of PH:

• Clinical history, symptoms, and signs evaluation
• Pulmonary function tests (including DLCO)
• Arterial blood gases analysis
• High-resolution CT of the chest
• Consider nocturnal oximetry if required 1

Step 3: Differential Diagnosis of PH Groups

Based on initial findings, determine if left heart disease (group 2) or lung disease (group 3) is present:

• If left heart or lung disease is confirmed with severe PH/RV dysfunction → refer to PH expert center
• If left heart or lung disease is not confirmed → proceed to ventilation/perfusion (V/Q) lung scan 1

Step 4: V/Q Scan Interpretation

• Multiple segmental perfusion defects → suspect CTEPH (group 4)
  • Requires CT pulmonary angiography, RHC, and selective pulmonary angiography for confirmation
• Normal or subsegmental "patchy" perfusion defects → suspect PAH (group 1) or rarer conditions (group 5) 1

Step 5: Definitive Diagnosis - Right Heart Catheterization

RHC is mandatory to confirm diagnosis with the following hemodynamic criteria:

• Mean PAP ≥25 mmHg
• For pre-capillary PH (including PAH): Pulmonary wedge pressure (PWP) ≤15 mmHg
• For post-capillary PH: PWP >15 mmHg 1, 2

Step 6: Additional Testing Based on Suspected Etiology

For suspected PAH (group 1):

• Immunology testing
• HIV testing
• Abdominal ultrasound (for portal hypertension)
• Thyroid function tests
• Connective tissue disease screening 1

For suspected CTEPH (group 4):

• CT pulmonary angiography
• Selective pulmonary angiography 1

Important Diagnostic Tests and Their Roles

1. Echocardiography:

   • Key screening tool
   • Estimates pulmonary pressure
   • Assesses right ventricular function
   • Helps exclude secondary causes 4

2. Right Heart Catheterization:

   • Gold standard for definitive diagnosis
   • Measures exact pulmonary pressures
   • Assesses vasoreactivity (important for treatment decisions)
   • Determines cardiac output and pulmonary vascular resistance 5

3. V/Q Scan:

   • Essential to rule out CTEPH
   • More sensitive than CT angiography alone for chronic thromboembolic disease 1

4. High-Resolution CT:

   • Evaluates lung parenchymal disease
   • May show signs of PVOD (pulmonary veno-occlusive disease) 1

5. Pulmonary Function Tests with DLCO:

   • Identifies underlying respiratory conditions
   • DLCO often reduced in PAH 1

6. Biomarkers:

   • BNP/NT-proBNP: diagnostic and prognostic value
   • Other markers: endothelin-1, uric acid, troponin 4, 5

Common Pitfalls to Avoid

• Misdiagnosis due to nonspecific symptoms: Dyspnea and fatigue are common in many conditions; maintain high index of suspicion 3
• Relying solely on echocardiography: While useful for screening, it cannot replace RHC for definitive diagnosis 1
• Missing CTEPH: CT pulmonary angiography alone may miss diagnosis; V/Q scan is essential 1
• Inadequate hemodynamic assessment: Proper RHC technique is crucial for accurate diagnosis 2
• Delayed diagnosis: Early symptoms are often nonspecific, leading to advanced disease at presentation 2
• Open lung biopsy: Not recommended in patients with PAH 1

Follow-up Assessment

After diagnosis, regular follow-up is essential to monitor disease progression and treatment response:

• Clinical assessment and functional class: Every 3-6 months
• ECG: Every 3-6 months
• Exercise capacity (6MWT): Every 3-6 months
• Echocardiography: Every 6-12 months
• Basic laboratory tests: Every 3-6 months
• RHC: At baseline and when clinical worsening occurs or after therapy changes 1

By following this systematic diagnostic approach, clinicians can accurately diagnose pulmonary hypertension, determine its etiology, and guide appropriate treatment decisions to improve patient outcomes.