7.3 Contemporary Management of Intermediate- and High-Risk Pulmonary Embolism

These proceedings summarize the educational activity of the 16th Biennial Meeting of the International Andreas Gruentzig Society held January 31-February 3, 2022 in Punta Cana, Dominican Republic

Faculty Disclosures     Vendor Acknowledgments

2022 IAGS Summary Document

Statement of the problem or issue

Hospitalizations for acute pulmonary embolism (PE) are growing and PE now represents the third-leading cause of cardiovascular mortality in the United States. High-risk (also known as “massive”) PE is defined by the presence of prolonged hypotension and/or the need for vasoactive agents, presence of shock, or cardiac arrest. While high-risk PE comprises only ~5% of all PE presentations, its associated mortality is ~30%. Available therapeutic interventions for high-risk PE include systemic full-dose thrombolysis, surgical embolectomy, and catheter-directed mechanical thrombectomy, all with or without extracorporeal membrane oxygenation (ECMO). Randomized controlled trials (RCTs) have found that when compared with anticoagulation, systemic thrombolysis reduces mortality and PE recurrence in high-risk PE patients, but at a cost of major bleeding (including intracranial hemorrhage). Observational studies have yielded mixed results when comparing systemic thrombolysis with catheter-directed therapies (CDTs), and outcomes are similar in studies comparing systemic thrombolysis with surgical embolectomy. However, robust comparative safety and effectiveness data are lacking.

Intermediate-risk (also known as “submassive”) PE is defined as a normal blood pressure without the need for vasoactive agents or other support, but with evidence of right ventricular (RV) dysfunction. Intermediate-risk PE represents 55% of all PE and the in-hospital mortality is variable, ranging from <3% up to 10%. One RCT demonstrated quicker resolution of RV dysfunction, reduction in pulmonary artery systolic blood pressures, and diminution of clot burden with ultrasound-assisted, catheter-directed, low-dose thrombolysis compared with systemic anticoagulation.

Gaps in knowledge

Despite the tremendous evolution in our understanding of PE and its therapies over recent years, many questions remain. Should we manage PE like we manage ST-segment-elevation myocardial infarction and acute ischemic stroke, where speed of therapy is critical and the concept of “time is tissue” applies? For high-risk PE, should CDT with mechanical thrombectomy replace systemic thrombolytics and surgical embolectomy? For intermediate-to-high risk PE, how can we better risk stratify patients to choose among available therapies? Similarly, what is the relative short- and long-term effectiveness of intravenous unfractionated heparin, catheter-directed thrombolysis with or without ultrasound assistance, and mechanical thrombectomy? Also, what are the most appropriate regimens (dose and duration) for catheter-directed thrombolysis? From a device-evolution standpoint, can we improve upon thrombus removal when using catheter-directed mechanical thrombectomy, and do we need to? How might existing therapies impact outcomes beyond survival, recovery of RV function, and pulmonary hemodynamics, such as quality of life (QoL) and functional status? And, finally, what therapies can be most effective for prevention and treatment of chronic thromboembolic pulmonary hypertension (CTEPH)? There is a clear need for additional registry and clinical trial data.

Possible solutions and future directions

Enrollment of patients in available PE registries should permit better characterization of long-term outcomes. Expansion of clinical trial endpoints to include functional status, QoL, cost, and incidence of CTEPH is needed. For high-risk PE patients, RCTs are unlikely to be undertaken, so large observational studies using registries are needed to compare available therapies. For intermediate-high risk PE patients, several ongoing and planned RCTs (eg, HI-PEITHO [ultrasound-facilitated, catheter-directed, thrombolysis vs anticoagulation] NCT04790370, PEERLESS [mechanical thrombectomy vs catheter-directed thrombolysis] NCT05111613, and STRATIFY [low dose systemic thrombolysis vs ultrasound-assisted thrombolysis vs heparin] NCT04088292) will help determine the relative safety and efficacy of available therapies in this ever-growing space. Finally, there is a need for further device innovation allowing for more extensive/distal pulmonary artery thrombectomy and potentially for the combination of mechanical thrombectomy with catheter-directed thrombolysis.