Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology

Abstract

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2), HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis), and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker. The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH. However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy.

Figures

FIGURE 1.

The key pathways and classes of drugs that have been approved for the treatment of pulmonary arterial hypertension. These may also have benefits in patients with chronic thromboembolic pulmonary hypertension, although further research is necessary to establish this. NO: nitric oxide; sGC: soluble guanylate cyclise; cGMP: cyclic guanosine monophosphate; COX: cyclo-oxygenase; NOS: NO synthase; ECE: endothelin converting enzyme; AC: adenylate cyclase; cAMP: cyclic adenosine monophosphate; ET: endothelin; GMP: guanosine monophosphate; PDE: phosphodiesterase; PH: pulmonary hypertension. Reproduced from [13] with permission from the publisher.

FIGURE 2.

The embolic hypothesis of chronic thromboembolic pulmonary hypertension (CTEPH). VTE: venous thromboembolism; PE: pulmonary embolism.