What is the recommended treatment for a patient diagnosed with chronic thrombotic pulmonary hypertension (CTPH)?

Chronic Thromboembolic Pulmonary Hypertension: Diagnosis and Treatment

Diagnosis

All patients with unexplained pulmonary hypertension must be evaluated for CTEPH, with ventilation/perfusion (V/Q) lung scanning as the mandatory initial screening test—a normal V/Q scan definitively rules out CTEPH. 1, 2

Diagnostic Algorithm

• First-line screening: Perform V/Q lung scan in any patient with unexplained PH or persistent dyspnea after pulmonary embolism 1, 2

  • A normal V/Q scan excludes CTEPH with high negative predictive value—no further testing needed 1, 2
  • Any mismatched perfusion defect warrants further investigation 3

• Second-line imaging: If V/Q scan shows perfusion defects or is indeterminate, proceed to multidetector CT angiography 1

  • Look for specific CTEPH signs: ring-like stenoses, webs, slits, chronic total occlusions, pouches, bands, or scalloped luminal edges 2
  • Critical caveat: Even modern CT angiography cannot definitively exclude operable CTEPH if negative 1

• Definitive diagnosis: Requires right heart catheterization demonstrating pre-capillary PH with all three criteria: mean PAP ≥25 mmHg, pulmonary capillary wedge pressure ≤15 mmHg, and PVR >2 Wood units 1, 2

  • These measurements must be obtained after at least 3 months of therapeutic anticoagulation to distinguish from acute/subacute PE 2
  • Traditional pulmonary angiography is usually required at expert centers to determine surgical candidacy 1

High-Risk Populations Requiring Heightened Suspicion

• History of previous venous thromboembolism 1
• Survivors of acute PE showing signs of PH or RV dysfunction during hospitalization (require follow-up echocardiography at 3-6 months) 1
• Prior splenectomy, ventriculoatrial shunts, myeloproliferative disorders, or chronic inflammatory bowel disease 1, 2

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Treatment

Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH as it is the only potentially curative option and should be pursued in all patients until definitively deemed inoperable by an experienced surgeon at an expert center. 1, 4

Treatment Algorithm

1. Universal Foundation: Lifelong Anticoagulation

• All CTEPH patients require lifelong therapeutic anticoagulation 1, 4
• Vitamin K antagonists (warfarin) targeting INR 2.0-3.0 remain the guideline-recommended standard 1, 4
• Direct oral anticoagulants (DOACs) show promise in recent research:
  • Meta-analyses demonstrate DOACs are noninferior to VKAs for major bleeding and all-cause mortality 5
  • However, one meta-analysis found higher recurrent PE risk with DOACs (RR 3.80) despite lower mortality 6
  • Clinical decision: Given guideline recommendations prioritize VKAs and conflicting DOAC data on recurrent PE, warfarin remains the safer choice until definitive RCT data emerge 1

2. Surgical Evaluation and Treatment

• Refer all suspected CTEPH patients to an expert center (≥20 PEA operations/year with <10% mortality) for interdisciplinary evaluation by internists, radiologists, and experienced surgeons 1
• Never consider a patient inoperable until reviewed by an experienced PEA surgeon 1
• Surgical candidacy depends on:
  • Location of organized thrombi (proximal lesions are ideal; distal obstructions may preclude success) 1
  • Degree of PH relative to thrombus burden 1
  • Age and comorbidities 1
• Expected outcome: Dramatic drop in PVR with near-normalization of pulmonary hemodynamics after successful PEA 1, 4

3. Medical Therapy for Specific Scenarios

PAH-targeted drug therapy has a role in three specific situations only: 1

• Inoperable patients (after expert surgical review confirms inoperability) 1
• Pre-operative hemodynamic optimization (if deemed appropriate by multidisciplinary team) 1
• Persistent/recurrent PH after PEA 1

Available agents include prostanoids, endothelin receptor antagonists (ERAs), and phosphodiesterase type-5 inhibitors 1

Evidence limitations: The only randomized controlled trial (BENEFIT study) showed bosentan reduced PVR in inoperable CTEPH but failed to improve 6-minute walk distance, functional class, or time to clinical worsening 1

Critical caveat: No medical therapy is approved for CTEPH in Europe or the USA as of the guideline publication 1

4. Balloon Pulmonary Angioplasty (BPA)

• Emerging interventional technique for patients ineligible for PEA or with residual PH post-PEA 3, 7, 8
• Recent randomized trials show BPA provides greater hemodynamic improvement than pulmonary vasodilators alone 7
• Requires specialized centers with experienced operators (≥50 procedures under supervision before independent practice) 8
• Treatment strategy: Prioritize ring-like stenoses, web-like lesions, and subtotal occlusions before complete occlusions to reduce complications 8

5. Lung Transplantation

• Bilateral lung transplantation is reserved for advanced cases unsuitable for PEA with severe functional impairment 1

Common Pitfalls to Avoid

• Never rely solely on CT angiography to exclude CTEPH—V/Q scanning is mandatory 1
• Never declare a patient inoperable without expert surgical evaluation at a high-volume center 1
• Never perform invasive diagnostic procedures at referring hospitals—all RHC, pulmonary angiography, and coronary angiography should occur at the expert center to minimize risks and repeated procedures 1
• Never assume CTEPH is excluded in post-PE patients without follow-up—survivors with PH or RV dysfunction during acute PE hospitalization require echocardiography at 3-6 months 1