Chronic pulmonary thromboembolism (CTEPD / CTEPH)

Definition. Chronic thromboembolic pulmonary disease (CTEPD) is the persistence of organised, fibrotic thromboembolic material obstructing the pulmonary arteries with mismatched perfusion defects, persisting after at least 3 months of therapeutic anticoagulation. When this is accompanied by pulmonary hypertension — mean pulmonary artery pressure > 20 mmHg with pulmonary vascular resistance > 2 Wood units and a pulmonary artery wedge pressure ≤ 15 mmHg (2022 ESC/ERS haemodynamic definition) — it is termed CTEPH, which is Group 4 pulmonary hypertension. CTEPD without PH is now a recognised entity in its own right.

Epidemiology and pathogenesis. CTEPH develops in about 2–4% of survivors of acute PE, typically within two years, and up to 25% have no documented previous PE. Pathogenesis is failure of thrombus resolution with organisation into fibrous webs, bands and stenoses, compounded by a secondary small-vessel microvasculopathy in non-obstructed territories that resembles pulmonary arterial hypertension and explains why haemodynamics may not improve after surgery. Risk factors: large or recurrent PE, unprovoked PE, splenectomy, ventriculo-atrial shunts, infected pacemaker leads, inflammatory bowel disease, chronic osteomyelitis, malignancy, thyroid replacement therapy, non-O blood group and antiphospholipid syndrome.

Clinical features. Progressive exertional breathlessness and reduced exercise tolerance, developing after an apparent "honeymoon period" following the acute PE. Later come fatigue, exertional chest pain, presyncope or syncope and haemoptysis. Signs of pulmonary hypertension and right heart failure: loud pulmonary component of the second heart sound, right ventricular heave, raised JVP with prominent v waves, tricuspid regurgitation murmur, hepatomegaly, ascites and peripheral oedema. A pulmonary flow murmur over the lung fields is relatively specific. In older adults the breathlessness is commonly misattributed to COPD, heart failure, obesity or deconditioning, and diagnosis is typically delayed by more than a year.

Diagnosis — the single most examinable point. Screen any patient with persistent breathlessness ≥ 3 months after PE. Start with echocardiography (raised tricuspid regurgitant velocity, right ventricular dilatation and dysfunction, flattened septum). The ventilation–perfusion (V/Q) scan is the screening investigation of CHOICE — a normal V/Q scan effectively excludes CTEPH, and CTPA may miss chronic organised disease. Confirmatory imaging is by CT pulmonary angiography (webs, bands, eccentric wall-adherent thrombus, abrupt vessel cut-off, calcified thrombus, mosaic perfusion, bronchial collaterals) and digital subtraction pulmonary angiography. Right heart catheterisation is mandatory to confirm haemodynamics and operability. Add lung function tests, ABG, six-minute walk test, NT-proBNP and a thrombophilia/antiphospholipid screen.

Management — pulmonary endarterectomy is the treatment of choice. Every patient must be referred to an expert CTEPH centre for multidisciplinary assessment of operability. Pulmonary endarterectomy (PEA) under deep hypothermic circulatory arrest is potentially curative for proximal, surgically accessible disease and is the first-line treatment; in experienced centres mortality is under 5%, and age alone is not a contraindication though frailty and comorbidity raise operative risk. All patients need lifelong therapeutic anticoagulation — vitamin K antagonists remain preferred, and DOACs are used with caution and are contraindicated in antiphospholipid syndrome.

Inoperable and residual disease. For patients who are technically inoperable (distal disease), unfit for surgery, or who have persistent/recurrent pulmonary hypertension after PEA — a group heavily weighted towards older patients — the options are: balloon pulmonary angioplasty (BPA), now an established treatment that improves haemodynamics, right ventricular function, exercise capacity and quality of life; and medical therapy with riociguat, a soluble guanylate cyclase stimulator and the only licensed drug for CTEPH (CHEST-1), with subcutaneous treprostinil for severe disease. Add diuretics for right heart failure, supplemental oxygen, supervised rehabilitation, vaccination and pregnancy avoidance; consider lung transplantation in the young with refractory disease. Calcium channel blockers and vasodilator testing have no role in CTEPH.

A multimodal, sequenced strategy is now the standard of care. The 2023 ESC Working Group clinical consensus statement on balloon pulmonary angioplasty establishes BPA as a complementary — not competing — treatment alongside PEA and riociguat, recommends medical pre-treatment with riociguat before BPA (the RACE trial showed fewer procedure-related complications with riociguat pre-treatment), and endorses BPA in CTEPD both with and without pulmonary hypertension. Importantly, the phase III MACiTEPH trial (2025) of macitentan was stopped for futility with no improvement in six-minute walk distance, so riociguat remains the only drug with proven benefit — a useful negative result to quote.