Chronic thromboembolic pulmonary arterial hypertension: a review of the literature and novel therapeutic approaches

Abstract

Chronic thromboembolic pulmonary hypertension is defined as pulmonary hypertension (PH) caused by single or recurrent pulmonary emboli and is characterized by chronic obstruction of the pulmonary arteries leading to increased vascular resistance and PH. Also, progressive remodeling may occur in occluded and nonoccluded territories. Better understanding of the underlying mechanisms and risk factors could improve diagnosis and allow appropriate interventions. Pulmonary endarterectomy is an established approach and is considered the definitive treatment for chronic PH, resulting from thromboembolic disease. Furthermore, percutaneous transluminal pulmonary angioplasty is technically feasible, especially for those with peripheral-type of the disease. In addition, several agents, including prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors, have been tested in selected patients yielding promising results. Several novel agents are under investigation, and extensive research is currently in progress aiming to resolve uncertainties in the understanding and treatment of the disease.

Keywords:

• endarterectomy
• medical treatment
• percutaneous transluminal pulmonary angioplasty
• pulmonary hypertension
• thromboembolic disease

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Chronic thromboembolic pulmonary hypertension is characterized by chronic obstruction of the pulmonary arteries leading to increased vascular resistance and pulmonary hypertension (PH).

• It has also been suggested that in situ thrombosis as a result of primary arteriopathy and endothelial dysfunction similar to that seen in pulmonary arterial hypertension may play a role in the pathophysiology.

• Accurate diagnosis is of major importance in the aim of improving outcome. Of note, despite advances in computed tomography and MRI, VQ scan remains the preferred test for screening and should be considered as an early step in the diagnosis of the disease.

• Better understanding of the underlying mechanisms and risk factors of chronic thromboembolic PH could improve diagnosis and allow appropriate interventions.

• Pulmonary endarterectomy (PEA) is an established approach for the treatment and is considered as the definitive treatment for chronic PH resulting from thromboembolic disease.

• Percutaneous transluminal pulmonary angioplasty could be performed in cases where PEA is not indicated, or in patients who continue to have residual PH, despite treatment with PEA.

• Several agents, such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors, have been successfully tested in selected patients.

• Other novel agents are under investigation, and extensive research is currently in progress aiming to resolve uncertainties in the understanding and treatment of chronic thromboembolic PH.

Notes