Pulmonary arterial hypertension and the state of limbo.

T he concept of limbo will be familiar to Catholic Christians. Traditionally, limbo was seen as place for the souls of infants dying before they had a chance to be baptised. It was a resting place that was neither heaven nor hell (fig. 1) [1]. The concept of a place that is neither heaven nor hell is also familiar to patients with pulmonary arterial hypertension (PAH). Prior to the discovery of new therapeutics for PAH, patients had an untreated life expectancy of ,3 yrs and were considered to reside in the ‘‘kingdom of the near dead’’ [2–4]. Nevertheless, despite substantial progress in our understanding of PAH and with new therapeutics, the current prognosis remains some distance from ‘‘heaven’’. While the majority of patients present with World Health Organization (WHO) functional class III symptoms, less than half will experience an improvement in functional class on a single oral agent and will, therefore, remain significantly disabled [5]. Furthermore, the 6-min walk distance improves, on average, by ,40 m when initiated on oral agents, implying significant residual exercise limitation [6]. Indeed, despite the use of combination therapy including prostacyclin, 45% of patients with newly diagnosed idiopathic PAH will be dead within 3 yrs of diagnosis as so-called ‘‘incident cases’’ [7].