What is the management for chronic thromboembolic pulmonary hypertension (CTEPH)?

Management of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Pulmonary endarterectomy (PEA) is the first-line, potentially curative treatment for CTEPH and should be pursued in all patients unless definitively deemed inoperable by an experienced surgical center. 1, 2

Immediate Management: Anticoagulation

• All patients with CTEPH require lifelong therapeutic anticoagulation with warfarin targeted to INR 2.0-3.0, regardless of whether they undergo surgery 1, 3
• Anticoagulation reduces recurrent PE risk and is the foundation of all CTEPH management 1
• There is no data supporting novel oral anticoagulants (dabigatran, rivaroxaban, apixaban) in CTEPH; warfarin remains standard 1

Primary Treatment: Pulmonary Endarterectomy (PEA)

Referral and Evaluation

• Refer all CTEPH patients immediately to an experienced center (≥20 PEA operations/year with <10% mortality) for surgical evaluation, even with mild symptoms 1, 3
• Do not label patients "inoperable" until reviewed by an experienced surgeon at a specialized center 1
• Evaluation should occur at the expert center rather than referring hospitals to minimize repeated procedures 1

Surgical Candidacy

• No upper limit of pulmonary vascular resistance (PVR) or degree of right ventricular dysfunction excludes surgery at experienced centers 1, 3, 2
• Patients with suprasystemic pulmonary artery pressures can safely undergo PEA 1
• Advanced age (≥80 years), renal insufficiency, and hepatic dysfunction are not absolute contraindications, though they increase risk 1
• Surgery is indicated for patients with hemodynamic or ventilatory impairment at rest or with exercise 1, 2

Surgical Outcomes

• Perioperative mortality: 4.7% overall, as low as 4% with preoperative PVR <900 dyne·s·cm⁻⁵, up to 20% with PVR >1200 dyne·s·cm⁻⁵ 3, 2
• Long-term survival: 75-92.3% at 6 years, compared to 51.9% for lung transplantation 1, 3, 2
• Functional improvement: 93% achieve NYHA class I or II post-surgery (compared to 95% in class III or IV pre-surgery) 2
• Near-normalization of pulmonary hemodynamics occurs in most patients 1, 2

Post-Operative Management

• Continue lifelong anticoagulation after PEA 3, 2
• Consider PAH-specific medical therapy for residual pulmonary hypertension post-operatively 3, 2

Management for Inoperable CTEPH

Medical Therapy

• Riociguat is the recommended medical therapy for inoperable CTEPH or persistent/recurrent PH after PEA, demonstrating improvements in exercise capacity and PVR 2, 4
• Bosentan showed significant PVR reduction in the BENEFIT trial but no change in 6-minute walk test, functional class, or time to clinical worsening 1
• Other PAH-specific therapies (prostanoids, endothelin receptor antagonists, phosphodiesterase type-5 inhibitors) may provide hemodynamic benefits but have limited controlled trial data 1

Balloon Pulmonary Angioplasty (BPA)

• BPA should be considered for technically inoperable patients with distal disease or unacceptable surgical risk-benefit ratio 2, 5
• BPA is also an option for persistent PH after PEA 2, 5

Lung Transplantation

• Bilateral lung transplantation may be considered for advanced cases unsuitable for PEA or other interventions 2
• Mean 1- and 5-year survival for lung/heart-lung transplantation for pulmonary hypertension: 75.1% and 51.9% respectively (inferior to PEA outcomes) 1

Supportive Care

• Diuretics for heart failure 2
• Oxygen therapy for hypoxemia (only 10% of post-PEA patients require oxygen) 1, 2

Treatment Algorithm

1. Confirm diagnosis: Pre-capillary PH (mean PAP ≥25 mmHg, PCWP ≤15 mmHg, PVR >2 Wood units) with chronic/organized thrombi in elastic pulmonary arteries 1
2. Initiate lifelong warfarin (INR 2.0-3.0) 1
3. Refer immediately to experienced CTEPH center for multidisciplinary evaluation 1, 2
4. If operable: Proceed with PEA 1, 3, 2
5. If inoperable or residual PH post-PEA: Initiate riociguat and/or consider BPA 2, 4
6. If refractory to all interventions: Evaluate for lung transplantation 2

Critical Pitfalls to Avoid

• Do not rely on CT angiography alone to exclude CTEPH; ventilation/perfusion scanning is the preferred screening test, as normal V/Q scan rules out CTEPH 1
• Do not declare patients inoperable based on severe hemodynamic abnormalities alone; experienced centers can operate on patients with extreme PVR elevations 1, 3
• Do not delay referral to specialized centers; median time from symptom onset to diagnosis is 14 months, contributing to poor outcomes 6
• The preoperative differentiation of operable versus inoperable CTEPH requires surgical expertise to assess microvascular disease contribution versus surgically accessible macroscopic disease 1, 2