Diagnosis and Treatment of Secondary (Non–Category 1) Pulmonary Hypertension

Abstract

Pulmonary hypertension occurs commonly in cardiopulmonary disease. In 1998, a new clinical classification was proposed that divided pulmonary hypertension into 5 categories on the basis of the presumed underlying etiology of the pulmonary vascular disease1 (Table 1). Although it was never intended that this classification be used as a guideline to determine appropriate therapy, somewhat surprisingly, the regulatory authorities decided that all medications that were clinically tested and approved for patients with idiopathic pulmonary arterial hypertension (PAH) and patients with pulmonary hypertension associated with connective tissue diseases be applied to all category 1 patients.2 The wisdom of this can be debated at a later date. However, it has left clinicians somewhat confused about the utilization of therapies to treat patients who fall outside of category 1 pulmonary hypertension, often referred to as secondary pulmonary hypertension. View this table: Table 1. Current Clinical Classification of Pulmonary Hypertension 1 There are 3 classes of approved therapies for PAH, all of which are considered to be pulmonary vasodilators: endothelin receptor blockers, phosphodiesterase-5 inhibitors, and prostacyclins.3 Their clinical efficacy has been based on a short-term improvement in exercise tolerance, as measured by a 6-minute walk test. In all of the clinical trials, an improvement in walk was apparent within the first 4 weeks of use, allowing a judgment about efficacy to be made quickly.4 Hemodynamically, their effects are modest, but they tend to raise cardiac output with little effect on pulmonary artery pressure. This has important implications when they are considered for unapproved use. We review the distinctive features of these causes of pulmonary hypertension and the data on the evidence that supports or refutes the use of these therapies in non–category 1 pulmonary hypertension. Patients with pulmonary venous hypertension have elevated pulmonary venous pressure (as reflected in the pulmonary capillary wedge pressure), …