Pulmonary Hypertension CME ACCREDITED Watch Time: 30 mins

touchEXPERT OPINIONS Medical therapy for CTEPH: From biology to new treatment options

Watch leading experts involved in the care of patients with CTEPH discuss the latest issues and controversies in the medical management of CTEPH and related comorbidities, including the evolving data supporting the use of oral therapy, the application of oral therapies in clinical practice and how the underlying biology impacts on treatment decisions.

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Prof. Irene Lang
University of Vienna, Vienna, Austria
How Biology informs treatment decisions

Prof. Irene Lang discusses the biological mechanisms of chronic thromboembolic pulmonary hypertension (CTEPH), which may occur as a rare complication after acute pulmonary embolism. While the exact epidemiology is unknown, Prof. Lang discusses the latest knowledge on how CTEPH develops, the role of vascular disease, and how small-vessel disease may impact on the severity of CTEPH and post-surgical outcomes.

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Interview Questions
  • What is the current understanding of CTEPH as a dual vascular disorder?
  • How does our knowledge of the pathophysiology of CTEPH influence clinical decision making?
  • What is the role of the NO-sGC-cGMP pathway in CTEPH?
About Prof. Irene Lang

Irene M. Lang is a clinical cardiologist and Professor of Vascular Biology at the Medical University of Vienna. She has been nominated as one of the WMA–Caring Physicians of the World 2005. She directs an out-patient clinic for pulmonary vascular diseases and is an active interventional and structural cardiologist. She also leads basic research on the biology of vascular occlusions, with a special focus on CTEPH. Prof. Lang is a Member of the Austrian and European societies of cardiology, Senate Member of the Medical University of Vienna, and Deputy Editor of Pulmonary Circulation, International Editorial Board Member for the European Heart Journal and Associate Editor of Atherosclerosis.

Disclosures:

Grants/research support: Actelion, AOPOrphan

Consultant/Advisory Boards: Actelion, AOPOrphan, Medtronic, Ferrer

 
Prof. Marc Humbert
Université Paris-Saclay, Le Kremlin-Bicêtre, France
What is currently the greatest unmet clinicsal need in CEPTH, and how might emerging data address these needs?

Prof. Marc Humbert discusses the important advances in the management of patients with inoperable disease or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. This includes discussion of how and when to use medical therapies, the role of balloon angioplasty and when to consider anticoagulation therapy.

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Interview Questions
  • Is balloon angioplasty comparable to pulmonary endarterectomy?
  • How does medical therapy target underlying microvascular disease?
  • What is the anticoagulant of choice in patients with CTEPH?
About Prof. Marc Humbert

Marc Humbert is Professor of Respiratory Medicine at the Université Paris-Saclay in Le Kremlin-Bicêtre, France. He is also Director of the Department of Respiratory and Intensive Care Medicine at the French Pulmonary Hypertension Reference Centre, Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, France. He has been the Chief Editor of the European Respiratory Journal from 2013 to 2017 and he is currently Section Editor in charge of pulmonary vascular medicine. He is the current Vice-President of the European Respiratory Society (ERS). Since 2017, Prof. Humbert has been the vice-coordinator of the European Reference Network for rare and low prevalence respiratory diseases (ERN-LUNG). Clarivate Analytics listed Marc Humbert as one of the world’s highly cited researchers in the field of Clinical Medicine (2018, 2019).

Disclosures:

Grants/research support: Bayer, GSK, Actelion

Consultant/Advisory Boards: Actelion, Bayer, GSK, Merck, United Therapeutics, Acceleron

 
Dr Mark Toshner
University of Cambridge, Cambridge, UK
The impact of new medical therapies in the clinic

Dr Mark Toshner discusses what we know about current and emerging medical therapies in the management of patients with CTEPH and how different treatments and procedures can be fully utilized to give patients the best outcomes.

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Interview Questions
  • What is the evidence for combination therapy (eg, targeted medical therapy with or without balloon angioplasty)?
  • What is the evidence for non-vasodilator drug and anti-inflammatory approaches in CTEPH?
  • What is the future role of medical therapy in the management of CTEPH
About Dr Mark Toshner

Mark Toshner undertook a British Heart Foundation Research Training Fellowship in Cambridge in 2007 where he trained in cell and molecular mechanisms of endothelial dysfunction in pulmonary hypertension. He was appointed as a Wellcome/NIHR Clinical Lecturer in 2010. He is currently a University Lecturer at the University of Cambridge School of Clinical Medicine where he is involved in translational and experimental research in pulmonary vascular diseases. He is currently the Chief-Investigator of the Transform-UK trial, the first investigator-led multicentre trial to involve all seven specialist centres in the UK. He is leading an international genotyping/phenotyping collaboration in CTEPH and has close ties to the Pulmonary Vascular Diseases Unit in Royal Papworth Hospital. His research group is focused on preclinical target identification and early phase trials in pulmonary vascular diseases.

Disclosures:

Consultant/Advisory Boards: Morphogen-IX

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Overview & Learning Objectives
Overview

In this activity, experts in cardiology, pulmonary vascular disorder and respiratory specialists discuss the biological and pathophysiological mechanisms of CTEPH and how they impact on treatment decisions relating to the use of medical therapies in daily clinical practice.

This activity has been jointly provided by Oakstone and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians.

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Target Audience

This activity is designed to meet the educational needs of pulmonologists, cardiologists, cardiopulmonary surgeons, rheumatologists and other HCPs involved in the care of patients with CTEPH globally.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Faculty

Prof. Irene Lang discloses: Grants/research support: Actelion, AOPOrphan, Consultant/Advisory Boards: Actelion, AOPOrphan, Medtronic, Ferrer

Prof. Marc Humbert discloses: Grants/research support: Bayer, GSK, Actelion, Consultant/Advisory Boards: Actelion, Bayer, GSK, Merck, United Therapeutics, Acceleron

Dr Mark Toshner discloses: Consultant/Advisory Boards: Morphogen-IX

Content Reviewer

Walter Murray Yarbrough, MD has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Writer

Paul Taylor has no financial interests/relationships or affiliations in relation to this activity.

Requirement for Successful Completion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™️. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

Date of original release: April 21, 2020. Date credits expire: April 21, 2021.

Learning Objectives

After watching this touchEXPERT OPINIONS, you should be able to:

  • Describe the biological and pathophysiological mechanisms of CTEPH
  • Summarize the evolving data supporting the use of oral therapies
  • Explain how new developments in medical therapy for the treatment of CTEPH will change daily practice

This content is for healthcare professionals only. Please confirm that you are a healthcare professional

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Question 1/4
Which of the following factors would be assessed as being a poor prognostic indicator when determining operability in patients with CTEPH?
Correct

An international registry reported that despite similarities in clinical presentation, operable and non-operable patients with CTEPH may have distinct associated medical conditions.1 Approximately 40% of the patients in the registry were considered inoperable due to concern for inaccessible vascular obstruction, PAP out of proportion to morphological lesions and significant prohibitive comorbidities.

CTEPH, chronic thromboembolic pulmonary hypertension; DVT, deep vein thrombosis; PAP, pulmonary artery pressure; PE, pulmonary embolism.

References

1. Pepke-Zaba J, et al. Circulation 2011;124:1973-1981.
2. Kim NH, et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J 2019;53:1801915.

Question 2/4
How do clinical agents used to treat CTEPH target the NO–sGC–cGMP pathway?
Correct

Recent evidence suggests the involvement of the NO–sGC–cGMP pathway in the pathophysiology of CTEPH. NO produced by vascular endothelium inhibits platelet aggregation and growth of smooth muscle cells. NO also activates sGC to synthesise cGMP, a second messenger with many actions including smooth muscle relaxation.

cGMP, cyclic guanosine monophosphate; CTEPH, chronic thromboembolic pulmonary hypertension; NO, nitric oxide; sGC, soluble guanylate cyclase.

Reference

Tonelli AR, et al. Pulm Circ 2013;3:20–30.

Question 3/4
Which of the following statements best describes the clinical outcomes reported for CHEST-1 study?
Correct

By week 16, the 6-minute walk distance had increased by a mean of 39 m in the riociguat group, as compared with a mean decrease of 6 m in the placebo group (least-squares mean difference, 46 m; 95% confidence interval [CI], 25 to 67; P<0.001). Pulmonary vascular resistance decreased by 226 dyn·sec·cm–5 in the riociguat group and increased by 23 dyn·sec·cm–5 in the placebo group (least-squares mean difference, –246 dyn·sec·cm–5; 95% CI, –303 to –190; P<0.001). Riociguat was also associated with significant improvements in the NT-proBNP level (P<0.001) and WHO functional class (P=0.003). The most common serious adverse events were right ventricular failure (in 3% of patients in each group) and syncope (in 2% of the riociguat group and in 3% of the placebo group).

WHO, World Health Organization.

Reference

Ghofrani HG, et al. N Engl J Med 2013;369:319-329.

Question 4/4
Your patient with CTEPH has recently undergone successful PEA. What would be your recommendations for anticoagulation therapy in this patient based on current guidelines?
Correct

The European Society of Cardiology guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society recommend lifelong anticoagulation for inoperable patients and those who have undergone successful PEA or BPA.
BPA, balloon pulmonary angioplasty; PEA, pulmonary endarterectomy.

References

Konstantinides SV, et al. Eur Respir J 2019;54:1901647.

Konstantinides SV, et al. Eur Heart J 2020;41:543–603.

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