Chapter 45: Pulmonary Arterial Hypertension

KEY CONCEPTS

• Pulmonary arterial hypertension (PAH) is defined as a mean pulmonary artery pressure (mPAP) ≥25 mm Hg at rest with a pulmonary wedge pressure or left ventricular end-diastolic pressure (LVEDP) ≤15 mm Hg and a pulmonary vascular resistance (PVR) >3 Wood units (WU) measured by right cardiac catheterization.

• Patients with PAH present with exertional dyspnea, fatigue, weakness, and exertion intolerance. As the disease progresses, symptoms of right heart dysfunction and failure, such as dyspnea at rest, lower extremity edema, chest pain, and syncope, may be present.

• The definitive diagnosis of PAH is done with a right heart catheterization. The right heart catheterization provides important prognostic information and can be used to assess pulmonary vasoreactivity prior to initiating therapy.

• Goals of treatment are to alleviate symptoms; improve quality of life, functional class, and exercise capacity; slow disease progression; and improve survival.

• Nonpharmacologic therapy, including counseling on pregnancy avoidance, immunizations, and low-sodium diets, should be provided to all patients with PAH.

• Conventional therapy of PAH includes oral anticoagulants, diuretics, oxygen, and digoxin.

• Prostacyclin analogs such as epoprostenol, treprostinil, and iloprost induce potent vasodilation of pulmonary vascular beds and are typically reserved for WHO functional class III and IV patients. Only epoprostenol has demonstrated improved survival.

• Patients with WHO functional class II or III are commonly initiated on oral therapy for PAH. Options include endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, riociguat, and selexipag. These agents have been shown to improve exercise capacity, functional class, and hemodynamics in PAH.

• Calcium channel blockers are only considered in a small number of patients who have a positive response to acute vasoreactivity testing. A very small number of patients have a long-term response to calcium channel blockers.

• Combination therapy may address more than one mechanism causing PAH. Combination therapy may be initiated sequentially or as the initial regimen in patients with worse functional classes. Evidence demonstrates that initial combination therapy is associated with a significant reduction in time to clinical failure and PAH hospitalizations.

Preclass Engaged Learning Activity

The mechanism of action of medications used in pulmonary arterial hypertension (PAH) is directly tied to the pathophysiology of the disease. Create a concept map of the site of action of the major drug classes utilized in PAH—prostacyclin analogs, endothelin-receptor antagonists, phosphodiesterase inhibitors, and guanylate cyclase stimulators. There is an excellent diagram published in the New England Journal of Medicine in 2004. While the information is slightly outdated, it is a great place to start creating a concept map. This activity is intended to prepare you for understanding the role of the medications in the treatment of PAH as well as to increase critical thinking skills related to evaluating side effects and monitoring parameters of these medications.