Overcoming Resistance to Catheter-Directed Therapy in Submassive Pulmonary Embolism

David Kirsch, MD

Editor’s note: This is a column by David Kirsch, MD, an interventional radiologist at Ochsner Health System in Baton Rouge, Louisiana. The presented analysis reflects his views, not necessarily those of the publication.

Health care professionals and researchers interested in responding to this piece or similarly contributing to MD Magazine® can reach the editorial staff by submitting a request here.

The optimal treatment of submassive pulmonary embolism (PE) remains controversial, despite growing evidence to support a role for catheter-directed therapy in carefully selected patients.

Treatment of PE is an inherently multidisciplinary endeavor, so it’s critical for clinicians from different specialties to concur on how to manage the up to 40% of cases that are classified as submassive¹, which is defined as PE with normal blood pressure but right ventricular dysfunction (as indicated by echocardiography, computed tomography or elevated cardiac biomarkers). Yet, in many institutions disagreement over the role for catheter-directed therapy (CDT) in management of submassive PE persists.

Growing evidence for catheter-directed therapy

As an interventional radiologist, I have been using ultrasound-accelerated catheter-directed thrombolysis (EKOS, BTG) to treat submassive PE for many years. I recently transferred to a 150-bed hospital, where I introduced this treatment approach, which has now been embraced with the full support of my colleagues in other disciplines. I have observed diminished resistance to catheter-based treatment of submassive PE as research has confirmed that this life-threatening condition can be managed with new protocols that minimize the risk for bleeding and other complications. At the same time, I have found that adopting certain strategies can help bridge gaps that often exist between clinicians from different disciplines, which I believe has helped us to improve patient care.When I arrived at my current post, I discovered that my colleagues in pulmonology, who are key players in management of PE, had an overall negative impression of the concept of administering CDT for submassive PE. They were consulted on all pulmonary embolism cases that presented at the hospital, and favored systemic anticoagulation for submassive cases. Their view was that intervening with CDT was too involved and complex. Moreover, they were concerned that directed therapy increased the risk of bleeding in these patients.

Much of the skepticism surrounding catheter-directed therapy for submassive pulmonary embolism exists because, for a time, there was relatively modest clinical data to suggest that an intervention such as ultrasound-accelerated catheter-directed thrombolysis (UCT) was safe and effective. However, that’s changing with the availability of data from several studies, including the ULTIMA trial², the SEATTLE II cohort³ and, most recently, OPTALYSE PE.⁴

The latter study randomized 101 patients with acute proximal pulmonary embolism to one of four cohorts. All patients received therapeutic anticoagulation along with UCT, with protocols ranging from 4mg of tissue plasminogen activator (tPA) per catheter over 2 hours to 12mg of tPA per catheter over 6 hours. All cohorts experienced a significant reduction in right ventricular to left ventricular (RV/LV) diameter ratio of approximately 23% to 26%, which is comparable to the benefits achieved in the earlier trials that used infusions lasting 12 to 24 hours. However, bleeding rates in OPTALYSE PE were significantly lower than in the SEATTLE II study.

Interdisciplinary collaboration

All doctors want to practice clinically based medicine, so having these new trials show that shorter intervals of UCT can safely and effectively resolve submassive PE has been extremely helpful in demonstrating the value of this treatment to my colleagues in pulmonology. The new protocol’s shorter duration reduces patients’ exposure to tPA, which will naturally be correlated with decreased morbidity.One of the most rewarding things I do as a physician is working closely with colleagues from other disciplines to discover ways we can collaborate to improve patient care. Openness and honesty are essential keys to building those relationships, bridging differences in the way we approach medicine and developing trust.

With regards to introducing UCT for treating submassive pulmonary embolism, I have been careful not to be aggressive and push for using the technology when it isn’t the right choice. Toward the goal of using UCT only when it’s indicated, I’ve worked closely with my colleagues in pulmonology to develop an evidence-based algorithm for identifying PE patients who are candidates for directed therapy. If a patient presents in our ER with a pulmonary embolism, but shows no evidence of right heart strain, then then he or she is treated with systemic heparin and monitored closely. If the patient’s clinical biomarkers improve, then there’s no reason to intervene.

On the other hand, if a patient presents with pulmonary embolism and imaging (either with computed tomography or echocardiography) indicates evidence of right heart strain, with RV/LV ratio of >.9 or abnormal echocardiogram, that triggers us to intervene with UCT. In most cases, I follow the OPTALYSE PE protocol. If the clot burden is smaller and the patient’s oxygen requirement is not too high and other clinical markers are relatively stable, I’ll choose the 4-hour protocol. I am very comfortable with either the 4- or 6-hour protocol—I feel like I’m going to get results either way. To be sure, patients have done very well with both protocols, which my colleagues in pulmonology appreciate.

¹ Sista A. Pulmonary Embolism: The Astute Interventional Radiology Clinician. Semin Intervent Radiol. 2017 Mar; 34(1): 11—15. doi: 10.1055/s-0036-1597759

² Kucher N, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129:479—486.

³ Piazza G, 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 Aug 24;8(10):1382-92.

⁴ Tapson V, et al. Optimum duration and dose of r-tPA with the acoustic pulse thrombolysis procedure for submassive pulmonary embolism. American Thoracic Society International Conference 2017; abstract.

The next step at our facility will be to establish a pulmonary embolism response team (PERT). Right now, I am the PERT, for all intents and purposes, but I have reached out to my colleagues in the ER and pulmonology to begin a process of creating a formal framework.