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Introduction

University Of California San Diego, California

Marius M. Hoeper, M.D.

Vienna Medical University Vienna, Austria

Gérald Simonneau, M.D.

Hôpital Antoine-Béclère Clamart, France

In July 2005, 32 international experts gathered in Zurich, Switzerland, to discuss chronic thromboembolic pulmonary hypertension (CTEPH). Although CTEPH has only recently evolved from being a diagnosis made primarily at autopsy to a recognized disease that is treatable and, in some, potentially curable, there remain many questions for which there are currently no clear answers. The aim of the CTEPH International Scientific Advisory Board (INSAB) was to review current knowledge of CTEPH, to evaluate therapeutic experience, to identify areas for future research, and to develop expert consensus and guidance for physicians involved in care. This supplement provides a comprehensive review of the two-day meeting in order to share important insights, opinions, and clinical approaches in the management of this life-threatening condition.

The first article in this issue, by Tapson and Humbert, reviews the scale of the problem. Overall, the true incidence and prevalence of CTEPH is yet to be fully determined and may be significantly underestimated. The authors discuss reasons for this and suggest that increased awareness among physicians and a more thorough diagnostic approach in at-risk patients may lead to improved management of the disease.

Having established that there is room for improvement regarding the early identification of CTEPH, Lang and Kerr go on to describe risk factors for the condition, including the relevance of thrombophilia, splenectomy, prior pulmonary embolism, chronic inflammatory states, and ventriculoatrial shunts. The authors emphasize the need for screening strategies, and highlight the need for treatments aimed at preventing CTEPH or reducing disease progression.

While obstruction of large pulmonary arteries by organized thromboemboli is recognized as the inciting event promoting progressive pulmonary hypertension and right heart failure in CTEPH, the involvement of pulmonary microvascular changes in the form of general pulmonary hypertensive arteriopathy is gaining increased recognition as an important contributor to disease progression. Galiè and Kim discuss pulmonary microvascular disease with regard to classification of subtypes and with emphasis on its occurrence and type in patients with inoperable disease and late-emergent small-vessel disease after pulmonary endarterectomy (PEA). Improvements in preoperative screening are required to identify patients with increased post-PEA mortality risk associated with significant microvascular disease, and there is a need for alternative therapies to improve outcomes in patients with persistent pulmonary hypertension.

Imaging techniques to help identify CTEPH and that also allow for other diagnoses in patients with pulmonary hypertension are discussed. In his article, Coulden explores the use of various diagnostic and imaging techniques including computed tomography, high-resolution computed tomography, magnetic resonance (MR), / scanning, chest radiograph, echocardiography, and angiography. Opportunities for the future exist regarding stress imaging for right ventricular function and flow, pulmonary flow waveform analysis, MR lung perfusion measurement, and delayed enhancement imaging.

Kim presents on the assessment of operability for CTEPH. PEA remains the treatment of choice for patients with CTEPH with major vessel disease, although a substantial proportion of patients (10–50%) are considered poor candidates for surgical intervention. Despite the growth in both expertise and number of PEA centers worldwide, we still lack a standardized preoperative classification system, and this is an urgent priority. A putative system is proposed in this article.

Mayer and Klepetko review techniques and outcomes of PEA, highlighting the need for systematic imaging and symptom work-up, discussing postoperative management and complications, and reviewing predictors of post-surgery outcome. The authors also propose that preoperative medical therapy may be appropriate to reduce postoperative mortality in patients undergoing PEA, yet which patients may benefit from such pharmacotherapy remains an issue for investigation.

Bresser, Pepke-Zaba, Jaïs, Humbert, and Hoeper draw on their clinical experience to provide insights into the possible utility of novel medical therapies in CTEPH, focusing on patients who are not suitable for surgery, and looking at possible use as a therapeutic bridge between diagnosis and PEA, or in patients with persistent postoperative pulmonary hypertension. Direct evidence from clinical trials in CTEPH is limited to date, but findings from small trials have provided some encouraging data.

There remain a number of questions regarding which treatment option is best suited to which patients, and when is best to apply medical and/or surgical treatment. Rubin, Hoeper, Klepetko, Galiè, Lang, and Simonneau present and discuss a possible treatment algorithm that may help decision-making and improve standardization of patient care. While the suggested approach received a positive opinion from the majority of meeting attendees, it was noted that there are a number of areas requiring further research and input before the system can be properly validated.

Finally, Peacock, Simonneau, and Rubin discuss controversies, uncertainties, and future research in the treatment of CTEPH. There are many issues that require investigation, not least because there continues to be significant disagreement amongst experts in the field regarding the natural history and pathophysiology of CTEPH. The importance of arteriopathy is an issue for debate regarding both the development and progression of CTEPH: the histologic comparability of small vessels from patients with CTEPH and patients with idiopathic pulmonary arterial hypertension may underlie the delay to diagnosis, or misdiagnosis, of CTEPH. There is, however, consensus among experts that a significant proportion of patients with CTEPH are not suitable for PEA, and that these patients may well benefit from medical intervention. Thus, the role of medical therapy, and how it should be used alongside surgical intervention to maximize outcomes, is an important priority.

FOOTNOTES

Conflict of Interest Statement: L.J.R. has served as a consultant and Advisory Board member for Actelion, for which he has received compensation of $25,000 annually for the past 4 years. He is a co-investigator in an Actelion-sponsored study of Bosentan in CTEPH. M.M.H. received honorariums from Actelion Pharmaceuticals and from Pfizer Ltd. for speaking at conferences, consultancies, and Advisory Board membership. In addition he received a research grant from Actelion Pharmaceuticals. He received speaker's fees from Schering, Germany. G.S. reports having received consulting and lecture fees and for Advisory Board Activities from Actelion ($15,000/yr), Schering ($10,000), Pfizer ($7,500/yr), United Therapeutics ($15,000/yr), and Encysive ($3,000/yr).

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rubin, L. J. Articles by Simonneau, G. Search for Related Content PubMed Articles by Rubin, L. J. Articles by Simonneau, G.