CTEPH is a chronic form of pulmonary hypertension that can develop after acute pulmonary embolism. It is caused by incomplete resolution of blood clots in the lungs leading to obstruction of pulmonary arteries and loss of lung tissue over time. Diagnosis involves perfusion scanning and pulmonary angiography to identify areas of obstruction. Treatment options include pulmonary endarterectomy surgery to remove clots from large arteries or balloon pulmonary angioplasty for inoperable cases. For patients who are inoperable or have residual pulmonary hypertension after procedures, targeted medical therapies approved for pulmonary hypertension have shown benefits in improving symptoms and hemodynamics.

1. CTEPH Diagnosis and Medical
Treatment Update
William R. Auger, MD
Adjunct Professor of Medicine
Duke University School of Medicine
15th Annual NC Research Triangle Pulmonary
Hypertension Symposium
November 17, 2023

2. Disclosures
• Consultant: Neptune Medical
• Invited speaker: Janssen PH, Merck, Bayer, Inari

3. Clinical Trial Publications in CTEPH
McGinnis MC et al. Global trends in chronic thromboembolic pulmonary hypertension clinical trials
and dissemination of results. Pulm Circ 2021; 11(40):1-8

4. What is Chronic Thromboembolic Disease?
• Acute Pulmonary Embolus
• Incomplete resolution (>3 months
AC)
• Loss of pulmonary vascular bed
• Progressive pulmonary
hypertension (mean PA >20)
• Right heart failure
Video courtesy of Fabio Jatene MD

5. Acute PE vs Chronic PE
Acute PE Chronic PE

6. Risk Factors for
CTEPH

7. Natural history of CTEPH
ACUTE
PE CTEPH
Resolution and
insignificant impact on pulmonary
hemodynamics
96% – 99%
Small vessel changes
(Adaptive vascular remodeling)
ACA, anticardiolipin antibodies; CTEPH, chronic thromboembolic pulmonary hypertension; LAC; lupus anticoagulant;
PE, pulmonary embolism; TE, thromboembolic.
Lang IM et al. Eur Respir J 2013;41:462–8.
Genetic (abnormal fibrinogen)
Abnormal Thrombus Angiogenesis; Inflammatory Mediators
Prothrombotic States (LAC, ACA, Factor VIII, von Willebrand, Splenectomy)
Medical Conditions: “High Risk” PE, Malignancy History, Chronic Venous
Disease; Chronic Intravenous Devices

8. Gérald Simonneau et al. Eur Respir Rev 2017;26:160112 modified from Azarian et al., J Nucl Med 1997
©2017 by European Respiratory Society
Pulmonary vascular obstruction not
associated with TPR in CTEPH

9. Small Vessel disease in CTEPH
Moser, Bloor Chest 1993; 103:685-692; Dorfmuller et al. Eur Resp J 2014; 44: 1275
Systemic vasa vasorum
Venule w/ intimal fibrosis
Partial occlusion septal vein

10. Macrovascular and
microvascular disease

11. Macrovascular disease from PTE
Am J Respir Crit Care Med. 2023 May 15;207(10):1358-1375.

12. Suspicion for CTEPH
• Acute PE patients with persistent CP symptoms after 3
months of anticoagulation
• ALL patients with pulmonary hypertension/Physical exam
findings of PH
• Unexplained exertional dyspnea with or without history
of thromboembolic event
• Dyspnea in patients “at risk”…indwelling catheters,
thrombophilia
• Incidental radiographic findings of cardiomegaly and/or
central PA enlargement (asymmetry)

13. ESC/ERS (2022)
Diagnostic
Algorithm for CTEPH
Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary
hypertension. Eur Heart J 2022; 43(38): 3618-3731
CTEPH Ruled Out
if Negative

14. Perfusion Scans
CTEPH
Segmental
CTEPH
Pulmonary
Arteritis
Sarcoma
PVOD

15. CTEPH: CTA Findings
Eccentric
thrombus
Lining
thrombus and
web
Vessel attentuation, web

16. CTEPH: CTA Findings
Bronchial
arterial
collateral
vessels
Mosaic Perfusion
Lining
thrombus,
Enlarged
main PA (PH)

17. Chest CTA: limited findings suggesting CTE
disease….lining thrombus posterior LLL with
vessel attenuation; eccentric thrombus posterior
RLL vessel; subtle mosaic perfusion

18. CTEPH: Pulmonary Angiogram

19. CTEPH Pulmonary Angiogram

20. Other Modalities ?
SPECT
scan
Dual Energy
CT
MR
Angiography
OCT

21. PH Medical Therapy for
Inoperable/Non-surgical
CTEPH
Pulmonary
Thromboendarterectomy
(operable)
Balloon Pulmonary
Angioplasty
(inoperable)

22. CTEPH
Treatment
Algorithm
Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of
pulmonary hypertension. Eur Heart J 2022; 43(38): 3618-3731

23. CTEPH
Treatment
Algorithm
Mahmud E, et al. Pulm Circ 2021; 11(2) 1-9

24. Chronic Thromboembolic
Pulmonary Hypertension
Role for PH targeted Medical Therapy?
Patients with inoperable CTEPH
(with or without BPA)
Treatment of residual PH post endarterectomy
(with or without BPA)
Treatment in Operable CTEPH prior to PTE

25. CTEPH: RCTs of PH Targeted Medical Therapy
.
De Perrot M. et al. Evaluation and Management of Patients with Chronic Thromboembolic Pulmonary Hypertension - Consensus Statement
from the ISHLT. J Hear Lung Transplant, On-line publication, August 2021.

26. • Randomized, placebo-controlled study
• 261 patients, 173 receiving drug
• 16 weeks
• Increase in 6 minute walk distance
(mean difference 46 m)
• Reduction in PVR
(mean difference -246 dyn-sec-cm-5)
• Improvements in WHO functional class, NT-proBNP
Ghofrani HA at al. N Engl J Med 2013; 369:319

27. Improvements in 6MWD and FC observed in CHEST-1
persisted at a year in this extension study (237
enrolled patients)
• 6MWD changed by +51 + 61 m (N=172) vs CHEST-1
baseline
• Functional class: (improved/stable/worse) in
47/50/3% of patients (N=176) vs CHEST-1 baseline
• Safety profile similar to CHEST-1

28. Lancet Respir Med 2017 Sep 8
N=80 (40 per arm, 40%/38% treatment naïve); 16 weeks
Treatment: 6MWD 355 vs 388 m
Control: 6MWD 351 vs 352 m
Treatment: PVR 929 to 723 d.s.cm-5
Control: PVR 984 to 899 d.s.cm-5

29. CTREPH: Subcutaneous treprostinil in severe
inoperable CTEPH
Sadushi-Kolici et al. Lancet Respir Med 7(3) 2019: 239
• Phase III trial: Low dose (3 ng/kg/min) vs High dose (30 ng/kg/min) SQ
treprostinil
• 105 patients; 30% background PH medications
• Primary endpoint: 6 min walk distance at 24 weeks
• 44.98 m in high dose (HD) grp vs 4.29 m
• PVR decrease 214.2 d.s.cm-5 (HD) vs 73.0 d.s.cm-5
• SAEs: 17% (16 events) in HD group vs 19% (12 events)

30. PH Medical Therapy
vs BPA
Lancet Respir Med 2022; Aug 1

31. PH Medical Therapy
vs BPA
Lancet Respir Med 2022; Aug 1

33. CTEPH has a “bi-component” pathology: larger vessel
obstructive disease with a pre- and post-alveolar small vessel
vasculopathy
CTEPH remains an under-recognized disease
V/Q scan is the recommended screening study in the
evaluation for CTEPH; advanced diagnostic tests required for
disease confirmation and operability assessment
PH medical therapy indicated for confirmed inoperable
disease and residual PH following endarterectomy; often
used in combination with other treatment modalities
Final Thoughts…

34. THANK YOU!!
williamrauger@icloud.com