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Original research
Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study
    1. 1 Department of Thrombosis and Hemostasis, Leiden Universitair Medisch Centrum, Leiden, The Netherlands
    2. 2 Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
    3. 3 Department of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands
    4. 4 Department of Pneumology, KU Leuven University Hospitals Leuven, Leuven, Belgium
    5. 5 Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warszawa, Poland
    6. 6 Department of Internal Medicine, Haga Teaching Hospital, The Hague, The Netherlands
    7. 7 Department of Pulmonology, Amsterdam UMC, VU University Medical Centre, Amsterdam, The Netherlands
    8. 8 Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, University Hospitals Leuven, Leuven, Belgium
    9. 9 Department of Cardiology, Leiden Universitair Medisch Centrum, Leiden, The Netherlands
    10. 10 Department of Cardiology, Haga Teaching Hospital, The Hague, The Netherlands
    1. Correspondence to Dr. Frederikus A Klok, Thrombosis and Hemostasis, Leiden Universitair Medisch Centrum, Leiden, Netherlands; f.a.klok{at}lumc.nl

    Abstract

    Background The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms.

    Methods In this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the ‘CTEPH prediction score’ indicated high pretest probability or matching symptoms were present, the ‘CTEPH rule-out criteria’ were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography.

    Results 424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation.

    Conclusions The InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.

    • Pulmonary Embolism

    Data availability statement

    Data are available upon reasonable request.

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • Collaborators InShape II study group: Authors: The Netherlands: FA Klok, GJAM Boon, YM Ende-Verhaar, MV Huisman, HW Vliegen, (Leiden University Medical Center, Leiden); ATA Mairuhu, LH El Bouazzaoui, JWJ Vriend (Haga Teaching Hospital, The Hague); S Middeldorp, R Bavalia (Amsterdam UMC, University of Amsterdam, Amsterdam); A Vonk Noordegraaf, D Ruigrok (Amsterdam UMC, VU University Medical Centre, Amsterdam); Poland: P Pruszczyk, O Dzikowska-Diduch, K Kurnicka (Medical University of Warsaw, Warsaw); Belgium: M Delcroix, P Verhamme (University Hospitals Leuven, Leuven). Collaborators: The Netherlands: SV Hendriks, LM van der Pol (Haga Teaching hospital, The Hague and Leiden University Medical Center, Leiden); IM Bistervels, PI Bonta (Amsterdam UMC, University of Amsterdam, Amsterdam); O Kamp, MJ Beeke (Amsterdam UMC, VU University Medical Centre, Amsterdam); Poland: M Roik (Medical University of Warsaw, Warsaw).

    • Contributors GJAMB was responsible for design of the study, data collection, analysis and interpretation, as well as drafting of the manuscript. YME-V was responsible for the design of the study, data collection, analysis and interpretation, as well as drafting of the manuscript. RB was responsible for data collection and critically revised the manuscript for important intellectual content. LHEB was responsible for data collection and critically revised the manuscript for important intellectual content. MD was responsible for design of the study, data collection and critically revised the manuscript for important intellectual content. OD-D was responsible for data collection and critically revised the manuscript for important intellectual content. MVH was responsible for design of the study, data collection, analysis and interpretation, as well as drafting of the manuscript. KK was responsible for data collection and critically revised the manuscript for important intellectual content. ATAM was responsible for design of the study, data collection, and critically revised the manuscript for important intellectual content. SM was responsible for design of the study, data collection and critically revised the manuscript for important intellectual content. PP was responsible for design of the study, data collection and critically revised the manuscript for important intellectual content. DR was responsible for data collection and critically revised the manuscript for important intellectual content. PV was responsible for design of the study, data collection, and critically revised the manuscript for important intellectual content. HWV was responsible for design of the study, data collection and critically revised the manuscript for important intellectual content. AVN was responsible for design of the study, data collection and critically revised the manuscript for important intellectual content. JWJV was responsible for data collection and critically revised the manuscript for important intellectual content. FAK was responsible for design of the study, data collection, analysis and interpretation, as well as drafting of the manuscript.

    • Funding GJAMB en FAK were supported by the Dutch Heart Foundation (2017T064). This work was supported by unrestricted grants from Bayer/Merck Sharp &Dohme (MSD) and Actelion Pharmaceuticals Ltd.

    • Competing interests GJAMB was supported by the Dutch Heart Foundation (2017T064). MH reports grants from ZonMW Dutch Healthcare Fund, grants and personal fees from Pfizer-BMS, grants and personal fees from Bayer Health Care, grants and personal fees from Daiichi-Sankyo, grants from Leo Pharma, outside the submitted work. SM reports grants and personal fees from Daiichi Sankyo, grants and personal fees from Bayer, personal fees from BMS-Pfizer, personal fees from Boehringer-Ingelheim, personal fees from Portola, personal fees from AbbVie, outside the submitted work. PV reports grants from Bayer, grants from Boehringer, grants from BMS, grants from Daiichi-Sankyo, grants from Pfizer, grants from Leo-Pharma, grants from Sanofi, grants from Anthos Therapeutics, outside the submitted work. AVN reports grants from Netherlands CardioVascular Research Initiative, grants from Netherlands Organization for Scientific Research, other from Johnson & Johnson and Ferrer in the past 3 years, non-financial support from member of scientific advisory board of Morphogen-XI, outside the submitted work. FAK reports research grants from Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Daiichi-Sankyo, MSD and Actelion, the Dutch Heart foundation (2017T064) and the Dutch Thrombosis association, all outside the submitted work.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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