Submassive Pulmonary Embolism: Current Perspectives and Future Directions

Abstract

Submassive pulmonary embolism (PE) lies on a spectrum of disease severity between standard and high-risk disease. By definition, patients with submassive PE have a worse outcome than the majority of those with standard-risk PE, who are hemodynamically stable and lack imaging or laboratory features of cardiac dysfunction. Systemic thrombolytic therapy has been proven to reduce mortality in patients with high-risk disease; however, its use in submassive PE has not demonstrated a clear benefit, with haemodynamic improvements being offset by excess bleeding. Furthermore, meta-analyses have been confusing, with conflicting results on overall survival and net gain. As such, significant interest remains in optimising thrombolysis, with recent efforts in catheter-based delivery as well as upcoming studies on reduced systemic dosing. Recently, long-term cardiorespiratory limitations following submassive PE have been described, termed post-PE syndrome. Studies on the ability of thrombolytic therapy to prevent this condition also present conflicting evidence. In this review, we aim to clarify the current evidence with respect to submassive PE management, and also to highlight shortcomings in current definitions and prognostic factors. Additionally, we discuss novel therapies currently in preclinical and early clinical trials that may improve outcomes in patients with submassive PE.

Contemporary management of intracardiac thrombi: a tale of two clots

“…Growing data suggest that specific high-risk patients with massive or submassive PE and/or clot in transit may have both survival and symptomatic benefit from advanced therapies in comparison to anticoagulation alone [ 1 , 3 – 7 , 9 – 10 ]. Long-term data for catheter-related therapies are lacking and mostly based on smaller case series [ 7 ].…”

“…In this approach, an aspiration cannula is inserted into one of the major veins and connected to a veno-venous bypass circuit which then captures the aspirated debris. Although there have been case series that focus on the reduction in thrombus burden and hospital survival, data are lacking on the impact of these devices long-term on survival and patient outcomes [ 6 , 7 ].…”

Pulmonary embolism in patients with severe COVID-19 treated with systemic low-dose thrombolytic therapy

“…The standard dosage of alteplase for PE is 100 mg over 2 h.[ 6 ] A recent report compared the 100 mg/2 h and 50 mg/2 h regimens which found that the reduced dosage exhibits similar efficacy and perhaps better safety profile. [ 7 ] Another case series used rtPA for sub-massive PE using 10 mg IV bolus over 1 min and continued with 40 mg IV over 2 h.[ 8 ]…”

Life-threatening pulmonary embolism: overview and management

“…Because patients with submassive PEs do not exhibit abnormal hemodynamics, they may be initially indistinguishable from low-risk PEs before the objective testing required to demonstrate cardiac dysfunction. Up to 10% of patients with submassive PEs may decompensate and progress toward massive PE 31 …”

“…Up to 10% of patients with submassive PEs may decompensate and progress toward massive PE. 31 PEs that do not cause heart strain or hemodynamic compromise are considered low-risk. 4(p1) Low-risk PEs generally pose a low mortality risk, with evidence showing little to no benefit from hospitalization after treatment is initiated.…”