Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary hypertension (WHO group 4) from persistent obstruction of pulmonary arteries by organised thromboemboli and secondary small vessel arteriopathy after pulmonary embolism.

Occurs in 2 to 4% of patients after acute pulmonary embolism; incidence 3 to 5 per million per year; may occur without recognised PE.

Risk factors: large perfusion defects at diagnosis, unprovoked PE, recurrent PE, antiphospholipid syndrome, splenectomy, ventriculoatrial shunts, infected pacemaker leads, inflammatory bowel disease, thyroid replacement, malignancy, non O blood group, high factor VIII.

Diagnosis requires mean PA pressure over 20 mmHg with PAWP 15 mmHg or less, PVR over 2 WU, and at least one segmental perfusion defect after 3 months of effective anticoagulation.

Untreated: progressive right heart failure; 3 year survival about 30% when mean pressure above 50 mmHg.

CTEPH disease (without PH, "CTEPD") exists with exertional symptoms.

• Progressive exertional dyspnoea after PE, fatigue, exercise intolerance, exertional syncope, haemoptysis, chest pain.
• Right heart failure signs: raised JVP, loud P2, right ventricular heave, oedema, hepatomegaly.
• Flow murmurs (bruits) over lung fields from stenosed pulmonary arteries.
• Ongoing dyspnoea more than 3 months after PE warrants evaluation.

• Echocardiography screening (probability of PH); NT proBNP.
• Ventilation perfusion scintigraphy is the screening test of choice (normal V/Q excludes CTEPH; unmatched segmental defects).
• CT pulmonary angiography (webs, bands, eccentric thrombus, mosaic perfusion, bronchial artery hypertrophy) and digital subtraction pulmonary angiography to define operability.
• Right heart catheterisation for haemodynamics.
• Thrombophilia screening: antiphospholipid antibodies (lupus anticoagulant), factor VIII; JAK2, malignancy screen as indicated.
• Multidisciplinary CTEPH team assessment of operability.

• Lifelong therapeutic anticoagulation: warfarin (INR 2 to 3) preferred, particularly with antiphospholipid syndrome (DOAC considered in others, apixaban 5 mg twice daily or rivaroxaban 20 mg daily, with lower evidence).
• Pulmonary endarterectomy (PEA) with deep hypothermic circulatory arrest is the treatment of choice for surgically accessible disease: mortality 2 to 5% in expert centres, normalisation of haemodynamics in majority, 5 year survival about 90%.
• Balloon pulmonary angioplasty for inoperable or residual distal disease (multiple sessions, improved haemodynamics, risk of reperfusion lung injury and vessel injury).
• Riociguat 1 to 2.5 mg three times daily (first line medical therapy for inoperable or persistent PH after PEA); macitentan 10 mg and treprostinil SC as alternatives; combination therapy in some.
• Diuretics, oxygen, pulmonary rehabilitation.
• Inferior vena cava filter not routinely recommended.
• Lung transplantation for non operable advanced disease.
• Follow up every 3 to 6 months initially; echo and BNP; repeat catheterisation 3 to 6 months after PEA.