Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature in which an ever increasing resistance to circulatory flow imposes a mounting afterload for the right heart to overcome. Without therapy, and frequently despite it, patients with PAH suffer progressive and inexorable right heart failure, functional decline, and ultimately die. Although rapid progress has resulted in the availability of therapy that can improve the outlook for many patients, long delays in disease recognition are common, exposing patients to prolonged suffering and potentially irreversible harm.
PAH is one of several possible causes of pulmonary hypertension. Pulmonary hypertension is defined as a mean pulmonary artery pressure greater than or equal to 25 mm Hg at rest. It can be due to diseases primarily isolated to the pulmonary vasculature itself, as in PAH, or can be a complication of other diseases, including hypoxemic lung disorders (e.g., chronic obstructive pulmonary disease [COPD]), left heart disease (e.g., systolic, diastolic, or valvular dysfunctions), or thromboembolism.1,2 Identification of its cause is essential, as appropriate therapy for pulmonary hypertension is aimed at its underlying cause—be that repair of a stenotic mitral valve, bronchodilators for obstructive lung disease or, in the case of PAH, the use of advanced therapies targeted at the pulmonary vasculature.
Classification of the Pulmonary Hypertensive Diseases
A “sclerosis of the pulmonary arteries” (“Uber Sklerose der Lungen Arterie”) without identifiable cause was first described by Ernst von Romberg in 1891.3 Exclusively descriptive reports of pathologic findings continued until the 1950s when the development of catheterization techniques allowed for hemodynamic evaluation. Using such methods, Dresdale and colleagues described a hypertensive vasculopathy of the pulmonary circulation involving vasoconstriction, elevation of pulmonary arterial pressures (PAPs), and a measurable response to the injection of the nonselective alpha adrenergic antagonist tolazoline.4 No cause could be identified for the pulmonary arteriopathy and the term primary pulmonary hypertension (PPH) was introduced.5
Subsequent classification schemes for diseases-causing pulmonary hypertension have been adopted by international consensus panels. These have evolved from systems based primarily on histopathologic findings to a current model that emphasizes the grouping of entities according to similarities in hemodynamic and clinical characteristics (Table 72-1).6 Importantly, accurate classification of pulmonary hypertension is essential to guide the rational and appropriate use of medications.
Table 72-1Updated Classification of Pulmonary Hypertensiona |Favorite Table|Download (.pdf) Table 72-1Updated Classification of Pulmonary Hypertensiona
|1. ||Pulmonary arterial hypertension |
| ||1.1 ||Idiopathic PAH |
| ||1.2 ||Heritable PAH |
| ||1.2.1 ||BMPR2 |
| ||1.2.2 ||ALK-1, ENG, SMADS, CAV1, KCNK3 |
| ||1.2.3 ||Unknown |
| ||1.3 ||Drug and toxin induced |
| ||1.4 ||Associated with: |
| ||1.4.1 ||Connective tissue disease |
| ||1.4.2 ||HIV infection |
| ||1.4.3 ||Portal hypertension |
| ||1.4.4 ||Congenital heart diseases |
| ||1.4.5 ||Schistosomiasis |
|1’ ||Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis |
|1’’. ||Persistent pulmonary hypertension of the newborn (PPHN) |
|2. ||Pulmonary hypertension due to left heart disease |