chronic thrombo-embolic pulmonary hypertension: classification and long term outcome

Conditions: Chronic Thromboembolic Pulmonary Hypertension; Idiopathic Pulmonary Arterial Hypertension

Summary: this study will help to provide more up to date prognostic data on the natural history of untreated proximal cteph which will be helpful in discussions regarding surgical versus medical treatment and by exploring the similarities and differences between distal cteph and ipah the investigators hope to get insights into disease mechanisms in patients with distal cteph.

chronic thrombo-embolic pulmonary hypertension (cteph) is thought to represent the consequence of failure of thrombus resolution after the establishment of thrombosis within the elastic pulmonary arteries. thrombotic material becomes fibrosed, with occlusive vascular remodeling and the development of a secondary small vessel arteriopathy, termed the two-compartment model. this results in an increase in pressure and vascular resistance in the pulmonary vasculature and leads eventually to right heart failure. it has been demonstrated that 2 year survival for cteph patients with mean pulmonary arterial pressure(mpap) \>50 mm hg was only 20%, however, preliminary data from sheffield teaching hospitals suggest that survival is significantly better than this. until recently surgery was the only treatment for cteph in selected patients. studies have shown the 10 year survival in patients with cteph after pea surgery was 74%. more recently, for patients with inoperable cteph, drug therapy has been shown to improve exercise capacity. despite recent publications the natural history and mechanisms underlying cteph are poorly understood. the main area of research focus in this study will be improving understanding of the natural history of chronic thromboembolic pulmonary hypertension. the purpose of this research protocol is to conduct a retrospective review of patients with cteph diagnosed at the sheffield centre between 2001 and 2014 to understand more about the natural history of disease including prognostic indicators. the sheffield service has one of the largest cohorts of cteph in the world (\>650 diagnosed cases since 2001). approximately half of these patients undergo curative surgery with pulmonary endarterectomy. however, a significant proportion of patients with operable disease decline surgery and a significant proportion of patients have disease that is too distal for surgery, so called distal cteph. there is a relative paucity of data on i) the natural history of this disease, ii) an understanding of the relative contribution of obstruction and distal vasculopathy to elevations in pulmonary vascular resistance iii) the effects of distal cteph on right ventricular function and iv) how distal cteph differs from idiopathic pulmonary arterial hypertension (ipah). the second part of this study will focus on understanding disease mechanisms utilising mr imaging techniques and using the sheffield ph biobank resource to understand differences in the ipah and distal cteph cohorts. the sheffield ph biobank has samples and detailed phenotypic data on over 400 treatment naïve patients with all forms of pulmonary hypertension with serial sampling and long term follow up providing a unique resource to make detailed comparisons across all forms of pulmonary hypertension.

Eligibility criteria:
inclusion criteria: * all patients with the diagnosis of chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension (as per the european society of cardiology guidelines) who presented to sheffield pulmonary vascular disease unit at the royal hallamshire hospital between 1st jan 2001 and 1st dec 2014. exclusion criteria: * patients with pulmonary hypertension who have other causes of pulmonary hypertension in addition to chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension.

Keywords: chronic thromboembolic pulmonary hypertension distal chronic thromboembolic pulmonary hypertension proximal chronic thromboembolic pulmonary hypertension operable disease in-operable disease pulmonary endarterectomy ph specific targeted therapy phosphodiesterase type 5 inhibitors endothelin receptor antagonist prostacyclin analogues soluble guanylate cyclase stimulator sildenafil tadalafil bosentan ambrisentan macitentan iloprost riociguat idiopathic pulmonary arterial hypertension