What is the recommended diagnostic and treatment approach for a patient with pulmonary hypertension?

Diagnostic and Treatment Approach for Pulmonary Hypertension

Echocardiography is the recommended first-line non-invasive diagnostic investigation for suspected pulmonary hypertension, followed by a systematic diagnostic algorithm to determine the specific type of PH and appropriate treatment strategy. 1

Diagnostic Algorithm

Initial Evaluation

• Echocardiography: First-line diagnostic test to estimate probability of PH 1
• Based on echocardiographic probability (high, intermediate, or low):
  • Low probability: No additional investigations needed, consider other causes for symptoms 1
  • Intermediate/High probability: Proceed with comprehensive workup

Comprehensive Workup

1. Clinical assessment and basic testing:

   • Clinical history, symptoms, signs
   • ECG, chest radiograph
   • Pulmonary function tests (PFTs) including DLCO
   • Arterial blood gases analysis
   • High-resolution CT of the chest 1

2. Identify presence of left heart or lung disease (Group 2 or 3 PH)

   • If confirmed: Treat underlying condition
   • If severe PH/RV dysfunction present: Refer to PH expert center 1

3. Ventilation/perfusion (V/Q) scan:

   • Required for all patients with unexplained PH to exclude CTEPH 1
   • Multiple segmental perfusion defects: Suspect Group 4 (CTEPH)
     • Confirm with CT pulmonary angiography, right heart catheterization (RHC), and selective pulmonary angiography 1
   • Normal or subsegmental "patchy" perfusion defects: Consider Group 1 (PAH) or Group 5

4. Right heart catheterization (RHC):

   • Essential for definitive diagnosis 1
   • Diagnostic criteria: mPAP ≥25 mmHg, PAWP ≤15 mmHg, PVR >3 Wood units 1, 2
   • Assess vasoreactivity during catheterization to guide therapy 3

5. Additional specific testing:

   • Routine biochemistry, hematology, immunology
   • HIV testing and thyroid function tests
   • Abdominal ultrasound (for portal hypertension)
   • High-resolution CT 1

Risk Assessment and Stratification

Risk assessment should be based on:

• WHO functional class
• 6-minute walk distance
• Right ventricular function
• BNP/NT-proBNP levels 4

Risk Category	Estimated 1-Year Mortality	Key Characteristics
Low Risk	<5%	WHO FC I-II, 6MWD >440m, No RV dysfunction
Intermediate Risk	5-10%	WHO FC III, 6MWD 165-440m, Moderate RV dysfunction
High Risk	>10%	WHO FC IV, 6MWD <165m, Severe RV dysfunction

Treatment Approach

General Measures

1. Supportive care:
   • Diuretics for RV failure and fluid retention 1, 4
   • Oxygen therapy when arterial blood O₂ pressure is <8 kPa (60 mmHg) 1, 4
   • Consider anticoagulation for IPAH, heritable PAH, and PAH due to anorexigens 1, 4
   • Immunization against influenza and pneumococcal infection 1
   • Supervised exercise rehabilitation for deconditioned patients 1
   • Avoid pregnancy (contraindicated due to 30-50% mortality risk) 1, 4

Pharmacological Therapy Based on Risk

1. Low/Intermediate Risk Patients:

   • Initial combination therapy with:
     • Endothelin receptor antagonist (ERA): Bosentan (125 mg twice daily), Ambrisentan (5-10 mg once daily), or Macitentan (10 mg once daily)
     • PLUS
     • Phosphodiesterase-5 inhibitor (PDE-5i): Sildenafil (20 mg three times daily) or Tadalafil (40 mg once daily) 4

2. High-Risk Patients:

   • Intravenous prostacyclin analogs:
     • Epoprostenol: Start at 2 ng/kg/min, increase by 2 ng/kg/min every 15 minutes until dose-limiting effects or tolerance established 4, 5
     • Treprostinil: Alternative for patients requiring transition from epoprostenol 6

Follow-up and Monitoring

• Systematic assessment every 3-6 months 4
• Monitor:
  • Clinical status and WHO functional class
  • Exercise capacity (6-minute walk test)
  • BNP/NT-proBNP levels
  • Echocardiographic parameters
  • Hemodynamics as needed 1, 4

Advanced Therapies

• Lung transplantation: Consider for patients with inadequate response to maximal medical therapy 4
• Atrial septostomy: Option for refractory patients 4

Important Considerations and Pitfalls

1. Treatment at specialized centers: Management should occur at centers with expertise in PAH 4

2. Medication interactions:

   • Combining bosentan with sildenafil may decrease sildenafil levels by 50%
   • PDE-5 inhibitors with nitrates can cause profound hypotension (contraindicated)
   • Warfarin dosing may need adjustment with certain PAH medications 4

3. Critical warnings:

   • Never abruptly withdraw or lower dose of prostacyclin analogs due to risk of rebound PH 5
   • Avoid high-altitude exposure and ensure supplemental oxygen during air travel 4
   • Use epidural rather than general anesthesia for elective surgeries when possible 1

4. Common diagnostic pitfalls:

   • CT pulmonary angiography alone may miss CTEPH diagnosis; V/Q scan is essential 1
   • Open or thoracoscopic lung biopsy is not recommended in patients with PAH 1
   • Failure to perform RHC for definitive diagnosis and hemodynamic assessment 1, 3