Development and web deployment of prediction model for pulmonary arterial pressure in chronic thromboembolic pulmonary hypertension using machine learning.

BACKGROUND AND PURPOSE: Mean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH. METHODS: A total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets. RESULTS: The optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG. CONCLUSION: We constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables.

Influencing factors on the time to CT in suspected pulmonary embolism: an explorative investigation.

Pulmonary embolism is a potentially fatal condition with increased mortality if anticoagulation is delayed. This study aimed to find influencing factors on the duration from requesting a computed tomography (CT) pulmonary angiography (CTPA) to performing a CTPA in suspected acute pulmonary embolism. In 1849 cases, automatically generated time data were extracted from the radiological information system. The impact of the distance to the scanner, case-related features (sector of patient care, triage), and workload (demand for CTs, performed CTs, available staff, hospital occupancy) were investigated retrospectively using multiple regression. The time to CTPA was shorter in cases from the emergency room (ER) than in inpatients and outpatients at distances below 160 m and 240 m, respectively. While requests from the ER were also performed faster than cases from regular wards (< 180 m), no difference was found between the ER and intensive care units. Compared to "not urgent" cases, the workflow was shorter in "urgent" (- 17%) and "life-threatening" (- 67%) situations. The process was prolonged with increasing demand (+ 5%/10 CTs). The presented analysis identified relevant in-hospital influences on the CTPA workflow, including the distance to the CT together with the sector of patient care, the case triage, and the demand for imaging.

Effects of right ventricular remodeling in chronic thromboembolic pulmonary hypertension on the outcomes of balloon pulmonary angioplasty: a 2D-speckle tracking echocardiography study.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.

[A case of right heart failure: when it is not pulmonary embolism]. / Un caso di insufficienza cardiaca destra: quando l'embolia polmonare non è un'embolia polmonare.

A 66-year-old patient with recent instrumental findings (echocardiogram, cardiac magnetic resonance imaging) of right ventricular failure was hospitalized due to worsening signs and symptoms of right heart failure, while waiting for diagnostic definition. Pulmonary computed tomography angiography revealed findings compatible with bilateral pulmonary thromboembolism involving the main pulmonary artery. Anticoagulant therapy was initiated with initial benefit, partial relief of symptoms, and moderate improvement in right ventricular function. However, after 4 weeks, the patient was readmitted for recurrence of heart failure and signs of low cardiac output. Echocardiography showed the presence of a conspicuous, mobile, isoechoic mass occupying much of the main pulmonary artery, once again suggestive of thrombosis. The patient underwent surgical thromboendoarterectomy; postoperatively, the procedure was complicated by severe refractory heart failure unresponsive to pharmacological treatments and mechanical support, leading to death in the subsequent days. Unexpectedly, histological analysis revealed a primary angiosarcoma of the endothelium of the main pulmonary artery, a very rare cause of pulmonary artery obstruction generally associated with worst prognosis and presenting with clinical features similar to pulmonary thromboembolism.

Diagnostic Performance of Perfusion-Only SPECT/CT for Chronic Thromboembolic Pulmonary Hypertension in Comparison With Ventilation-Perfusion Planar, SPECT, and SPECT/CT Imaging.

PURPOSE: The aim of this study was to assess the diagnostic performance of perfusion-only SPECT/CT (Q SPECT/CT) in comparison with that of ventilation/perfusion planar scintigraphy (V/Q planar), perfusion SPECT with ventilation scan (V/Q SPECT), and perfusion SPECT/CT with ventilation scan (V/Q SPECT/CT) in chronic thromboembolic pulmonary hypertension (CTEPH). PATIENTS AND METHODS: Patients with pulmonary hypertension who underwent ventilation-perfusion planar and SPECT/CT were retrospectively recruited. Two nuclear medicine physicians interpreted V/Q planar, V/Q SPECT, V/Q SPECT/CT, and Q SPECT/CT according to the European Association of Nuclear Medicine criteria. The diagnostic accuracy of these modalities for CTEPH was compared using a composite reference standard of pulmonary angiography, imaging test, cardiorespiratory assessment, and follow-up. RESULTS: A total of 192 patients were enrolled, including 85 with CTEPH. The sensitivity of Q SPECT/CT was 98.8%, which similar to that of V/Q planar (97.6%), V/Q SPECT (96.5%), or V/Q SPECT/CT (100.0%). In contrast, Q SPECT/CT exhibited significantly lower specificity (73.8%) compared with V/Q planar (86.9%, P = 0.001), V/Q SPECT (87.9%, P < 0.001), and V/Q SPECT/CT (88.8%, P < 0.001). The significantly lower specificity of Q SPECT/CT, compared with the 3 others, was observed in the subgroup aged ≥50 years ( P < 0.001 for all), but not in those <50 years. CONCLUSIONS: Q SPECT/CT exhibited lower specificity compared with V/Q planar, V/Q SPECT, and V/Q SPECT/CT in diagnosing CTEPH. It might underscore the essential role of a ventilation scan in patients with PH, even with the introduction of SPECT/CT.

Ultrasound-Assisted Catheter-Directed Thrombolysis for the Management of Pulmonary Embolism: A Single Center Experience in a Community Hospital.

Current guidelines recommend anticoagulation alone for low-risk pulmonary embolism (PE) with the addition of systemic thrombolysis for high-risk PE. However, treatment recommendations for intermediate-risk PE are not well-defined. Due to bleeding risks associated with systemic thrombolysis, ultrasound-assisted catheter-directed thrombolysis (USAT) has evolved as a promising treatment modality. USAT is thought to decrease the rate of major bleeding by using localized delivery with lower thrombolytic dosages. Currently, there is little guidance on the implementation of USAT in the real-world clinical setting. This study was designed to evaluate our experience with USAT at this single community hospital with a newly initiated Pulmonary Embolism Response Team (PERT). All patients identified by the PERT with an acute PE diagnosed by a computed tomography (CT) scan from January 2021 to January 2023 were included. During the study period, there were 89 PERT activations with 40 patients (1 high-risk and 37 intermediate-risk PE) receiving USAT with alteplase administered at a fixed rate of 1 mg/h per catheter for 6 h. The primary efficacy outcome was the change in Pulmonary Embolism Severity Index (PESI) score within 48 h after USAT. The primary safety outcome was major bleeding within 72 h. The mean age was 57.4 ± 17.4 years and 50% (n = 20) were male, 17.5% (n = 7) had active malignancy, and 20% (n = 8) had a history of prior deep vein thrombosis (DVT) or PE. The mean PESI score decreased from baseline to 48 h post-USAT (84.7 vs 74.9; p = 0.025) and there were no major bleeding events. The overall hospital length of stay was 7.5 ± 9.8 days and ICU length of stay was 2.2 ± 2.8 days. This study outlined our experience at this single community hospital which resulted in an improvement in PESI scores and no major bleeding events observed.

Retrieval of an inferior vena cava Greenfield filter 34 years after insertion.

Inferior vena cava (IVC) filters are engineered medical devices deployed in the IVC primarily to prevent a pulmonary embolism from occurring. In this article, we present a case of an IVC filter that was successfully retrieved from a patient after being in place for 34 years. The patient presented to hospital for trauma in which subsequent imaging showed tines of an IVC filter protruding outside of the vessel with one of the tines penetrating the duodenal wall. The filter was successfully removed with no complications. This report adds to the existing literature by yielding an example of an adverse risk that can be associated with the placement of IVC filters. In addition, to the authors' best knowledge, this is the longest reported length of time that an IVC filter has stayed in a patient before being removed, thus adding another intriguing detail to the case.

A Good Prognosis of Patients with Acute Pancreatitis Combined with Pulmonary Embolism: Early Identification and Intervention.

BACKGROUND: Pulmonary embolism (PE) is a relatively rare vascular complication of acute pancreatitis (AP), and its mortality rate is high. To our knowledge, relevant literature reports still need to be summarized. In this study, we analyzed the clinical characteristics, treatment, and prognosis of five patients with AP complicated by PE and summarized and reviewed the relevant literature. METHODS: Clinical data of patients with AP complicated by PE treated in Taizhou Hospital of Zhejiang Province between January 2017 and September 2022 were retrospectively collected. Combined with the relevant literature, the clinical characteristics, treatment, and prognoses of patients with AP combined with PE were analyzed and summarized. RESULTS: Five patients were eventually enrolled in this study. Among the five patients with AP complicated by PE, all (100%) had symptoms of malaise, primarily chest tightness, shortness of breath, and dyspnea. All patients (100%) had varied degrees of elevated D-dimer levels and a significant decrease in the pressure of partial oxygen (PO2) and pressure of arterial oxygen to fractional inspired oxygen concentration ratio (PaO2/FiO2). Computed tomographic angiography (CTA) or pulmonary ventilation/perfusion imaging revealed a pulmonary artery filling defect in these patients. One patient (20%) had left calf muscular venous thrombosis before the occurrence of PE. Four patients (80%) were treated with lowmolecular- weight heparin (LMWH), and one patient (20%) was treated with rivaroxaban during hospitalization; all continued oral anticoagulant therapy after discharge. All patients (100%) were cured and discharged. No patients showed recurrence of AP or PE. CONCLUSION: PE is a rare but life-threatening complication of AP. However, once diagnosed, early treatment with anticoagulation or radiological interventional procedures is effective, and the prognosis is good. Core Tips: Pulmonary embolism (PE) is a rare but life-threatening complication of acute pancreatitis (AP). Its early diagnosis and timely anticoagulation or radiological intervention can reduce mortality. However, only nine cases have been reported in the English literature thus far, and they are all case reports. Our study is the first systematic analysis of patients with AP combined with PE with a review of the relevant literature. Our patients and those reported in the literature were discharged with good prognoses under treatment such as anticoagulation and vascular intervention. These cases remind clinicians that, in patients with AP, especially those with risk factors for venous thrombosis, it is necessary to monitor the D-dimer level dynamically. Clinicians should pay attention to AP patients' symptoms and related examinations to reduce the chance of a missed diagnosis or misdiagnosis of PE.

Prevalence, risk factors, and clinical characteristics of pulmonary embolism in patients with acute exacerbation of COPD in Plateau regions: a prospective cohort study.

BACKGROUND AND OBJECTIVE: To investigate pulmonary thromboembolism (PE) in acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) patients in plateau regions, we performed a prospective cohort study to evaluate the prevalence, risk factors and clinical characteristics of PE in the cohort of hospitalized patients at high altitude. METHODS: We did a prospective study with a total of 636 AE-COPD patients in plateau regions. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities and cardiac ultrasound, and computed tomographic pulmonary angiography (CTPA) variables were obtained, and comparisons were made between groups with and without PE. We also conducted logistic regression to explore the risk factors of PE. RESULTS: Of the 636 patients hospitalized with AE-COPD (age 67.0 ± 10.7 years, 445[70.0%] male), 188 patients developed PE (29.6% [95% CI: 26.0%, 33.1%]). Multivariable logistic regression showed that ethnic minorities, D-dimer > 1 mg/L, AST > 40 U/L, chest pain, cardiac insufficiency or respiratory failure, Padua score > 3, and DVT were associated with a higher probability of PE. CONCLUSIONS: The prevalence of PE is high and those with a higher Padua score, the occurrence of deep venous thrombosis, higher neutrophil count, chest pain, cardiac insufficiency or respiratory failure, higher levels of AST, and a higher level of D-dimer had a higher risk of PE. The analysis of AE-COPD may help to provide more accurate screening for PE and improve clinical outcomes of patients with AE-COPD in plateau regions.

External validation of the RSNA 2020 pulmonary embolism detection challenge winning deep learning algorithm.

PURPOSE: To evaluate the diagnostic performance and generalizability of the winning DL algorithm of the RSNA 2020 PE detection challenge to a local population using CTPA data from two hospitals. MATERIALS AND METHODS: Consecutive CTPA images from patients referred for suspected PE were retrospectively analysed. The winning RSNA 2020 DL algorithm was retrained on the RSNA-STR Pulmonary Embolism CT (RSPECT) dataset. The algorithm was tested in hospital A on multidetector CT (MDCT) images of 238 patients and in hospital B on spectral detector CT (SDCT) and virtual monochromatic images (VMI) of 114 patients. The output of the DL algorithm was compared with a reference standard, which included a consensus reading by at least two experienced cardiothoracic radiologists for both hospitals. Areas under the receiver operating characteristic curve (AUCs) were calculated. Sensitivity and specificity were determined using the maximum Youden index. RESULTS: According to the reference standard, PE was present in 73 patients (30.7%) in hospital A and 33 patients (29.0%) in hospital B. For the DL algorithm the AUC was 0.96 (95% CI 0.92-0.98) in hospital A, 0.89 (95% CI 0.81-0.94) for conventional reconstruction in hospital B and 0.87 (95% CI 0.80-0.93) for VMI. CONCLUSION: The RSNA 2020 pulmonary embolism detection on CTPA challenge winning DL algorithm, retrained on the RSPECT dataset, showed high diagnostic accuracy on MDCT images. A somewhat lower performance was observed on SDCT images, which suggest additional training on novel CT technology may improve generalizability of this DL algorithm.

Kidney Transplant Recipient With Cerebral Paradoxical Embolism Following Recurrent Idiopathic Deep Vein Thrombosis and Pulmonary Embolism: Case Report and Review of the Literature.

Paradoxical embolism occurs when a thrombus crosses an intracardiac defect into the systemic circulation. Here, we present the case of a 35-yearold male kidney transplant recipient with a cerebral paradoxical embolism associated with a spontaneous venous thromboembolism. This patient had recurrent deep venous thrombosis and showering emboli to the lung and paradoxically to the brain through patent foramen ovale, and we treated him successfully. The role of bubble echocardiography was essential in diagnosis to avoid contrast-induced nephropathy. This is the first successfully managed case of a kidney transplant recipient with recurrent idiopathic deep vein thrombosis, pulmonary embolism, and cerebral paradoxical embolism. Bubble echocardiography was an excellent alternative to contrast angiography to avoid nephrotoxicity. Vitamin K antagonists are superior to direct oral anticoagulants, especially among nonadherent/noncompliant patients.

Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism in SARS-CoV-2.

INTRODUCTION: Chronic thromboembolic pulmonary disease (CTEPD) consists of persistent pulmonary vascular obstruction on imaging and involves long-term functional limitations, with or without chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to evaluate the incidence and risk factors of both persistent pulmonary vascular defects and CTEPH after hospitalization in patients with COVID-19 and PE during a 2-year follow-up. METHODS: A prospective observational study was carried out in a tertiary hospital center. Patients were hospitalized between March 2020 and December 2021 with a diagnosis of PE during SARS-CoV-2 infection. Patients received anticoagulant treatment for at least 3 months and were followed up for 2 years. Between the third and fourth months after discharge, all patients were evaluated for the presence of residual thrombotic defects by CTPA and/or perfusion pulmonary scintigraphy. Clinical findings, lung function tests with DLCO, exercise capacity, and echocardiograms were also assessed. RESULTS: Of the 133 patients included, 18% had persistent thrombotic defects on lung imaging at follow-up. The incidence of CTEPD was 0.75% at 2 years of follow-up. Patients with persistent defects were significantly older, had a higher prevalence of systemic arterial hypertension, higher D-dimer and NT-proBNP levels, and more severe PE at diagnosis. Furthermore, there was a higher prevalence of right ventricular dysfunction on echocardiogram at diagnosis of PE (25.0% vs. 2.7%, p = 0.006). This was the only variable independently related to persistent defects in multivariate analyses (OR: 8.13 [95% CI: 1.82-36.32], p = 0.006). CONCLUSION: The persistence of thrombotic defects after PE is a common finding after SARS-CoV-2 infection, affecting 18% of the population. However, the incidence of CTEPH appears to be lower (0.75%) in COVID-19-related PE compared to that previously observed in PE unrelated to COVID-19.

Ventilation perfusion functional difference images in lung SPECT: A linear and symmetrical scale as an alternative to the ventilation perfusion ratio.

PURPOSE: Ventilation Perfusion SPECT is important in the diagnostics of e.g. pulmonary embolism and chronic obstructive pulmonary disease. Classical and reverse mismatched defects can be identified by utilizing the ventilation-perfusion ratio. Unfortunately, this ratio is only linear in the ventilation, the scale is not symmetrical regarding classical and reversed mismatches and small perfusion values give rise to artifacts. The ventilation-perfusion (VQ) difference is developed as an alternative. METHODS: For both VQ-ratio and VQ-difference a scaling factor for the perfusion is computed, so that voxels with matched ventilation and perfusion (on average) yield zero signal. The relative VQ-difference is calculated by scaling with the summed VQ-signal in each voxel. The scaled VQ-difference is calculated by scaling with the global maximum of this sum. RESULTS: The relative and scaled differences have a scale from -1 (perfusion only) to + 1 (ventilation only). Image quality of relative VQ-difference and VQ-ratio images is hampered by artifacts from areas with both low perfusion and low ventilation. Ratio and differences have been investigated in ten patients and are shown for three patients (one without defects). Clinical thresholds for the difference images are derived resulting in color maps of relevant (reversed) mismatches with a (reciprocal) ratio larger than two. CONCLUSIONS: The relative ventilation-perfusion difference is a methodological improvement on the ventilation-perfusion ratio, because it has a symmetrical scale and is bound on a closed domain. A better diagnostic value is expected by utilizing the scaled difference, which represents functional difference instead of relative difference.

Maternal and Fetal Radiation-Induced Cancer Risk From Computed Tomography Pulmonary Angiography During Pregnancy: A Retrospective Cohort Study Across a Multihospital Integrated Health Care Network.

OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is important to evaluate suspected pulmonary embolism in pregnancy but has maternal/fetal radiation risks. The objective of this study was to estimate maternal and fetal radiation-induced cancer risk from CTPA during pregnancy. METHODS: Simulation modeling via the National Cancer Institute's Radiation Risk Assessment Tool was used to estimate excess cancer risks from 17 organ doses from CTPA during pregnancy, with doses determined by a radiation dose indexing monitoring system. Organ doses were obtained from a radiation dose indexing monitoring system. Maternal and fetal cancer risks per 100,000 were calculated for male and female fetuses and several maternal ages. RESULTS: The 534 CTPA examinations had top 3 maternal organ doses to the breast, lung, and stomach of 17.34, 15.53, and 9.43 mSv, respectively, with a mean uterine dose of 0.21 mSv. The total maternal excess risks of developing cancer per 100,000 were 181, 151, 121, 107, 94.5, 84, and 74.4, respectively, for a 20-, 25-, 30-, 35-, 40-, 45-, and 50-year-old woman undergoing CTPA, compared with baseline cancer risks of 41,408 for 20-year-old patients. The total fetal excess risks of developing cancer per 100,000 were 12.3 and 7.3 for female and male fetuses, respectively, when compared with baseline cancer risks of 41,227 and 48,291. DISCUSSION: Excess risk of developing cancer from CTPA was small relative to baseline cancer risk for pregnant patients and fetuses, decreased for pregnant patients with increasing maternal age, and was greater for female fetuses than male fetuses.

Computed tomography-based radiomics model to predict adverse clinical outcomes in acute pulmonary embolism.

This preliminary study investigated the feasibility of a combined model constructed using radiomic features based on computed tomography (CT) and clinical features to predict adverse clinical outcomes in acute pulmonary embolism (APE). Currently, there is no widely recognized predictive model. Patients with confirmed APE who underwent CT pulmonary angiography were retrospectively categorized into good and poor prognosis groups. Seventy-four patients were randomized into a training (n = 51) or validation (n = 23) cohort. Feature extraction was performed using 3D-Slicer software. The least absolute shrinkage and selection operator regression was used to identify the optimal radiomics features and calculate the radiomics scores; subsequently, the radiomics model was developed. A combined predictive model was constructed based on radiomics scores and selected clinical features. The predictive efficacy of the three models (radiomics, clinical and combined) was assessed by plotting receiver operating characteristic curves. Furthermore, the calibration curves were graphed and the decision curve analysis was performed. Four radiomic features were screened to calculate the radiomic score. Right ventricular to left ventricular ratio (RV/LV) ≥ 1.0 and radiomics score were independent risk factors for adverse clinical outcomes. In the training and validation cohorts, the areas under the curve (AUCs) for the RV/LV ≥ 1.0 (clinical) and radiomics score prediction models were 0.778 and 0.833 and 0.907 and 0.817, respectively. The AUCs for the combined model of RV/LV ≥ 1.0 and radiomics score were 0.925 and 0.917, respectively. The combined and radiomics models had high clinical assessment efficacy for predicting adverse clinical outcomes in APE, demonstrating the clinical utility of both models. Calibration curves exhibited a strong level of consistency between the predictive and observed probabilities of poor and good prognoses in the combined model. The combined model of RV/LV ≥ 1.0 and radiomics score based on CT could accurately and non-invasively predict adverse clinical outcomes in patients with APE.

Prospective Multicenter International Registry of Ultrasound-Facilitated Catheter-Directed Thrombolysis in Intermediate-High and High-Risk Pulmonary Embolism (KNOCOUT PE).

BACKGROUND: Prior clinical trials have demonstrated the efficacy of ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk pulmonary embolism (PE) using reduced thrombolytic doses and shorter infusion durations. However, utilization and safety of such strategies in broader PE populations remain unclear. The KNOCOUT PE (The EKoSoNic Registry of the Treatment and Clinical Outcomes of Patients With Pulmonary Embolism) registry is a multicenter international registry designed to study the treatment of acute PE with USCDT, with focus on safety outcomes. METHODS: The KNOCOUT PE prospective cohort included 489 patients (64 sites internationally) with acute intermediate-high or high-risk PE treated with USCDT between March 2018 and June 2020. Principal safety outcomes were independently adjudicated International Society on Thrombosis and Haemostasis major bleeding at 72 hours post-treatment and mortality within 12 months of treatment. Additional outcomes included change in right ventricular/left ventricular ratio and quality of life measures over 12 months. RESULTS: Mean alteplase (r-tPA [recombinant tissue-type plasminogen activator]) infusion duration was 10.5 hours. Mean total r-tPA dose was 18.1 mg, with 31.0% of patients receiving ≤12 mg. Major bleeding events within 72 hours occurred in 1.6% (8/489) of patients. One patient experienced worsening of a preexisting subdural hematoma after USCDT and therapeutic anticoagulation, which ultimately required surgery. All-cause mortality at 30 days was 1.0% (5/489). Improvement in PE quality of life score was observed with a 41.1% (243/489, 49.7%) and 44.2% (153/489, 31.3%) mean relative reduction by 3 and 12 months, respectively. CONCLUSIONS: In a prospective observational cohort study of patients with intermediate-high and high-risk PE undergoing USCDT, mean r-tPA dose was 18 mg, and the rates of major bleeding and mortality were low. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03426124.