Chapter 28: Pulmonary Arterial Hypertension

KEY CONCEPTS

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

• Diagnosis of PAH is growing because of increased awareness and knowledge of the disease state, leading to earlier and improved evaluation and identification.

• Regardless of the etiology, be it unknown or related to an associated medical condition, subgroups of PAH are based on similar clinical and pathologic physiology.

• The underlying cause of PAH is a complicated amalgam of endothelial cell dysfunction, a procoagulant state, platelet activation, vasoconstriction, loss of relaxing factors, cellular proliferation, hypertrophy, fibrosis, and inflammation.

• 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, are seen.

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

• The goals of treatment are to alleviate symptoms, improve the quality of life, slow the progression of the disease, and improve survival.

• A general goal of PAH treatment is to correct the imbalance between vasoconstriction and vasodilation and prevent adverse thrombotic events to improve oxygenation, functional class, exercise capacity, and quality of life.

• Nonpharmacologic therapy is frequently used to address comorbid conditions that often accompany 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. Only epoprostenol has demonstrated improved survival.

• Endothelin receptor antagonists, bosentan, ambrisentan and macitentan, improve exercise capacity, hemodynamics, and functional class in PAH. Macitentan also significantly decreases the composite end point of events related to PAH or death.

• Phosphodiesterase-5 inhibitors, including sildenafil and tadalafil, are potent and highly specific drugs that have been shown to reduce mPAP and improve functional class.

• Riociguat is a novel soluble guanylate cyclase stimulator shown to improve exercise capacity, hemodynamic parameters, and functional class.

• Calcium channel blockers may be considered in a small number of patients who have a positive response on acute vasoreactivity testing.

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