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Background: 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: 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: A total of 133 patients were included (mean age, 58.3 years; 44% women; 29% catheter-directed thrombolysis; 68% mechanical thrombectomy; and 3% both). The median time to intervention was 6.1 hours in the early group and 20.8 hours in the delayed group ( P <0.001). A total of 16 patients (12% of patients) experienced the primary composite outcome. Early CBT was associated with a significantly lower rate of the primary composite outcome (4% versus 18%; log-rank P <0.001; inverse probability of treatment weighting [hazard ratio, 0.13 (95% CI, 0.03-0.58); P =0.007]) and secondary composite outcome (0% versus 9%; log-rank P =0.02). The early CBT group also had lower intensive care unit (3.0 versus 3.4 days; P =0.01) and hospital length of stay (5.0 versus 6.1 days; P =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: 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., Competing Interests: Dr Taslakian is a consultant for Advarra and Siemens. Dr Bangalore is on the advisory board of and is a consultant for Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, Shockwave, REATA, Inari, Imperial Health, and Argon. The other authors report no conflicts.

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: 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: 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., (© 2024 Wiley Periodicals LLC.)

Background and Aims: Patients with intermediate-risk pulmonary embolism (PE) commonly present with a significantly reduced cardiac index (CI). However, the identification of this more severe profile requires invasive hemodynamic monitoring. Whether inferior vena cava (IVC) contrast reflux, as a marker of worse right ventricular function, can predict invasive hemodynamics has not been explored., Methods: This was a single-center retrospective study over a 3-year period of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization. CT pulmonary angiograms were reviewed, and contrast reflux was graded as no/minimal reflux (limited to the IVC) or substantial (opacification including hepatic veins) based on an established scale., Results: Substantial contrast reflux was present in 29 of 85 patients (34 %) and associated with a lower CI (1.8 ± 0.4 L/min/m 2 v. 2.6 ± 1.0 L/min/m 2 , p < 0.001), higher pulmonary artery systolic pressure (53.2 ± 19.5 mmHg v. 44.0 ± 12.1 mmHg, p = 0.025), and worse right ventricular systolic function. An IVC contrast reflux grade > 3 was a significant predictor for a CI ≤2.2 L/min/m 2 (OR: 22.5, 95 % CI: 4.8, 104.4, p < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for substantial contrast reflux for a CI ≤2.2 L/min/m 2 were 62.6 %, 93.1 %, 94.6 %, and 56.2 %, respectively. These findings remained significant in a multivariable model and were similar when isolating for intermediate-risk patients (n = 72, 85 %)., Conclusions: The degree of contrast reflux is highly specific for a reduced cardiac index in PE even when isolating for intermediate-risk patients. Real-time prediction of a hemodynamic profile may have added value in the risk-stratification of PE., Competing Interests: Declaration of competing interest Sripal Bangalore - Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, Argon. JMH - funding from Inari Medical. EY, RSZ, PZ, Samuel Bernard, AAG, RP, VM, KH, LE, CLA, NMK report no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to compare the hemodynamic impact and clinical outcomes of saddle vs non-saddle pulmonary embolism (PE)., Methods: This was a retrospective analysis of clinical characteristics and outcomes among patients with saddle and non-saddle PE within a cohort referred for catheter-based thrombectomy (CBT) with invasive hemodynamic assessments. Patients who underwent CBT between August 2020 and January 2024 were included. The primary outcome was the proportion of patients with a low cardiac index (CI less than 2.2 L/min/m²). Secondary outcomes included 30-day mortality, intensive care unit (ICU) length of stay (LOS), and hospital LOS., Results: A total of 107 patients (84 intermediate risk, 23 high-risk; mean age 58 years, 47.6% female) were included in the study, with 44 patients having saddle PE and 63 having non-saddle PE. There were no significant differences in baseline demographics and clinical characteristics between saddle and non-saddle PE, including rates of high-risk PE (25% vs 16%, P = .24), rates of RV dysfunction, pulmonary artery systolic pressure (55 vs 53 mm Hg, P = .74), mean pulmonary artery pressure (34 mm Hg vs 33 mm Hg), low cardiac index (56% vs 51%, P = .64), rates of normotensive shock (27% vs 20%, P = .44), or Composite Pulmonary Embolism Shock scores (4.5 vs 4.7, P = .25). Additionally, 30-day mortality (6% vs 5%, P = .69), ICU LOS, and hospital LOS were similar between the groups., Conclusions: Among patients undergoing CBT, there were no significant differences in invasive hemodynamic parameters or clinical outcomes between those with saddle and non-saddle PE.

Background: Patients with intermediate-risk pulmonary embolism (PE) and normotensive shock may have worse outcomes. However, diagnosis of normotensive shock requires invasive hemodynamics. Our objective was to assess the predictive value of McConnell's sign in identifying normotensive shock in patients with intermediate-risk PE., Methods: Patients with intermediate-risk PE who underwent percutaneous mechanical thrombectomy between August 2020 and April 2023 at a large academic public hospital were included in the study. Normotensive shock was defined as systolic blood pressure ≥ 90 mmHg without vasopressor support with pre-procedural invasive measures of cardiac index ≤2.2 L/min/m 2 and clinical evidence of hypoperfusion (i.e. elevated lactate, oliguria). The primary outcome was the association between McConnell's sign and normotensive shock., Results: Those with McConnell's sign (29/40, 72.5 %) had higher heart rate (114 vs 99 beats/min, p = 0.008), higher rates of elevated lactate (86 % vs 55 %, p = 0.038), lower cardiac index (1.9 vs 3.1 L/min/m 2 , p = 0.003), and higher rates of normotensive shock (76 % vs 27 %, p = 0.005). McConnell's sign had a sensitivity of 88 % and specificity of 53 % for identifying intermediate-risk PE patients with normotensive shock. Patients with McConnell's sign had an increased odds (odds ratio 8.38, confidence interval: 1.73-40.53, p = 0.008; area under the curve 0.70, 95 % confidence interval: 0.56-0.85) of normotensive shock., Conclusion: This is the first study to suggest that McConnell's sign may identify those in the intermediate-risk group who are at risk for normotensive shock. Larger cohorts are needed to validate our findings., Competing Interests: Declaration of competing interest Dr. Sripal Bangalore - Advisory board - Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, Argon. Dr. Allison Greco - Board Member of ABIM Critical Care., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Right ventricular-pulmonary arterial coupling describes the relation between right ventricular contractility and its afterload and is estimated as the ratio of the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) by way of echocardiography. Whether TAPSE/PASP is reflective of invasive hemodynamics or occult shock in acute pulmonary embolism (PE) is unknown. This was a single-center retrospective study over a 3-year period of consecutive patients with PE who underwent mechanical thrombectomy and simultaneous pulmonary artery catheterization with echocardiograms performed within 24 hours before the procedure. A total of 70 patients (81% intermediate risk) had complete invasive hemodynamic profiles and echocardiograms, with TAPSE/PASP calculated. The optimal cutoff for TAPSE/PASP as a predictor of a reduced cardiac index (CI) (CI ≤2.2 L/min/m 2 ) was 0.34 mm/mm Hg, with an area under the curve of 0.97 and sensitivity, specificity, positive predictive value, and negative predictive value of 97.3%, 90.9%, 92.3%, and 96.8%, respectively. Every 0.1 mm/mm Hg decrease in TAPSE/PASP was associated with a 0.24-L/min/m 2 decrease in the CI. This relation was similar when restricted to intermediate-risk PE. The TAPSE/PASP ratio was predictive of normotensive shock with an odds ratio of 2.63 (95% confidence interval 1.42 to 4.76, p = 0.002) per unit decrease in the ratio. In conclusion, in patients with acute PE who underwent mechanical thrombectomy, TAPSE/PASP was a strong predictor of a reduced CI and normotensive shock. This means that noninvasive point-of-care assessment of hemodynamics may have added value in PE risk stratification., Competing Interests: Declaration of competing interest Dr. Bangalore reports being part of the advisory board for Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer (New York, New York), Merck, REATA, Inari, Truvic, and Argon. Dr. Horowitz receives funding from Inari Medical. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study explores the implementation and outcomes of catheter-based thrombectomy (CBT) for acute pulmonary embolism (PE) within a safety-net hospital (SNH), addressing a critical gap in the literature concerning CBT in underserved and vulnerable populations., Methods: This is a retrospective study of patients undergoing CBT between October 2020 and January 2024 at a SNH. The primary outcome was 30-day all-cause mortality., Results: A total of 107 patients (47.6 % female, mean age 58.4 years) underwent CBT for acute PE, with 23 (21.5 %) high-risk and 84 (78.5 %) intermediate-risk PE. Demographically, 64 % identified as Black, 10 % White, 19 % Hispanic or Latino, and 5 % Asian. In terms of insurance coverage, 50 % had private insurance or Medicare, 36 % had Medicaid, and 14 % were uninsured. Notably, 67 % of the patients resided in high poverty rate zip codes and 11 % were non-citizen non-residents. Over a median follow up period of 30 days, 6 (5.6 %) patients expired (all high-risk PE), 3 of whom presented with cardiac arrest. No patients who presented with intermediate-risk PE died at 30 days. There was no difference in 30-day mortality based on race, insurance type, poverty level or citizenship status., Conclusion: Our study findings reveal no disparities in access or outcomes to CBT at our SNH, emphasizing the feasibility and success of implementing PERT and CBT at a SNH, offering a potential model to address healthcare disparities in acute PE on a broader scale., Competing Interests: Declaration of competing interest Dr. Bangalore- Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without a clinically apparent shock. The purpose of this study is to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy., Methods and Results: This was a single-centre retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period. Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds [odds ratio = 7.9; 95% confidence interval (CI) 3.49-18.1, P < 0.001] for an elevated CO2 gap. There was an inverse relationship between the CI and the CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (P = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved the CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in the in-hospital mortality rate (9 vs. 0%; P = 0.10; hazard ratio: 1.24; 95% CI 0.97-1.60; P = 0.085)., Conclusion: Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to the CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification., Competing Interests: Conflict of interest: S.B.—advisory board—Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, and Argon. J.M.H.—funding from Inari Medical. The remaining authors report no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Data comparing catheter-based thrombectomy (CBT) and catheter-directed thrombolysis (CDT) in acute pulmonary embolism are lacking. To address this, we performed a meta-analysis of prospective and retrospective studies of CBT and compared it to performance goal rates of mortality and major bleeding from a recently published network meta-analysis. When compared with performance goal for CDT based on historical studies, CBT was noninferior for all-cause mortality (6.0% vs 6.87%; P-value NI < .001), non-inferior and superior for major bleeding (4.9% vs 11%; P-value NI < .001 and P < .001 for superiority)., Competing Interests: Conflict of interest Dr. Bangalore- Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic., (Copyright © 2024. Published by Elsevier Inc.)

Background: Our study aims to present clinical outcomes of mechanical thrombectomy (MT) in a safety-net hospital., Methods: This is a retrospective study of intermediate or high-risk pulmonary embolism (PE) patients who underwent MT between October 2020 and May 2023. The primary outcome was 30-day mortality., Results: Among 61 patients (mean age 57.6 years, 47% women, 57% Black) analyzed, 12 (19.7%) were classified as high-risk PE, and 49 (80.3%) were intermediate-risk PE. Of these patients, 62.3% had Medicaid or were uninsured, 50.8% lived in a high poverty zip code. The prevalence of normotensive shock in intermediate-risk PE patients was 62%. Immediate hemodynamic improvements included 7.4 mmHg mean drop in mean pulmonary artery pressure (-21.7%, p < 0.001) and 93% had normalization of their cardiac index postprocedure. Thirty-day mortality for the entire cohort was 5% (3 patients) and 0% when restricted to the intermediate-risk group. All 3 patients who died at 30 days presented with cardiac arrest. There were no differences in short-term mortality based on race, insurance type, citizenship status, or socioeconomic status. All-cause mortality at most recent follow up was 13.1% (mean follow up time of 13.4 ± 8.5 months)., Conclusion: We extend the findings from prior studies that MT demonstrates a favorable safety profile with immediate improvement in hemodynamics and a low 30-day mortality in patients with acute PE, holding true even with relatively higher risk and more vulnerable population within a safety-net hospital., (© 2024 Wiley Periodicals LLC.)

Bupropion is a substituted cathinone (β-keto amphetamine) norepinephrine/dopamine reuptake inhibitor andnoncompetitive nicotinic acetylcholine receptor antagonist that is frequently used to treat major depressive disorder. Bupropion overdose can cause neurotoxicity and cardiotoxicity, the latter of which is thought to be secondary to gap junction inhibition and ion channel blockade. We report a patient with a confirmed bupropion ingestion causing severe cardiotoxicity, for whom prophylactic veno-arterial extracorporeal membrane oxygenation (ECMO) was successfully implemented. The patient was placed on the ECMO circuit several hours before he experienced multiple episodes of hemodynamically unstable ventricular tachycardia, which were treated with multiple rounds of electrical defibrillation and terminated after administration of lidocaine. Despite a neurological examination notable for fixed and dilated pupils after ECMO cannulation, the patient completely recovered without neurological deficits. Multiple bupropion and hydroxybupropion concentrations were obtained and appear to correlate with electrocardiogram interval widening and toxicity., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Pires et al.)

Competing Interests: Disclosures Dr Bangalore was a participant in Advisory board—Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic. Dr Sharp was a consultant to Medtronic, Boston Scientific, Recor Medical, Penumbra, Philips. Dr Sethi participated in Honoraria/consulting at Boston Scientific, Chiesi, Janssen, Inari, Penumbra, Terumo. Dr Giri received research funds to the institution and advisory boards for Boston Scientific, Edwards, Inari Medical, Recor Medical, and Abiomed. Honoraria from Cordis, Inari Medical, Abiomed.

The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE., Competing Interests: Conflict of interest Dr. Bangalore- Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, Argon., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven., Objectives: The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure., Methods: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit., Results: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection., Conclusion and Relevance: Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

The adult heart responds to contraction demands by hypertrophy, or enlargement, of cardiac myocytes. Adaptive hypertrophy can occur in response to hyperoxic conditions such as exercise, while pathological factors that result in hypoxia ultimately result in heart failure. The difference in the outcomes produced by pathologically versus physiologically induced hypertrophy suggests that the cellular signaling pathways or conditions of myocytes may be different at the cellular level. The structural and functional changes in myocytes resulting from hyperoxia (simulated using hydrogen peroxide) and hypoxia (using oxygen deprivation) were tested on fetal chick cardiac myocytes grown in vitro. Structural changes were measured using immunostaining for α-sarcomeric actin or MyoD, while functional changes were assessed using immunostaining for calcium/calmodulin-dependent kinase (CaMKII) and by measuring intracellular calcium fluxes using live cell fluorescence imaging. Both hypoxic and hyperoxic stress resulted in an upregulation of actin and MyoD expression. Similarly, voltage-gated channels governing myocyte depolarization and the regulation of CaMK were unchanged by hyperoxic or hypoxic conditions. However, the dynamic features of calcium fluxes elicited by caffeine or epinephrine were different in cells subjected to hypoxia versus hyperoxia, suggesting that these different conditions differentially affect components of ligand-activated signaling pathways that regulate calcium. Our results suggest that changes in signaling pathways, rather than structural organization, may mediate the different outcomes associated with hyperoxia-induced versus hypoxia-induced hypertrophy, and these changes are likely initiated at the cellular level.