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

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.

Keywords

pulmonary embolism - deep vein thrombosis - venous thromboembolism - pulmonary vascular obstruction

• 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