Most cases of pulmonary embolism (PE) resolve. Some patients may experience “post-PE syndrome”, which consists of one or more symptoms of chest discomfort, dyspnea or exercise intolerance.[294]Klok FA, van der Hulle T, den Exter PL, et al. The post-PE syndrome: a new concept for chronic complications of pulmonary embolism. Blood Rev. 2014 Nov;28(6):221-6.
http://www.ncbi.nlm.nih.gov/pubmed/25168205?tool=bestpractice.com
Chronic thromboembolic disease (CTED) refers to unresolved perfusion abnormalities on imaging following completion of at least 3 months of anticoagulant therapy. CTED and post-PE syndrome may coexist, but patients may experience one without the other. The most serious long-term sequelae of PE is chronic thromboembolic pulmonary hypertension, in which CTED is associated with pulmonary arterial hypertension and right heart abnormalities. This complication occurs in 3% to 5% of patients after acute PE and has several management options.[295]Ishisaka Y, Watanabe A, Takagi H, et al. Anticoagulation in chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis. Thromb Res. 2023 Nov;231:91-8.
http://www.ncbi.nlm.nih.gov/pubmed/37839150?tool=bestpractice.com
The Pulmonary Embolism Severity Index (PESI) and simplified Pulmonary Embolism Severity Index (sPESI) classify patients with confirmed PE without shock or hypotension into categories associated with increasing 30-day mortality.[3]Konstantinides SV, Meyer G, Becattini C, et al. 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 Jan 21;41(4):543-603.
https://academic.oup.com/eurheartj/article/41/4/543/5556136
[124]Konstantinides SV, Barco S, Lankeit M, et al. Management of pulmonary embolism: an update. J Am Coll Cardiol. 2016 Mar 1;67(8):976-90.
http://www.onlinejacc.org/content/67/8/976
http://www.ncbi.nlm.nih.gov/pubmed/26916489?tool=bestpractice.com
Studies indicate that PESI and sPESI predict short-term mortality with comparable accuracy, but the latter is easier to use.[205]Vinson DR, Ballard DW, Mark DG, et al; MAPLE Investigators of the KP CREST Network. Risk stratifying emergency department patients with acute pulmonary embolism: does the simplified pulmonary embolism severity index perform as well as the original? Thromb Res. 2016 Dec;148:1-8.
http://www.ncbi.nlm.nih.gov/pubmed/27764729?tool=bestpractice.com
[206]Zhou XY, Ben SQ, Chen HL, et al. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis. Respir Res. 2012 Dec 4;13:111.
https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-13-111
http://www.ncbi.nlm.nih.gov/pubmed/23210843?tool=bestpractice.com
Using sPESI, patients in the high-risk category have a short-term mortality of 10.9%, while patients in the low-risk category have 30-day mortality of 1%.
Mortality is often due to cardiogenic shock secondary to right ventricular (RV) collapse. One systematic review and meta-analysis of 3283 hemodynamically stable patients with acute PE found that the risk of short-term mortality was significantly greater in those with RV dysfunction than those without RV dysfunction (odds ratio 2.29, 95% CI 1.61 to 3.26).[296]Cho JH, Kutti Sridharan G, Kim SH, et al. Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis. BMC Cardiovasc Disord. 2014 May 6;14:64.
https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/1471-2261-14-64
http://www.ncbi.nlm.nih.gov/pubmed/24884693?tool=bestpractice.com
In-hospital or 30-day mortality was reported in 167 of 1223 patients (13.7%) with RV dysfunction and in 134 of 2060 patients (6.5%) without RV dysfunction.[296]Cho JH, Kutti Sridharan G, Kim SH, et al. Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis. BMC Cardiovasc Disord. 2014 May 6;14:64.
https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/1471-2261-14-64
http://www.ncbi.nlm.nih.gov/pubmed/24884693?tool=bestpractice.com
Registry data confirm that, in patients with acute PE, hypotension (systolic BP <90 mmHg) is associated with increased mortality.[297]Lin BW, Schreiber DH, Liu G, et al. Therapy and outcomes in massive pulmonary embolism from the Emergency Medicine Pulmonary Embolism in the Real World Registry. Am J Emerg Med. 2012 Nov;30(9):1774-81.
http://www.ncbi.nlm.nih.gov/pubmed/22633723?tool=bestpractice.com
Of the 1875 patients enrolled in the prospective observational Emergency Medicine Pulmonary Embolism in the Real World Registry, all-cause inpatient mortality (13.8% vs. 3.0%, P <0.001) and 30-day mortality (14.0% vs. 1.8%, P <0.001) were significantly greater among the 58 patients with hypotension than those without.[297]Lin BW, Schreiber DH, Liu G, et al. Therapy and outcomes in massive pulmonary embolism from the Emergency Medicine Pulmonary Embolism in the Real World Registry. Am J Emerg Med. 2012 Nov;30(9):1774-81.
http://www.ncbi.nlm.nih.gov/pubmed/22633723?tool=bestpractice.com
In the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry, the 90-day mortality rate for the 248 patients with symptomatic PE with hypotension (systolic BP <90 mmHg) was 9.27%, compared with 2.99% for patients with symptomatic nonmassive PE.[123]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 Apr 1;117(13):1711-6.
http://circ.ahajournals.org/content/117/13/1711.long
http://www.ncbi.nlm.nih.gov/pubmed/18347212?tool=bestpractice.com
Recurrence
Consensus guidelines recommend 3 months of oral anticoagulant therapy, unless contraindicated by bleeding, in all patients with venous thromboembolism (VTE) with reassessment for possible extended therapy after the initial 3 months of treatment.[278]Decousus H, Leizorovicz A, Parent F, et al; Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med. 1998 Feb 12;338(7):409-15.
https://www.nejm.org/doi/10.1056/NEJM199802123380701
http://www.ncbi.nlm.nih.gov/pubmed/9459643?tool=bestpractice.com
Patients with VTE occurring in the setting of a major or minor transient provocation will usually stop anticoagulants after completion of at least 3 months of therapy. Consideration should be given to indefinite treatment among patients who have idiopathic or unprovoked VTE.[298]Rosenborg L, Rogberg L, Fredricsson B. Comparison between a conventional index of progressive sperm motility and movement variables analysed by CellSoft. Andrologia. 1991 Jan-Feb;23(1):21-4.
http://www.ncbi.nlm.nih.gov/pubmed/1897751?tool=bestpractice.com
Patients with cancer continue anticoagulants, as long as they are tolerated, while the cancer is active, and if the risk of bleeding remains low to moderate without any recent major bleeding episodes.[19]Stevens SM, Woller SC, Baumann Kreuziger L, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. 2021 Dec;160(6):e545-608.
https://journal.chestnet.org/article/S0012-3692(21)01506-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34352278?tool=bestpractice.com
Regular reassessment is necessary in patients with cancer as the risks of VTE and bleeding regularly change given modifications in pharmacotherapeutic, surgical, and radiation therapies.[20]National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. Aug 2023 [internet publication].
https://www.nice.org.uk/guidance/ng158
[46]Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol. 2023 Jun 1;41(16):3063-71.
https://ascopubs.org/doi/full/10.1200/JCO.23.00294?role=tab
http://www.ncbi.nlm.nih.gov/pubmed/37075273?tool=bestpractice.com
Many studies have attempted to identify subgroups of patients with unprovoked VTE who do not need to be treated indefinitely with oral anticoagulation. There is strong evidence that the risk of recurrent VTE is higher in the following patients: male sex; those with a diagnosis of a proximal deep vein thrombosis (DVT) (versus isolated calf DVT); those with ultrasound evidence of residual clot; those who have an elevated D-dimer 1 month following stopping a 3- to 6-month course of oral anticoagulation; and those who had an unprovoked VTE.[19]Stevens SM, Woller SC, Baumann Kreuziger L, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. 2021 Dec;160(6):e545-608.
https://journal.chestnet.org/article/S0012-3692(21)01506-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34352278?tool=bestpractice.com
[45]Mazzolai L, Ageno W, Alatri A, et al. Second consensus document on diagnosis and management of acute deep vein thrombosis: updated document elaborated by the ESC working group on aorta and peripheral vascular diseases and the ESC working group on pulmonary circulation and right ventricular function. Eur J Prev Cardiol. 2022 May 27;29(8):1248-63.
https://academic.oup.com/eurjpc/article/29/8/1248/6319853
http://www.ncbi.nlm.nih.gov/pubmed/34254133?tool=bestpractice.com
Several risk assessment models have been developed for this purpose, including the DASH score, the Vienna Prediction Model, and the “Men Continue and HER-DOO2” model.[261]Kyrle PA, Eichinger S. Clinical scores to predict recurrence risk of venous thromboembolism. Thromb Haemost. 2012 Dec;108(6):1061-4.
http://www.ncbi.nlm.nih.gov/pubmed/22872143?tool=bestpractice.com
The latter model identifies a subset of women with low risk for recurrent VTE after an initial unprovoked event, and a prospective validation study of this model was published.[262]Rodger MA, Le Gal G, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ. 2017 Mar 17;356:j1065.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6287588
http://www.ncbi.nlm.nih.gov/pubmed/28314711?tool=bestpractice.com