TITLE: Demographics, BMPR2 status and outcomes in Distal Chronic Thromboembolic Pulmonary Hypertension

Rationale Although pulmonary endarterectomy (PEA) is potentially curative in Chronic Thromboembolic Pulmonary Hypertension (CTEPH), some patients have distally distributed disease that is not amenable to surgery. The aetiology and characteristics of this patient group are currently not well understood. Objectives This study compares the baseline demographics and outcomes of subjects with distal CTEPH, proximal CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH). This will help determine whether these conditions represent separate entities, or whether they in fact exist along the same spectrum of disease. Methods The medical history, clinical characteristics, Bone Morphogenetic Receptor type 2 (BMPR2) mutation status and outcomes of 96 IPAH, 35 distal CTEPH and 68 proximal CTEPH subjects referred to a single specialist centre between 1994 and 2005 were reviewed. Results There were significant differences between the distal CTEPH, proximal CTEPH and IPAH groups in age (55.9yrs vs 54.8yrs vs 46.2yrs p<0.0001), proportion who were male (43% vs 69% vs 29% p<0. Both distal CTEPH and IPAH subjects were managed similarly, and had comparable survival characteristics (77% 1yr, 53% 3yrs vs 86% 1yr, 60% 3yrs p=0.68). Conclusions Distal and proximal CTEPH groups share certain demographic features that not only indicate a common aetiology but also help differentiate them from IPAH patients. Despite more favourable haemodynamic parameters in the distal CTEPH group, subjects displayed a poor long term outcome similar to that of IPAH subjects.INTRODUCTION Chronic thromboembolic pulmonary hypertension (CTEPH) is an important cause of pulmonary hypertension that is commonly considered to be the consequence of acute pulmonary embolic disease(1). Following an acute event, unresolved residual thrombus becomes organised and fibrosed, leading to ongoing obstruction to pulmonary blood flow. Untreated, this leads to progressive pulmonary hypertension, right ventricular dysfunction and death(2). Recent evidence suggests that CTEPH may be more common than originally anticipated and may complicate up to 3.8% of acute pulmonary embolic events(3). In patients with predominantly 'proximal' disease surgical intervention (Pulmonary Endarterectomy or PEA) can be very effective, often leading to normalisation of pulmonary arterial pressures(4). However, when the degree of haemodynamic compromise is out of proportion to the quantity of surgically accessible disease, surgery is often inappropriate(5). Pulmonary endarterectomy in these patients is less successful, and is associated with a higher mortality(6). In this inoperable or 'distal' disease, where the majority of organised thrombus lies beyond the subsegmental level, management has historically consisted of supportive therapy alone.