Chronic thromboembolic pulmonary hypertension (ORPHA:70591)
A rare complication of acute pulmonary embolism (PE), either symptomatic or not, that is characterized by fibrotic intravascular material occlusion of pulmonary arteries in combination with a secondary microvasculopathy of vessels less than 500 µm. The consequence is an increase in pulmonary vascular resistance (PVR) and progressive right heart failure.
Epidemiology
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease but the true prevalence is difficult to evaluate since the disease is potentially underdiagnosed. Epidemiological analysis of CTEPH in different countries estimate incidence ranging from 1/20,000-33,000 in the USA and Europe. CTEPH is usually considered as a complication of pulmonary embolism (PE), since 50-75% of patients have a history of PE and from a large meta-analysis, the weighted pooled incidence of CTEPH after an episode of PE is estimated at 0.56-3.2%.
Clinical description
Patients commonly present with progressive dyspnea on exertion with or without signs of right heart dysfunction. A period between the initial event (acute PE) and the development of clinical signs is common and may last from a few months to many years (median time of 14 months between symptom onset and diagnosis in expert centers).
Etiology
The pathophysiology of CTEPH is assumed to be associated with obstruction of pulmonary arteries by unresolved organized fibrotic clots and a secondary microvasculopathy in pulmonary vessels of less than 500 µm in diameter. The underlying causes of the disease remain unknown.
Diagnostic methods
The diagnosis of CTEPH is suspected when ventilation/perfusion (VQ) lung scan shows mismatched perfusion defects and echocardiography shows high or intermediate probability of pulmonary hypertension (PH). The diagnosis is confirmed by right heart catheterization and pulmonary vascular imaging including CT pulmonary angiography (CTPA) and/or digital subtraction angiography (DSA) which should be performed in expert centres after at least 3 months of effective anticoagulation in order to discriminate this condition from PE. Specific diagnostic signs for CTEPH seen by multidetector CTPA or DSA include ring-like stenoses, webs/slits and chronic total occlusions (pouch lesions or tapered lesions).
Differential diagnosis
Differential diagnosis includes idiopathic pulmonary artery hypertension, Takayasu arteritis, congenital proximal interruption of a pulmonary artery, tumor thrombus, Von Recklinghausen disease, Osler-Weber-Randu disease or, very rarely, primary sarcoma of the pulmonary artery, and right heart failure with acute pulmonary thromboembolism.
Management and treatment
Patients should be treated with lifelong anticoagulation. In addition, three treatment options have been successfully developed: pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and PH medications. PEA is the treatment of choice for operable patients. Operability is determined by multiple factors including surgical accessibility of the organized thrombi and comorbidities which are assessed during a multidisciplinary meeting in expert centres. Non-operable patients should be treated by PH-targeted therapy with or without BPA. Monotherapy with riociguat is currently the standard-of-care in inoperable CTEPH or persistent/recurrent PH after PEA. More recently, subcutaneous treprostinil, a prostacyclin analogue, has been also approved for the treatment of patients with inoperable CTEPH or persistent/recurrent PH after PEA. Other PH medications or oral combination therapy may be used off-label. Eligibility for BPA depends on the location and type of lesions which are also assessed through a multidisciplinary team approach and many expert centres use PH-targeted therapy prior to BPA to improve its safety by optimizing pre-BPA pulmonary hemodynamics. Multimodality treatment approach needs to be confirmed by further studies and is currently considered in selected patients after multidisciplinary team assessment in expert centers.
Prognosis
Prognosis depends on several factors such as operability, hemodynamic impairment and patient's comorbidities. A survival of 89% at 3 years and 72% at 10 years was reported in operated patients. Encouraging observations on improved survival with BPA and PH-targeted therapy in the inoperable CTEPH population have been observed but long-term results are missing.

                            Last update: 
                            October 2021


                            - Expert reviewer(s): 
                            Dr Xavier JAIS  - Dr Mitja JEVNIKAR