Faculty Bibliography

BACKGROUND:Patients with intermediate-risk pulmonary embolism (PE) have outcomes worse than uncomplicated ST elevation myocardial infarction. Yet, no large-scale study has compared the outcomes of large-bore mechanical thrombectomy (LBMT) with anticoagulation alone (AC). The aim of this study was to compare the clinical outcomes among patients receiving LBMT vs AC alone. METHODS:This was a two-center retrospective study that included patients with intermediate-risk PE from October 2016 - October 2023 from the institution's Pulmonary Embolism Response Team (PERT) database. The primary outcome was a composite of 30-day mortality, resuscitated cardiac arrest or hemodynamic decompensation. Inverse probability of treatment weighting (IPTW) was used to balance covariates; Kaplan Meir curves and IPTW multivariable Cox regression were used to assess the relationship between treatment groups and outcomes. RESULTS:Of the 273 patients included in the analysis, 192 (70 %) patients received AC alone and 81 (30 %) patients received LBMT and AC. A total of 30 (10.9 %) patients experienced the primary composite outcome over a median follow-up of 30 days. The primary composite outcome was significantly lower in the group that received LBMT compared to those on AC alone (1.2 % vs 15.1 %, log-rank p < 0.001; adjusted HR: 0.02; 95 % CI: 0.002-0.17, p < 0.001) driven by a lower rate of 30-day all-cause mortality (0 % vs 7.3 %, log-rank p = 0.01), resuscitated cardiac arrest (0 % vs 6.8 %, log-rank p = 0.016) and new or worsening hemodynamic instability (4 % vs 11.1 %, log-rank p = 0.007). CONCLUSION/CONCLUSIONS:In this largest cohort to date comparing LBMT versus AC alone in acute intermediate-risk PE, LBMT had a significantly lower rate of the primary composite outcome including a lower rate of all-cause mortality when compared to AC alone. Ongoing randomized trials will test these associations.

BACKGROUND/UNASSIGNED:The aim of this study was to examine the impact of early versus delayed catheter-based therapies (CBTs) on clinical outcomes in patients with acute intermediate-risk pulmonary embolism (PE). METHODS/UNASSIGNED:This retrospective cohort study analyzed data from 2 academic centers involving patients with intermediate-risk PE from January 2020 to January 2024. Patients were divided into early (<12 hours) and delayed CBT (≥12 hours) groups. The primary outcome was a composite of 30-day mortality, resuscitated cardiac arrest, hemodynamic instability, and 90-day readmission. Secondary outcomes included a composite of 30-day mortality, resuscitated cardiac arrest, and hemodynamic instability. Inverse probability of treatment weighting was used to balance covariates. RESULTS/UNASSIGNED:=0.046). When patients were stratified by timing of CBT (early/late) and the composite PE shock score (high ≥3; low <3), all 16 patients who experienced the primary composite outcome had a high composite PE shock score, with 14/16 (87.5%) having a high composite PE shock score and delayed intervention. CONCLUSIONS/UNASSIGNED:Early CBT was associated with improved clinical outcomes in patients with acute intermediate-risk PE. The composite PE shock score may help identify patients who will benefit from early CBT. Further prospective studies are needed to validate these findings.

BACKGROUND:The recently published PEERLESS trial compared catheter-directed thrombolysis (CDT) and catheter-based thrombectomy (CBT) in acute pulmonary embolism (PE). However, it included a low proportion of patients with contraindications to thrombolytic therapy (4.4%), leaving uncertainty about how CDT would perform relative to CBT in a real-world cohort with higher bleeding risk. AIMS/OBJECTIVE:This study aims to address this gap by comparing real-world outcomes of CDT and CBT in patients with acute PE. METHODS:This retrospective analysis included patients who underwent CDT and CBT at two tertiary care centers from January 2020 to January 2024. The primary outcome was a composite of 30-day mortality, resuscitated cardiac arrest, or hemodynamic decompensation. Secondary outcomes included major bleeding and intracranial hemorrhage (ICH). Inverse probability treatment weighting (IPTW) was used to adjust for baseline variables. RESULTS:A total of 162 (mean age 58 years, 45.7% women, 17.3% high-risk, 28% contraindication to lytics, 28% CDT, 72% CBT) patients were included, with 12.4% patients experiencing the primary outcome. There was no difference in the rates of the primary outcome between CBT versus CDT (11.2% vs. 15.2%, IPTW HR: 0.80; 95% CI: 0.27-2.38, p = 0.69). CBT was associated with a lower risk of hemodynamic decompensation (5% vs. 21.7%, p = 0.036), major bleeding (7.8% vs. 17.4%, IPTW HR 0.26; 95% CI: 0.07-0.95, p = 0.042) and ICH (0 vs. 4.3%, p = 0.024) compared to CDT. CONCLUSION/CONCLUSIONS:Among a real-world cohort of patients with acute PE with higher bleeding risk than PEERLESS undergoing catheter-based therapies, CBT was associated with a lower rate of hemodynamic deterioration, major bleeding, and ICH with similar rate of primary composite outcome when compared with CDT. Additional randomized controlled trials are needed to validate these findings.

BACKGROUND/UNASSIGNED:In hemodynamically stable patients with acute pulmonary embolism (PE), the Composite Pulmonary Embolism Shock (CPES) score predicts normotensive shock. However, it is unknown if CPES predicts adverse clinical outcomes. The objective of this study was to determine whether the CPES score predicts in-hospital mortality, resuscitated cardiac arrest, or hemodynamic deterioration. METHODS/UNASSIGNED:Patients with acute intermediate-risk PE admitted from October 2016 to July 2019 were included. CPES was calculated for each patient. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation. Secondary outcomes included individual components of the primary outcome. The association of CPES with primary and secondary outcomes was evaluated. RESULTS/UNASSIGNED:=0.005). CONCLUSIONS/UNASSIGNED:In patients with acute intermediate-risk PE, the CPES score effectively risk stratifies and prognosticates patients for the prediction of clinical events and provides incremental value over baseline demographics and European Society of Cardiology intermediate-risk subcategories.

INTRODUCTION/UNASSIGNED:Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study. MATERIAL AND METHODS/UNASSIGNED:We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load. RESULTS/UNASSIGNED:While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p<0.05), while there was no such association with antibody levels in the systemic circulation. DISCUSSION/UNASSIGNED:Our data highlight the critical role of local adaptive immunity in the airways as a key defence mechanism against primary SARS-CoV-2 infection.

BACKGROUND/UNASSIGNED:Clot-in-transit is associated with high mortality, but optimal management strategies remain uncertain. The aim of this study was to compare the outcomes of different treatment strategies in patients with clot-in-transit. METHODS/UNASSIGNED:This is a retrospective study of patients with documented clot-in-transit in the right heart on echocardiography across 2 institutions between January 2020 and October 2023. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation. RESULTS/UNASSIGNED:=0.067). CONCLUSIONS/UNASSIGNED:In this study of CBT in patients with clot-in-transit, CBT or systemic thrombolysis was associated with a significantly lower rate of adverse clinical outcomes, including a lower rate of death compared with anticoagulation alone driven by the CBT group. CBT has the potential to improve outcomes. Further large-scale studies are needed to test these associations.

UNLABELLED:Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Single academic center. PATIENTS/METHODS:We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late). INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:= 0.523). CONCLUSIONS:Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.

OBJECTIVES/OBJECTIVE:This study sought to evaluate the efficacy and safety of tissue-plasminogen activator (t-PA) infused via a Pharmacomechanical catheter-directed thrombolysis (PM-CDT) device called the Bashir Catheter in intermediate-risk acute pulmonary embolism (PE) patients. BACKGROUND:Catheter-directed thrombolysis (CDT) has been associated with rapid recovery of right ventricular (RV) function. The Bashir catheter was developed for enhanced thrombolysis in large vessels like the pulmonary artery (PA) with lower doses of t-PA. METHODS:Patients with symptoms of acute PE with CT evidence of RV dilatation were enrolled. The Bashir Catheter was used to deliver 7 mgs of t-PA into each PA over 5 hours. The primary efficacy endpoint was the core laboratory assessed change in CTA-derived right ventricular/left ventricular (RV/LV) diameter ratio at 48 hours and the primary safety endpoint was serious adverse events including major bleeding at 72 hours. RESULTS:At 18 US sites, 109 patients were enrolled. The median device placement time was 15 minutes. At 48 hours after PM-CDT the RV/LV ratio decreased by 0.56 (33.3%: p<0.0001). The PA obstruction as measured by the Refined Modified Miller Index (RMMI) was reduced by 35.9% (p <0.0001). One patient (0.92%) had two serious adverse events (SAE) which included a retroperitoneal bleed (procedure-related) and iliac vein thrombosis (device-related). Two other procedure-related SAEs included epistaxis, and non-access site hematoma with anemia. CONCLUSIONS:PM-CDT with the Bashir endovascular catheter is associated with significant reduction in RV/LV ratio and a very low rate of adverse events or major bleeding in intermediate-risk acute PE patients. The notable finding was a significant reduction in PA obstruction with low dose t-PA. (Recombinant tPA by Endovascular Administration for the treatment of Submassive pulmonary embolism using pharmaco-mechanical Catheter directed thrombolysis for the redUction of thrombus burdEn - The RESCUE Study IDE # G200009 NCT - 04248868).

BACKGROUND:The impact of pulmonary embolism response teams (PERTs) on treatment choice and outcomes of patients with acute pulmonary embolism (PE) is still uncertain. OBJECTIVE:To determine the effect of PERTs in the management and outcomes of patients with PE. METHODS:PubMed, Embase, Web of Science, CINAHL, WorldWideScience and MedRxiv were searched for original articles reporting PERT patient outcomes from 2009. Data were analysed using a random effects model. RESULTS:16 studies comprising 3827 PERT patients and 3967 controls met inclusion criteria. The PERT group had more patients with intermediate and high-risk PE (66.2%) compared to the control group (48.5%). Meta-analysis demonstrated an increased risk of catheter-directed interventions, systemic thrombolysis and surgical embolectomy (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.74-2.53; p<0.01), similar bleeding complications (OR 1.10, 95% CI 0.88-1.37) and decreased utilisation of inferior vena cava (IVC) filters (OR 0.71, 95% CI 0.58-0.88; p<0.01) in the PERT group. Furthermore, there was a nonsignificant trend towards decreased mortality (OR 0.87, 95% CI 0.71-1.07; p=0.19) with PERTs. CONCLUSIONS:The PERT group showed an increased use of advanced therapies and a decreased utilisation of IVC filters. This was not associated with increased bleeding. Despite comprising more severe PE patients, there was a trend towards lower mortality in the PERT group.