Thromb Haemost 2021; 121(07): 955-963
DOI: 10.1055/s-0040-1722190
Stroke, Systemic or Venous Thromboembolism

The Impact of Pulmonary Vascular Obstruction on the Risk of Recurrence of Pulmonary Embolism: A French Prospective Cohort

Charles Orione
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
,
Cécile Tromeur
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
,
Raphael Le Mao
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
,
Pierre-Yves Le Floch
2   Service de radiologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM 1412, FCRIN INNOVTE, Brest, France
,
Philippe Robin
3   Service de Médecine Nucléaire, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, GIRC Thrombose, Brest, France
,
Clément Hoffmann
4   Service d'Echo-doppler Vasculaire, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM 1412, FCRIN INNOVTE, Brest, France
,
Luc Bressollette
4   Service d'Echo-doppler Vasculaire, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM 1412, FCRIN INNOVTE, Brest, France
,
Michel Nonent
2   Service de radiologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM 1412, FCRIN INNOVTE, Brest, France
,
Pierre-Yves Le Roux
3   Service de Médecine Nucléaire, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, GIRC Thrombose, Brest, France
,
Pierre-Yves Salaun
3   Service de Médecine Nucléaire, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, GIRC Thrombose, Brest, France
,
Marie Guegan
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
5   Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM 1412, FCRIN INNOVTE, Brest, France
,
Elise Poulhazan
5   Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM 1412, FCRIN INNOVTE, Brest, France
,
Karine Lacut
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
,
Christophe Leroyer
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
,
Catherine A. Lemarié
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
6   Département des sciences de la santé, Université de Bretagne Occidentale, UMR1078, Brest, France
,
Francis Couturaud
1   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, CIC INSERM, FCRIN INNOVTE, Brest, France
› Institutsangaben
Funding The study was supported by grants from the “Programme Hospitalier de Recherche Clinique” (French Department of Health), the Foundation “Archipel Santé” and the sponsor was the University Hospital of Brest. The funding source was not involved in designing or conducting the study, collecting, managing, analyzing or interpreting the data, preparing, reviewing or approving the manuscript, or deciding to submit this for publication. An academic steering committee assumed overall responsibility for all these steps. Dr. Couturaud takes responsibility for data access and integrity of the data.

Abstract

Background We aimed to assess whether high pulmonary vascular obstruction index (PVOI) measured at the time of pulmonary embolism (PE) diagnosis is associated with an increased risk of recurrent venous thromboembolism (VTE).

Study Design and Methods French prospective cohort of patients with a symptomatic episode of PE diagnosed with spiral computerized tomography pulmonary angiography (CTPA) or ventilation-perfusion (V/Q) lung scan and a follow-up of at least 6 months after anticoagulation discontinuation. PVOI was assessed based on the available diagnostic exam (V/Q lung scan or CTPA). All patients had standardized follow-up and independent clinicians adjudicated all deaths and recurrent VTE events. Main outcome was recurrent VTE after stopping anticoagulation.

Results A total of 418 patients with PE were included. During a median follow-up period of 3.6 (1.2–6.0) years, 109 recurrences occurred. In multivariate analysis, PVOI ≥ 40% was an independent risk factor for recurrence (hazard ratio 1.77, 95% confidence interval 1.20–2.62, p < 0.01), whether PE was provoked by a major transient risk factor or not. A threshold at 41% was identified as the best value associated with the risk of recurrence 6 months after stopping anticoagulation (area under curve = 0.64).

Conclusion PVOI ≥ 40% at PE diagnosis was an independent risk factor for recurrence VTE. Further prospective validation studies are needed.

Authors' Contributions

F.C. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: C.O., C.T., F.C., K.L., C.L. Acquisition of data: E.P. Statistical analysis: C.O. Analysis and interpretation of data: All. Drafting of the manuscript: C.O., F.C., C.L. Critical revision of the manuscript for important intellectual content: All. Final approval of the manuscript: All. Obtaining funding: F.C. Administrative, technical, or material support: F.C., C.T., K.L., C.L. Study supervision: F.C., C.T.


Supplementary Material



Publikationsverlauf

Eingereicht: 30. August 2020

Angenommen: 12. November 2020

Artikel online veröffentlicht:
14. Januar 2021

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  • References

  • 1 Laporte S, Mismetti P, Décousus H. et al; RIETE Investigators. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 2008; 117 (13) 1711-1716
  • 2 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
  • 3 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
  • 4 Sanchez O, Benhamou Y, Bertoletti L. et al. Recommandations de bonne pratique pour la prise en charge de la maladie veineuse thromboembolique chez l'adulte. Version courte. Rev Mal Respir 2019; 36 (02) 249-283
  • 5 Khan F, Rahman A, Carrier M. et al; MARVELOUS Collaborators. Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ 2019; 366: l4363
  • 6 Agnelli G, Prandoni P, Santamaria MG. et al; Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. N Engl J Med 2001; 345 (03) 165-169
  • 7 Couturaud F, Sanchez O, Pernod G. et al; PADIS-PE Investigators. Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: the PADIS-PE randomized clinical trial. JAMA 2015; 314 (01) 31-40
  • 8 Linkins L-A, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139 (11) 893-900
  • 9 Rodger MA, Kahn SR, Wells PS. et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 179 (05) 417-426
  • 10 Tosetto A, Iorio A, Marcucci M. et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 2012; 10 (06) 1019-1025
  • 11 Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation 2010; 121 (14) 1630-1636
  • 12 Raj L, Presles E, Mao RL, Robin P, Sanchez O, Pernod G. et al; PADIS-PE Investigators. Evaluation of venous thromboembolism recurrence scores in an unprovoked pulmonary embolism population: a post-hoc analysis of the PADIS-PE trial. Am J Med 2020; 133 (08) e406-e421
  • 13 Tromeur C, Sanchez O, Presles E. et al; PADIS-PE Investigators18. Risk factors for recurrent venous thromboembolism after unprovoked pulmonary embolism: the PADIS-PE randomised trial. Eur Respir J 2018; 51 (01) 1701202
  • 14 Planquette B, Ferré A, Peron J. et al. Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism. A single center cohort study. Thromb Res 2016; 148: 70-75
  • 15 Chopard R, Genet B, Ecarnot F. et al. Detection of residual pulmonary vascular obstruction by ventilation-perfusion lung scan late after a first pulmonary embolism. Am J Cardiol 2017; 119 (11) 1883-1889
  • 16 Le Mao R, Tromeur C, Bazire A. et al. Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study. Eur Respir J 2017; 50 (01) 1700094
  • 17 Mollard LM, Le Mao R, Tromeur C. et al. Antipsychotic drugs and the risk of recurrent venous thromboembolism: a prospective cohort study. Eur J Intern Med 2018; 52: 22-27
  • 18 Meyer G, Collignon MA, Guinet F, Jeffrey AA, Barritault L, Sors H. Comparison of perfusion lung scanning and angiography in the estimation of vascular obstruction in acute pulmonary embolism. Eur J Nucl Med 1990; 17 (6-8): 315-319
  • 19 Qanadli SD, El Hajjam M, Vieillard-Baron A. et al. New CT index to quantify arterial obstruction in pulmonary embolism: comparison with angiographic index and echocardiography. Am J Roentgenol 2001; 176 (06) 1415-1420
  • 20 Gray RJ. A class of $K$-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141-1154
  • 21 Becattini C, Giustozzi M, Cerdà P, Cimini LA, Riera-Mestre A, Agnelli G. Risk of recurrent venous thromboembolism after acute pulmonary embolism: role of residual pulmonary obstruction and persistent right ventricular dysfunction. A meta-analysis. J Thromb Haemost 2019; 17 (08) 1217-1228
  • 22 Raj L, Robin P, Le Mao R. et al; PADIS-PE Investigators. Predictors for residual pulmonary vascular obstruction after unprovoked pulmonary embolism: implications for clinical practice-the PADIS-PE trial. Thromb Haemost 2019; 119 (09) 1489-1497