What is the approach to evaluate for pulmonary hypertension?

Evaluation for Pulmonary Hypertension

Begin with transthoracic Doppler echocardiography when pulmonary hypertension is clinically suspected, followed by right heart catheterization to confirm the diagnosis and establish hemodynamic severity. 1

Initial Clinical Assessment

When to Suspect PH

• Unexplained dyspnea on exertion is the most common presenting symptom, particularly when unresponsive to conventional treatment 1, 2
• Syncope (especially in children), fatigue, chest pain, palpitations, dry cough, or lower extremity edema 1, 2
• Physical examination findings: loud P2 component of second heart sound, right ventricular heave, elevated jugular venous pressure, hepatomegaly, peripheral edema, tricuspid regurgitation murmur 1

Risk Factor Assessment

Screen all patients for: 1

• Connective tissue disease (especially systemic sclerosis)
• Congenital heart disease with shunts
• Portal hypertension/liver disease
• HIV infection
• History of anorexigen or stimulant use
• Family history of pulmonary hypertension
• Thromboembolic disease history

Diagnostic Algorithm

Step 1: Initial Screening Tests (Pivotal Tests)

Perform these tests in all patients with suspected PH: 1

• ECG: Look for right axis deviation, right ventricular hypertrophy, right atrial enlargement, right bundle branch block 1
• Chest radiograph: Enlarged pulmonary arteries, right heart enlargement, peripheral pruning of vessels 1
• Basic laboratory tests: CBC, comprehensive metabolic panel, liver function tests, thyroid function (TSH), BNP or NT-proBNP 1
• HIV serology (all patients should be tested) 1
• Autoimmune screening: ANA initially; if positive or clinical suspicion exists, obtain anti-centromere, anti-Scl-70, anti-RNP, anti-dsDNA, anti-SSA, anti-SSB 1

Step 2: Echocardiography (Critical Screening Tool)

Transthoracic Doppler echocardiography is the next appropriate study when PH is suspected. 1

• Estimate right ventricular systolic pressure (RVSP); RVSP >40-45 mmHg warrants further evaluation 1
• Assess for right atrial enlargement, right ventricular enlargement, interventricular septal flattening, pericardial effusion 1
• Evaluate left ventricular systolic and diastolic function to exclude left heart disease as cause 1
• Use contrast echocardiography to detect intracardiac shunting 1
• Note: Echocardiography may be imprecise in determining actual pressures compared to invasive evaluation 1

Step 3: Determine PH Etiology (Contingent Tests)

Pulmonary Function Testing

• Perform spirometry, lung volumes, and DLCO to evaluate for obstructive or restrictive lung disease 1
• Arterial blood gas analysis to assess PaO2, PaCO2, and alveolar-arterial gradient 1
• Overnight oximetry or polysomnography if sleep-disordered breathing suspected 1
• In systemic sclerosis patients, perform PFTs with DLCO every 6-12 months for early detection 1

Exclude Chronic Thromboembolic PH (CTEPH)

• Ventilation-perfusion (V/Q) scanning is mandatory to rule out CTEPH; a normal scan effectively excludes CTEPH 1, 3
• Do NOT use contrast-enhanced chest CT or MRI alone to exclude CTEPH 1
• If V/Q scan suggests CTEPH, pulmonary angiography is required for definitive diagnosis and assessment of operability 1
• CT angiography can be used as initial screen but V/Q scan remains gold standard 1

Additional Imaging

• High-resolution chest CT to evaluate for interstitial lung disease, emphysema, or pulmonary veno-occlusive disease 1
• Abdominal ultrasound with Doppler to assess for portal hypertension and liver cirrhosis 1

Step 4: Right Heart Catheterization (Mandatory for Diagnosis)

Right heart catheterization is required to confirm the presence of PH, establish the specific diagnosis, determine severity, and guide therapy. 1, 4, 3

Diagnostic Criteria

• Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest 2
• Pulmonary arterial wedge pressure (PAWP) ≤15 mmHg to confirm pre-capillary PH 3
• Measure cardiac output/index, pulmonary vascular resistance, right atrial pressure, mixed venous oxygen saturation 1

Vasoreactivity Testing

• Perform acute vasoreactivity testing in patients with idiopathic PAH using short-acting agents (IV epoprostenol, adenosine, or inhaled nitric oxide) 1, 3
• Positive response defined as: fall in mPAP ≥10 mmHg to ≤40 mmHg with increased or unchanged cardiac output 1
• Only perform vasoreactivity testing at centers experienced in pulmonary vascular disease management 1
• Consider testing in PAH associated with scleroderma or congenital heart disease 1

Step 5: Baseline Functional Assessment

Establish baseline severity for monitoring: 1

• WHO functional class determination 1
• 6-minute walk test (6MWT) with Borg dyspnea score 1
• Cardiopulmonary exercise testing (CPET) with peak VO2 and VE/VCO2 slope 1
• BNP or NT-proBNP levels 1

Risk Stratification at Diagnosis

Classify patients as low, intermediate, or high risk based on comprehensive assessment: 1

Low Risk (1-year mortality <5%):

• WHO FC I-II, 6MWD >440m, peak VO2 >15 mL/min/kg, BNP <50 ng/L, NT-proBNP <300 ng/L, cardiac index ≥2.5 L/min/m², RAP <8 mmHg 1

Intermediate Risk (1-year mortality 5-10%):

• WHO FC III, 6MWD 165-440m, peak VO2 11-15 mL/min/kg, BNP 50-300 ng/L, NT-proBNP 300-1400 ng/L, cardiac index 2.0-2.4 L/min/m², RAP 8-14 mmHg 1

High Risk (1-year mortality >10%):

• WHO FC IV, 6MWD <165m, peak VO2 <11 mL/min/kg, BNP >300 ng/L, NT-proBNP >1400 ng/L, cardiac index <2.0 L/min/m², RAP >14 mmHg, pericardial effusion, repeated syncope 1

Common Pitfalls to Avoid

• Do not rely solely on echocardiography for diagnosis—right heart catheterization is mandatory for confirmation 1, 4
• Do not use calcium channel blockers empirically without documented vasoreactivity 1
• Do not perform lung biopsy routinely due to high risk; reserve for specific diagnostic questions only 1
• Do not miss CTEPH—always perform V/Q scanning as CT alone is insufficient 1, 3
• Refer urgently to specialized PH center if patient has syncope, rapidly progressing symptoms, or heart failure 3, 2
• In systemic sclerosis patients, low DLCO (<60% predicted) should trigger echocardiographic screening even without symptoms 1