This chapter will review the pharmacotherapy for treatment of pulmonary arterial hypertension (PAH) according to the 2019 CHEST Guideline.
Pulmonary hypertension (PH) is characterized by mean pulmonary arterial pressure (mPAP) ≥20 mm Hg at rest and pulmonary vascular resistance three or more wood units measured by right heart catheterization. The World Health Organization (WHO) classifies PH into five groups based on etiologies ( Table 17.1 ).
PH caused by left heart disease
PH caused by lung disease and/or hypoxia
Chronic thromboembolic PH
Unclear multifactorial mechanisms
PAH is Group 1 PH caused by idiopathic and heritable causes, drugs, connective tissue disease, congenital heart disease, human immunodeficiency virus, portopulmonary hypertension, schistosomiasis, pulmonary venoocclusive disease, or PH of the newborn.
See Table 17.2
|I||No symptoms (dyspnea, fatigue, syncope, chest pain) with normal activities|
|II||Symptoms with strenuous normal daily activities; slight limitations in functional status/activity level|
|III||Symptoms with normal daily activities; severe limitation in functional status/activity level|
|IV||Symptoms at rest; unable to perform normal daily activities without symptoms|
Management of PAH
Oxygen: maintain SaO 2 ≥90% and PaO 2 ≥60 mm Hg.
Diuretics: for the symptomatic management of right ventricular (RV) dysfunction and fluid overload.
Digoxin: consider in atrial tachyarrhythmias.
Anticoagulation: may consider in idiopathic PAH, heritable PAH, and PAH secondary to anorexigenic agent use (conflicting data).
See Fig. 17.1
Vasodilator therapy with calcium channel blockers if demonstrates acute vasoreactivity.
Diltiazem extended-release (ER) 240–720 mg daily.
Amlodipine up to 20 mg daily.
Nifedipine ER 120–240 mg daily.
Avoid in RV dysfunction, depressed cardiac output, or WHO Functional Class IV symptoms.
Agents targeting the prostacyclin pathway ( table 17.3 )
Mechanism of action (MOA): Prostacyclin produced in vascular endothelium causes potent vasodilation and inhibits smooth muscle cell growth and platelet aggregation. A relative deficiency in prostacyclin production may contribute to the pathogenesis of PAH, and drugs targeting the prostacyclin pathway are one of the pharmacotherapeutic options for PAH.