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March/April 2025
Ask The Experts: How Does PE Clot Location/Distribution Affect Your Therapy Decision-Making?
Reflections on how device selection and therapeutic approach for pulmonary embolism are impacted by factors such as thrombus location, clot burden, and patient risk profile.
With Taisei Kobayashi, MD; Riyaz Bashir, MD, FACC, RVT; and Kenneth Rosenfield, MD, MHCDS
Management decisions for pulmonary embolism (PE) should be guided by the risk category of presentation for the patient, with treatment options including anticoagulation alone, systemic thrombolysis, catheter-based thrombolysis, catheter-based embolectomy, and surgical embolectomy.1-3 Institutional strengths/resources should be taken into account when deciding the appropriate next step in management. Given the recent large expansion of innovation in catheter-based therapies, how PE clot location or distributions could affect the choice of catheter-based therapy is an important discussion.
Overall, the original trials examining catheter-directed thrombolytic therapies did not delineate clot location or burden. In the SEATTLE II study, which used the Ekos ultrasound-assisted catheter-directed thrombolysis system (Boston Scientific Corporation), patients were enrolled regardless of both clinical risk stratification into high or intermediate risk and thrombus location or distribution.4 From baseline to 48 hours postprocedure the right ventricular/left ventricular (RV/LV) ratio decreased from 1.55 to 1.13 (P < .0001) and mean modified Miller index decreased from 22.5 to 15.8 (P < .0001), proving the efficacy of the ultrasound-assisted catheter-directed thrombolysis approach for these patients. Similarly, pharmacomechanical approaches such as the Bashir catheter (Thrombolex, Inc.) showed a reduction of RV/LV ratio (1.66 to 1.10; 95% CI, 0.48-0.64; P < .0001), as well as a decrease in pulmonary artery obstruction index using the modified Miller index (reduction by 8.05 + 3.9; 95% CI, 7.3-8.8; P < .0001) at 48 hours.5 These examples prove the efficacy of catheter-directed thrombolysis and pharmacomechincal thrombolysis as viable and effective strategies for PE, regardless of the PE location.
Thrombus location becomes more important in studies investigating catheter-based embolectomy devices. In the FLARE study, which studied the role of FlowTriever (Inari Medical) in intermediate-risk PE, the inclusion criteria included “CT evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery).”6 This trial showed efficacy, with an average drop in RV/LV ratio of 0.38 (P < .0001), and was instrumental in the approval of FlowTriever for use for PE. Studies examining the FlowTriever device have since included main or lobar clot evidence as inclusion criteria for entry into their trials.7,8 AlphaVac (AngioDynamics), another large-bore embolectomy system, was studied in the APEX-AV trial and did not differentiate the location of thrombus, suggesting that not all large-bore embolectomy systems require central or proximal clot locations.9 Similarly, a large trial examining the Indigo aspiration system (Penumbra, Inc.), a medium-bore embolectomy device, did not have an anatomic clot location as an inclusion criterion. However, 34.5% of patients in the trial had main pulmonary artery PE with bilateral emboli.10 Investigational medium-bore devices such as the new Helo thrombectomy system (Endovascular Engineering) have adopted the inclusion of proximal PE as anatomic inclusion criteria.11 Thus, many of the catheter-directed embolectomy systems have been primarily studied in more proximal PEs.
The only comparative data between thrombectomy and catheter-directed thrombolysis for similar proximal clot locations was studied in the PEERLESS randomized controlled trial, which randomized patients with intermediate-risk PE with proximal PEs to catheter-directed thrombolysis or FlowTriever.8 Although there was no difference in mortality, there appeared to be lower rates of clinical deterioration and intensive care use with the use of large-bore embolectomy, and thus there has been a shift toward large-bore embolectomy in these patients.
Finally, while not in the pulmonary arteries, most recent data suggest that the presence of a clot in transit has a high association with in-hospital mortality.12 When these are large, serpiginous, highly mobile clots, and recognizing that there are no current data to suggest higher safety or efficacy with a thrombectomy approach for this clinical scenario, our institution typically favors large-bore embolectomy. If the clot in transit spans across the interatrial septum, a surgical approach is favored to limit instrumentation and paradoxical emboli from occurring.
Thus, in patients who are deemed appropriate candidates for catheter-based PE, large central clot burdens may benefit from large-bore embolectomy. For more distal PE, medium-caliber embolectomy or catheter-directed thrombolytic therapy can be used. However, in institutions where large-bore embolectomy is not readily available, patients with large central thrombus burden can still be treated with medium-caliber embolectomy, pharmacomechanical thrombolysis, and ultrasound-assisted catheter-directed thrombolytic therapy as these trials did not differentiate central versus peripheral clot burden in their seminal studies.
1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603. doi: 10.1093/eurheartj/ehz405
2. Giri J, Sista AK, Weinberg I, et al. Interventional therapies for acute pulmonary embolism: current status and principles for the development of novel evidence: a scientific statement from the American Heart Association. Circulation. 2019;140:e774-e801. doi: 10.1161/CIR.0000000000000707
3. Goldberg JB, Giri J, Kobayashi T, et al. Surgical management and mechanical circulatory support in high-risk pulmonary embolisms: historical context, current status, and future directions: a scientific statement from the American Heart Association. Circulation. 2023;147:e628-e647. doi: 10.1161/CIR.0000000000001117
4. 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;8:1382-1392. doi: 10.1016/j.jcin.2015.04.020
5. Bashir R, Foster M, Iskander A, et al. Pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter for acute pulmonary embolism: the RESCUE study. JACC Cardiovasc Interv. 2022;15:2427-2436. doi: 10.1016/j.jcin.2022.09.011
6. Tu T, Toma C, Tapson VF, et al. A prospective, single-arm, multicenter trial of catheter-directed mechanical thrombectomy for intermediate-risk acute pulmonary embolism: the FLARE study. JACC Cardiovasc Interv. 2019;12:859-869. doi: 10.1016/j.jcin.2018.12.022
7. Giri J, Mahfoud F, Gebauer B, et al. PEERLESS II: A randomized controlled trial of large-bore thrombectomy versus anticoagulation in intermediate-risk pulmonary embolism. J Soc Cardiovasc Angiogr Interv. 2024;3:101982. doi: 10.1016/j.jscai.2024.101982
8. Jaber WA, Gonsalves CF, Stortecky S, et al. Large-bore mechanical thrombectomy versus catheter-directed thrombolysis in the management of intermediate-risk pulmonary embolism: primary results of the PEERLESS randomized controlled trial. Circulation. 2025;151:260-273. doi: 10.1161/CIRCULATIONAHA.124.072364
9. Ranade M, Foster MT, Brady PS, et al. Novel mechanical aspiration thrombectomy in patients with acute pulmonary embolism: results from the prospective APEX-AV trial. J Soc Cardiovasc Angiogr Interv. 2025;4:102463.
10. Sista AK, Horowitz JM, Tapson VF, et al. Indigo aspiration system for treatment of pulmonary embolism: results of the EXTRACT-PE trial. JACC Cardiovasc Interv. 2021;14:319-329. doi: 10.1016/j.jcin.2020.09.053
11. Kobayashi T, Secemsky EA, Klein AJ, et al. A safety and feasibility single-arm study of a novel catheter thrombectomy device for the treatment of pulmonary embolism (ENGULF). J Soc Cardiovasc Angiogr Interv. 2024;3:102049. doi: 10.1016/j.jscai.2024.102049
12. Kobayashi T, Pugliese S, Sethi SS, et al. Contemporary management and outcomes of patients with high-risk pulmonary embolism. J Am Coll Cardiol. 2024;83:35-43. doi: 10.1016/j.jacc.2023.10.026
In our experience, PE clot location and distribution are useful in determining the appropriate catheter-based treatment strategy. Although the patient’s risk profile primarily guides the decision to proceed with catheter-based therapy, clot characteristics influence device selection and therapeutic approach. For patients with extensive and occlusive thrombus burden involving both main pulmonary arteries and severe RV dilation, a more aggressive strategy like large-bore mechanical thrombectomy is the preferred intervention to restore pulmonary blood flow and reduce RV strain rapidly. However, when clot distribution is confined to the interlobar and segmental arteries, pharmacomechanical catheter-directed thrombolysis (PCDT) remains our preferred modality of catheter-based therapy, offering a safe and effective solution with reduced risk of bleeding complications.1,2 The core laboratory analysis of the RESCUE study showed that PCDT was associated with a 71% reduction in the total and subtotal occlusions of the segmental arteries.3 We use PCDT as pulse sprays only (on-the-table RESCUE II protocol4 or a combination of pulse sprays with a 5-hour tissue plasminogen activator (tPA) infusion (RESCUE I protocol5). In these patients, thrombolytic dosing is individualized based on clot burden, delivering higher doses to segments with occlusive obstruction while limiting exposure in areas with nonocclusive thrombus burden. In cases of extensive clot burden, a combination of pulse-spray tPA administration and recombinant tPA infusion enhances thrombus resolution and reduces pulmonary artery obstruction. Particular attention is given to occlusions in the posterior trunk of the lower lobe and upper lobe truncus, where selective catheter placement and targeted therapy improve clot dissolution. The placement of wire and catheters in the posterior trunk is best visualized in contralateral oblique views.
Patients presenting with signs of acute-on-chronic PE—marked by CTA findings like bronchial collaterals, RV hypertrophy, and enlarged tortuous pulmonary arteries—require special consideration. In such cases, we prefer PCDT over mechanical thrombectomy, as the severely stenotic distal pulmonary artery branches can become totally occluded by even small thrombus fragments. When clot distribution is confined to interlobar and segmental arteries and the patient is actively bleeding or has an absolute contraindication to thrombolysis, we prefer small-bore rather than large-bore thrombectomy. Patients with relative contraindications to thrombolytics are excellent candidates for PCDT. This precision-guided approach ensures that the therapy is tailored to the anatomic distribution of clot burden while minimizing the risk of distal embolization and vessel occlusion. This strategic and nuanced approach to PE management optimizes patient outcomes by balancing clot removal efficacy with procedural safety.
1. Monteleone P, Ahern R, Banerjee S, et al. Modern treatment of pulmonary embolism (USCDT vs MT): results from a real-world, big data analysis (REAL-PE). J Soc Cardiovasc Angiogr Interv. 2023;3:101192. doi: 10.1016/j.jscai.2023.101192
2. Warren BE, Tan KT, Jaberi A, et al. Procedure-related mortality in aspiration thrombectomy for pulmonary embolism: a MAUDE database analysis of the Inari FlowTriever and Penumbra Indigosystems. J Endovasc Ther. Published online December 23, 2024. doi: 10.1177/15266028241307848
3. Bashir R, Piazza G, Firth B, et al. Effect of pharmacomechanical catheter-directed thrombolysis on segmental artery occlusions: insights from the RESCUE trial. JACC Adv. 2023;2:100670. doi: 10.1016/j.jacadv.2023.100670
4. Bichard C. First-in-Human study of a novel pharmacomechanical thrombolysis catheter for the treatment of acute intermediate-risk pulmonary embolism: the RESCUE II study. Presented at: Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium; October 27-30, 2024; Washington, DC.
5. Bashir R, Foster M, Iskander A, et al. Pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter for acute pulmonary embolism: the RESCUE study. JACC Cardiovasc Interv. 2022;15:2427-2436. doi: 10.1016/j.jcin.2022.09.011
First, no matter where the clot is, it is important to understand that it could well respond to multiple different therapies, including anticoagulation alone. Second, the only circumstances where I might not consider thrombectomy are when the clot is very distal and dispersed throughout the distal pulmonary artery bed. Central clots (eg, saddle clot or clot in the proximal main pulmonary arteries) are “low-hanging fruit” for thrombectomy because clinicians can see a large burden of thrombus, and it seems natural to want to remove or dissolve it. It is important to keep in mind that even central clots will respond to catheter-directed lysis, for example, using the Bashir catheter (which in its investigational device exemption trial demonstrated the largest thrombus reduction over any other therapy) or the Ekos catheter (with which there is a large accumulated experience). That said, if there is a huge central thrombus, clinicians are often anxious to remove these via thrombectomy to decrease the clot burden. There is satisfaction associated with quick thrombus removal and having an immediate positive impact on the right ventricle and associated clinical status. At least in theory, along with rapid resolution of right ventricular strain, the patient is now in a better condition to further reperfuse with anticoagulation or supplemental tPA.
Overall, thrombectomy catheters are improving in design and function. Second- and third-generation devices being developed now are more flexible and less traumatic. And, with their 16-F and 12-F telescoping catheters, they have the ability to safely “reach” relatively far out into the branch arteries. One can start centrally with a 24-F catheter, then use a 20-F catheter to get a little farther out, followed by a 16-F catheter for getting into the branches. Furthermore, newer devices incorporate adjunct devices to “grab,” “engage,” or macerate the thrombus, thus preventing the challenging “lollipop” phenomenon. We are all excited about the promise of clearing more thrombus using this next generation of thrombectomy catheters.
Someday in the future, we may be using a combination of thrombectomy followed by local thrombolysis to optimize the distal perfusion. While some of the current iteration of thrombectomy devices are quite stiff, if we can be assured that future, newer devices enable thrombectomy without trauma to the pulmonary vasculature, we might even feel safe using local lysis immediately afterward. Ultimately, I do think this could be a option for certain patients.
Our challenge now is knowing which patient is appropriate for which device. The reality is that there is a gray zone. Patients will respond to multiple approaches, and none is right or wrong. If there is proximal thrombus, one can use thrombectomy, or one can still use catheter-directed lysis. So how does one decide which approach to use? This is very challenging because we don’t yet have a sufficient evidence base upon which to base those decisions. That said, The PERT Consortium Database, for which the Consortium has now engaged the MCORRP (Michigan Clinical Outcomes Research and Reporting Program), is actively enrolling patients and accruing data. These data will be very informative. There are approximately 15,000 patients in the existing database, and already another thousand patients or more in this next generation of the database that is a bit more descriptive and more refined. I encourage every institution and clinician treating PE to participate in The PERT Consortium Database so that we can better answer these questions regarding which therapeutic approach—anticoagulation, catheter-based lysis, and/or thrombectomy—produces the best outcome for any given patient.
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