Research Consensus Panel Follow-up: 8-Year Update on Submassive Pulmonary Embolism

Clinical Question

What is the current state of endovascular pulmonary embolism practice and the Pulmonary Embolism–Thrombus Removal with Catheter-Directed Therapy trial, now 8 years since the 2015 Research Consensus Panel?

Take Away Point

The article discussed the catheter-directed therapy (CDT) trials and their outcomes since the 2015 Research Consensus Panel. Catheter-directed lysis (CDL) studies showed reduction in RV/LV ratio but inconsistent major bleeding rates. Mechanical thrombectomy (MT) studies demonstrated safety and effectiveness but lack comparison to AC alone. PE-TRACT and other upcoming randomized clinical trials (RCT) will define role of CDT in submassive PE.

Reference

Research Consensus Panel Follow-up: 8-Year Update on Submassive Pulmonary Embolism. Sista et al. Journal of Vascular and Interventional Radiology, Volume 34, Issue 10, P1658-1663, 10.1016/j.jvir.2023.06.032

Study Design

Narrative Review

Funding Source

The authors of this article report grants and funding from various organizations, including the NIH, AngioDynamics, Cook Medical, Boston Scientific, Gore, Medtronic, Penumbra, Becton Dickinson, Philips, Cordis, Bayer, NHLBI, BMS, Janssen, and Pfizer.

Setting

United States

Figure 2
Completed, Enrolling, and Upcoming Randomized Controlled Trials

Summary

In 2015, a panel of 19 pulmonary embolism (PE) experts from multiple disciplines convened to discuss the current knowledge and determine the future questions that need to be answered. This article is a follow-up to the 2015 Research Consensus Panel (RCP), discussing what has changed since then. Several consequential studies of catheter-directed therapy (CDT) have been published, and two mechanical thrombectomy devices have been cleared by the FDA to treat PE. In addition, the PE-TRACT trial has begun enrolling patients.

Several catheter-directed thrombolysis (CDL) trials and studies have been published. The article briefly discusses trials such as the ULTIMA, SEATTLE II, OPTALYSE, RESCUE, PEERLESS, SUNSET, and CANARY. All of which evaluated different aspects of CDL, including dosing, duration, and associated thrombus clearance. Despite promising results reported in some studies, limitations, such as low power and variable dosing were noted. Most trials demonstrated a reduction in the right ventricular to left ventricular ratio with CDL. Major bleeding rates were inconsistent across the different trials, up to 10% in SEATTLE II. Some concluded no significant difference in outcomes between CDL and standard treatment of anticoagulation (CANARY). Of note, SUNSET demonstrated no difference in thrombus clearance or bleeding between US-assisted and standard CDL.

Mechanical thrombectomy (MT) serves as an alternative to CDL in treating PE. Since the RCP, several studies, including the FLARE and EXTRACT trials, have looked at the efficacy of MT. These studies specifically evaluated two FDA-cleared devices, the Flowtriever and the Indigo Aspiration System, respectively. Both of these have shown promising results in single-arm trials, including reduction in right ventricular to left ventricular ratio, similar to those of CDL in prior published studies, and low major adverse event rates. However, the studies were limited by low power and a lack of anticoagulation-only control groups. The PEERLESS II and STORM-PE trials aim to compare mechanical thrombectomy devices to anticoagulation alone.

The 2015 RCP emphasized the critical need for rigorous study of CDT for submassive PE. Two complementary randomized clinical trials are ongoing. The HI-PEITHO trial seeks to evaluate ultrasound-guided CDL plus anticoagulation versus anticoagulation alone. The second study, the PE-TRACT trial, stems from the 2015 RCP incorporating many of the clinical questions and goals discussed by the PE experts. It is a phase III, multicenter, randomized, open-label, 2-arm controlled clinical trial. The study will evaluate two primary outcomes: the first being physiologic outcomes measured by peak oxygen uptake during cardiopulmonary exercise testing at 3 months; the second being patient-reported functional outcomes measured at 12 months. The study aims to enroll 500 patients across 30-50 clinical sites in the US, with completion expected by the end of 2026. 

Commentary

This article is an informative narrative review of the current state of knowledge on submassive pulmonary embolism. The authors briefly outlined the specific questions identified by the RCP as high interest and high impact. Additionally, the authors described the primary outcomes and limitations of the studies that followed the 2015 RCP. Furthermore, the authors analyzed the study designs of the upcoming trials. As a narrative review and update to the 2015 RCP, this article effectively presents the current knowledge and upcoming research concerning submassive PE treatment. Moving forward, the next step would likely involve conducting a comprehensive systematic review to provide robust, objective data and insights in study design for future studies focusing on submassive PE. Overall, the authors accomplished their goal of providing a summary of the current state of knowledge on submassive PE as well as providing key insights into the future direction of research.

Post Author

Aric Patel, MS
OMS IV
University of New England
College of Osteopathic Medicine

Intraoperative Multivessel Embolization Reduces Blood Loss by Half Compared to Balloon Placement During Caesarian Hysterectomy for Placenta Accreta Spectrum

Intraoperative Multivessel Embolization Reduces Blood Loss and Transfusion Requirements Compared to Internal Iliac Artery Balloon Placement during Caesarian Hysterectomy for Placenta Accreta Spectrum

Clinical Question

Is prophylactic multivessel selective embolization (MVSE) safer and more effective than internal iliac artery occlusion balloon (IIABO) placement in patients undergoing caesarian hysterectomy for placenta accreta spectrum (PAS)?

Take Away Point

MVSE demonstrated more than 50% reduction in median blood loss compared to the IIABO along with significantly reduced percentage of cases requiring packed red blood cells transfusions and median number of cases used. However, the former demonstrated increased procedural time, radiation dosage, and contrast usage.

Reference

Berman Z, Boone C, Melber DJ, et al. Intraoperative Multivessel Embolization Reduces Blood Loss and Transfusion Requirements Compared to Internal Iliac Artery Balloon Placement during Cesarean Hysterectomy for Placenta Accreta Spectrum. Journal of Vascular and Interventional Radiology. 2023;34(11). doi:https://doi.org/10.1016/j.jvir.2023.07.024

Study Design

Retrospective, observation, and cohort studies ultimately comprising of 54 patients, 20 of which received embolization and 34 of which received balloon placement

Funding Source

No reported funding

Setting

Academic, Keck School of Medicine, Los Angeles, CA
Academic, Stanford University, Stanford, CA

Figure

Summary

Placenta accreta spectrum (PAS) has been associated with an increased risk of severe hemorrhage during delivery. Traditionally, it was managed by Caesarian section followed by hysterectomy, leaving placenta in situ in order to minimize hemorrhage. A meta-analysis of 13 studies consisting of over 800 patients demonstrated significantly lower mean estimated blood loss (EBL) among patients who underwent balloon-occlusion in internal iliac artery or infrarenal aorta compared to the patients in the control group who did not undergo any endovascular intervention prior to C-section. At present, no optional treatment strategies are available, and the authors of this paper set out to compare the safety and efficacy of multivessel selective embolization (MVSE) versus internal iliac artery balloon occlusion (IIABO).

The authors of this study performed a retrospective study. The researchers searched through the database from January 2010 to January 2021 of all the patients with PAS that underwent C-section, yielding 20 patients in the embolization group and 34 patients in the balloon-occlusion group. The primary endpoints of this study were EBL and transfusion requirements, with the secondary endpoints being fluoroscopic time, radiation doses, and IR procedural time. Adverse events were also recorded.

The results of the study demonstrated the following: Median EBL was significantly less in the MVSE group compared to IIABO group (713 mL versus 2 L, respectively). The percentage of cases requiring transfusion among embolization cases was 20% versus 65% in the balloon occlusion cases. These results were well within statistical significance. The embolization group demonstrated higher contrast usage, increased fluoroscopic times, and subsequently increased radiation dosages compared to the balloon occlusion group.

Despite the disadvantages of MVSE including increased procedural timing and radiation dosages on the patient, MVSE was shown by this study to be a safe and more effective alternative for the management of PAS patients undergoing Caesarian hysterectomy.

Commentary

The authors in this study were investigating the safety and efficacy of MVSE compared to IIABO in patients with PAS. The data demonstrated favorable results of the former when comparing EBL and transfusion requirements at the cost of fluoroscopy time and radiation dosage.

In my opinion, the advantages of potentially reducing adverse events and blood transfusion requirements outweigh the disadvantages posed by length of procedure time and radiation dosage, provided that optimal strategies are implemented to minimize radiation exposure. Additionally, MVSE was shown to be associated with decreased length of stay in the hospital, an important benefit to the patient and to the healthcare system in general.

Post author

Naeem Patel, DO
Radiology Resident, PGY4
Department of Radiology, Interventional Radiology Division
Hartford Hospital, Hartford, CT
@Naeemp7Patel

Pre-Procedural Intravenous Thrombolysis Does Not Change Function and Cognitive Outcome As Long As Thrombectomy is Performed within 6 Hours of Stroke Onset

Direct Thrombectomy versus Bridging Thrombectomy within 6 Hours of Stroke Onset: A Prospective Cohort Study on Cognitive and Physical Function Outcomes

Clinical Question

Are there significant differences in outcomes regarding the physical and cognitive function of patients with acute large vessel occlusion who underwent either direct thrombectomy or bridging thrombectomy (with intravenous thrombolysis prior to thrombectomy)?

Take Away Point

Patients with anterior circulation large vessel occlusions treated within 6 hours of symptom onset demonstrated comparable outcomes regarding physical and cognitive function with both direct thrombectomy or bridging thrombectomy.

Reference

Direct Thrombectomy versus Bridging Thrombectomy within 6 Hours of Stroke Onset: A Prospective Cohort Study on Cognitive and Physical Function Outcomes. Li, Bing-Hu et al. Journal of Vascular and Interventional Radiology, Volume 34, Issue 11, P1875-1881, 10.1016/j.jvir.2023.07.008

Study Design

Prospective, observational, cohort study

Funding Source

This study was supported by grants from Department of Sichuan Provincial Science and Technology and Bureau of Chengdu Science and Technology.




Figure 2
Comparison of modified Rankin Scale between direct thrombectomy and bridging thrombectomy

Setting

Academic Medical Center, Chengdu, China

Summary

Acute ischemic strokes (AIS) account for 69.6% of all strokes in China, with endovascular thrombectomy being the standard and effective treatment for patients with large vessel occlusion (LVO). However, the question of whether intravenous thrombolysis before endovascular thrombectomy has a role in patients with acute anterior circulation LVO remains controversial. Recognizing the inconsistent data and limited data on bridging thrombectomy’s effects on cognitive function, the authors conducted this prospective study to assess both physical and cognitive function in anterior circulation LVO patients undergoing direct or bridging thrombectomy within 6 hours of stroke onset.

A total of 125 patients with LVO of the anterior circulation, including the intracranial internal carotid, middle cerebral artery segment 1 and/or segment 2, were confirmed by computed tomography angiography (CTA) or digital subtraction angiography (DSA) and included in the study. The median age of the patients was 71.0 (24.0-95.0) years, and among them 60 were men. The median time interval between stroke onset and reperfusion was 348 minutes (150 - 1,295). Patients in the bridging group underwent thrombectomy after receiving a standard dose of intravenous alteplase (0.9mg/kg; 10% as a bolus followed by a 1-hour infusion) within 4.5 hours or intravenous urokinase (1,000,000-1,500,000 units) within 6 hours. Meanwhile, patients in the direct group solely underwent thrombectomy.

The study assessed physical function at the 3-month mark using the Modified Rankin Score (mRS), a 7-point global disability scale that ranges from 0 (no symptoms) to 7 (death). Cognitive function was evaluated at the 6-month mark using the Clinical Dementia Rating (CDR), which ranges from 0 to 3. A score of 0 indicating absence of symptoms, 0.5 indicating questionable dementia, 1 indicating mild dementia, 2 indicating moderate dementia, and 3 indicating severe dementia. Both mRS and CDT assessments were performed via telephone calls by two trained neurologists using a blinded method. Symptomatic intracranial hemorrhage (sICH) was defined as the presence of intracranial hemorrhage with neurologic deterioration of 4 or more points on the NIH stroke scale.

The study included 75 patients in the direct group and 50 patients in the bridging group. The study determined that the direct group exhibited shorter reperfusion times (323.0 [160.0-820.0 minutes) compared to the bridging group (390.0 [150.0-1,295.0] minutes). Analysis of the results found no statistically significant differences between the direct and bridging groups in terms of the percentage of patients with an mRS score of 0-2 (25.3% vs 22.0%, P=.83.) or 0-3 (37.3% vs 44.0%, P=.58), the incidence of sICH within 24 hours (17.3% vs 14.0%, P=.80), or 90-day all-cause mortality rates (36.3% vs 30.0%, P=.34). Furthermore, the proportion of patients with normal cognition at 6 months was comparable between the direct and bridging group. Additionally, the proportion of patients with post-stroke dementia was comparable between the direct and bridging groups (42.1% vs 22.6%, P=.12).

Conflicting outcomes from various RCTs has resulted in an ongoing debate surrounding whether intravenous thrombolysis should precede thrombectomy for acute LVO strokes. While some previously published studies favor direct thrombectomy, others conclude that direct thrombectomy is noninferior to bridging thrombectomy. This prospective cohort study demonstrated that both direct thrombectomy and bridging thrombectomy have comparable physical function outcomes. Additionally, the study demonstrated that the bridging group observed a trend of lower cognitive impairment, however, the results were not statistically significant. The authors noted that the presence of diabetes was associated with a lower CDR score, suggesting a potential influence of antidiabetic drugs on preserving cognitive function. Overall, the study findings indicate that direct thrombectomy is comparable to bridging thrombectomy in patients with acute LVO strokes treated within 6 hours in regards to physical and cognitive function.

Commentary

The study was appropriately designed and executed effectively. While the original sample size was appropriate, the study experienced a considerable number of deaths and losses to follow-up in both treatment groups, impacting the power of the study. The authors employed appropriate statistical tests, including the X2, Fischer exact test, and Mann-Whitney U test, to analyze the data. Given the conflicting results in the published literature regarding direct and bridging thrombectomy for the treatment of LVO strokes, this study aimed to compare the effects of both treatment modalities on physical and cognitive function to determine their relative efficacy. Although the study did not definitively establish a superior treatment modality it effectively demonstrated that both treatment options are comparable. The results, while not statistically significant, offer convincing data that could potentially impact clinical decision-making. Ultimately, the paper provides valuable evidence that can contribute to the ongoing discussion about the management of patients with acute LVO strokes. However, further research with a more robust study design, such as an RCT, a larger sample size, a more diverse patient population, and more diversity in clinical sites, could lead to more robust conclusions and potentially significant changes in patient care.

Post Author 

Aric Patel, MS
OMS-IV
University of New England
College of Osteopathic Medicine