Approximately 60,000 to 100,000 patients die from pulmonary embolism (PE) each year in the United States, and PE is the third leading cause of cardiovascular mortality.¹

A wide spectrum of severity exists in PE presentations, ranging from mild shortness of breath to cardiac arrest. A PE is classified into one of three categories: low risk, submassive, and massive. Low-risk and submassive PEs do not have hemodynamic compromise (i.e., no hypotension). A submassive PE does not result in hypotension but does result in right ventricular (RV) dysfunction (as evidenced by CT or ECG) and/or signs of myocardial injury, such as elevated B-type natriuretic peptide, elevated troponin, or new ECG changes. A massive PE, the most severe, causes hemodynamic instability and carries the most morbidity and mortality.² With varying clinical pictures, unique patient profiles, and risk factors, the treatment of PE provides complex challenges.

Thrombolysis

Although systemic thrombolysis has been the standard treatment for submassive and massive PEs, its risk of major bleeding and intracranial hemorrhage continues to raise concern, particularly in older patients with comorbidities.³ Use of systemic thrombolysis carries a 20 percent risk for major bleeding, including a two to three percent risk for intracranial bleeding.³ Therefore, new interventions using catheter-based or mechanical removal strategies are becoming increasingly more common for the treatment of PE causing hemodynamic instability, myocardial injury, or severe hypoxia.^3,4 In addition, for patients with contraindications or those who have failed thrombolysis, catheter-directed thrombolysis and surgical thrombectomy are useful treatment modalities that are associated with low major complication rates and improved patient outcomes.⁵

As opposed to systemic therapy, catheter-directed thrombolysis is a minimally invasive technique that delivers targeted lytic therapy locally to the clot using catheterization. Ekosonic Endovascular System (EKOS), a form of pharmacomechanical thrombolysis, uses a catheter to deliver thrombolytics directly to the target pulmonary artery in combination with high-frequency ultrasound to enhance lytic penetration and encourage thrombus fragmentation.^6,7 Moreover, as the risk for bleeding with systemic thrombolytic therapy is dose-dependent, catheter-directed thrombolysis (CDT) allows for use of lower doses, making its use appropriate even for patients with relative contraindications.⁸ The prospective SEATTLE II trial demonstrated that this unique approach to thrombolysis therapy reduced clot burden, improved RV function, and reduced pulmonary hypertension, all while minimizing occurrence of intracranial hemorrhage in patients with massive and submassive PE.⁶

The second common catheter-directed approach is mechanical thrombectomy. This approach may be used as monotherapy or in combination with lytic therapy based on the clinical picture. The Inari FlowTriever System treats PE without the use of thrombolytics by using a large lumen catheter and large-bore syringe to mechanically remove large volumes of clots via aspiration.^4,9 The FLARE study, a prospective multicenter trial, demonstrated that implementation of Inari FlowTriever in management of PE provided rapid thrombus removal allowing for faster improvement of pulmonary  artery pressures and SpO2 without the presence of thrombolytic complications.¹⁰ Using this approach to eliminate systemic lytic exposure from the equation provides an alternative treatment option for patients with absolute contraindications to thrombolysis. In addition to the reduced risk for major bleeding, use of mechanical thrombectomy techniques has been shown to decrease hospital costs by reducing the need for post-procedural critical care following intervention.^10,11

Complications, Limitations

Although some studies have shown promising safety profiles for these interventions, more robust trials are needed as these techniques still carry complications such as access site bleeding, arrhythmias, pulmonary artery dissection, and tamponade.¹² In addition to complications, limitations to the implementation of EKOS and Inari FlowTriever include the fact that use requires technical expertise to navigate pulmonary vasculature and resources that not every facility is equipped with.⁷ Aside from equipment and device costs, use of these therapies usually requires multidisciplinary involvement from specialties like pulmonology, interventional cardiology, vascular surgery, interventional radiology, and more, to which smaller institutions may not have access.

The clinical presentation and effect of acute PE are highly variable and make management decisions, which include weighing risks and benefits of certain interventions, difficult and complex. How and whether to perform a catheter-based intervention is a multidisciplinary decision initiated in the emergency department, which factors in the patients’ clinical picture, bleeding risk, available personnel, expertise, and devices. Targeted approaches such as EKOS and Inari FlowTriever, appear promising because they reduce bleeding complications by lowering or eliminating the overall systemic dose of the thrombolytic delivered.

Given the rapid ability to restore favorable hemodynamics with catheter-directed intervention for PE, patients who display signs of RV dysfunction, myocardial injury, severe hypoxia, or hemodynamic instability are now considered for early intervention using these methods. Furthermore, these techniques provide a useful alternative in patients who fail systemic thrombolysis or those with relative or absolute contraindications to thrombolysis. Although the popularity of these techniques has grown, limitations of their clinical use must still be considered. With more devices and techniques being developed and approved for use in managing PE, it remains important to continue exploring their efficacy, accessibility, and safety profiles.

Dr. Ghanim is a third-year emergency medicine resident physician at the Baylor College of Medicine in Houston,Texas.

Dr. McArthur is a board-certified emergency medicine physician and assistant professor at the Baylor College of Medicine in Houston, Texas.

References

1. Silver MJ, Giri J, Duffy Á, et al. Incidence of mortality and complications in high-risk pulmonary embolism: a systematic review and meta-analysis. J Soc Cardiovasc Angiogr Interv. 2023;2(1):100548.
2. Shah IK, Merfeld JM, Chun J, et al. Pathophysiology and management of pulmonary embolism. Int J Angiol. 2022;31(3):143-149.
3. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.
4. Mathbout MF, Al Hennawi H, Khedr A, et al. Inari largebore mechanical thrombectomy in intermediate-high risk submassive PE patients: case series and literature review. Glob Cardiol Sci Pract. 2022;2022(1-2):e202208.
5. Bloomer TL, El-Hayek GE, McDaniel MC, et al. Safety of catheter-directed thrombolysis for massive and submassive pulmonary embolism: results of a multicenter registry and meta-analysis. Catheter Cardiovasc Interv. 2017;89(4):754-760.
6. Piazza G, Hohlfelder B, Jaff MR, et al. A prospective, single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEATTLE II study. JACC Cardiovasc Interv. 2015;8(10):1382-1392.
7. Khan K, Yamamura D, Vargas C, et al. The role of Eko-Sonic Endovascular System or EKOS® in pulmonary embolism. Cureus. 2019;11(12):e6380.
8. Wang C, Zhai Z, Yang Y, et al. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010;137(2):254-262.
9. Capanegro J, Quinn E, Arndt M, et al. Successful removal of a life-threatening PE using the INARI flow triever device. Radiol Case Rep. 2021;16(7):1878-1881.
10. Tu T, Toma C, Tapson VF, et al. A prospective, singlearm, multicenter trial of catheter-directed mechanical thrombectomy for intermediate-risk acute pulmonary embolism: the FLARE study. JACC Cardiovasc Interv. 2019;12(9):859-869.
11. Callese TE, Moriarty JM, Maehara C, et al. Cost drivers in endovascular pulmonary embolism interventions. Clin Radiol. 2023;78(2):e143-e149.
12. Mostafa A, Briasoulis A, Telila T, et al. Treatment of massive or submassive acute pulmonary embolism with catheter-directed thrombolysis. Am J Cardiol. 2016;117(6):1014-1020.