How to evaluate a patient for Chronic Thromboembolic Pulmonary Hypertension (CTPH)?

Evaluation for Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Any patient with unexplained pulmonary hypertension or persistent dyspnea after pulmonary embolism should undergo ventilation/perfusion (V/Q) lung scanning as the initial screening test, as a normal V/Q scan effectively rules out CTEPH. 1

Clinical Scenarios Requiring CTEPH Evaluation

Evaluate for CTEPH in these specific situations:

• Patients with history of DVT or PE presenting with dyspnea, exercise intolerance, or clinical signs of right heart failure 1
• Any patient with unexplained pulmonary hypertension of unclear etiology 1
• Survivors of acute PE who develop persistent symptoms after the acute episode 1
• Patients with acute PE showing signs of pulmonary hypertension or RV dysfunction during hospitalization (perform follow-up echocardiography 3-6 months post-discharge) 1

Diagnostic Algorithm

Step 1: Initial Screening with V/Q Scan

• Perform V/Q scintigraphy first - this is the best screening test with high sensitivity and negative predictive value 1, 2, 3
• A normal V/Q scan definitively excludes CTEPH and no further testing is needed 1
• Any mismatched perfusion defects warrant further evaluation 3

Critical pitfall: CT angiography alone is insufficient for screening. A relatively normal CT angiogram can occur in CTEPH despite substantial V/Q scan abnormalities, making CT an unreliable screening tool 1

Step 2: Advanced Imaging if V/Q is Abnormal

• Proceed to multidetector CT angiography when V/Q scan is indeterminate or shows perfusion defects 1
• Look for specific CTEPH signs on imaging: ring-like stenoses, webs, slits, chronic total occlusions, pouches, bands, or scalloped/serrated luminal edges 1
• Even with modern CT scanners, normal CT angiography does not exclude operable CTEPH 1

Step 3: Hemodynamic Confirmation via Right Heart Catheterization

CTEPH diagnosis requires ALL three hemodynamic criteria: 1

1. Mean pulmonary artery pressure ≥25 mmHg at rest
2. Pulmonary capillary wedge pressure ≤15 mmHg
3. Pulmonary vascular resistance >2 Wood units (or ≥3 Wood units per some guidelines) 1

These measurements must be obtained after at least 3 months of therapeutic anticoagulation to distinguish CTEPH from acute/subacute PE 1, 3

Step 4: Exclude Alternative Causes of Pulmonary Hypertension

• Rule out WHO Group II (left-sided heart disease): wedge pressure must be ≤15 mmHg 1
• Rule out WHO Group III (parenchymal lung disease): perform pulmonary function testing and review chest imaging 1
• In patients with severe RV dilation causing interventricular dependence and LV diastolic dysfunction, wedge pressure may be elevated but PVR is typically high (≥600 dyne·s·cm⁻⁵) 1

Step 5: Conventional Pulmonary Angiography for Surgical Planning

• Once CTEPH is confirmed, refer to an expert CTEPH center 1
• Perform conventional invasive pulmonary angiography to define vascular anatomy, determine surgical accessibility, and plan operative approach 1
• Biplane imaging is preferred for superior anatomic detail 1
• This should be performed at the surgical center or a facility with established cooperation with the surgical team 1

Complete Diagnostic Workup Components

The comprehensive evaluation should include: 1

• History and physical examination (looking specifically for signs of right heart failure: jugular venous distension with large V waves, RV heave at left lower sternal border, loud P2, S3/S4 gallop, peripheral edema, hepatomegaly) 1
• Posteroanterior and lateral chest radiograph
• Electrocardiogram
• Pulmonary function testing
• Arterial blood gases
• V/Q lung scanning
• Right heart catheterization
• Conventional invasive pulmonary angiography
• Coronary angiography (for surgical candidates with coronary artery disease risk factors) 1

Risk Factors Increasing Clinical Suspicion

Maintain heightened suspicion in patients with: 1, 4

• Multiple episodes of PE, larger perfusion defects, or younger age 1
• Prior splenectomy, permanent intravenous catheters, or ventriculoatrial shunts 1, 4
• Chronic inflammatory conditions (inflammatory bowel disease, chronic osteomyelitis) 1, 4
• Lupus anticoagulant or antiphospholipid antibodies 4
• Elevated factor VIII levels 4
• History of inadequate anticoagulation or recurrent VTE 4

Common Diagnostic Pitfalls

Avoid these critical errors:

• Relying on CT angiography alone for screening - it misses cases that V/Q scanning detects 1
• Using echocardiography alone for diagnosis - it is useful for screening but insufficient for definitive diagnosis 1
• Failing to wait 3 months of therapeutic anticoagulation before making the diagnosis 1, 3
• Not referring patients to expert CTEPH centers once imaging suggests the diagnosis 1
• Performing invasive procedures at referring hospitals rather than at the expert center where surgery would be performed 1

Clinical Context

The median time from symptom onset to diagnosis is 14 months, reflecting the diagnostic challenge 1. Approximately 60% of CTEPH cases occur without antecedent history of acute VTE 4. Untreated CTEPH carries mortality rates of 70% when mean pulmonary artery pressure exceeds 40 mmHg, increasing to 90% above 50 mmHg 1, 4, making early diagnosis critical for mortality reduction.