What You Need to Know About
CTEPH Today: A Status Update
Moderator
David Langleben, MD, FRCPC
Professor of Medicine
McGill University
Director
Center for Pulmonary Vascular Disease
Division of Cardiology
Jewish General Hospital
Montreal, Quebec
Panelists
Deepa Gopalan, MD, MSc, MRCP, FRCR
Consultant Cardiovascular Radiologist
Department of Radiology
Papworth Hospital
Cambridge, United Kingdom
David Jenkins, MD, FRCS
Director
National Pulmonary Endarterectomy Program
Consultant Cardiothoracic Surgeon
Papworth Hospital
Cambridge, United Kingdom
CTEPH
Pathophysiology
• CTEPH develops from the obstruction of
pulmonary arteries following episodes of PE
with incomplete thrombus resolution,
formation of fibrosis, and remodeling of
pulmonary blood vessels.
• Consequently, PVR is increased, leading to
PH and progressive right heart failure.
Jenkins D, et al.[1]
Dartevelle P, et al.[2]
CTEPH
Underdiagnosed and Treatable
• CTEPH is more common than people
realize.
− It is hard for general physicians to make the
diagnosis because many of the symptoms are
nonspecific, such as fatigue and
breathlessness on exertion.
• It is one of the most treatable forms of PH.
− There is a curative treatment available in the
form of PEA.
Jenkins D, et al.[1]
Pulmonary Hypertension
Classification
Group 1
Group 2
Group 3
Group 4
Group 5
Simonneau G, et al.[7]
Pulmonary arterial hypertension
PH owing to left heart disease
PH owing to
lung diseases and/or hypoxia
CTEPH
PH with unclear
or multifactorial etiologies
CTEPH
Incidence
• Earlier estimates suggested that < 1% of
people would develop CTEPH following an
acute PE.
• Some of the more recent studies report:
− 1%a
− 3.8%b
− 8.8%c
a. Becattini C, et al.[4]
b. Pengo V, et al.[3]
c. Dentali F, et al.[5]
CTEPH
Risk Factors
• CTEPH should be considered in all patients with
unexplained PH.
• Other risk factors include:
− Ventriculo-atrial shunt
− Indwelling catheters and leads (such as chronic
dialysis catheters and pacemakers or automated
implantable cardiac defibrillator leads)
− Splenectomy
− Thyroid replacement therapy
− Inflammatory bowel disease
− History of malignancy
Jenkins D, et al.[1]
Patients With Untreated CTEPH
Survival and PPA
Green dotted line represents predicted survival among men 40-50 years old.
Riedel M, et al.[13]
CTEPH
Diagnosis
• Chest radiography and echo are used in the initial
assessment of suspected PH.
− PH is defined by a mean PPA > 25 mm mercury.
• The key thing is, within the population diagnosed
with PH, not to miss any patients with CTEPH.
− One of the problems is that some of the signs on
imaging are relatively subtle and can be easily
missed. That is why if you suspect it, get an
expert’s advice.
Jenkins D, et al.[1]
Pulmonary Hypertension
Imaging Algorithm
McCann C, et al.[14]
PH Imaging Modalities
V/Q scan
Thromboembolic Disease
Courtesy of Dr Gopalan.
IPAH
PH Imaging Modalities
CT Pulmonary Angiography
Courtesy of Dr Gopalan.
CT Pulmonary Angiography
Acute vs Chronic PE
Courtesy of Dr Gopalan.
CT Pulmonary Angiography
Proximal vs Distal CTEPH
Courtesy of Dr Gopalan.
PH Imaging Modalities
Catheter Pulmonary Angiography
Courtesy of Dr Gopalan.
PH Imaging Modalities
Cardiac MRI
McCann C, et al.[14]
Conditions That Mimic CTEPH
Pulmonary Artery Sarcoma
Courtesy of Mr Jenkins.
CTEPH
Patient Evaluation for PEA
• It is important to give every patient a chance at
operability because it makes such a huge difference
for them.
− PEA is the only approved and potentially curative treatment
currently available.
• The experience of the PEA team determines which
lesions are considered surgically treatable.
− High PH, PVR, and very low cardiac output are associated
with increased perioperative risk.
− Proximal occlusive webs in the lower lobes and a positive
history of PE that is relatively short are associated with good
results from surgery.
Jenkins D, et al.[1]
Dartevelle P, et al.[2]
Auger WR, et al.[6]
Pulmonary Endarterectomy
Current Mortality Rates
• In experienced centers around the world,
current mortality rates are quite low,
approaching that of conventional cardiac
surgery.
• Some of the more recent studies report:
− 2.2%a
− 4.7%b
− 1.4%c
a. Madani MM, et al.[21]
b. Mayer E, et al.[22]
c. Vuylsteke A, et al.[23]
Pulmonary Endarterectomy
Difficulties to Overcome
•
•
•
•
Central location PA
5-L/min blood flow
Thin-walled vessel
Dual circulation
Courtesy of Mr Jenkins.
Pulmonary Endarterectomy
Technique Overview
• Median sternotomy incision, for
approach to both lungs
• Cardiopulmonary bypass, with cooling to
20o C (circulatory arrest for 20 minutes)
• Clearance of PA obstruction to reduce
PVR
• Full distal dissection to every segmental
vessel
Courtesy of Mr Jenkins.
Pulmonary Endarterectomy
Verbal Recognition
Memory Immediate Test (%
of Patients Who Scored 24)
Perioperative Cognitive Function
Vuylsteke A, et al.[23]
Pulmonary Endarterectomy
Conditional Survival
Freed DH, et al.[24]
Pulmonary Hypertension
Potential for Targeted Drug Therapy
Although PEA is potentially curative, medical therapy is needed
in patients with inoperable disease or persistent/recurrent PH.
Sitbon O, et al.[25]
Bosentan
BENEFiT Trial
Trial Design
• Inoperable CTEPH or persistent pulmonary PH after PEA
• N = 157, randomized to placebo or bosentan
• Treatment duration = 16 weeks
Results
• PVR mean treatment effect: -24.1%, P = .0001
• 6-minute walk distance mean treatment effect: 2.2 meters
Jaïs X, et al.[26]
Riociguat
CHEST-1 Trial
Trial Design
• Inoperable CTEPH or persistent pulmonary PH after PEA
• N = 261, randomized in a 2:1 ratio to riociguat
(≤ 2.5 mg 3x daily) or placebo
• Treatment duration = 8 weeks titration + 8 weeks maintenance
Results
• Primary end point, 6-minute walk distance: 46-meter
improvement compared with placebo (P <.0001)
• Significant improvement in most secondary end points,
including PVR, NT-proBNP, and WHO functional class change
compared with placebo
Ghofrani H, et al.[27]
CTEPH
Summary
• CTEPH is a disease recognized with increased
frequency through radiologic detection with a
variety of imaging techniques.
• Pulmonary endarterectomy, the treatment of
choice, is potentially curative and associated
with a reasonably low risk.
• Drug therapies for the remaining patients who
are not surgically approachable are being
developed.
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