Chronic Thromboembolic Pulmonary Hypertension – Overview of Pathophysiology, Diagnosis, and Treatment
Chronic thromboembolic pulmonary hypertension (CTEPH) is defined by the 2015 ESC/ERS guidelines as symptomatic pulmonary hypertension with persistent defects in lung perfusion despite adequate anticoagulation therapy. Significant values for determining a diagnosis of pulmonary hypertension are a mean pulmonary artery pressure > 25 mmHg. However, this condition remains significantly underdiagnosed, mainly due to its nonspecific symptoms.
Etiology and Pathogenesis
The etiology of CTEPH often remains unclear. Approximately 50–70% of newly diagnosed patients have a history of acute pulmonary embolism, but over 25% do not report such an event in their medical history. The incidence of CTEPH after an acute pulmonary embolism ranges from 0.1–9.1%. Other risk factors include autoimmune, oncological, and hematological diseases, splenectomy, the presence of antiphospholipid antibodies, or replacement therapy for hypothyroidism.
Several factors contribute to the pathogenesis of this disease. A hypercoagulable state, the presence of inflammatory components, and abnormalities in the structure of fibrinogen and platelets can lead to defective recanalization of pulmonary vessels after embolization. Inadequate breakdown of emboli results in the formation of stenoses up to complete occlusions of the vessel lumen. The obstruction can affect both large pulmonary arteries and small distal arteries.
Clinical Presentation
The most common manifestations of CTEPH include exertional dyspnea, and in later stages, syncope and progressive edema. Based on these nonspecific symptoms, it is very difficult to establish a correct diagnosis, especially in the presence of comorbidities (e.g., chronic obstructive pulmonary disease or obesity).
Diagnosis
Some changes in electrocardiogram (P pulmonale, right bundle branch block, deviation of the right axis) and in chest X-ray (enlargement of the right ventricle and dilatation of the pulmonary artery) can already indicate the presence of CTEPH.
The main diagnostic method is echocardiography. This examination allows determining the transtricuspid pressure gradients, detecting right heart enlargement, and abnormalities in flow in the right ventricular outflow tract.
The basic imaging method is ventilation-perfusion scintigraphy, the so-called "V/Q scan." This examination helps to differentiate CTEPH from other causes of pulmonary hypertension. Its advantage is the relatively low radiation burden without the need to administer an intravenous contrast agent. The V/Q scan shows a mismatch between ventilation and perfusion in lung tissue. A negative V/Q scan excludes the presence of CTEPH with 96% probability.
CT angiography effectively detects post-thrombotic changes in the pulmonary lobes and segments, as well as visualizing vessel obstructions, organized emboli, and calcifications.
Other diagnostic modalities include digital subtraction angiography and right heart catheterization.
Therapy
The care for patients with CTEPH is very complex and concentrated in centers specializing in pulmonary hypertension.
According to the ERS/ESC guidelines, the treatment of choice and the only curative option is pulmonary endarterectomy (PEA). This procedure corrects the mismatch between ventilation and perfusion in lung tissue and improves the function of the right heart, enhances patient performance, and partially alleviates exertional dyspnea. The indication for the procedure is made by a multidisciplinary team consisting of a pulmonologist, radiologist, and surgeon. PEA should be offered to every symptomatic patient regardless of the severity of pulmonary hypertension and right ventricular dysfunction. The procedure is performed in deep hypothermia during 20-minute episodes of cardiac arrest, utilizing cardiopulmonary bypass. The most common complications of PEA are residual pulmonary hypertension and reperfusion pulmonary edema, where extracorporeal membrane oxygenation (ECMO) can be used to bridge the condition. Despite a successfully performed surgery, pulmonary hypertension can persist in up to 30% of patients.
Patients not indicated for this procedure or with residual pulmonary hypertension are treated pharmacologically. Endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and other vasodilatory agents are used. Every patient with CTEPH must also undergo anticoagulation therapy, either in the form of warfarin or NOACs.
The prognosis of patients with CTEPH is still quite poor. However, the rapid development of pharmacological therapy and comprehensive care in specialized centers could slow the progression of the disease and improve the quality of life for patients.
(kali)
Source: Opitz I., Ulrich S. Chronic thromboembolic pulmonary hypertension. Swiss Med Wkly 2018; 148: w14702, doi: 10.4414/smw.2018.14702.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.