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. 2024 Mar 14;63(3):2300846.
doi: 10.1183/13993003.00846-2023. Print 2024 Mar.

Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry

Charlotte Durrington  1   2 , Judith A Hurdman  1 , Charlie A Elliot  1 , Rhona Maclean  3 , Joost Van Veen  3 , Giorgia Saccullo  3 , Duneesha De-Foneska  1 , Andrew J Swift  2   4   5   6 , Rajaram Smitha  2   4 , Catherine Hill  4 , Steven Thomas  4 , Krit Dwivedi  2   4 , Samer Alabed  2   4 , James M Wild  4   5   6 , Athanasios Charalampopoulos  1 , Abdul Hameed  1   2 , Alexander M K Rothman  1   2   6 , Lisa Watson  1 , Neil Hamilton  2 , A A Roger Thompson  1   2   6 , Robin Condliffe  1   2   6   7 , David G Kiely  8   2   5   6   7
Affiliations

Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry

Charlotte Durrington et al. Eur Respir J. .

Abstract

Background: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined.

Methods: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included.

Results: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents.

Conclusions: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.

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Conflict of interest statement

Conflict of interest: C. Durrington reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports lecture honoraria from Janssen Pharmaceuticals, outside the submitted work. C.A. Elliot reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D. De-Fonseka reports a leadership role on the Pleural Specialist Advisory Group and Pleural Disease Guideline Committee for the British Thoracic Society, outside the submitted work. A.J. Swift reports support for the present manuscript from a Wellcome Trust fellowship, and also reports grants from Janssen Pharmaceuticals, NIHR and Wellcome Trust, and consulting fees from Janssen Pharmaceuticals, outside the submitted work. K. Dwivedi reports support for the present manuscript from Wellcome 4Ward North fellowship, and also reports grants from Janssen, and lecture honoraria from Royal College of Radiologists, and is a committee member for the Royal College of Radiologists Artificial Intelligence Working Group and Royal College of Radiologists RADIANT group, outside the submitted work. A. Charalampopoulos reports lecture honoraria from Janssen and Boehringer, outside the submitted work. A. Hameed reports lecture honoraria and travel support from Janssen, outside the submitted work. A.M.K. Rothman reports grants from a Wellcome Trust Clinical Research Career Development Fellowship (206632/Z/17/Z), MRC (experimental medicine grant MR/W026279/1), Abbott Laboratories, Medtronic Inc., Endotronix, SoniVie, NXT Biomedical, Gradient and Neptune Medical, outside the submitted work. N. Hamilton reports consulting fees and travel support from Janssen, lecture honoraria from MSD and Janssen, advisory board participation with Bayer, MSD, Janssen and Vifor, and a leadership role as pharmacist for the NHS Specialist Respiratory Clinical Reference Group, outside the submitted work. A.A.R. Thompson reports grants from the British Heart Foundation and NIHR, and lecture honoraria and travel support from Janssen-Cilag Ltd, outside the submitted work. R. Condliffe reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D.G. Kiely reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports grants from Janssen Pharmaceuticals, NIHR Sheffield Biomedical Research Centre and Ferrer, consulting fees and lecture honoraria from Janssen Pharmaceuticals, Ferrer, Altavant, MSD and United Therapeutics, travel support from Janssen, Ferrer, MSD and United Therapeutics, advisory board membership for Janssen and MSD, and leadership roles as a member of the Clinical Reference Group for Specialised Respiratory Medicine (NHS England) and lead of the UK National Audit of Pulmonary Hypertension, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Acute PE follow-up pathway and assessment for suspected CTEPH
Abbreviations. PE= pulmonary embolism; SOB= shortness of breath; CTEPH= chronic thromboembolic pulmonary hypertension; CTEPD= chronic thromboembolic pulmonary disease; Q SPECT= Perfusion single-photon emission computerised tomography; CTPA= computerised tomography pulmonary angiogram; 3D MR= 3 dimensional magnetic resonance imaging; PFT= pulmonary function tests; DLco: diffusing capacity of the lungs for carbon monoxide; Echo= echocardiogram; RHC= right heart catheterisation; CPET: cardiopulmonary exercise testing. Note patients also receive a follow-up appointment with a thrombosis nurse specialist within the first week of discharge. To assess for CTEPD patients underwent Q SPECT or CTPA or less frequently 3DMR imaging.
Figure 2
Figure 2. Total and 2-year cumulative incidence of chronic thromboembolic pulmonary hypertension from index pulmonary embolism event (n=1956)
Abbreviations. PE=pulmonary embolism; CTEPH=chronic thromboembolic pulmonary hypertension
Figure 3
Figure 3. Flow chart showing acute PE pathway and impact of risk factors for acute PE on diagnosis of CTEPH
Abbreviations. PE= pulmonary embolism; CTEPH=chronic thromboembolic pulmonary hypertension. *All patients diagnosed at RHC apart from 2 patients who declined RHC, diagnosis in these cases was made based on multimodality imaging and expert opinion.
Figure 4
Figure 4. Kaplan-Meier Survival curve for patients who attended the pulmonary embolism clinic split into those diagnosed or not diagnosed with CTEPH
Abbreviations. CTEPH= chronic thromboembolic pulmonary hypertension; PE= pulmonary embolism
Figure 5
Figure 5. CTPAs from the Sheffield PE Clinic from the index PE in a patient who did not go on to develop CTEPH (Top) and a patient who went on to develop CTEPH (Bottom)
Figure 5 Top: of a patient from the time of the index PE who did not go on to develop CTEPH; note mild PA dilation, but a RV:LV ratio <1, no RVOTH and no features of CTEPD, filling defects shown by blue arrows. Figure 5 Bottom: of a patient from the time of the index PE who went on to develop CTEPH; note all 3 features of pulmonary hypertension: PA≥30mm, RVOTH≥6mm (between black arrows) and RV:LV≥1 and 3 features of CTEPD; arterial webs (white arrows) attenuated vessels (white asterix) and mosaic parenchymal perfusion pattern + and -). Ao: aorta; CTEPD: chronic thromboembolic pulmonary disease; CTEPH: chronic thromboembolic pulmonary hypertension; LV: left ventricle; PA:pulmonary artery; RV:right ventricle; RVOTH: right ventricular outflow tract hypertrophy
Figure 6
Figure 6. Central figure illustrating key results including population-based CTEPH diagnostic rates and pulmonary endarterectomy rates
Abbreviations. PE= pulmonary embolism; RHC= right heart catheterisation; CTEPH= chronic thromboembolic pulmonary hypertension; PH= pulmonary hypertension; mRAP= mean right atrial pressure, mPAP= mean pulmonary artery pressure; CI= cardiac index; PVR= pulmonary vascular resistance. Created with BioRender.
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