The Role of Ultrasound-Facilitated Catheter-Directed Thrombolysis in Submassive Pulmonary Embolism

Walid Saber, MD, FACC, FSCAI, RPVI*

Dr. Walid Saber can be contacted at wsaber@oscvc.com.

Kenneth, 64, arrived at a nearby emergency department (ED) with chest pain, hypotension, low oxygen, and two episodes of syncope, and was on the verge of cardiogenic shock. Kenneth had a significant iliofemoral deep vein thrombosis (DVT) in his leg and a large submassive bilateral pulmonary embolism (PE), with right ventricle (RV) dilation on computed tomography angiography (CTA) and transthoracic echocardiography, and elevated cardiac troponin on initial labs. He had undergone recent abdominal surgery for colon cancer, raising concerns about treatment with systemic tissue plasminogen activator (tPA), because of a high risk of bleeding. After consulting with our cardiology department, the ED physician transferred the patient to our hospital for treatment with ultrasound-facilitated, catheter-directed thrombolysis (EKOS; BTG International).

Figure 1. Initial EKG showing Sinus Tachycardia, S1Q3T3 Pattern.

Figure 2. Initial CTA showing saddle embolus and bilateral pulmonary emboli.

Figure 3. 4-chamber echo showing RV>LV consistent with RV dilation.

Kenneth was brought to the cath lab. Via right internal jugular vein access, two sheaths were placed and two Ekos devices were placed in the right and left pulmonary arteries, respectively. Kenneth received 12 mg of tPA in each pulmonary circulation at a rate of 1 mg/hour, with a total dose of 24 mg of tPA.   

The mechanism of action for the Ekos device depends on the delivery of a local dose of tPA into the target circulation, thereby greatly reducing the amount of tPA — typically 24 mg — needed to effectively lyse the clot. Ekos delivers high-frequency, low-energy ultrasound during infusion that increases the permeability of the thrombolic agent into the thrombus, increasing effectiveness. In the randomized, controlled ULTIMA trial, which compared Ekos to anticoagulation, there were no intracranial hemorrhages or major bleeding events.[1] In the prospective single-arm SEATTLE II, which evaluated the safety and efficacy of Ekos, there were no intracranial hemorrhages, while 10% of participants had moderate bleeding events and 1 had a severe bleed.[2]  In treating patients with DVT and PE with Ekos, we’ve never experienced a major bleeding event.  

Figure 4. Bilateral Ekos catheters positioned in each pulmonary artery.

Forty-eight hours post procedure, a CTA and echocardiogram showed that RV function had significantly improved and the clot burden was greatly reduced. A few weeks later, we successfully treated Kenneth’s extensive iliofemoral DVT with Ekos. Another advantage of Ekos is that placement of an inferior vena cava (IVC) filter is unnecessary. Unlike other catheter-directed thrombolysis modalities, the Ekos system causes minimal downstream emboli showering. This is because the Ekos system uses ultrasound to help the thrombolytic agent penetrate locally in the clot as opposed to the use of mechanical fragmentation.

Figure 5. Post therapy CTA showing resolution of clot.

Like Kenneth, most patients with PE also have an index DVT. Seventy-nine percent of patients presenting with PE have evidence of DVT, and PE occurs in up to 50% of patients with proximal DVT.[3] We always look for DVT in patients with PE, and treat extensive proximal DVTs with Ekos to prevent subsequent post-thrombotic syndrome, venous hypertension, lipedema, varicose veins, and venous ulcers. We recently treated a 26-year-old woman with an extensive iliofemoral DVT that developed after a C-section. By aggressively treating her DVT with Ekos, we undoubtedly spared her multiple significant venous problems in middle age.

The recent ATTRACT clinical trial, which evaluated pharmacomechnical catheter-directed thrombolysis plus anticoagulation compared with anticoagulation alone for the treatment of DVT, found no benefit to catheter-directed modalities.[4] However, we believe the study had significant limitations, as 40% to 45% of patients treated had no involvement of the common femoral or iliac veins, which would be classified as iliofemomal DVTs.  We aggressively treat all iliofemomal DVTs unless there is a contraindication, such as the patient having a terminal disease, prior hemorrhagic stroke, or active bleeding.

Equally controversial is how to aggressively treat submassive PEs. Many pulmonary critical care physicians and some cardiologists believe that all submassive PEs should be treated with oral anticoagulants alone. There are data, however, that show that patients with submassive PEs with RV dysfunction and elevated troponin levels have higher mortality if they are not treated aggressively.[5] Recurrent pulmonary emboli can also lead to pulmonary hypertension, which can cause RV dysfunction.

Admittedly, we need strong evidence from large clinical trials with a long duration of follow-up in order to confidently incorporate catheter-directed thrombolysis into clinical guidelines for the treatment of submassive PE. Currently, catheter-directed thrombolysis for the management of acute submassive PE is classified as level 2B evidence. We believe, however, that this technology should have a level 1 indication and expect that clinical guidelines will be revised when future clinical trials prove what clinicians who use these endovascular options already know. We currently use Ekos therapy to treat all submassive PEs with a right ventricle/left ventricle (RV/LV) ratio ˃ 1.0 and with elevated cardiac biomarkers, such as troponin.

Venous thromboembolic disease is common, costly, and deadly. Advanced, catheter-based therapies offered to properly selected patients can help reduce long-term morbidity and mortality. Further research is needed with large-size, randomized, controlled studies and long-term follow-up, which will establish a higher level of recommendation across different practice guidelines.

*Dr. Walid Saber is Chief of Cardiology; Director of Vascular Medicine, Interventional Vascular Services, Non-invasive Vascular Lab; and Medical Director of the Wound Center and Hyperbaric Chamber at Landmark Medical Center in Woonsocket, Rhode Island. He is also Clinical Assistant Professor at the Warren Alpert Medical School at Brown University and a partner at Oceanstate Cardiovascular & Vein Center.

References

1. Kucher N, Boekstegers P, Muller, OJ, et al. Randomized, controlled trial of ultrasound-assisted, catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014; 129:479-486.
2. Piazza G, Hohlfelder B, Jaff MR, et al. A prospective, single-arm, multicenter trial of ultrasound-facilitated, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: The SEATTLE II study. Cardiovascular Interventions 2015; 8 [10]: 1382-1392.
3. Tapson VF. Acute pulmonary embolism. N Engl J Med 2008; 358:1037-1052.
4. Vedantham S, Goldhaber SZ, Julian JA, et al. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med 2017; 377: 2240-2252.
5. Tapson VF, Sterling K, Jones N, et al. A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism. JACC: Cardiovascular Interventions Jul 2018, 11 (14) 1401-1410.