key: cord-0068108-ev5yp0rt
authors: Lewis, Alexander E.; Gerstein, Neal S.; Venkataramani, Ranjani; Ramakrishna, Harish
title: Evolving Management Trends and Outcomes in Catheter Management of Acute Pulmonary Embolism
date: 2021-10-04
journal: J Cardiothorac Vasc Anesth
DOI: 10.1053/j.jvca.2021.09.050
sha: 85d7d9d938bc856b49f2dbf2fe2a2f501ada05da
doc_id: 68108
cord_uid: ev5yp0rt

nan

Venous thromboembolism (VTE) and its resulting sequelae (pulmonary embolism (PE), chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome) are responsible for a significant number of hospitalizations in the United States with estimates of VTE affecting as many as 900,000 Americans annually. 1, 2 PE constitutes a large proportion of complications of VTE having an incidence of 0.95-per-1000 persons-per-year hospitalized in developed countries prior to the COVID epidemic. There are nearly 600,000 acute PE cases annually in the United States. 3, 4 Many of reports underestimate the concomitant increasing burden from COVID-19 patients in addition to subclinical cases. 5 The optimal management of PE treatment is based primarily on risk stratification and the given PE subtypes. Patients with a high bleeding risk or those with hemodynamic compromise lack a consensus treatment protocol despite recently published guidelines that highlight specific patients within this high-risk population. 6 Despite rapid advances in VTE treatment technology over the past decades, PE outcomes and mortality have remained relatively unchanged. 7 Furthermore, multiple studies continue to report a greater than 65% morbidity and mortality in many VTE scenarios especially when stratified by age. [8] [9] [10] Depending on the classification of the PE, mortality ranges from 1% for submassive PEs to over 65% for massive PEs. [11] [12] [13] Limited guidance of the management provided for acute interventional therapy of PE in part corroborates the controversial nature of the available and evolving therapies. Individual institutional guidelines and protocols further convolutes VTE and PE management consensus. 14, 15 This manuscript examines the most contemporary trials and studies centered on the advanced management, specifically catheter-directed therapies (CDTs), in the management of acute PE.

The term PE denotes mechanical (clot, air, tumor, or fat) obstruction to pulmonary blood flow by material originating from a distal location. PE has a broad clinical presentation ranging from asymptomatic to hemodynamic instability to sudden death. 14 Identifying the severity of PE based on the RV ventriculo-arterial compliance, hemodynamic instability and RV strain using imaging and clinical symptoms is crucial for determining necessary therapeutic interventions and prognostication. 14 See Table 1 for PE classification schema. Right heart failure due to acute increases in right ventricular (RV) pressure is the primary cause of death in massive PE and frequently occurs within the first few hours after presentation. 16 Massive PE is distinguished by the presence of hemodynamic instability defined by one of the following: cardiac arrest, persistent hypotension (systolic blood pressure (SBP) < 90 mmHg, ≥ 40 mmHg decrease in SBP from baseline for > 15 minutes, and not due to other etiology), or obstructive shock (either SBP < 90 mmHg or need for vasoactive drug support to achieve SBP ≥ 90 mmHg along with signs of end-organ ischemia (i.e. oliguria, lactic acidosis, altered mental status)). 16 Moreover, in massive PE, especially with signs or symptoms of RV failure, there is an increased risk of early death that persists up to 30 days after initial presentation. 16 Hence, patients presenting with massive PE necessitate a more aggressive treatment plan as compared to less severe forms of acute PE.

Submassive PE, associated with an intermediate-risk level of early mortality reported as high as 14%, is further subdivided into intermediate-high and intermediate-low subgroups. [17] [18] [19] In those with a confirmed PE but without hemodynamic instability (submassive), progressive RV dysfunction remains extant and requires further assessment as a means of determining needed management strategies and risk level. 16 It is important to highlight that a massive PE may not be limited only to central anatomic locations but may due to a high clot burden that is peripherally located(i.e. subsegmental). In addition, in patients with significant preexisting cardiovascular (CV) disease, known history of chronic thrombo-embolic pulmonary hypertension, pulmonary hypertension from other causes, lower clot burdens may precipitate hemodynamic instability as well. Hence, evaluation of patients with submassive PE should take into consideration signs of RV dysfunction, RV strain and patients' cardiopulmonary reserve emphasizing the upsurge in PERTs (Pulmonary Embolism Response Teams) to ensure adequate risk stratification and treatment pathways.

The initial pharmacological treatment of acute PE includes therapeutic anticoagulation using unfractionated heparin, or subcutaneous low-molecular-weight heparin followed by direct oral anticoagulants. 20 Massive PE and certain submassive PE subtypes (those with clinical deterioration causing worsening RV failure) have traditionally been treated with systemic thrombolysis (STT). However, major bleeding is one of the primary contraindications to using STT. The PEITHO trial is commonly used to define hemodynamic collapse, moderate bleeding, and severe bleeding as described in Table 2 21 . The rate of major bleeding (intracranial hemorrhage (ICH), extracranial bleeding needing transfusions/interventions) associated with STT has been estimated as high as 20% with a 2-3% risk of ICH. 22, 23 Predictors of bleeding include age, weight, gender, patients with end-organ damage, low hematocrit, previous ICH, and stroke. 24 Surgical pulmonary thrombectomy is an option for massive PE and submassive PE subtypes with a high-risk for hemodynamic collapse, those who cannot receive STT, those unstable after STT administration, or have failed therapy and in those with right heart thrombus at risk for left-sided embolization. 25 Surgical pulmonary thrombectomy while previously thought to have been associated with high mortality, has been shown to have improved mortality due to advances in surgical technique and shorter durations of cardiopulmonary bypass. 25 See Table 3 for a description of current PE therapies. Limited utilization of surgical embolectomy has led to interest in less invasive yet effective therapies in reducing clot burden in the pulmonary circulation.

Catheter-directed interventions have become an alternative to STT as an evolving therapy for acute PE patients while being able to mitigate the prohibitive bleeding risks with STT. The first catheter-based intervention to be approved in the United States was the Greenfield suction catheter (Medi-Tech/Boston Scientific, Watertown, MA, USA) which utilized suction to aspirate thrombus from the pulmonary arteries. 26 It was however quick to fall out of common use due to the bulky nature of the catheter necessitating a venous cutdown for its use.

Interventional therapies for acute PE can be classified into two major groups:

A. Mechanical thrombectomy / embolectomy a. Direct thrombectomy b. Suction/aspiration embolectomy

a. Ultrasound-assisted catheters b. Non-ultrasound assisted catheters Mechanical embolectomy refers to mechanical thrombus disruption using devices to reduce clot burden without infusion of lytic medications. This can be accomplished by direct thrombectomy, suction embolectomy, and aspiration embolectomy. Mechanical embolectomy is commonly performed with the Amplatz thrombectomy device (ATD) (Microvena, White Bear Lake, Minnesota) which consists of a 6 Fr or 8 Fr catheter with a 1 cm long metallic capsule at its end.

The capsule houses an impeller that is driven coaxially up to 150,000 rotations per minute by high air pressure (50 -100 psi). Negative pressure at the catheter tip draws adjacent thrombus into the end port of the capsule, where it becomes fragmented by the rotating blades. The fragmented thrombus is then expelled radially through two side ports, and cleaved particles are repeatedly aspirated, further macerating the thrombus. The thrombus is broken down to small particles of which are less than 13 µm in size. 27 Although characterized by good success rates in improving thrombus burden, lack of adequate directionality made this a less popular option in the management of acute PE. 28 Suction or aspiration embolectomy is accomplished by several different catheters systems:

A. Aspirex catheter (Straub Medical, Switzerland): is an 11 Fr device that aspirates thrombus through a flexible catheter tip. The catheter shaft contains a high-speed rotating coil, which creates negative pressure for aspiration and also serves to macerate clot that is brought into the catheter. 29 B. Angiovac system (Angiodynamics Inc., Latham, New York): The Angiovac cannula is a 22 Fr nitinol reinforced cannula with a length of 90 cm, an expandable funnel shaped distal tip, and a variable angulation of the tip. The expanded funnelshaped tip aids in suction aspiration of clot while being able to reinfuse suctioned 7 blood after passing through a filter serving as an extracorporeal bypass circuit. The disadvantages with the Angiovac apparatus include the large cannula size, hemodynamic perturbations from blood loss, need for an extracorporeal circulation and risk of right heart perforation due to due to the device's limited maneuverability. 30, 31 C. Penumbra Indigo System (Penumbra Inc., Alameda, California): 32, 33 The Penumbra system is a suction aspirator device that has a proprietary "smart" catheter tubing system that can adjust the suction applied across the catheter to establish suction. Sista et al evaluated the Penumbra system in a multi-center single-arm study that enrolled 119 acute submassive PE patients in the EXTRACT-PE study. 38 The primary safety endpoint was the rate of major adverse events (composite of device-related: death, major bleeding, and serious adverse events) at 48 hours. The authors found a mean reduction in the right ventricle (RV) / left ventricle (LV) ratio of 0.43 between baseline and at 48 hours post intervention (95%CI: 0.38 -0.47; p < 0.0001). 38 Rates of cardiac injury, pulmonary vascular injury, clinical deterioration, major bleeding, and device-related death at 48 h were 0%, 1.7%, 1.7%, 1.7%, and 0.8%, respectively. D. Flowtriever system (Inari Medical, Irvine, California): 34

The Flowtriever system is a combined aspiration and mechanical thrombectomy device. It is comprised of a set of distal nitinol mesh discs that are retracted after deployment distal to clot carrying with it an inherent advantage of being able to combine clot aspiration with mechanical removal. Newer iterations of this device with a longer catheter segment (up to 120 cm length) to clear distal clots is also 

Catheter-directed thrombolysis (CDT) is a technique of directing thrombolytic agents directly to affected pulmonary arteries to deliver higher effective concentration of thrombolytic drug in close proximity to the thrombus as opposed to systemic drug delivery. The benefit of CDT is enhanced local drug delivery at the target site as systemically administered drug could be maldistributed to unintended sites such as the systemic circulation or the non-diseased pulmonary artery in cases of unilateral pulmonary emboli. See Table 4 for a description of various CDT modalities.

CDT without ultrasound is a technique that involves using a 4 -5 Fr catheter such as The ULTIMA trial was a multicenter randomized controlled trial that enrolled 59 submassive PE patients to heparin alone (n = 29) versus US-CDT (n = 30). The primary outcome, a change in RV/LV ratio after 24 hours of therapy, was reduced in the ultrasound assisted thrombolysis utilizing tPA (tissue plasminogen activator, brand name Activase) group from 1.28 ± 0.19 to 0.99 ± 0.17 (p < 0.001) but not in the systemic heparin group (1.20 ± 0.14 to 1.17 ± 0.20, (p = 0.31)). At 90 days, bleeding events were not different between the heparin and US-CDT groups (3 in the US-CDT group and 1 in the heparin group; p = 0.61). The ULTIMA trial reported three non-ICHs defined as minor bleeds in the total study population.

The SEATTLE-II trial was a prospective, single-arm, multi-center trial that evaluated the efficacy of US-CDT using the EKOS system in 31 massive PE patients and 119 submassive PE patients using either 1 mg / hr for 24 hours by a single catheter or 1mg / hr / catheter for 12 hours with bilateral catheters (both groups received 24 mg total tPA). 38 The primary outcome was a change in RV/LV ratio from baseline to 48 hours and the primary safety outcome was major bleeding within 72 hours of intervention. The trial found improved RV/LV ratios in all 150 patients (1.55 vs. 1.13; p < 0.0001), improved mean pulmonary artery systolic pressures (51.4 mmHg vs. 36.9 mmHg; p < 0.0001), and improved Miller Index scores (22.5 vs. 15.8; p < 0.0001). The Miller index is composed of a score for arterial obstruction (objective score with 3 points for total occlusion and 0 points for no occlusion) and a score for reduction of the peripheral perfusion of the lungs (subjective evaluation). 40 The modified Miller score adds scoring for location of PE within the pulmonary artery with a point of 1 for periphery vasculature and a maximal score of 16 for central vasculature (i.e. saddle emboli). SEATTLE-II bleeding rates were lower than the previous PEITHO trial reporting extracranial bleeding occurring in 32 patients (6.3%) in the Tenecteplase group, the SEATTLE-II had the upper boundary of the 95% confidence interval on this estimate was 2.4% for full-dose STT with a single serious bleeding event reported (groin hematoma associated with hypotension) along with 15 patients experiencing a moderate bleeding event; there were no ICHs. 21, 41 The PERFECT trial was a prospective multicenter international registry in which the investigators examined the efficacy of CDT versus mechanical thrombectomy for massive (n = 28) and submassive (n = 73) PE patients. The primary outcome, described as 'clinical success', included meeting the following three end-points: a) stabilized hemodynamics (SBP > 90 mmHg without chemical support), b) improved pulmonary hypertension (systolic pulmonary artery pressure < baseline at presentation), right heart strain (as determined by qualitative echocardiography), or both, and c) survival to hospital discharge. The primary safety outcomes were procedure complications and major bleeding. All patients except one submassive PE patient (who under mechanical thrombectomy) received CDT with a mixture of both non-US-CDT (64%) and US-CDT (36%). Clinical success was achieved in 86% (95%CI: 67.3 -96.0%) massive PE patients and 97% (95%CI: 90.5 -99.7%) of submassive PE patients. Among those who underwent CDT, there were no reported major bleeding events and a 5.9% in-hospital mortality rate. 39 The OPTALYSE trial was a small randomized multicenter trial that examined the efficacy of lower thrombolysis dosing during US-CDT in 101 submassive PE patients compared to STT in PE patients using RV/LV ratio as a primary outcome. 37, 42 Patients were randomized to one of four arms of varying tPA dosing: a) 4 mg / lung / 2 hrs; b) 4 mg / lung / 4 hrs; c) 6 mg / lung / 6 hrs; d) 12 mg / lung / 6 hrs. The trial found a significant 25% improvement in RV/LV diameter ratio from baseline to 24 hours, as well as reduced clot burden as measured by the modified Miller score in all four arms when using lower doses (4 -12 mg / lung) and with shorter infusion times 2 -6 hours). 43 The bleeding risk was noted to be about 4% with two patients developing ICH in the trial group. Improvement in Miller scores was also seen in all groups. Additionally, of two ICH events, one was attributed to tPA delivered by USCDT. 42 The trial had the drawback of not having a control group with heparin alone to compare these findings with a group that did not receive US-CDT. Notably low dose heparin (300-500 U / hr) was continued during the treatment period with tPA via the US-CDT catheter.

In all four of the aforementioned trials, ULTIMA, SEATTLE II, PERFECT and OPTALYSE, there were no reported fatal ICHs, an improvement to the previous systemic therapy trials: PEITHO, MAPPET, MOPETT, and TOPCOAT (Table 5) . 21, [44] [45] [46] Only the SEATTLE II trial reported a complication of transfusion for extracranial bleeding. 38 All four of these studies were limited to a 90 day or less outcome period and none of these trials provide clear data on long-term outcomes of catheter-directed therapy compared to STT in these outcome periods.

Much of the current PE-related therapeutic investigations, particularly those involving CDTs, are focused on submassive PE therapies. In contrast to massive acute PE (mortality of > 50% without intervention) as well as low-risk PE scenarios that also require anticoagulation, submassive PE patients present a gray area with enough clinical equipoise in terms of enabling the study as to what is the optimal intervention in this context. Avgerinos ; relatively higher tPA doses were used in both these patients (~28 mg total). In the context of submassive PEs, as compared to a bleeding rate of over 11% in STT groups as reported in the PEITHO trial, the SUN-SET sPE trial bleeding rate of 2.5% supports CDT therapies as being associated with an overall lower bleeding risk. 21 One in-hospital death occurred on day 58 in a US-CDT patient attributed to hypersensitivity pneumonitis. 47 Criticisms of SUN-SET sPE include a lack of protocol standardization concerning for confounders affecting the primary outcome and its relatively small sample size and attendant low study power. 48 Various trials of CDT use in acute PE are currently underway that address prior trials' lack of randomization, lack of specific and meaningful clinical endpoints (i.e., long-term cardiopulmonary health as measured by a 6-minute walk distance or development of CTEPH), as well as risk-benefit ratios. 49 Completed in September 2020, the KNOCOUT-PE (An International Pulmonary Embolism Registry Using EKOS) trial included 1,500 subjects from 80 study locations to examine both retrospective data (those who had received US-CDT for PE) and prospective data (de-novo PE patients who ultimately received US-CDT as part of their therapy) where the EKOS system was chosen as the modality to treat both submassive and massive PE.

KNOCOUT-PE included a variety of primary outcome measures and in part were RV/LV ratio change at 24 and 48 hrs, persistent pulmonary hypertension at three months, other urgent interventions for index PE following US-CDT, need for US-CDT as an adjunct, serious adverse events (i.e., major bleeding), all-cause mortality, and various quality-of-life assessments.

KNOCOUT-PE findings are still pending. 50

The USAT-CDT (Standard vs Ultrasound-assisted Catheter Thrombolysis for Submassive Pulmonary Embolism) trial completed its enrollment in December 2020 which included 18 patients in a randomized, controlled, parallel design to compare US-CDT versus non-US-CDT in acute submassive PE patients. USAT-CDT's primary outcome is a reduction in thrombus as determined by CTA from baseline to 72 hours along with 17 various secondary outcomes (i.e., early, and late mortality, major and minor bleeding, RV/LV ratios, echocardiographic markers of RV dysfunction, 6-minute walk tests at three and six months, cost analyses, and various quality of life assessments). Results are still pending for USAT-CDT. 51

See Table 6 for current societal recommendations on the use of CDTs in the context of acute PE. Of note, the most current of these guidelines comes from the European Society of Cardiology published in 2019. As this present review has in part highlighted, a significant amount of new research has emerged addressing CDT use in PE; hence, even the most current published PE-related guidelines lag and have yet to assimilate the most recent data into their respective advanced PE treatment recommendations. Moreover, significant variation and ambiguity exists between the varying societal guidelines in part due to insufficient robust clinical trials examining key clinical endpoints as relate to catheter-based therapies.

Current societal guidelines recommend STT in addition to anticoagulation, but there is no single unified guideline or specific accepted set of guidelines for treatment of submassive PE and no expert consensus on the role of endovascular therapy in these clinical situations. This ambiguity has led to hospitals creating PERTs responsible for the identification and risk stratification of patients presenting with PE. 52, 53 Although the exact constituents of PERTs varies, the ultimate goal is to have an expert multidisciplinary team able to rapidly evaluate PE patients for medical, surgical, and endovascular therapies. Several recent studies analyzing the efficacy of PERTs have shown a significant increase in the utilization of STT and CDTs in massive PE and a decrease in intensive care unit length of stay and decrease in elapsed time from diagnosis to therapeutic anticoagulation following the creation of a PERT without a change in major bleeding or overall cost. 22, 42, [54] [55] [56] [57] PERTs also demonstrate a significant decrease in 30-day inpatient mortality when compared to hospitals without such (8.5% vs 4.7%, p = 0.03) 54-56 Many hospitals do not have the comprehensive surgical or endovascular facilities to implement the therapy indicated by a PERT compared to technically simpler STT and anticoagulation. 58 Due to system limitations, many facilities elect to use a bridging therapy to transfer acute PE patients to a referral center with capabilities of CDT and or surgical thrombectomy.

Extracorporeal membrane oxygenation (ECMO) has been used as a bridging therapy between failed STT and the need for advanced intervention. 59 By using ECMO, the RV can recover while the patient is transferred or prepared for definitive therapy such as CDT or surgical embolectomy. Veno-arterial (VA) -ECMO used in the context of acute PE provides hemodynamic support, oxygenation, and is a temporizing means during treatment of the underlying clot burden in parallel with RV function recovery. Nonetheless and in part due to a lack of controlled trials, 2019 ESC guidelines give VA-ECMO use in acute PE a low grade (IIb-C) recommendation and should be considered for select high-risk, hemodynamically unstable, or arrest PE patients. 16 Similarly, in the 2011 AHA PE management guideline paper, ECMO is not recommended; however, as part of the 2020 AHA ' Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care', ECMO use is given a '2b' recommendation and states that though there is lacking evidence for routine use of ECMO-assisted CPR (E-CPR), its use should be considered for select cardiac arrest patients especially if for reversible causes requiring limited durations of mechanical support. 60 A recent systematic review of VA-ECMO for cardiac arrest due to massive PE that included 301 patients from 77 publications, reported that the use of VA-ECMO led to improved outcomes with an overall survival rate of 61%; however, no descriptions of the combined use of VA-ECMO with catheter-directed thrombolysis (CDT) was noted in the cohort. 61 (12%) patients were treated with ultrasound-assisted CDT using the EKOS system. 63 Their primary outcome was in-hospital death and 90-day survival. Among the 6 patients in their ECMO + CDT cohort, the median ICU length of stay was 6 days (IQR 5 -6 days), hospital length of stay was 9 days (interquartile range 7 -11 days), and all patients survived to hospital discharge. 63 In a similar series, a single center report from George et al on 32 patients with similar baseline characteristics placed on VA-ECMO for massive PE over a three-year period, noted 21 patients (66%) survived to decannulation and 17 (53%) survived to hospital discharge. 64 Eleven of 15 patients in their series who received catheter-directed thrombolysis using the EKOS system survived to discharge in contrast to all five patients in the systemic thrombolysis group dying. ECMO was utilized beforehand in the CDT group in contrast to those receiving systemic thrombolytics who had ECMO initiation afterwards. Overall, the only baseline feature associated with non-survivors was a history of malignancy (p = 0.038). A pre-ECMO lactate level of ≤ 6 mmol/L had the greatest combined sensitivity (76.2%) and specificity (100%) for predicting the ability to successfully wean from ECMO and survive to discharge (sensitivity (82.4%) and specificity (84.6%)). 64 In a 2019 single-center case series, Al-Bawardy et al reported on 13 patients undergoing VA-ECMO for massive acute PE. 59 All 13 patients were in cardiac arrest upon presentation or had an in-hospital arrest prior to ECMO institution. Three patients (23%) received catheterdirected thrombolysis therapy with the EKOS system, 8 received systemic thrombolysis, one patient received both systemic thrombolysis and CDT, and four patients ultimately underwent surgical embolectomy (none of which were in the CDT group). For the entire cohort, 30-day mortality was 31% and one-year mortality 54%. In a single case report, combined VA-ECMO and CDT was utilized in a 27-year-old pregnant patient at 31 weeks-gestation with pre-existing CTEPH presenting with RV failure secondary to an acute massive PE. 65 Urgent cesarean section was performed under general anesthesia with vasoactive drug support only. Immediately after delivery, the patient's hemodynamic status deteriorated and VA-ECMO support was instituted followed by catheter-directed thrombolytic and localized suction embolectomy. The patient was successfully separated from ECMO on Day 4 and was discharged from the ICU on Day 23. 65 In select PE scenarios, the use of VA-ECMO and CDT in combination appears to be beneficial in terms of providing needed circulatory support while simultaneously treating the underlying pathophysiology. 66 Based on available series and reports, these combined interventions appear safe, associated with few complications, and may enable an optimal means in which to enable RV recovery after massive PE. However, until further investigation occurs on the use of this combined modality, it remains unclear in which exact patients and in which PE scenarios that combined ECMO, and CDT therapies should be the treatment of choice.

There has been tremendous research into the pathophysiology of acute PE including risk stratification and treatment modalities. Early intervention of acute PE with classical STTs is not always feasible or possible. STT nonetheless remains the mainstay of therapy given its rapid effect on the clot burden if decompensation or patient hemodynamics or bleeding risk allow.

Catheter-directed interventions (mechanical embolectomy and CDT) or surgical embolectomy are options in patients with a high bleeding risk. These interventions require a multidisciplinary approach (i.e. PERTs) to identify appropriate patients, risk stratify these patients, and provide appropriate therapies to these patients. PERTs facilitate the careful assessment of factors that elevate risk of decompensation, including signs of reduced organ perfusion, severe RV strain and dysfunction, and respiratory insufficiency. In patients without the above signs of hemodynamic deterioration or RV strain, there is no clear consensus for the use of catheter-directed interventions such as CDT. CDT has distinct advantages however it can be expensive, time consuming, and response to a therapy is often nonuniform among stratified patient cohorts.

In patients with submassive PE with clinical deterioration and signs of RV strain with an elevated bleeding risk, CDT may be considered. 14 Given the wide spectrum of catheter-therapy devices, the various mechanisms of action, and clinical indications, the decision to use advanced therapies must be decided by a case-by-case basis. 67 PERTs may serve as the platform in weighing the risk of endothelial injury, hemolysis, major and minor bleeding, intracranial 20 hemorrhage, and inherent procedural risk. Though CDT usage has increased, the EKOS system remains the only United States approved device for the treatment of acute PE. Robust highpowered prospective random control trials are needed to prove benefit in submassive PE and the results of current trials and studies are anticipated to aid in further treatment guidance. Study outcomes are needed that transcend the analysis of initial RV/LV dimension improvements to also include insight into various long-term clinical outcomes (6-minute walk test, mortality at 30, 90, 365 days) and whether the risks associated with a given treatment modality outweighs the potential benefit. It is imperative that CDT be considered with sound clinical judgement and risk stratification in equal stance to classic interventions.

Bankier Massive (high-risk) -Defined by hemodynamic instability.

-Highest risk of early mortality.

-Necessitates early and aggressive treatment.

Saddle -3% -6% of all PE.

-Embolic material at the bifurcation of main PA. 

Mechanical embolectomy Mechanical thrombus disruption using devices to reduce clot burden without infusion of any lytic medications.

Employs the venturi effect in enabling clot fragmentation and aspiration using a saline jet directed at the thrombus.

The catheter itself has an aspiration guide that can suction clots using negative pressure. 

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Incomplete echocardiographic recovery at 6 months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial

Benefit of combining quantitative cardiac CT parameters with troponin I for predicting right ventricular dysfunction and adverse clinical events in patients with acute pulmonary embolism

Indigo Aspiration System for Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial

Design and rationale of a randomized trial comparing standard versus ultrasound-assisted thrombolysis for submassive pulmonary embolism

Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis: 1-year follow-up data of a randomized-controlled trial

One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report

Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium

Heart Association; ECMO, extracorporeal membrane oxygenation

level of evidence; PE, pulmonary embolism; PERT, Pulmonary Embolism Response Team