Subsegmental Pulmonary Embolism

How do you manage the patient with subsegmental pulmonary embolism(SSPE) or the incidental finding of a Pulmonary Embolism(PE)?

Pulmonary embolism has a spectrum of presentations, from incidental(asymptomatic) to life threatening. Intervention of high risk and haemodynamically unstable presentations is established, however we have less robust research on the management of the lower risk, isolated SSPE or incidentally found PE.

In this review I look at what the guidelines say and the potential impact of a large prospective trial, whose results were released after the guidelines were published.

The evolution of imaging modalities, ie., the increased sensitivity and use of CTPA, has led to the diagnosis of an increased number of SSPEs. Although we don’t know the true incidence of SSPEs, there is evidence that imaging artifacts are being misread as SSPEs, given the high interobserver variability in interpretation and the high rate (up to 50%) of initial positive CTPAs being reinterpreted as normal (1).

Further evidence that there is potential overdiagnosis of PE, is that although the incidence of pulmonary embolism has increased, the overall mortality remains unchanged and the case fatality has decreased (2).

Which lower risk PEs do we need to treat and how do we balance the risk-benefit profile associated with anticoagulants?

We do not have robust trials that look at the risks of bleeding from anticoagulation in SSPE, which has been assumed to be a lower risk form of pulmonary embolism(3). We also don’t have definitive evidence that SSPE is in fact a lower risk form of PE. Studies have shown that it may have equal (or even higher) risk of recurrent thromboembolism than more proximal PE(4,5).

Incidental and symptomatic SSPE were found to have similar adverse outcomes(6).

What do the Guidelines Recommend?

European Society of Cardiology
In isolated subsegmental PE with no active cancer or proximal DVT, surveillance is recommended. However, anticoagulation is recommended in patients with subsegmental PE and active cancer or a proximal DVT, or with simply multiple SSPEs

The Chest Guidelines (7)
Surveillance is recommended in patients with SSPE (weak recommendation with low certainty evidence) if there is no proximal DVT in the legs plus there is an absence of high risk criteria such as:

1. Hospitalized or have reduced mobility for another reason
2. Active cancer
3. Have no reversible risk factor for VTE such as recent surgery
4. Are pregnant

In patients incidentally found to have asymptomatic PE, anticoagulation is recommended, as it is for symptomatic PE (weak recommendation, moderate certainty evidence).

In summary the guidelines tell us:

1. Cases of incidentally found PE, even if asymptomatic require anticoagulation
2. In the case of SSPE:
   1. If isolated, with no active cancer or proximal DVT; surveillance is an appropriate approach
   2. When multiple, should be anticoagulated
   3. With active cancer, no reversible risk factors, pregnancy or hospitalised or have reduced mobility, anticoagulation is recommended.

Following these guidelines a multicenter Prospective Cohort Study The SubSegmental Pulmonary Embolism (SSPE) Study was published (8)

The Study

Le Gal G et al. Risk of Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation. a multi-center prospective cohort study. Ann Intern Med 2022;175(01):29–35

This study found, surprisingly, a higher rate of recurrent venous thromboembolism in patients with isolated SSPE (a group assumed to be at lower risk). The rate was similar to those patients with a more proximal PE.

Read the Full Review at EM Mastery.

We need a study to tell us what the risks of anticoagulation are in these groups. We await the results of the SAFE-SSPE Trial, currently being completed. In this trial low-risk patients with SSPE, and no DVT on bilateral lower extremity ultrasound, are randomized to placebo (no anticoagulation) or treatment with rivaroxaban for 90 days.

In my personal practice I will screen patients for high risk factors if there is a finding of a SSPE. The patient will have a lower extremeties ultrasound performed to exclude DVT. If all of these are negative and the patient is young, I will consider surveilance until followup ultrasonography is performed. In all other patients I will consider anticoagulation, following a review of the patient’s bleeding risk.

References

1. Miller WT Jr, et al. Small pulmonary artery defects are not reliable indicators of pulmonary embolism. Ann Am Thorac Soc 2015;12(07):1022–1029
2. Bikdeli B, et al. Pulmonary embolism hospitalization, readmission, and mortality rates in US older adults, 1999–2015. JAMA. 2019;322:574-6.
3. Ikesaka R, et al. Clinical significance and management of subsegmental pulmonary embolism. J Thromb Thrombolysis 2015;39(03):311–314
4. Stoller N, et al. Clinical presentation and outcomes in elderly patients with symptomatic isolated subsegmental pulmonary embolism. Thromb Res 2019;184:24–30
5. Fernández-Capitán C, et al; RIETE Investigators. Symptomatic subsegmental versus more central pulmonary embolism: clinical outcomes during anticoagulation. Res Pract Thromb Haemost 2020;5(01):168–178
6. Rodríguez-Cobo A, et al; The Riete Investigators. Clinical significance and outcome in patients with asymptomatic versus symptomatic subsegmental pulmonary embolism. J Clin Med 2023;12(04):1640
7. Stevens SM, et al. Antithrombotic therapy for VTE disease: second update of the CHEST Guideline and Expert Panel Report. Chest 2021;160(06):e545–e608
8. Le Gal G et al. Risk of Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation. a multi-center prospective cohort study. Ann Intern Med 2022;175(01):29–35