BACKGROUND:Urine albumin-to-creatinine ratio (UACR) provides a reliable method for chronic kidney disease screening in patients with type 2 diabetes, yet its use remains underutilized. METHODS:The CKD-DETECT randomized clinical trial included outpatients ≥18 years with type 2 diabetes without UACR testing in the prior 12 months and no chronic kidney disease. Physicians were randomized to receive either an alert prompting UACR testing or no alert (control). The primary outcome was the proportion of UACR orders within 90 days. The secondary outcome was new chronic kidney disease stage 3-5 diagnoses. Tertiary outcomes were referral to a nephrologist and prescription of chronic kidney disease-related medications, and post-hoc outcomes were UACR ≥10 mg/g and ≥30 mg/g. RESULTS:Overall, 400 patients (mean age 64.7 years; 51.5% female) were included. UACR was ordered in 72 (36.0%) patients in the alert group vs. 23 (11.5%) in the control group (odds ratio [OR] 5.71; 95% confidence interval [CI] 2.58-12.64; P < 0.001). New diagnoses of chronic kidney disease occurred in 1 (0.5%) patient in the alert and 2 (1.0%) in the control group (OR 0.50, 95%CI 0.04-5.53; P = 0.570). There were no referrals to nephrologists or new prescriptions of chronic kidney disease-related medications. The alert group was associated with increased identification of UACR ≥10 mg/g (21.0% vs. 8.5%; OR 3.41; 95%CI 1.37-8.48; P = 0.008) and ≥30 mg/g (9.5% vs. 4.0%; OR 3.71; 95%CI 1.36-10.12; P = 0.011). CONCLUSION:The alert-based CDS program was associated with increased UACR testing and early detection of elevated albuminuria in patients with diabetes. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT05342545 (prospectively registered on April 18, 2022) FUNDING: This work was supported by a research grant from Bayer.

BACKGROUND:Practitioners recommending transcatheter aortic valve implantation (TAVI) currently lack reliable tools to predict periprocedural risk of ischaemic stroke. AIMS:We aimed to develop and internally validate a clinical risk score to accurately stratify this risk. METHODS:Using data from the nationwide, multicentre FRANCE-TAVI registry, we developed a clinical predictive risk score for 30-day ischaemic stroke post-TAVI using multivariable logistic regression analysis. The model was internally validated through cross-validation techniques. RESULTS:Among 62,747 patients, 1712 (2.7%) experienced ischaemic stroke within 30 days. Nine clinical predictors were identified: female sex, age >85 years, weight <60kg, symptomatic status, history of stroke or transient ischaemic attack, multiple (i.e. >1) episodes of acute heart failure, severe mobility reduction, diabetes and creatinine clearance <60mL/min. The resulting scoring model demonstrated good accuracy (Brier score 0.18), moderate discrimination (C-index 0.63) and excellent calibration as assessed by calibration plots, calibration-in-the-large and calibration slope. The score categorized patients into low - (90.2% of the population), intermediate - (8.0%) and high-risk (1.8%) groups. Observed stroke rates increased progressively across these groups, from 2.25% in the low-risk group to 6.51% in the intermediate-risk group and 10.10% in the high-risk group. CONCLUSIONS:This newly developed STRAT score is a clinical, practical and effective tool for predicting early ischaemic stroke in patients undergoing TAVI. It was derived and internally validated in the FRANCE-TAVI registry and may help tailor preventive strategies. Further studies are necessary to externally validate this score and evaluate its impact on clinical decision-making.

INTRODUCTION:Catheter-based interventions (CBI) have yielded promising data in selected patients with acute pulmonary embolism (PE). Despite growing clinical use, high-quality comparative evidence on the efficacy and safety of CBI, especially in relation to standard anticoagulation or systemic thrombolysis, is limited. As new randomized controlled trials (RCTs) rapidly accumulate, this living evidence synthesis will aim to systematically and continuously evaluate the comparative efficacy and safety of reperfusion strategies vs standard of care in patients with high- and intermediate-risk acute PE. METHODS:This living systematic review and meta-analysis will include RCTs comparing reperfusion strategies to standard of care in adult patients with high- or intermediate-risk PE. The primary analysis will pertain to trials that are powered and designed to assess hard clinical outcomes, such as death and hemodynamic deterioration. A secondary analysis will include additional studies reporting clinical outcomes, including those primarily evaluating hemodynamic or surrogate outcomes. Analyses will be stratified by PE severity (high- and intermediate-risk) and also conducted using a frequentist network meta-analysis framework. The review is ongoing, with new eligible trials added prospectively. RESULTS:As of the initial search on 28 May 2025, 23 RCTs are included. Thirteen additional ongoing trials were identified for future inclusion, including trials with clinical outcomes such as PEITHO-3, HI-PEITHO, PEERLESS II, PE-TRACT, and PRAGUE-26 for intermediate-risk PE, and CATCH-PE II, PERSEVERE, and TORPEDONL for high-risk PE. CONCLUSION:This living meta-analysis will offer continuously updated, comparative evidence on reperfusion strategies for acute PE, with a focus on informing the role of catheter-based interventions in clinical decision-making. REGISTRATION:PROSPERO: CRD420251207053. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251207053.

Background Upper extremity deep vein thrombosis (UEDVT) is common in patients with cancer. Data on recurrence and bleeding after cancer-associated UEDVT are limited. Objectives The objectives were to identify factors associated with venous thromboembolism (VTE) recurrence and bleeding in patients with cancer and UEDVT, overall and by cancer site, during and after anticoagulation. Methods We analyzed patients from the Registro Informatizado de Pacientes con Enfermedad TromboEmbólica (RIETE), an international, prospective, observational registry of objectively confirmed VTE. We estimated cumulative incidence functions at 6, 12, 18, and 24 months and used proportional subdistribution hazard models to assess associations. Analyses were performed during and after discontinuation, using a landmark at the day of discontinuation if anticoagulation was stopped within 180 days or at day 180 if anticoagulation continued more than 180 days. Results Of 5,195 patients with UEDVT, 2,210 had cancer. At 24 months, the cumulative incidence of recurrent VTE was 3.9% (95% CI: 3.1-4.9) in patients with cancer vs 2.5% (95% CI: 1.8-3.5) in those without cancer, and the cumulative incidence of bleeding was 6.8% (95% CI: 5.7-8.1) vs 4.3% (95% CI: 3.4-5.3), respectively (both P < 0.001). Among patients with cancer, 24-month recurrence varied by cancer site: lung, 6.4% (95% CI: 4.0-9.5); gastrointestinal, 4.0% (95% CI: 2.6-6.0); genitourinary, 3.6% (95% CI: 1.6-6.8); breast, 2.5% (95% CI: 1.2-4.5); and hematologic, 1.4% (95% CI: 0.5-3.4). During anticoagulation, lung cancer (subdistribution hazard ratio [sHR]: 10.1; 95% CI: 1.31-78.06) and younger age (per-year sHR: 0.97; 95% CI: 0.95-0.99) were associated with recurrence, whereas genitourinary cancer (sHR: 4.95; 95% CI: 1.16-21.17) and transient risk factors (sHR: 1.75; 95% CI: 1.16-2.64) were associated with bleeding. After anticoagulation discontinuation, 91 to 180 days (sHR: 0.49; 95% CI: 0.24-1.00) and more than 180 days (sHR: 0.35; 95% CI: 0.17-0.71) of anticoagulation were associated with lower recurrence vs 30 days or less. Conclusions Cancer-associated UEDVT carries higher risks of recurrence and bleeding than noncancer UEDVT. Lung cancer showed the greatest recurrence during treatment. Anticoagulation beyond 90 days was associated with a lower post-treatment recurrence. (Computerized Registry of Patients With Venous Thromboembolism [RIETE]; NCT02832245)

BACKGROUND:The simplified Pulmonary Embolism Severity Index (sPESI) is widely used for risk stratification in patients with acute symptomatic pulmonary embolism (PE). Electrocardiography (ECG) provides information on cardiac stress, including right ventricular (RV) stress, but is not included in current guidelines for PE risk stratification. METHODS:We analyzed 32,113 hemodynamically stable patients with acute symptomatic PE enrolled in the RIETE registry. ECGs obtained within 24h of diagnosis were classified as normal or abnormal according to predefined criteria. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day PE-related mortality and a composite endpoint of 30-day all-cause mortality, early hemodynamic deterioration, or need for escalated therapy. The prognostic performance of sPESI was compared with an ECG-augmented strategy (sPESI-ECG) using diagnostic accuracy metrics and multivariable logistic regression. A prespecified subgroup analysis was performed in patients with CT-assessed RV/LV ratio. RESULTS:An abnormal ECG was present in 63.1% of patients and was associated with more severe presentation and markers of RV dysfunction. Thirty-day mortality was higher in patients with abnormal vs normal ECG findings (5.4% vs 2.9%). For the primary outcome, sPESI-ECG showed higher sensitivity than sPESI alone (97.7% vs 94.5%) with lower specificity. Patients classified as low risk by sPESI-ECG represented a smaller subgroup with numerically lower 30-day all-cause mortality than those classified as low risk by sPESI (0.62% vs 0.82%). Findings were consistent in multivariable analysis and in the CT subgroup. CONCLUSIONS:Incorporating ECG findings into sPESI may help identify a smaller subgroup of patients at very low short-term risk.

Ankylosing spondylitis (AnkS) has been associated with an increased risk of venous thromboembolism (VTE). Data comparing VTE events in AnkS with other immune-mediated inflammatory diseases and non-inflammatory patients are lacking. This study aimed to compare clinical outcomes between VTE patients with AnkS, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and patients without inflammatory disease. We analyzed 112,539 VTE patients enrolled in the RIETE registry. A Greedy Nearest Neighbor Matching approach was used to select a comparable non-inflammatory VTE cohort. Outcomes included recurrent VTE, mortality, and major bleeding at 1 year, and were compared using Cox regression or sub-hazard models. Among the inflammatory-disease cohort of 2,427 VTE patients (mean age ± standard deviation, 64.1 ± 16 years, 41.4% males), 6.4% had AnkS, 50.6% had RA, 10.8% had SLE, and 32.2% had IBD. The matched population without inflammatory disease comprised 7,800 VTE patients. The rate of recurrent VTE was 11.5%, all-cause mortality 5.1%, and major bleeding 1.9% in AnkS patients. Similar rates were observed in patients with RA, SLE, or IBD. Recurrent VTE was significantly higher in AnkS patients than in the non-inflammatory group (HR, 7.43, 95% CI, 2.28–24.23). AnkS patients who discontinued anticoagulation earlier than 1 year experienced higher adverse outcomes (a composite of mortality, major bleeding, recurrent VTE) compared with those who pursued extended therapy. VTE patients with AnkS have clinical outcomes comparable to other inflammatory diseases but a significantly increased risk of recurrent VTE compared with non-inflammatory patients, suggesting that extended anticoagulation strategies may be warranted.

BACKGROUND AND OBJECTIVES:Fractional flow reserve (FFR) is a validated tool for assessing epicardial coronary stenosis. In myocardial infarction (MI), microvascular dysfunction may impair hyperemic flow, potentially affecting the interpretation of FFR measurement. The FLOVITA Study (NCT04818918) aimed to assess the impact of prior myocardial necrosis on absolute coronary blood flow and resistance using pressure wire-based continuous thermodilution. METHODS:This prospective pilot study included 40 patients undergoing coronary physiological assessment of the left anterior descending (LAD) artery between May 2021 and February 2024. Patients were stratified into two groups: recent anterior ST-elevation MI (n = 23) and controls without history or imaging evidence of MI (n = 17). Absolute coronary blood flow and microvascular resistance were measured using pressure wire-derived continuous thermodilution. This novel technique allows direct, operator-independent quantification of coronary flow and microvascular resistance, offering high reproducibility. Multivariable linear regression identified factors associated with absolute coronary blood flow. RESULTS:LAD absolute blood flow was significantly lower in the MI group compared to controls (0.169 ± 0.005 vs. 0.215 ± 0.05 L/min; p = 0.006), despite similar FFR values and macrovascular resistance. Infarct size and microvascular resistance were independently associated with reduced flow. Each 10% increase in infarct size was associated with a 0.01 L/min reduction in LAD flow (p = 0.026), while a 100 WU increase in microvascular resistance corresponded to a 0.02 L/min decrease (p < 0.001). CONCLUSION:The FLOVITA study is a proof-of-concept analysis suggesting that MI significantly reduces coronary blood flow through increased microvascular resistance. These findings underscore the importance of accounting for microvascular dysfunction when interpreting post-MI coronary physiology. Registered with ClinicalTrials.gov under the identifier NCT04818918.

Background: The relationship between obesity (defined as body mass index [BMI] >= 30 kg/m2) and mortality in venous thromboembolism remains controversial. Objectives: We aimed to compare outcomes after pulmonary embolism (PE) between patients with obesity and nonobese, nonunderweight patients. Methods: Using a multicenter registry of prospectively recorded individual patient data, we compared outcome rates using multivariable logistic or Cox regression for 30-day and 6-month outcomes respectively (etiologic analysis). We assessed the incremental value of adding BMI information on top of the 30-day European Society of Cardiology (ESC) prognostic algorithm (prognostic analysis). Results: We included 2390 patients with BMI of >= 18.5 kg/m2 (mean age, 66.9 +/- 16.8 years; 1188 men [49.7%]); 686 patients [28.7%] were in the obese group. Mortality rates were significantly lower in patients with obesity than that in patients who were nonobese at 30 days (3.2% [95% CI, 2.0-4.8] vs 5.9% [95% CI, 4.8-7.1]), and 6 months (8.1% [95% CI, 6.2-10.4] vs 16.3% [95% CI, 14.6-18.1]). Rates of secondary nonfatal outcomes (including bleeding, recurrent venous thromboembolism, myocardial infarction, and stroke) did not differ between groups. The addition of the obesity information on top of the ESC prognostic model improved global model fit and discriminatory (Harrell C index from 0.636 to 0.657; P = .07) and calibration capacities (P (Hosmer-Lemeshow) = .02 vs .13), yielding significant reclassification (ie, 10.3%) based on the observed mortality rates with the ESC model as reference. Findings were confirmed in an external validation using 35,796 patients with PE from the RIETE registry. Conclusion: We present evidence indicating lower early-and mid-term mortality after PE in patients classified as obese based on BMI, compared with nonobese, nonunderweight patients. BMI should likely be incorporated into algorithms or scoring systems for predicting early mortality following PE.

BACKGROUND:Left ventricular pseudoaneurysm is a rare condition whose prognosis and treatment are not well described. CASE SUMMARY:We report a case of left ventricular pseudoaneurysm of iatrogenic origin, occurring after transcatheter mitral implantation. The patient underwent successful percutaneous closure with an occluder. DISCUSSION:The formation of a pseudoaneurysm is potentially fatal. The main causes are ischemic, postsurgical, and infectious and after percutaneous valve replacement. Diagnosis is based on nonspecific symptoms and multimodal imaging. Treatment may be medical, surgical, or percutaneous, depending on the clinic, imaging, and the decision of the heart team. TAKE-HOME MESSAGES:Left ventricular pseudoaneurysm after percutaneous valve implantation is a rare complication. Physicians could consider pseudoaneurysm percutaneous exclusion with an occluder.

Introduction: Venous thromboembolism (VTE) is the third leading cause of acute cardiovascular events and is associated with significant morbidity and mortality. Anticoagulation is the cornerstone of pharmacologic treatment for VTE. The addition of an antiplatelet agent to an anticoagulant, known as dual antithrombotic therapy (DAT), has shown promise in improving outcomes in prior observational studies. However, evidence from patients undergoing coronary stenting suggests that the safety and efficacy of DAT may differ depending on the anticoagulant regimen used. To date, no such data are available for patients with VTE. We aimed to evaluate the safety and efficacy of different DAT strategies based on the type of anticoagulant administered. Methods: Data from patients with a VTE event enrolled in the Computerized Registry of Patients with Venous Thromboembolism (RIETE) between January 1, 2001, and June 16, 2025, were used for analysis. Patients were categorized into those receiving DAT and those receiving anticoagulation monotherapy. Patients in the DAT group were further stratified based on the antithrombotic regimen into direct oral anticoagulant (DOAC)-based DAT, vitamin K antagonist (VKA)-based DAT, and heparinoid-based DAT. The primary endpoint was the 2-year incidence of net adverse clinical events (NACE), defined as a composite of all-cause death, VTE recurrence, and any bleeding. Secondary endpoints included the individual components of the primary endpoint and major bleeding. Bleeding events were classified according to the criteria of the International Society on Thrombosis and Haemostasis (ISTH). Clinical outcomes were compared between groups after 1:1 propensity score matching to adjust for baseline differences in age, sex, inpatient evaluation at diagnosis, intensive care unit admission, history of diabetes, coronary artery disease, and VTE risk factors including prior VTE, antineoplastic treatment, recent surgery, and immobilization of at least four weeks. Cox regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results: From a total of 132,679 patients with VTE, 4,222 were treated with DAT. Before matching, patients receiving DAT were older, more often male, more frequently diagnosed in an outpatient setting, less likely to be admitted to the intensive care unit, and more likely to have a history of atherosclerotic cardiovascular disease. After propensity score matching, 8,444 patients were included, and baseline differences were no longer significant. At 2 years, patients receiving DAT had a lower risk of NACE compared to those receiving anticoagulation monotherapy (21.7% vs 39.2%; HR 0.57, 95% CI 0.52–0.62; p<0.001) and lower all-cause mortality (8.1% vs 23.3%; HR 0.40, 95% CI 0.34–0.47; p<0.001). However, DAT was associated with a higher risk of any bleeding (13.6% vs 11.4%; HR 1.36, 95% CI 1.17–1.59; p<0.001) and major bleeding (6.2% vs 5.2%; HR 1.28, 95% CI 1.01–1.62; p=0.039). No significant differences were observed in VTE recurrence (11.6% vs 15.6%; HR 0.88, 95% CI 0.74–1.04; p=0.124). When evaluating the specific type of DAT regimen, results were consistent across anticoagulant types. However, DOAC-based DAT demonstrated the most favorable risk-benefit profile, being the only regimen not associated with an increased risk of bleeding, either any bleeding (10.5% vs 11.4%; p=0.697) or major bleeding (4.8% vs 5.2%; p=0.643). Conclusions: Among patients with VTE, DAT reduces net adverse clinical events and mortality, although at the expense of a higher risk of bleeding, including major bleeding. DOAC-based DAT appears to have the most favorable risk-benefit profile as not associated with increased bleeding.

Objective: Venous thromboembolism (VTE) is a global disease with significant morbidity and mortality. However, variations in presentation and management of VTE between different continents have not been studied. This retrospective analysis of prospectively collected registry data compares presenting symptoms and treatment modalities of patients with VTE in three continents: Europe, America, and Asia. Methods: The data from the Registro Informatizado de la Enfermedad ThromboEmb & oacute;lica registry (2011-2021) were reviewed. The Registro Informatizado de la Enfermedad ThromboEmb & oacute;lica is the largest international registry dedicated to VTE that started in Spain and expanded worldwide. Patient characteristics and treatments were compared between Europe, America, and Asia using standardized differences. Results: There were a total of 61,531 patients with VTE with the majority from Europe (90.3%), followed by Asia (6.3%) and America (3.3%). Patients diagnosed with VTE in America were significantly younger than the other continents. VTE patients in America were more likely to be Black and patients in Asia were more likely to have a lower body mass index when compared with patients from Europe and America. Patients with VTE in Asia presented with significantly more comorbidities including diabetes, coronary artery disease, and ischemic stroke. Also, patients from Asia were more likely to have recent major bleeding and active cancer. Conversely, patients from America had a significantly greater likelihood of having VTE related to travel. Anatomically, European patients were more likely to present with proximal DVT compared with patients from Asia and America. Patients in America were more likely to have low-risk pulmonary embolism (PE) and less likely to have intermediate-risk PE compared with patients from Europe and Asia. There was no difference in the proportion of patients with high-risk PE between continents. There was significant variation in the choice of initial and outpatient anticoagulation; vitamin K antagonists were more commonly used in Europe, whereas direct oral anticoagulants were more commonly used in America, and low-molecular-weight heparins were favored in Asia. Patients in Asia were less likely to receive systemic thrombolytic therapy. In terms of endovascular treatment, pharmacological thrombolysis was used more often for the treatment of PE in Europe compared with Asia and open pulmonary embolectomy was more common among American patients in the registry. Conclusions: There is significant intercontinental variation in VTE presentation and management. Future analyses should evaluate the relationship of these variations with clinical outcomes. Comparative research using a global registry could shed light on VTE biology and treatment. (JVS-Vascular Insights 2025;3:100201.)

Background:Right ventricular pseudoaneurysm is a rare and poorly documented condition. Case Summary:This paper reports a case of right ventricular pseudoaneurysm of iatrogenic origin, which developed after placement of internal jugular central venous catheter. The patient underwent successful percutaneous closure. Discussion:The formation of a pseudoaneurysm is potentially fatal. The main causes are ischemic, postsurgical, infectious, and after percutaneous valve replacement. Diagnosis is based on nonspecific symptoms and multimodal imaging. Treatment may be medical, surgical, or percutaneous, depending on the clinic, imaging, and decision of the heart team. Take-Home Messages:Right ventricular pseudoaneurysm is a rare and poorly documented condition that can complicate even a routine procedure (eg, central venous line placement). Due to its lethal potential, treatment is primarily interventional, requiring careful multimodal imaging assessment. Coil embolization appears to be an effective and safe therapeutic option for managing small-sized pseudoaneurysms in patients at high surgical risk.

We investigated whether the simultaneous presence of both elevated BNP and anemia would improve prediction of one-year mortality compared to the MAGGIC score, in patients with stable chronic heart failure (CHF). Single-centre, retrospective study. We calculated the MAGGIC score for all patients with stable chronic heart failure, and retrieved additional socio-demographic and medical data from electronic medical records (age, sex, left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) levels, anemia, comorbidities) for all patients being followed for CHF. From 17 July 2005 to 19 October 2020, 981 patients were included, mean age 62.9±13.0 years, 734 (74.8%) men. Mean LVEF was 34.3±12.3%. Median MAGGIC score was 21 (Q1-Q3, 16-26). Overall, 295 patients (29.6%) had elevated BNP, 295 patients (29.7%) had anemia, and 117 patients (11.9%) had both. Over 1-year follow-up, 74 patients (7.5%, 95%CI, 5.9-9.3%) died, median time to death was 169.5 days [Q1-Q3, 72-256]. By multivariable analysis, we identified a 2.33-fold increased risk (95% CI, 1.82-3.00) of 1-year mortality in patients with both elevated BNP level and anemia. Cumulative adjusted 1-year mortality was 2.3% (95% CI, 2.16-2.76) for non-BNP/no-anemia patients and 14.5% (95% CI, 13.7-11.0) (p < 0.001) for patients with both elevated BNP and anemia (Figure). The addition of BNP and anemia on top of MAGGIC score improved global model fit, with significant improvement in risk classification. These results suggest that the association of both elevated BNP and anemia on top of the MAGGIC score identifies CHF patients with a higher risk of mortality. This could assist providers in potentially adjusting HF management, in a framework of shared decision-making with individual patients.

BACKGROUND:Aortic annulus rupture is a rare but life-threatening complication of transcatheter aortic valve replacement (TAVR), often linked to balloon-expandable valves and anatomic risk factors. CASE SUMMARY:An 85-year-old man with severe aortic stenosis underwent successful transfemoral TAVR. Two hours later, he developed tamponade because of a supra-annular rupture. A second, higher-positioned valve was implanted, followed by a third prosthesis after valve migration. Days later, a subannular rupture with pseudoaneurysm was identified. Coil embolization via radial access achieved complete exclusion. DISCUSSION:Annulus rupture may occur at various levels (supra-, intra, or subannular) and requires individualized management. This case highlights a staged rupture progression and successful percutaneous management, offering a less invasive alternative for high-risk patients. TAKE-HOME MESSAGES:Annulus rupture is a rare but critical TAVR complication. Rapid diagnosis and multidisciplinary coordination are essential. Percutaneous strategies, including valve-in-valve and coil embolization, may be lifesaving in selected cases.

BACKGROUND:Catheter-directed therapies are increasingly used to treat acute pulmonary embolism (PE). However, randomized data on reperfusion treatments, including large-bore mechanical thrombectomy (LBMT), for patients with High-Risk PE are lacking. METHODS:PERSEVERE (NCT06588634) is a multinational randomized controlled trial comparing the FlowTriever LBMT system vs. standard of care (SoC) in patients with High-Risk PE, with the modified intention-to-treat population planned for 200 patients from 40 sites in Europe and the US. Patients are randomized 1:1 to LBMT or SoC (systemic thrombolysis [ST], surgical embolectomy, extracorporeal membrane oxygenation [ECMO], or anticoagulation alone). Key inclusion criteria are the presence of proximal pulmonary thrombus on computed tomography plus ≥1 of the following: (1) systolic hypotension or need for vasopressors, (2) venous lactate ≥4 mmol/L with clinical signs suggesting obstructive shock, (3) need for mechanical circulatory support, (4) resuscitated cardiac arrest. Exclusion criteria include known chronic thromboembolic pulmonary hypertension and key absolute contraindications to ST. Patients are followed for 3 months. The primary endpoint is a composite of events through hospital discharge or 7 days post randomization, whichever occurs first: (1) all-cause death, (2) cardiac arrest requiring cardiopulmonary resuscitation, (3) bailout to rescue treatment, (4) major bleeding, and (5) ECMO in place on day 7. Secondary endpoints include a broad spectrum of functional and patient-reported outcomes (quality of life, functional status and healthcare resource utilization) at 3 months. The trial is funded by Inari. CONCLUSION:The PERSEVERE study will assess the potential superiority of LBMT over SoC for the treatment of High-Risk PE. CLINICALTRIALS:gov Identifier: NCT06588634.