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CTEPH Diagnosis and Medical Treatment Update
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
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
7. Natural history of CTEPH
ACUTE
PE CTEPH
Resolution and
insignificant impact on pulmonary
hemodynamics
96% â 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;41:462â8.
Genetic (abnormal fibrinogen)
Abnormal Thrombus Angiogenesis; Inflammatory Mediators
Prothrombotic States (LAC, ACA, Factor VIII, von Willebrand, Splenectomy)
Medical Conditions: âHigh Riskâ PE, Malignancy History, Chronic Venous
Disease; Chronic Intravenous Devices
8. GĂŠrald Simonneau et al. Eur Respir Rev 2017;26:160112 modified from Azarian et al., J Nucl Med 1997
Š2017 by European Respiratory Society
Pulmonary vascular obstruction not
associated with TPR in CTEPH
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 âat riskââŚindwelling 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
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
24. Chronic Thromboembolic
Pulmonary Hypertension
Role for PH targeted Medical Therapy?
ďPatients with inoperable CTEPH
(with or without BPA)
ďTreatment of residual PH post endarterectomy
(with or without BPA)
ďTreatment 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 naĂŻve); 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)
33. ďźCTEPH has a âbi-componentâ pathology: larger vessel
obstructive disease with a pre- and post-alveolar small vessel
vasculopathy
ďźCTEPH remains an under-recognized disease
ďźV/Q scan is the recommended screening study in the
evaluation for CTEPH; advanced diagnostic tests required for
disease confirmation and operability assessment
ďźPH medical therapy indicated for confirmed inoperable
disease and residual PH following endarterectomy; often
used in combination with other treatment modalities
Final ThoughtsâŚ
Relationship between pulmonary vascular obstruction (PVO) and pulmonary vascular resistance in chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (PE). a) Patient AL: 24-year-old female with CTEPH. Percentage of PVO estimated on perfusion lung scan at 75%. Total occlusion of left lung and occlusion of right middle and lower lobes. Haemodynamics: mean pulmonary arterial pressure (PAP) 32â mmHg; cardiac index 1.7â L¡min-1¡m-2; total pulmonary vascular resistance (TPR) 18.8â mmHg¡L-1¡min¡m2. Despite 75% PVO, the TPR was only 18.8. b) Patient BJ: 54-year-old female with CTEPH. Percentage of PVO estimated on perfusion lung scan at 35%; multiple bilateral segmental and subsegmental perfusion defects. Haemodynamics: mean PAP 45â mmHg; cardiac index 1.4â L¡min-1¡m-2; TPR 32.1â mmHg¡L-1¡min¡m2. c) Relationship between percentage of PVO assessed by perfusion lung scan and TPR in patients with acute PE (n=31). A strong hyperbolic correlation was found. d) For a given degree of PVO, most patients with CTEPH (n=45) have higher TPR values than patients with acute PE (n=31), suggesting that, in addition to mechanical obstruction by organised clots, they have small-vessel disease. Patient AL is located on the hyperbolic correlation (no microvasculopathy), whereas patient BJ has a disproportionate and very high level of TPR compared to mild PVO (severe microvasculopathy). Reproduced and modified from [86] with permission.