Catheter-directed thrombolysis (CDT)
CDT was originally developed to treat arterial, dialysis graft and deep vein thromboses, but is now approved by the FDA for the treatment of acute submassive or massive PE.
A wire is passed through the embolus and a multihole infusion catheter is placed, through which a thrombolytic drug is infused over 12-24 hours. The direct delivery of the drug into the thrombus is thought to be as effective as systemic therapy but with a lower risk of bleeding. If more rapid thrombus removal is indicated due to large clot burden and hemodynamic instability, mechanical therapies, such as fragmentation and aspiration, can be used as an adjunct to CDT. However, these mechanical techniques carry the risk of pulmonary artery injury, and therefore should only be used as a last resort. An ultrasound-emitting wire can be added to the multihole infusion catheter to expedite thrombolysis by ultrasonically disrupting the thrombus, a technique known as ultrasound-enhanced thrombolysis (EKOS).7,10
The ULTIMA 2014 trial,8 a small, randomized, open-label study of Ultrasound-Assisted Catheter Directed Thrombolysis (USAT, the term can be used interchangeably with EKOS) versus heparin anticoagulation alone in 59 patients, was designed to study if the former strategy was better at improving the primary outcome measure of RV/LV ratio in submassive PE patients. The mean reduction in RV/LV ratio was 0.30 +/– 0.20 in the USAT group compared to 0.03 +/– 0.16 in the heparin group (P less than .001). However, no significant difference in mortality or bleeding was observed in the groups at 90-day follow up.
The PERFECT 2015 Trial,9 a multicenter registry-based study, prospectively enrolled 101 patients who received CDT as first-line therapy for massive and submassive PE. Among patients with submassive PE, 97.3% were found to have “clinical success” with this treatment, defined as stabilization of hemodynamics, improvement in pulmonary hypertension and right heart strain, and survival to hospital discharge. There was no major bleeding or intracranial hemorrhage. Subgroup analyses in this study comparing USAT against standard CDT did not reveal significant difference in average pulmonary pressure changes, average thrombolytic doses, or average infusion times.
A prospective single-arm multicenter trial, SEATTLE II 2015,10 evaluated the efficacy of EKOS in a sample of 159 patients. Patients with both massive and submassive PE received approximately 24 mg tPA infused via a catheter over 12-24 hours. The primary efficacy outcome was the chest CT-measured RV/LV ratio decrease from the baseline compared to 48 hours post procedure. The pre- and postprocedure ratio was 1.55 versus 1.13 respectively (P less than .001), indicating that EKOS decreased RV dilation. No intracranial hemorrhage was observed and the investigators did not comment on long-term outcomes such as mortality or quality of life. The study was limited by the lack of a comparison group, such as anticoagulation with heparin as monotherapy, or systemic thrombolysis or standard CDT.
Treatment of submassive PE varies between different institutions. There simply are not adequate data comparing low dose systemic thrombolysis, CDT, EKOS, and standard heparin anticoagulation to make firm recommendations. Some investigators feel low-dose systemic thrombolysis is probably as good as the expensive catheter-based thrombolytic therapies.11,12 Low-dose thrombolytic therapy can be followed by use of oral direct factor Xa inhibitors for maintenance of antithrombotic activity.13
Bottom line
In our institution, the interventional radiology team screens patients who meet criteria for submassive PE on a case-by-case basis. We use pulmonary angiographic data (nature and extent of the thrombus), clinical stability, and analysis of other comorbid conditions to decide the best treatment modality for an individual patient. Our team prefers EKOS for submassive PE patients as well as for massive PE patients and as a rescue procedure for patients who have failed systemic thrombolysis.
Until more data are available to support firm guidelines, we feel establishing multidisciplinary teams composed of interventional radiologists, intensivists, cardiologists, and vascular surgeons is prudent to make individualized decisions and to achieve the best outcomes for our patients.14
IVC filter
Since the patient in this case already has a submassive PE, can she tolerate additional clot burden should her remaining DVT embolize again? Is there a role for IVC filter?
The implantation of IVC filters has increased significantly in the past 30 years, without quality evidence justifying their use.15
The 2016 Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report states clearly: In patients with acute DVT of the leg or PE who are treated with anticoagulants, the use of an IVC filter is not recommended (Grade 1B).3 This recommendation is based on findings of the Prevention du Risque d’Embolie Pulmonaire par Interruption Cave (PREPIC) randomized trial,16 and the recently published PREPIC 2 randomized trial,17 both showing that in anticoagulated patients with PE and DVT, concurrent placement of an IVC filter for 3 months did not reduce recurrent PE, including fatal PE.
CHEST guidelines state that an IVC filter should not be routinely placed as an adjunct in patients with PE and DVT. However, what about in the subgroup of patients with submassive or massive PE in whom another PE would be catastrophic? Clinical data are lacking in this area.
Deshpande et al. reported on a series of six patients with massive PE and cardiopulmonary instability; patients all received an IVC filter with anticoagulation. The short-term outcome was excellent, but long-term follow-up was not done.18 Kucher and colleagues reported that from the ICOPER in 2006, out of the 108 massive PE patients with systolic arterial pressure under 90 mm Hg, 11 patients received adjunctive IVC filter placement. None of these 11 patients developed recurrent PE in 90 days and 10 of them survived at least 90 days; IVC filter placement was associated with a reduction in 90-day mortality. In this study, the placement of an IVC filter was entirely decided by the physicians at different sites.19 In a 2012 study examining case fatality rates in 3,770 patients with acute PE who received pulmonary embolectomy, the data showed that in both unstable and stable patients, case fatality rates were lower in those who received an IVC filter.20
Although the above data are favorable for adjunctive IVC filter placement in massive PE patients, at least in short-term outcomes, the small size and lack of randomization preclude establishment of evidence-based guidelines. The 2016 CHEST guidelines point out that as it is uncertain if there is benefit to place an IVC filter adjunctively in anticoagulated patients with severe PE, in this specific subgroup of patients, the recommendation against insertion of an IVC filter in patients with acute PE who are anticoagulated may not apply.3
