Less common causes in Group 1 include connective tissue disorders and exposure to toxins. Drugs and toxins that have a well-defined association with PAH include aminorex, fenfluramine, dexfenfluramine, benfluorex, methamphetamines, dasatinib, and toxic rapeseed oil.
Group 2 PH comprises patients whose disease results from left heart dysfunction, the most common cause of PH. This subgroup has an elevated pulmonary artery wedge pressure > 15 mm Hg.8 Patients have either isolated postcapillary PH or combined pre-capillary and postcapillary PH.
Group 3 PH comprises patients whose PH is secondary to chronic and hypoxic lung disease. Patients in this group have pre-capillary PH; even a modest elevation in mPAP (20-29 mm Hg) is associated with a poor prognosis. Group 3 patients have elevated PVR, even with mild PH.2 Exertional dyspnea disproportionate to the results of pulmonary function testing, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation with exercise all point to severe PH in these patients.9
Group 4 PH encompasses patients with pulmonary artery obstruction, the most common cause of which is related to chronic thromboembolism. Other causes include obstruction of the pulmonary artery from an extrinsic source. Patients with chronic thromboembolic pulmonary hypertension (CTEPH) also have pre-capillary PH, resulting from elevated pulmonary pressures secondary to thromboembolic burden, as well as pulmonary remodeling in unobstructed small arterioles.
Group 5 PH is a miscellaneous group secondary to unclear or multiple causes, including chronic hematologic anemia (eg, sickle cell disease), systemic disorders (eg, sarcoidosis), and metabolic disorders (eg, glycogen storage disease). Patients in Group 5 can have both pre-capillary and postcapillary hypertension.
Classification by functional status
The World Health Organization (WHO) Functional Classification of Patients with Pulmonary Hypertension is divided into 4 classes.10 This system is used to guide treatment and for prognostic purposes:
Class I. Patients have no limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near-syncope.
