Advances in Percutaneous Management of Pulmonary Embolism

Abstract

Acute pulmonary embolism (PE) is a leading cause of morbidity and mortality worldwide. Systemic anticoagulation remains the recommended treatment for low-risk PE. Systemic thrombolysis is the recommended treatment for PE with hemodynamic compromise (massive/high-risk PE). A significant number of patients are not candidates for systemic thrombolysis due to the bleeding risk associated with thrombolytics. Historically, surgical pulmonary embolectomy (SPE) was recommended for massive PE with hemodynamic compromise for these patients. In the last decade, catheter-directed thrombolysis (CDT) has largely replaced SPE in the patient population with intermediate risk PE (submassive), defined as right heart strain (as evidenced by right ventricle enlargement on echocardiogram and/or computed tomography, usually along with elevation of troponin or B-type natriuretic peptide). Use of CDT increased in the last few years due to high incidence of PE in hospitalized patients with coronavirus disease 2019 pneumonia, and the use of mechanical thrombectomy (initially reserved for those with contraindications to thrombolysis) has also grown. In this article, we discuss the value of the PE response team, our approach to management of submassive (intermediate risk) and massive (high risk) PE with systemic thrombolytics, CDT, mechanical thrombectomy, and surgical embolectomy.

Pulmonary embolism (PE) is a major cause of morbidity and mortality in the United States. ¹ Over the past decade several new devices have become available for the treatment of PE. Despite these advances, when and how to utilize these tools is not well understood due to the lack of robust randomized control trial data comparing these newer technologies to standard anticoagulation alone. PE response teams (PERTs) were created to immediately and simultaneously engage multiple specialists to determine the best course of action and coordinate the clinical care for patients with acute PE. PERTs allow local experts to share in decision-making and management of these complex patients to provide optimal care. The idea of PERT originated in 2012 at Massachusetts General Hospital with the aim to take advantage of multidisciplinary hospital expertise in the absence of robust randomized control trials. This group published a fall in mortality from massive PE of 25% compared with national averages. ²

At our hospital in Nashville, we started our PERT in 2019 as a joint venture between the pulmonary critical care division and the interventional cardiology group. We have since invited cardiothoracic surgery, interventional radiology, emergency medicine, internal medicine, and vascular surgery to join our endeavor. Our robust multidisciplinary team allows swift treatment and triage for patients in our hospital with massive and submassive PE. One “throughput” person activates PERT, which allows for all available specialists to sign in and provide input. Prior to the development of our PERT program, treatment of PE varied depending on the admitting team or location of the patient. Since the establishment of PERT, there has been rapid development of a treatment plan for acute and submassive PE, similar to the benefits seen when developing other teams designated to take care of acute stroke or myocardial infarction. The development of artificial intelligence to integrate patient data and visualization of radiologic studies (including automated PE detection, calculation of right ventricle [RV]/left ventricle [LV] ratios, and classification of patients into low, intermediate, or high risk PE) hopes to streamline this process.

Although the benefits of PERT are quite evident in the inpatient setting, it is also important to track long-term patient outcomes. Although we can prove increased efficiency with time to diagnosis, time to anticoagulation or other treatment, and rapid throughput through the hospital, it is important to see if these variables affect patient outcomes, whether they receive interventions or not. The PERT Consortium (pertconsortium.org) research database helps to build these cohorts of patients, which will allow for large database analysis to answer these questions that will hopefully allow for a more objective comparison of the various available interventions.

Systemic Thrombolysis for PE Treatment

The standard of care for treatment of massive PE (defined as PE with hypotension [systolic less than 90 mm Hg for over 15 minutes or the requirement for vasopressors to maintain systolic blood pressure] or cardiac arrest) has been systemic thrombolysis. Unfortunately, in most series, fewer than half of patients with massive PE receive thrombolytics, usually due to contraindications. ³ For these patients, surgical or percutaneous embolectomy with or without hemodynamic support remains an option for management, as discussed later in this article.

The question of whether systemic thrombolytics were beneficial in patients with submassive PE was explored in the PEITHO trial. ⁴ A total of 1,005 patients at 76 sites in 13 countries were randomized to heparin with placebo versus heparin plus tenecteplase (dosed as a single bolus, based on weight) ( Table 1 ). All had RV dysfunction on computed tomography or echocardiogram along with an abnormal troponin. The average patient was a female in her 60s with a systolic blood pressure in the 130s, heart rate in the 90s, and a respiratory rate in the 20s, requiring supplemental oxygen. For patients receiving tenecteplase, there was a reduction in further hemodynamic decompensation (1.6% vs. 5.0%, odds ratio 0.30 [0.14–0.68]) which drove a reduction in the primary endpoint of all-cause mortality (which was not independently significant) and decompensation. There was no difference in recurrent PE in the first week, or hospital length of stay (LOS). For patients receiving tenecteplase, there was a significant increase in the risk of major extracranial bleeding (6.3% vs. 1.2%, p  < 0.001) and stroke (2.4% vs. 0.2%, p  = 0.003). Of the 12 patients who had a stroke after receiving tenecteplase, 10 were hemorrhagic; 40% of those who had a hemorrhagic stroke died before 30 days. As a result of this trial, systemic fibrinolysis has failed to become the standard of care for the treatment of submassive PE, leading to the development of alternative catheter-based strategies, as outlined below.

Table 1. Tenecteplase dosing regime.

Weight (kg)	Dose (mg)	Dose (units)	Volume (mL)
< 60	30	6,000	6
≥ 60 to < 70	35	7,000	7
≥ 70 to < 80	40	8,000	8
≥ 80 to < 90	45	9,000	9
≥ 90	50	10,000	10

Administration of systemic thrombolytics is absolutely contraindicated for patients with structural intracranial disease (i.e., tumor or arteriovenous [AV] malformation), previous intracranial hemorrhage, ischemic stroke within 3 months, active bleeding, recent brain or spinal surgery, recent head trauma with fracture or brain injury, or who have a bleeding diathesis. Relative contraindications include systolic blood pressure over 180 mm Hg or diastolic blood pressure over 110 mm Hg, recent bleeding (nonintracranial), recent surgery, recent invasive procedure, ischemic stroke more than 3 months previously, anticoagulation (e.g., vitamin K antagonist therapy), traumatic cardiopulmonary resuscitation, pericarditis or pericardial fluid, diabetic retinopathy, pregnancy, age over 75 years, or low body weight (e.g., less than 60 kg). ⁵

Catheter-Based Treatments for Pulmonary Embolism

Catheter-Directed Thrombolysis

Due to the risk of bleeding events with systemic thrombolytics, catheter-directed thrombolysis (CDT) has evolved to reduce the duration and dose of thrombolytic therapy. Multihole catheters (Angiodynamics, Latham, NY) can be placed directly into the pulmonary artery (PA) to allow for increased concentrations of thrombolytics to be locally delivered. Despite the lack of randomized trials, multicenter and national registries have reported on the improved clinical outcomes of patients receiving CDT versus systemic thrombolysis. ^{6 7} The National Readmission Database reported on the outcomes of 3,107 patients receiving systemic thrombolysis and 1,319 patients treated with CDT. Patients receiving CDT had lower rates of mortality (14.9% vs. 6.12%), readmissions (10.6% vs. 7.6%), and bleeding-related mortality (18.1% vs. 8.4%) when compared with those receiving systemic thrombolysis. ⁷ PE therapies integrating the use of CDT with ultrasound waves have emerged in the form of the EKOS ( Fig. 1 , Boston Scientific, Natick, MA) system. ⁸ The EKOS or EkoSonic endovascular system originally received Food and Drug Administration (FDA) approval in 2004 and is currently indicated for PE, deep vein thrombosis, and arterial occlusions. ⁹ The system is composed of an infusion catheter, an ultrasound core wire, and a control unit ( Fig. 1 ). Single or dual catheters are delivered in the unilateral or bilateral pulmonary arteries where the pulmonary emboli are located. Venous access is most commonly obtained in either the femoral or internal jugular veins. Depending on the site of venous access and location/extent of thrombus, an appropriate working length and treatment zone of catheter can be selected.

Fig. 1.

EkoSonic endovascular system (EKOS).

Through the 5.4 F infusion catheter, high concentrations of thrombolytics are able to be delivered into the PA. The ultrasound energy transmitted through the core of the catheter is low power and high frequency. This ultrasound-assisted thrombolysis accelerates the lytic delivery by disrupting the fibrin strands. In addition to the ultrasound energy mechanically disrupting the clot, it exposes the plasminogen receptor sites to enhance the action of the thrombolytics. ¹⁰

In the ULTIMA trial, 59 patients with submassive PE were randomized to EKOS plus unfractionated heparin (UFH) or UFH alone. The group receiving EKOS plus UFH demonstrated a decreased RV/LV ratio within 24 hours of treatment. Furthermore, significant recovery in RV function was noted in the EKOS plus UFH compared with the UFH alone group. However, at 90 days there was no difference in mortality rates between the groups. ¹¹ The SEATTLE II trial published by Piazza et al ¹² was a prospective randomized single-arm study of patients with submassive or massive PEs. The trial enrolled 150 patients undergoing EKOS plus UFH therapy. The study reported a decrease in RV/LV ratio, lower PA pressures, and decreased RV strain. The OPTALYSE trial was a randomized trial of patients with submassive PE investigating the optimal dosing and duration of thrombolytic therapy with EKOS. In the 101 patients studied, the low-dose, shorter duration of thrombolytics was as clinically effective as those regimens used in the SEATTLE II and ULTIMA trials. ¹³

Most recently, a meta-analysis published by Avgerinos et al reported on the outcomes of 1,168 patients with high and intermediate risk PE who had received CDT or EKOS therapies. High-risk patients had higher rates of clinical success when undergoing EKOS compared with CDT (83.1% vs. 70.8%). However, there was no detectable difference between the therapies in those patients that were intermediate risk (97.5% vs. 95%). The authors concluded that EKOS is more effective than regular CDT for those patients defined as high risk but is equivalent in the submissive population. ¹⁴

Despite the advancements in ultrasound-facilitated CDT (EKOS), some studies have demonstrated similar clinical outcomes with the use of CDT. Several retrospective studies have reported no difference in 30-/90-day mortality or bleeding complications. In addition, hemodynamic improvement and hospital/intensive care unit (ICU) LOS were also found not to be significantly different when comparing standard CDT with EKOS. ^{15 16 17}

Given the lack of prospective randomized controlled trials comparing EKOS and standard systemic anticoagulation therapy, the currently enrolling HI-PEITHO trial was designed to address this question. This multicenter international trial has an estimated enrollment of 406 patients with intermediate-high risk PE. The primary endpoints include PE-related mortality, PE recurrence, and cardiorespiratory decompensation/collapse (Ultrasound-facilitated, Catheter-directed, Thrombolysis in Intermediate-high Risk Pulmonary Embolism - Full Text View - ClinicalTrials.gov). This trial is currently enrolling in the U.S. and European Union (EU), with an expected primary completion date of July 2024.

Percutaneous Thrombectomy

Initially reserved for patients with submassive (intermediate risk) or massive (high-risk) PE that were not candidates for systemic or catheter-directed thrombolytics due to contraindications, catheter-based thrombectomy has quickly grown and, in some centers, become the preferred approach for management of PE when intervention is indicated. This section will review the currently available methods for performance of mechanical thrombectomy and, where available, discuss the trial data supporting the safety and/or efficacy of each.

Rheolytic Thrombectomy

Use of the AngioJet Thrombectomy System (Boston Scientific) was previously reported in the treatment of PE, in conjunction with a purpose-built 6F PE catheter. The catheter was 6F and is advanced over a 0.035” wire; it had a flow rate of 60 mL/min and allowed for “Power Pulse” to deliver thrombolytics through the catheter, which were then allowed to marinate to facilitate removal of clot. The removal of clot was via a rheolytic mechanism, which used high pressure/velocity saline jets to create a low-pressure zone that caused a vacuum effect, which was used to remove thrombus. While several trials exist exploring the use of rheolytic thrombectomy in other pathologies (deep venous thrombosis, peripheral arterial thrombus, and AV access conduits) ^{18 19} and it is frequently used for other peripheral applications, the device was found to cause adenosine release from disrupted platelets, leading to bradycardia, pulmonary vasospasm, worsening hypoxia, and a potential increase in mortality, which led the FDA to issue a “black box warning” discouraging use of the AngioJet device for the treatment of PE. ²⁰ As such, use of this device in the U.S. in minimal, and limited case reports are available discussing outcomes.

Suction Thrombectomy

Two devices are commercially available for the performance of suction/mechanical thrombectomy for the treatment of PE, and several others are in development for this indication. The Indigo System ( Fig. 2 , Penumbra, Alameda, CA) uses a catheter (usually 7, 8, or 12F, with the 12F catheter most frequently being used in the treatment of PE, though the 8F CAT8 is also indicated for treatment of PE) that is attached to a canister mounted on the Penumbra ENGINE that generates continuous vacuum at –29.2 inHg to perform thrombectomy. Additionally, when needed, a separator is used to macerate thrombus into smaller pieces that are more easily removed by the thrombectomy catheter. The most recent innovation in the use of the Indigo System has been the release of the Lightning Intelligent Aspiration Tubing, which minimizes blood loss by sensing when aspiration is too brisk, changing the system from continuous to intermittent aspiration.

Fig. 2.

The Indigo system.

From a practical standpoint, after gaining access to the femoral vein (ideally using ultrasound guidance and mini stick techniques), the right heart is traversed with either a pigtail or a Swan-Ganz catheter that can accommodate a 0.035” wire. Once in the PA, the pigtail or Swan can be exchanged over an atraumatic 0.035” wire (usually a Versacore or Bentson) for a catheter (usually a JR4, HH1, or multipurpose) that is used to select a distal branch of a PA that is to be treated. After advancing the wire/catheter to the distal branch, a supportive wire (i.e., an Amplatz Super Stiff) is advanced. After removal of the catheter and initial sheath, a 12F long sheath (usually a Gore DrySeal) is advanced through the right heart and into either the main or right/left PA. Through this sheath, the Lightning 12 catheter is advanced just proximal to the area of thrombus, and aspiration is activated, using gentle catheter manipulation to remove clot. As aforementioned, if the thrombus is large and/or adherent, the separator (a bullet-shaped device) is advanced through the catheter and used in an in-and-out fashion to clear the thrombus from the catheter tip and to macerate the clot into smaller pieces. When the thrombus has been removed from the area of interest, the thrombectomy catheter is redirected over a 0.035” wire to other areas in need of treatment. Once done, the device and sheath are removed, and closure is either achieved via a preclosure technique, a figure of 8 stitch, or manual compression hemostasis.

The only clinical trial describing the use of the Indigo System in the treatment of PE was the EXTRACT-PE trial, published in early 2021. ²¹ This was a prospective, multicenter, single-arm investigational device exemption (IDE) trial enrolling 119 patients at 22 U.S. centers. All patients had acute submassive PE (patients with signs/symptoms of less than 2 weeks' duration, systolic blood pressure over 90 mm Hg, right ventricular dilation [RV/LV ratio > 0.9]). Most patients were male, averaged around 60 years of age, and were white. Simplified Pulmonary Embolism Severity Index (sPESI) was 0 in 46.2%, 1 in 35.3%, and 2 in 18.5%. Nearly 23% were tachycardic, 70.6% had elevated troponin, and 60.4% had right ventricular systolic dysfunction on echocardiogram. Overall, in 99.2% of patients, the Indigo device was able to reach the thrombus (85.7% femoral, 14.3% jugular). Note that 1.7% of patients required the use of adjunctive intraprocedural thrombolytics, the average time from device insertion to removal was 37.0 minutes, and the average ICU LOS was 1 day. At 48 hours, a 27.3 ± 12.99% reduction in RV/LV ratio was seen. The overall major adverse event (MAE) rates within 48 hours were 1.7%, with a 1.7% rate of major bleeding and 0.8% device-related death rate. Device-related serious adverse events (SAEs) included clinical deterioration (0.8%) and pulmonary vascular injury (0.8%). Thirty-day all-cause mortality was 2.5%. As a follow-up to EXTRACT-PE, STRIKE-PE ²² is an ongoing single-arm study of the Indigo device for the treatment of PE in 600 patients with primary endpoints including composite MAEs and change in RV/LV ratio. The study is anticipated to complete enrollment in September 2024.

Another mechanical thrombectomy system which is also indicated for the treatment of PE is the FlowTriever system ( Fig. 3 , Inari Medical, Irvine, CA), which allows for a combination of manual aspiration thrombectomy through a Triever Aspiration Catheter (which comes in 16, 20, and 24F versions, with a highly curved version of the 20F catheter [Triever20 Curve] available, as well) using a 60-mL large bore “smart locking” syringe to generate negative pressure, and mechanical thrombectomy using self-expanding nitinol mesh disks to “engage, disrupt, and deliver clot to the Triever Aspiration Catheter for extraction.” ²³ The first-generation FlowTriever catheter comes in four sizes (small, medium, large, and extra-large), but a second-generation FlowTriever catheter is anticipated, which simplifies the choice to a sole product, though the FlowTriever 2 is as of now only indicated for use in the peripheral vasculature. For use with the FlowTriever system, the FlowSaver blood return system is a device designed to reduce blood loss by filtering thrombus from blood through a 40-μm filter, allowing return of the filtered blood products to the patient. Finally, the FlowStasis suture retention device is often used with the system after the procedure is complete, when a figure-of-8 stitch is often placed to provide hemostasis. The benefits of the use of this device over a traditional three-way stopcock or simply suturing the figure-of-8 stitch are patient comfort and ease of removal.

Fig. 3.

FlowTriever system.

The initial steps for use of the FlowTriever system are like those used for advancing Indigo. After advancing the supportive wire, as described above, the femoral sheath is exchanged for a larger sheath (historically a 33-cm long Gore DrySeal, usually in a 22F or 24F size, though a new Inari sheath, Intri24, is now available, which is a 33-cm hydrophilic introducer sheath). Through this, over the 0.035” wire, the Triever Aspiration Catheter is advanced over an included dilator until it is either just proximal or is engaged with the thrombus. Manual aspiration using the 60-mL locking syringe is then performed, with a series of “whooshes,” each of which is a rapid volume-limited aspiration that draws in thrombus. After three “whooshes,” the device is slowly retracted under negative pressure until the thrombus clears the catheter into the attached syringe, or the entire device is removed from the body and the “corked” thrombus cleared from the catheter (usually necessary only when a large amount of thrombus is engaged, as may happen with proximal PE). The resulting blood and thrombus mixture is then filtered through the FlowSaver, and the filtered blood is returned to the patient through the sidearm of the femoral venous sheath. Throughout this process, the 0.035” wire is maintained in the distal PA, allowing for readvancement over the dilator so that repeat treatments can be performed. Once all clot is removed, through the Triever catheter, a directional catheter (again, usually a JR4, multipurpose, or HH1) is advanced, the stiff wire is exchanged for a soft wire, and a different lobe is selected, if desired. After advancing the directional catheter over the soft wire, the stiff wire is readvanced, the directional catheter is removed, and the Triever catheter is advanced over its dilator. The same process is then repeated to remove thrombus. If the thrombus is especially adherent to the vessel wall, the FlowTriever disks are advanced over the same 0.035” wire and are unsheathed in thrombus to perform mechanical thrombectomy. The disks are allowed to sit in the thrombus for 2 to 3 minutes, at which time they are retracted into the Triever catheter under aspiration, when “whooshes” are performed or the catheter is removed from the body and the thrombus cleared. Once thrombus removal is complete, the device and sheath are removed, and closure is either achieved via a preclosure technique, a figure of 8 stitch (using the optional FlowStasis device), or manual compression.

The FLARE study was the IDE trial describing the use of the FlowTriever system for PE treatment; this was published in 2019. ²⁴ FLARE prospectively enrolled 106 patients at 18 U.S. centers with submassive PE (patients with signs/symptoms of less than 2 weeks' duration, systolic blood pressure over 90 mm Hg, heart rate under 130, right ventricular dilation [RV/LV ratio > 0.9]). Most patients were male, averaged around 55 years of age, and were mostly white. sPESI was 0 in 55.8% and 1 in 44.2%. Note that 59.6% had elevated troponin, 72.4% had elevated natriuretic peptides, and 9.6% had prior PE. Femoral venous access was used in all procedures, and technical complications (kinking) occurred in 1.9% of patients. Note that 1.9% of patients received thrombolytics after thrombectomy due to large thrombus burden. Average ICU stay was 1.5 ± 2.1 days, and hospital LOS was 4.1 ± 3.5 days. Also 41.3% of patients did not require any ICU stay. At 48 hours, the RV/LV ratio was reduced by 25.1%, and mean PA pressures fell immediately on the table from 29.8 to 27.8 mm Hg ( p  = 0.001). Note that 3.8% of patients experienced MAEs within 48 hours, none of which were adjudicated to be device related; one had pulmonary vascular injury leading to one major bleeding event, two had respiratory deterioration requiring intubation, and one patient had a ventricular fibrillation arrest requiring cardioversion/intubation, at which time a ST-elevation myocardial infarction was diagnosed and treated. Thirty-day mortality was 0.9% (due to respiratory failure from metastatic breast cancer).

The follow-up to FLASH, FLARE is an ongoing single-arm registry of the FlowTriever system in 1,000 patients with acute PE, studying composite MAE at 48 hours with individual components of the MAE, all-cause mortality, and device-related SAEs as secondary endpoints. ²⁵ Interim results have been published that examine the first 250 patients treated from 19 sites. ²⁶ As seen in other trials, most were male, and the average age was 60.9 years. Note that 93.2% of patients were intermediate risk, with 85.8% of those being classified as intermediate-high. Also 6.8% had massive pulmonary emboli. sPESI was 0 in 15.7 and ≥ 1 in 84.3%. Femoral access was used in 98.8%, with one patient (0.4%) having an access site complication. Median thrombectomy time was 46 minutes, with a median estimated blood loss (EBL) of 255 mL. Note that 4.8% of patients received adjunctive treatments. And 43.2% of patients went to the ICU after the procedure, with a median postprocedure ICU LOS of 0.0 days, and an overall median postprocedure hospital LOS of 3.0 days. Forty-eight-hour all-cause mortality was 0%, and 30-day mortality was 0.4% (an 80-year-old woman who passed from septic shock and ischemic bowel). The composite MAE rate was 1.2%, with all being major bleeds (none were intracerebral hemorrhages). Acute reduction in mean PA pressure was 22.2% (31.9 ± 8.3 to 24.8 ± 8.6 mm Hg) and heart rate was 12.6% (101.4 ± 15 to 87.9 ± 13.3 beats per minute), with improvement in RV stroke work index noted as well (8.4 ± 4.9 to 7.0 ± 8.3 g·m/m ² , –15.5%). RV/LV ratio decreased by 28.3% at follow-up, with improvement in RV systolic function noted, as well. Six percent of patients were readmitted to the hospital within 30 days, but only one was due to the patient's PE (readmitted with recurrent hemoptysis).

A larger FLASH data set was presented at the Transcatheter Cardiovascular Therapeutics in 2021, ²⁷ though this is yet to be fully published, reporting on the results from the first 500 patients treated with the FlowTriever system. Still, over 93% of patients had intermediate risk PE, average sPESI was 1.6, and 95.4% had abnormal biomarkers. Access site complications remained at 0.4%, median device time improved to 43 minutes, and median EBL was stable at 260 mL. Adjunctive therapy was used in 3.8% of patients, and both postprocedure median ICU and hospital LOS remained 0.0 and 3.0 days, respectively. Note that 63.1% of patients had no overnight ICU stay. The 48-hour MAE rate was 1.4% (6 major bleeds, 1 procedure-related event). All-cause mortality at 30 days was 1.3% (48 hours was 0.2%), and 6-month mortality was 8.6%. Mean PA pressure was again noted to improve on the table (23% decrease), with improvement in heart rate and oxygen requirement also noted at 48 hours. RV/LV ratio and RV systolic function improved as well, as seen in the 250-patient analysis. The 30-day readmission rate was 6.2% overall, with 1.3% related to treatment of PE. Finally, 6-month dyspnea score (modified Medical Research Council) and quality of life (PEmb-QoL frequency of complaints) were significantly improved when compared with baseline and 48 hours after the index procedure, respectively, 1.6% of patients had been diagnosed with chronic thromboembolic pulmonary hypertension, and 1.5% had been diagnosed with chronic thromboembolic disease at the time of 6-month follow-up.

Two additional trials are ongoing examining the role of the FlowTriever system in the treatment of PE. The FLAME trial ²⁸ is a prospective nonrandomized study of patients with massive PE, comparing the “composite incidence of all-cause mortality, clinical deterioration, bailout, and major bleeding” from the time of treatment to discharge (or 45 days, whichever is sooner) for 71 patients in the FlowTriever arm compared with a literature-based performance goal. In addition, at least 71 (up to 142) patients undergoing other non-FlowTriever treatments will also be enrolled in a Context arm. The other ongoing trial is PEERLESS, ²⁹ which is a randomized, controlled trial of FlowTriever versus catheter-directed thrombolytics in patients with intermediate-high risk PE. A total of 550 patients will be randomized to treatment with either FlowTriever or CDT, with another 150 patients who have an absolute contraindication to lytics enrolled in a nonrandomized cohort. The primary outcome is a win ratio at discharge, consisting of a composite of all-cause mortality, intracranial hemorrhage, International Society on Thrombosis and Haemostasis major bleeding, clinical deterioration and/or bailout, and ICU admission/ICU LOS. The first PEERLESS patient was enrolled in early 2022, and the study is actively enrolling in both the U.S. and EU.

There are several devices that are either not yet commercially available or are not yet FDA approved for the treatment of PE. The WOLF device ( Fig. 4 , Boston Scientific) is a mechanical thrombectomy catheter-within-a-catheter that uses a woven sleeve that comes from an inner catheter as a conveyor to pull clot from the blood vessel into an outer catheter for removal. ³⁰ The WOLF device has been FDA approved since 2019 but is currently only indicated for the removal of thrombus from peripheral arteries.

Fig. 4.

The WOLF device.

The JETi Thrombectomy System ( Fig. 5 , Abbott Laboratories, Abbott Park, IL) is a device that uses a high-pressure jet of saline to break up thrombus, facilitating removal. ³¹ The JETi, too, currently has an indication for use only in the peripheral vasculature, with specific contraindications for use in the “coronary, pulmonary, and neurovasculature.” ³²

Fig. 5.

JET1 thrombectomy system.

The first of two products from AngioDynamics, the AlphaVac ( Fig. 6 ) is a mechanical aspiration device that is currently indicated for removing thrombus from the venous system. This is assembled at the table, comprised of a handle (service as the vacuum source), a 22F aspiration catheter, an obturator, and a waste bag. ³³ In case reports, the ease of use and minimal blood loss are noted to be benefits of the AlphaVac when compared with other devices. ³⁴

Fig. 6.

The Alpha-Vac.

The AngioVac is an extracorporeal bypass machine that is used to remove fresh, soft thrombi/emboli; aspirated blood is reinfused back into the patient's body after being filtered to minimize blood loss. ³⁵ The system is relatively bulky, and use of the AngioVac requires a perfusionist, which limits its availability in many centers.

Mechanical Circulatory Support in the Management of PE

The history of extracorporeal membrane oxygenation (ECMO) was born from the experience of Dr. John Gibbon, helpless to save a patient with PE, inspiring him (together with his wife) to develop a freestanding roller pump that would make possible extracorporeal support. The use of mechanical circulatory support in PE remains in a state of soft evidence-base. However, the more than 700% increase in utilization in ECMO in the U.S. between 2002 and 2012 has translated to greater collective experience in the use of extracorporeal support for patients presenting with unstable PE. ³⁶ In the management of PE, venoarterial ECMO is generally preferred to bypass the pulmonary circulation and decompress the RV. In a retrospective analysis of 180 high-risk PE patients in France between 2014 and 2015 with refractory cardiogenic shock, the 30-day mortality in patients receiving ECMO and conventional anticoagulation was 77% as compared with 29% in patients in whom there was deployment of ECMO in conjunction with surgical embolectomy. ³⁷ Interestingly, the 30-day mortality in those receiving systemic fibrinolysis with ECMO support was 76.5%. Therefore, the risk of death was more than two times higher when surgical embolectomy was not used. This analysis is limited in that catheter-based thrombectomy technologies were not included and it is unknown if the results with these less invasive methods would provide a similar or better outcome than surgical embolectomy.

In addition to ECMO, various forms of right ventricular assist devices (RVADs) have been used to treat right heart failure developing as a consequence of PE. These include Impella RP (ABIOMED, Danvers, MA), TandemHeart pVAD (LivaNova PLC), and CentriMag Circulatory Support System (Abbott). As of 2020, the literature only included a total of 17 patients with PE treated with an RVAD, with these communications being in the form of case reports. To date, no randomized trial has been performed exploring RVAD performance and outcomes in PE.

Surgical Pulmonary Embolectomy

Historically, surgical pulmonary embolectomy (SPE) was the preferred treatment for massive PE with hemodynamic compromise. SPE requires cardiopulmonary bypass and sternotomy, and not all health care facilities have cardiac surgery programs and are able to perform SPE. The procedure is also high risk, associated with significant morbidity and cost. SPE is not the focus of this article, as it is discussed in detail elsewhere in the journal.

Conclusion/Future Directions

Systemic lysis, CDT, and mechanical thrombectomy have largely replaced SPE in our center and in many other hospitals. The currently available percutaneous thrombectomy devices include the Inari FlowTriever and the Penumbra Indigo System. Neither has randomized controlled data comparing their use to either SPE, systemic thrombolysis, or systemic anticoagulation. These tools, though, have become an important part of the interventional armamentarium for the treatment of massive and submassive PE, particularly in patients for whom thrombolytics are contraindicated. Additionally, through the use of mechanical circulatory support, we hope to support our sickest patients to allow recovery of cardiac function in conjunction with anticoagulation, thrombolytics, or thrombectomy. Further research, especially with randomized trials, will continue to help elucidate the role of these therapies in the broader patient population.