What are the diagnosis, classification, and management strategies for a patient with suspected pulmonary hypertension?

Diagnosis, Classification, and Management of Pulmonary Hypertension

Diagnostic Approach

Echocardiography is the mandatory first-line diagnostic test when pulmonary hypertension is suspected, followed by a systematic algorithm to identify the underlying cause before proceeding to right heart catheterization for definitive diagnosis. 1

Initial Screening and Risk Assessment

• Obtain transthoracic echocardiography as the initial non-invasive test to estimate probability of PH (high, intermediate, or low) 1, 2
• Perform chest radiography to identify cardiomegaly, enlarged central pulmonary arteries (right interlobar artery >15 mm in women, >16 mm in men), or pruning of peripheral vessels 1
• Obtain ECG to assess for right ventricular hypertrophy or strain 1
• Complete laboratory evaluation including: complete blood count, comprehensive metabolic panel, liver function tests, thyroid function tests, HIV serology, immunology panel (ANA, RF, anti-Scl-70), and BNP/NT-proBNP 1

Algorithmic Workup Based on Echocardiographic Probability

For high or intermediate probability of PH on echocardiography:

• Evaluate for Group 2 (left heart disease) and Group 3 (lung disease) causes through clinical assessment, pulmonary function tests with DLCO, arterial blood gases, and high-resolution CT chest 1, 2
• If left heart or lung disease is confirmed without severe PH/RV dysfunction, treat the underlying condition and reassess 1
• If severe PH or RV dysfunction is present despite left heart/lung disease, refer to PH expert center 1

If left heart and lung disease are excluded:

• Perform ventilation/perfusion (V/Q) lung scan to exclude chronic thromboembolic PH (CTEPH) - this is mandatory and superior to CT angiography alone 1, 2
• If V/Q scan shows mismatched perfusion defects, proceed with CT pulmonary angiography, right heart catheterization, and consider selective pulmonary angiography 1, 2
• Obtain abdominal ultrasound to screen for portal hypertension 1

For low probability of PH on echocardiography:

• If asymptomatic without risk factors: no additional workup required 1
• If symptomatic with risk factors for PAH: perform echocardiographic follow-up 1
• If symptomatic without risk factors: evaluate alternative diagnoses 1

Definitive Diagnosis

Right heart catheterization is essential for accurate diagnosis and must be performed in all patients with suspected PAH or CTEPH 1, 3. Diagnostic criteria include:

• Mean pulmonary arterial pressure ≥25 mmHg at rest 1, 3
• For PAH specifically: pulmonary artery wedge pressure ≤15 mmHg AND pulmonary vascular resistance >3 Wood units 1, 3

Critical Diagnostic Pitfalls

• Never perform open or thoracoscopic lung biopsy in patients with PAH - this is contraindicated 1
• CT pulmonary angiography alone may miss CTEPH; V/Q scan is more sensitive and must be performed 1, 2
• Normal chest radiograph does not exclude PH, particularly mild disease 1

Clinical Classification

The 2013 updated WHO classification divides PH into five groups 1, 4:

Group 1: Pulmonary Arterial Hypertension (PAH)

• Idiopathic PAH
• Heritable PAH (BMPR2, ACVRL1, ENG, KCNK3, CAV1 mutations) 1
• Drug/toxin-induced
• Associated with connective tissue disease, HIV, portal hypertension, congenital heart disease, schistosomiasis
• Pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) 1

Group 2: PH due to left heart disease 1, 4

Group 3: PH due to lung diseases and/or hypoxia 1, 4

Group 4: Chronic thromboembolic PH (CTEPH) and other pulmonary artery obstructions 1, 4

Group 5: PH with unclear and/or multifactorial mechanisms 1, 4

Functional Classification and Prognostic Assessment

WHO Functional Class (Modified NYHA)

• Class I: No limitation of physical activity 1
• Class II: Slight limitation; comfortable at rest, ordinary activity causes symptoms 1
• Class III: Marked limitation; comfortable at rest, less than ordinary activity causes symptoms 1
• Class IV: Unable to perform any activity without symptoms; signs of right heart failure at rest 1

Prognostic Indicators

Better prognosis: 1, 3

• No clinical evidence of right ventricular failure
• Slow symptom progression
• WHO Functional Class I-II
• 6-minute walk distance >500 meters
• Peak oxygen consumption >15 mL/min/kg
• Normal or near-normal BNP/NT-proBNP
• No pericardial effusion on echo
• TAPSE >2.0 cm, cardiac index >2.5 L/min/m²
• Right atrial pressure <8 mmHg

Worse prognosis: 1, 3

• Clinical right ventricular failure
• Rapid symptom progression
• WHO Functional Class III-IV
• 6-minute walk distance <300 meters
• Peak oxygen consumption <12 mL/min/kg
• Markedly elevated and rising BNP/NT-proBNP
• Pericardial effusion present
• Cardiac index <2.0 L/min/m²
• Right atrial pressure >15 mmHg

Management Strategies

Group 1 PAH - Targeted Therapies

FDA-approved targeted therapies for PAH include: 3, 5, 4

• Prostacyclin analogues: Epoprostenol (continuous IV infusion via central line, initiated at 2 ng/kg/min with increments of 2 ng/kg/min every 15 minutes until dose-limiting effects or tolerance established) 5
• Endothelin receptor antagonists 3, 4
• Phosphodiesterase-5 inhibitors 3, 4
• Soluble guanylate cyclase stimulators 3, 4
• Prostacyclin receptor agonists 4

Critical management warnings for prostacyclin therapy:

• Never abruptly discontinue or reduce dose - can cause rebound PH crisis 5
• Contraindicated in congestive heart failure due to severe left ventricular systolic dysfunction and pulmonary edema 5
• Administered only via continuous IV infusion through central venous catheter 5

Group 4 CTEPH

Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH 3, 4. For inoperable or persistent/recurrent CTEPH, riociguat (soluble guanylate cyclase stimulator) is the only licensed targeted therapy 4

Groups 2 and 3

Management primarily involves treating the underlying left heart disease or lung disease 4. Long-term oxygen therapy is indicated when arterial oxygen pressure is consistently <60 mmHg (8 kPa) 3

Supportive Therapies

• Diuretics for volume management (caution: may reduce blood pressure when combined with vasodilators) 5
• Anticoagulation consideration (increases bleeding risk with antiplatelet agents) 5
• Digoxin with caution (epoprostenol may elevate digoxin levels) 5

Follow-Up Monitoring

Perform assessments every 3-6 months in stable patients: 1, 3

• WHO Functional Class
• 6-minute walk test
• BNP/NT-proBNP levels
• Echocardiography
• Cardiopulmonary exercise testing (at baseline and with changes)
• Right heart catheterization (at baseline, with therapy changes, or clinical worsening) 1

All patients with confirmed PAH or CTEPH must be referred to a specialized PH center for ongoing management 1, 4.