Primary pulmonary hypertension (PPH) is a disease associated with significant morbidity and mortality that occurs most commonly in young and middle aged women.1 Until recently, there had been only a limited number of therapies available to treat this disease. Over the years, however, endeavours in cellular and molecular research have improved our understanding of this disease process and allowed for the development of targeted approaches to treatment. These new therapies have created an atmosphere of optimism in the management of a disease was considered untreatable.

Pulmonary vasoconstriction was long considered to be the only “treatable” aspect of PPH. Accordingly, the treatment of PPH focused on the administration of oral vasodilators, mainly calcium channel blockers, in the hope of countering the vasoconstrictive process. The treatment of this subset of “vasoreactive” patients with calcium channel blockers has been shown to result in improvements in symptoms, exercise tolerance, cardiopulmonary haemodynamics, and survival.2 Unfortunately, only a small number (20%) of patients demonstrate a beneficial response to calcium channel blockade and, in fact, calcium blockers lead to numerous adverse effects in “non-responders”. Therefore utility of these agents is limited and their use should be confined to those in whom a clear acute vasodilator response is demonstrated haemodynamically.

Looking beyond simple pulmonary vasoconstriction, it is now recognised that defects in endothelial function, pulmonary vascular smooth muscle cells, and circulating blood factors may all be involved in the pathogenesis and progression of PPH. The pathophysiologic and histopathologic consequences of these derangements are complex and variable, but serve as a framework for understanding …