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Pulmonary embolism (PE) is a major cause of morbidity and mortality in the United States. Although new therapeutic tools and strategies have recently been developed for the diagnosis and treatment of patients with PE, the outcomes for patients who present with massive or high‐risk PE remain dismal. To address this crisis, pulmonary embolism response teams (PERTs) are being created around the world in an effort to immediately and simultaneously engage multiple specialists to determine the best course of action and coordinate the clinical care for patients with acute PE. The scope of this review is to describe the PERT model and purpose, present the structure and organization, examine the available evidence for efficacy and usefulness, and propose future directions for research that is needed to demonstrate the value of PERT and determine if this multidisciplinary approach represents a new standard of care.

•Men and women with acute PE present with different baseline characteristics.•Women were sicker and had increased signs of right heart strain compared with men.•Sex did not predict receipt of advanced intervention for PE.•High-risk PE had lower odds of receiving advanced therapy than intermediate-risk PE.•Full code status and assisted ventilation predicted receipt of advanced intervention. Advanced interventions are increasingly used to treat intermediate- and high-risk acute pulmonary embolism (PE). While sex-based differences exist in treatment of other diseases, it is unknown whether these disparities extend to PE. This is a secondary analysis of a prospective cohort study of adult patients diagnosed with radiographically confirmed intermediate- and high-risk acute PE at a tertiary hospital between 1/1/2012 and 12/31/2021 for whom the PE Response Team was activated. Primary outcome was receipt of any advanced intervention. Descriptive and inferential analyses using Chi-square tests, t tests, and logistic regression were performed to evaluate for factors associated with the primary outcome. We analyzed 902 patients, of whom 439 (49%) were female. Although women were more likely to present with right heart strain on echo (78.6% vs 71.1% P = 0.012) and elevated NT-proBNP (69.2% vs 55.7% P < 0.001), there was no significant sex-based difference in clinical PE severity, defined as intermediate- versus high-risk, at presentation. Primary outcome did not differ significantly by sex (18.7% vs 23.5% P = 0.129). In multivariate models, high-risk PE decreased odds of receiving an advanced therapy (0.50 [0.31, 0.79] P = 0.003), while receiving assisted ventilation (4.70 [2.90, 7.62], P < 0.001) and full code status (4.18 [1.60, 10.91], P = 0.003) increased odds. This study adds to the scant literature on sex differences in interventions for acute PE. Significant baseline variation exists between female and male patients presenting with acute PE. Clinical factors were predictive of receiving advanced PE therapies, while sex was not.

Some individuals living with obesity may be relatively metabolically healthy, whilst others suffer from multiple conditions that may be linked to adverse metabolic effects or other factors. The extent to which the adverse metabolic component of obesity contributes to disease compared to the non-metabolic components is often uncertain. We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases. We selected 37 chronic diseases associated with obesity and genetic variants associated with different aspects of excess weight. These genetic variants included those associated with metabolically 'favourable adiposity' (FA) and 'unfavourable adiposity' (UFA) that are both associated with higher adiposity but with opposite effects on metabolic risk. We used these variants and two sample MR to test the effects on the chronic diseases. MR identified two sets of diseases. First, 11 conditions where the metabolic effect of higher adiposity is the likely primary cause of the disease. Here, MR with the FA and UFA genetics showed opposing effects on risk of disease: coronary artery disease, peripheral artery disease, hypertension, stroke, type 2 diabetes, polycystic ovary syndrome, heart failure, atrial fibrillation, chronic kidney disease, renal cancer, and gout. Second, 9 conditions where the non-metabolic effects of excess weight (e.g. mechanical effect) are likely a cause. Here, MR with the FA genetics, despite leading to lower metabolic risk, and MR with the UFA genetics, both indicated higher disease risk: osteoarthritis, rheumatoid arthritis, osteoporosis, gastro-oesophageal reflux disease, gallstones, adult-onset asthma, psoriasis, deep vein thrombosis, and venous thromboembolism. Our results assist in understanding the consequences of higher adiposity uncoupled from its adverse metabolic effects, including the risks to individuals with high body mass index who may be relatively metabolically healthy. Diabetes UK, UK Medical Research Council, World Cancer Research Fund, National Cancer Institute.

The Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (β = 0.45, p = 3.48x10-22), and using a significance level of p = 0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR = 2.17, 95% CI: 1.79-2.63, p = 2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.

The novel coronavirus SARS-CoV-2 (COVID-19) pandemic has created diagnostic uncertainty with regards to distinguishing this infection from pulmonary embolism (PE). Although there appears to be an increased incidence of thromboembolic disease in patients with COVID-19 infection, recommendations regarding anticoagulation are lacking. We present the case of a 61-year-old woman with clinically significant venous and arterial thromboemboli in the setting of COVID-19 infection requiring tissue plasminogen activator (tPA).

Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at P  < 0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95% CI 1.02–1.12, P  = 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (OR = 1.59, 95% CI 1.30–1.93 per standard deviation increase in BMI, P  = 5.8 × 10 −6 ). Our study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE.

Computed tomography pulmonary angiogram (CTPA) provides a volumetric assessment of clot burden in acute pulmonary embolism (PE). However, it is unclear if clot burden is associated with right-sided heart strain (RHS) or adverse clinical events (ACE). We prospectively enrolled Emergency Department patients with PE (in CTPA) from 2008 to 2011. We assigned 1 to 9 points as clot burden score, based on whether emboli were saddle, central, lobar, segmental, and subsegmental. We evaluated a novel score (the “CT-PASS”) based on the sum (in millimeters) of the largest filling defects in the right and left pulmonary vasculature. Our primary outcome was RHS, defined by imaging (echocardiography or CTPA) or cardiac biomarkers. Our secondary outcomes included 5-day ACE. We included 271 patients (50% women), with a mean age of 59 ± 17 years. Based on CTPA, 131 patients (48%) had central PE (clot burden score ≥5 points). The median CT-PASS was 9.1 mm (interquartile range 4.9 to 16.4). In univariate analysis, higher clot burden (highest quartile CT-PASS) was associated with RHS (p = 0.003). In multivariate analysis, after adjusting for RHS, age, and gender, central PE (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.10 to 7.81) and CT-PASS >20 mm (OR 3.54, 95% CI 1.39 to 8.97) were significantly associated with ACE. However, this association of central PE with ACE was not statistically significant after excluding patients with shock index >1 (OR 2.56, 95% CI 0.62 to 10.64). In conclusion, highest quartile CT-PASS was associated with RHS and central PE and ACE, but this association was not statistically significant in hemodynamically stable PE.

Background We provide the first multicenter analysis of patients cared for by eight Pulmonary Embolism Response Teams (PERTs) in the United States (US); describing the frequency of team activation, patient characteristics, pulmonary embolism (PE) severity, treatments delivered, and outcomes. Methods We enrolled patients from the National PERT Consortium™ multicenter registry with a PERT activation between 18 October 2016 and 17 October 2017. Data are presented combined and by PERT institution. Differences between institutions were analyzed using chi-squared test or Fisher's exact test for categorical variables, and ANOVA or Kruskal-Wallis test for continuous variables, with a two-sided P value < 0.05 considered statistically significant. Results There were 475 unique PERT activations across the Consortium, with acute PE confirmed in 416 (88%). The number of activations at each institution ranged from 3 to 13 activations/month/1000 beds with the majority originating from the emergency department (281/475; 59.3%). The largest percentage of patients were at intermediate–low (141/416, 34%) and intermediate–high (146/416, 35%) risk of early mortality, while fewer were at high-risk (51/416, 12%) and low-risk (78/416, 19%). The distribution of risk groups varied significantly between institutions (P = 0.002). Anticoagulation alone was the most common therapy, delivered to 289/416 (70%) patients with confirmed PE. The proportion of patients receiving any advanced therapy varied between institutions (P = 0.0003), ranging from 16% to 46%. The 30-day mortality was 16% (53/338), ranging from 9% to 44%. Conclusions The frequency of team activation, PE severity, treatments delivered, and 30-day mortality varies between US PERTs. Further research should investigate the sources of this variability.

Background Studies have reported COVID-19 as an independent risk factor for arterial thromboemboli. Methods From a cross-sectional sample, we determined the incidence and location of arterial thromboemboli (myocardial infarction, ischemic stroke, peripheral artery), stratified by COVID-19 status, in the RECOVER database, which included data on patients at 45 United States medical centers in 22 states. Epidemiological factors, clinical characteristics and outcomes were collected through a combination of individual chart review and automatic electronic query and recorded in REDCap®. We investigated the association of baseline comorbidities on the development of arterial thromboemboli and analyzed results based on the presence or absence of concomitant COVID-19 infection, testing this association with Chi-squared. We also described use of anticoagulants and statins. Results Data were collected on 26,974 patients, of which 13,803 (51.17%) tested positive for COVID-19. Incidence of arterial thromboemboli during hospitalization was 0.13% in patients who tested positive for COVID-19 and 0.19% in patients who tested negative. Arterial thromboemboli tended to be more common in extremities than in core organs (heart, kidney, lung, liver) in patients with COVID-19, odds ratio 2.04 (95% CI 0.707 – 5.85). Patients with COVID-19 were less likely to develop an arterial thrombus when on baseline statin medication ( p =0.014). Presence of metabolic syndrome predicted presence of core arterial thrombus ( p =0.001) and extremity arterial thrombus ( p =0.010) in those with COVID-19. Arterial thromboemboli were less common in patients with COVID-19 than in those who tested negative for COVID-19. Conclusions Presence of a composite metabolic syndrome profile may be associated with arterial clot formation in patients with COVID-19 infection.

Background and Objectives: The pulmonary artery pulsatility index (PAPi) is an emerging marker of right ventricular (RV) injury but has not been well investigated in acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to investigate its discriminatory capabilities and ability to detect therapeutic effects in acute PE and CTEPH. Materials and Methods: This was a secondary analysis of data from both experimental studies of autologous PE and human studies of acute PE and CTEPH. PAPi was calculated and compared in (1) PE versus sham and (2) before and after interventions aimed at reducing RV afterload in PE and CTEPH. The correlations between PAPi, cardiac output, and RV to pulmonary artery coupling were investigated. Results: PAPi did not differ between animals with acute PE versus sham, nor was it affected by clot burden (p = 0.673) or at a 30-day follow-up (p = 0.242). Pulmonary vasodilatation with oxygen was associated with a reduction in PAPi (4.9 [3.7–7.8] vs. 4.0 [3.2–5.6], p = 0.016), whereas positive inotropes increased PAPi in the experimental PE. In humans, PAPi did not change consistently with interventions. Balloon pulmonary angioplasty did not significantly increase PAPi (6.5 [4.3–10.7] vs. 9.8 [6.8–14.2], p = 0.1) in patients with CTEPH, and a non-significant reduction in PAPi (4.3 ± 1.6 vs. 3.3 ± 1.2, p = 0.074) was observed in patients with acute PE who received sildenafil. PAPi did not correlate well with cardiac output or measures of RV to pulmonary artery coupling in either species. Conclusions: PAPi did not detect acute, experimental PE or changes as a result of therapeutic interventions in patients with hemodynamically stable acute PE or CTEPH. However, it did change with pharmacological interventions in the experimental PE. Further research should establish its utility in detecting and monitoring RV injury in different clinical phenotypes of acute PE and CTEPH.