C-reactive Protein and Risk of Right Ventricular Dysfunction and Mortality in Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: Right ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE. METHODS: This cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis. RESULTS: The study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0-76.4]mg/L vs n=124, 45.4 [16.0-111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00-1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00-1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively. CONCLUSIONS: As an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE.

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Statin use and mortality in patients with deep vein thrombosis. Data from the RIETE Registry.

BACKGROUND: The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. METHODS: We used the data in the RIETE registry to examine the association between statin use and mortality at 3 months. We used mixed effects survival models accounting for clinical covariates and clustering of patients in enrolling centers. RESULTS: From January 2009 through April 2022, there were 46,440 patients with isolated DVT in RIETE (in the lower-limbs 42,291, in the upper limbs 4149). Of these, 21 % and 18 %, respectively, were using statins. Statin users were older than non-users (72 ± 12 vs. 62 ± 18 years), and more likely had diabetes, hypertension, prior myocardial infarction or ischemic stroke, or were receiving antiplatelets. The 3-month mortality rates were: 6.0 % vs. 5.8 %, respectively. On multilevel multivariable analysis, the adjusted hazard ratio (aHR) for all-cause death in statin users vs. non-users was 0.77 (95%CI: 0.69-0.86). The 3-month risk of death in statin users was significantly lower than in non-users in patients with upper-limb DVT (aHR: 0.81; 95%CI: 0.72-0.91), distal lower-limb DVT (aHR: 0.48; 95%CI: 0.32-0.72), or proximal lower-limb DVT (aHR: 0.69; 95%CI: 0.50-0.95), and in those receiving simvastatin (aHR: 0.73; 95%CI: 0.60-0.90), atorvastatin (aHR: 0.70; 95%CI: 0.59-0.85), or rosuvastatin (aHR: 0.47; 95%CI: 0.27-0.80). Major bleeding, used as a falsification endpoint, did not show an association with use of statins at 3-month follow-up. CONCLUSIONS: Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users.

When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review.

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.

Validation of Echocardiographic Measurements in Patients with Pulmonary Embolism in the RIETE Registry.

Background In acute pulmonary embolism (PE), echocardiographic identification of right ventricular (RV) dysfunction will inform prognostication and clinical decision-making. Registro Informatizado Enfermedad TromboEmbolica (RIETE) is the world's largest registry of patients with objectively confirmed PE. The reliability of site-reported RV echocardiographic measurements is unknown. We aimed to validate site-reported key RV echocardiographic measurements in the RIETE registry. Methods Fifty-one randomly chosen patients in RIETE who had transthoracic echocardiogram (TTE) performed for acute PE were included. TTEs were de-identified and analyzed by a core laboratory of two independent observers blinded to site-reported data. To investigate reliability, intraclass correlation coefficients (ICCs) and Bland-Altman plots between the two observers, and between an average of the two observers and the RIETE site-reported data were obtained. Results Core laboratory interobserver variations were very limited with correlation coefficients >0.8 for all TTE parameters. Agreement was substantial between core laboratory observers and site-reported data for key parameters including tricuspid annular plane systolic excursion (ICC 0.728; 95% confidence interval [CI], 0.594-0.862) and pulmonary arterial systolic pressure (ICC 0.726; 95% CI, 0.601-0.852). Agreement on right-to-left ventricular diameter ratio (ICC 0.739; 95% CI, 0.443-1.000) was validated, although missing data limited the precision of the estimates. Bland-Altman plots showed differences close to zero. Conclusion We showed substantial reliability of key RV site-reported measurements in the RIETE registry. Ascertaining the validity of such data adds confidence and reliability for subsequent investigations.

Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

Shock score for prediction of clinical outcomes among stable patients with acute symptomatic pulmonary embolism.

BACKGROUND: The Composite Pulmonary Embolism Shock (CPES) score has been developed to identify normotensive patients with acute pulmonary embolism (PE) and a low cardiac index (referred to as normotensive shock). We aimed to externally assess the validity of this model for predicting a complicated course among hemodynamically stable patients with acute PE. METHODS: Using prospectively collected data from the PROgnosTic valuE of Computed Tomography scan (PROTECT) study, we calculated the CPES score for each patient and the proportion of patients with a score > 3. We calculated the test performance characteristics to predict a complicated course (i.e., death from any cause, hemodynamic collapse, or recurrent PE) and the discriminatory power using the area under the receiver operating characteristic curve. RESULTS: Sixty-three of the 848 (7.4 %) patients had a complicated course during the 30-day follow-up period. Of the 848 enrolled patients, the CPES score was positive (i.e., score > 3) in 78 (9.2 %). The specificity was 92.1 % (723/785), the positive predictive value was 20.5 % (16/78), and the positive likelihood ratio was 3.22 for a complicated course. The areas under the receiver operating characteristic curve for a complicated course were 0.71 (95 % confidence interval [CI], 0.65-0.78). With the higher score risk classification threshold (cutoff score > 4), the proportion of patients designated as positive was 2.1 %, and the specificity was 98.1 %. When echocardiographic right ventricle (RV) dysfunction was replaced by computed tomographic RV enlargement, the specificity was 85.4 %, the positive predictive value was 14.2 %, and the positive likelihood ratio was 2.06 for a complicated course. When analyses were restricted to the subgroup of patients with intermediate-risk PE, the specificity and the positive predictive value for a complicated course were identical to the overall cohort. CONCLUSIONS: The CPES score has acceptable C-statistic, excellent specificity, and low positive predictive value for identification of hemodynamic deterioration in normotensive patients with PE. CLINICALTRIALS: gov number: NCT02238639.

High-Sensitivity vs Conventional Troponin Cutoffs for Risk Stratification in Patients With Acute Pulmonary Embolism.

Importance: High-sensitivity troponin tests can detect even milder cardiac troponin elevations in plasma, beyond the threshold of conventional troponin tests. Whether detection of low-grade cardiac troponin elevation is associated with outcomes of patients with hemodynamically stable pulmonary embolism (PE) and helps with risk stratification is unknown. Objective: To determine the association between high-sensitivity cardiac troponin I (hs-cTnI) compared with conventional cardiac troponin I (cTnI) and PE risk designations according to the European Society of Cardiology (ESC) 2019 classification scheme and clinical outcomes in patients with hemodynamically stable PE. Design, Setting, and Participants: This is a post hoc analysis of data from the prospective Prognostic Value of Computed Tomography (PROTECT) multicenter cohort study enrolling patients from 12 hospital emergency departments in Spain. In this analysis, cTnI and hs-cTnI were compared with respect to ESC risk designation, and the association between troponin values and a complicated course after PE diagnosis was evaluated. Of 848 patients enrolled in PROTECT, 834 (98.3%) had hsTnI and cTnI values available and were included in the present analysis. Data were analyzed from May to December 2022. Exposures: Troponin blood testing with cTnI (threshold of >0.05 ng/mL) vs hs-cTnI (threshold of >0.029 ng/mL) assays at the time of PE diagnosis. Main Outcomes: Complicated course, defined as hemodynamic collapse, recurrent PE, or all-cause death, within 30 days after PE. Results: Of 834 patients (mean [SEM] age, 67.5 [0.6] years; 424 [50.8%] female), 139 (16.7%) had elevated cTnI and 264 (31.7%) elevated hs-TnI, respectively. During follow-up, 62 patients (7.4%; 95% CI, 5.7-9.4) had a complicated course. Analyzing troponin elevation as a binary variable, elevated cTnI (odds ratio [OR], 2.84; 95% CI, 1.62-4.98) but not hs-cTnI (OR, 1.12; 95% CI, 0.65-1.93) was associated with increased odds of a complicated course. Of 125 patients who had elevated hs-cTnI but normal cTnI, none (0; 95% CI, 0.0-2.9) developed a complicated course. Using the 2019 ESC risk stratification scheme, hs-TnI classified fewer patients as low risk compared with cTnI. Among 78 patients designated as ESC low risk when using cTnI but not with hsTnI, none (0; 95% CI, 0.0-4.6) had a complicated course. Conclusions and Relevance: In this study of patients with hemodynamically stable PE, hs-cTnI identified modest elevations in cardiac troponin levels. However, the results did not provide additive clinical value compared with cTnI. These findings suggest that use of hs-cTnI may result in overestimation of the risk in patients with stable PE.

Association of vena cava filters and catheter-directed thrombolysis for deep vein thrombosis with hospital readmissions.

BACKGROUND: Acute deep vein thrombosis (DVT) affects >350,000 patients each year in the United States. Contemporary rehospitalization rates and predictors of acute DVT have not been well-characterized. We aimed to evaluate the all-cause 30-day readmission rate and its association with catheter-directed thrombolysis and vena cava filters in patients with proximal and caval DVT. METHODS: Patients with an index hospitalization for acute proximal lower extremity DVT were evaluated for unplanned readmission rates at 30 days using the Nationwide Readmission Database from 2016 to 2017. We used Cox proportional hazard model to determine the predictors of 30-day readmissions and their association with inferior vena cava (IVC) filter and CDT use. RESULTS: We identified 58,306 adult patients with an index hospitalization for acute proximal DVT. The unplanned 30-day rehospitalization rate was 14.7% (95% confidence interval [CI], 14.5-15.0%). There were 4995 patients (10.0%) who underwent CDT and 6085 (12.2%) who underwent IVC filter placement. In multivariable analysis, only CDT was associated with a lower hazard for rehospitalization (hazard ratio [HR], 0.77; 95% CI, 0.71-0.84; P < .001), whereas IVC filter placement (HR, 1.26; 95% CI, 1.19-1.34; P < .001), Charlson Comorbidity Index of >3 (HR, 1.47; 95% CI, 1.38-1.56; P < .001), malignancy (HR, 1.45; 95% CI, 1.34-1.57; P < .001), and length of stay >5 days (HR, 1.39; 95% CI, 1.33-1.46; P < .001), and acute kidney injury (HR, 1.18; 95% CI, 1.11-1.25; P < .001) were associated with higher readmission rates. CONCLUSIONS: The 30-day unplanned rehospitalization rate continues to be high in patients with acute proximal DVT. CDT was associated with lower rehospitalization rates, whereas IVC filter placement was associated with increased rehospitalization rates.

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis.

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer. METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT. RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58). CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials.

BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.

Identification of Low-risk Patients With Acute Symptomatic Pulmonary Embolism

Background: Identification of patients with acute symptomatic pulmonary embolism (PE) who are at low-risk for short-term complications to warrant outpatient care lacks clarity. Method: In order to identify patients at low-risk for 30-day all-cause and PE-related mortality, we used a cohort of haemodynamically stable patients from the RIETE registry to compare the false-negative rate of four strategies: the simplified Pulmonary Embolism Severity Index (sPESI); a modified (i.e., heart rate cutoff of 100beats/min) sPESI; and a combination of the original and the modified sPESI with computed tomography (CT)-assessed right ventricle (RV)/left ventricle (LV) ratio. Results: Overall, 137 of 3117 patients with acute PE (4.4%) died during the first month. Of these, 41 (1.3%) died from PE, and 96 (3.1%) died from other causes. The proportion of patients categorized as having low-risk was highest with the sPESI and lowest with the combination of a modified sPESI and CT-assessed RV/LV ratio (32.5% versus 16.5%; P<0.001). However, among patients identified as low-risk, the 30-day mortality rate was lowest with the combination of a modified sPESI and CT-assessed RV/LV ratio and highest with the sPESI (0.4% versus 1.0%; P=0.03). The 30-day PE-related mortality rates for patients designated as low-risk by the sPESI, the modified sPESI, and the combination of the original and modified sPESI with CT-assessed RV/LV ratio were 0.7%, 0.4%, 0.7%, and 0.2%, respectively. Conclusions: The combination of a negative modified sPESI with CT-assessed RV/LV ratio ≤1 identifies patients with acute PE who are at very low-risk for short-term mortality. (AU)

Antithrombotic Therapy in Arterial Thrombosis and Thromboembolism in COVID-19: An American College of Chest Physicians Expert Panel Report.

BACKGROUND: Evidence increasingly shows that the risk of thrombotic complications in COVID-19 is associated with a hypercoagulable state. Several organizations have released guidelines for the management of COVID-19-related coagulopathy and prevention of VTE. However, an urgent need exists for practical guidance on the management of arterial thrombosis and thromboembolism in this setting. RESEARCH QUESTION: What is the current available evidence informing the prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19? STUDY DESIGN AND METHODS: A group of approved panelists developed key clinical questions by using the Population, Intervention, Comparator, and Outcome (PICO) format that address urgent clinical questions regarding prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19. Using MEDLINE via PubMed, a literature search was conducted and references were screened for inclusion. Data from included studies were summarized and reviewed by the panel. Consensus for the direction and strength of recommendations was achieved using a modified Delphi survey. RESULTS: The review and analysis of the literature based on 11 PICO questions resulted in 11 recommendations. Overall, a low quality of evidence specific to the population with COVID-19 was found. Consequently, many of the recommendations were based on indirect evidence and prior guidelines in similar populations without COVID-19. INTERPRETATION: The existing evidence and panel consensus do not suggest a major departure from the management of arterial thrombosis according to recommendations predating the COVID-19 pandemic. Data on the optimal strategies for prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19 are sparse. More high-quality evidence is needed to inform management strategies in these patients.

Trends in Pulmonary Embolism Deaths Among Young Adults Aged 25 to 44 Years in the United States, 1999 to 2019.

A concerning increase in mortality from acute pulmonary embolism (PE) in young adults in the United States has been reported. We extracted PE-related mortality rates (number of deaths per US population) from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from 1999 to 2019, focusing on subjects aged 25 to 44 years. Age-adjusted mortality rates (AAMRs) were assessed using the Joinpoint regression modeling and expressed as the estimated average annual percentage change (AAPC) with relative 95% confidence intervals (95% CIs) and stratified by urbanization, gender, age, and race. Between 1999 and 2019, the AAMR from acute PE in US adults aged 25 to 44 years linearly increased without any difference between genders (AAPC +1.5%, 95% CI 1.2 to 1.8, p <0.001). AAMR increase was more pronounced in American-Indians/Alaska Natives and in Asian/Pacific Islanders (AAPC +2.5%, 95% CI 1.6 to 3.4, p <0.001), Whites (AAPC +1.7%, 95% CI 1.4 to 2.0, p <0.001), Latinx/Hispanic patients (AAPC +1.7%, 95% CI 0.6 to 3.0, p = 0.003), and residents of rural areas (AAPC +2.4%, 95% CI 1.9 to 2.8, p <0.001). A higher AAMR (4.02 per 100,000 residents, 95% CI 3.90 to 4.15) and absolute number of PE-related deaths were observed in the South. PE-related mortality in adults aged 25 to 44 years has increased over the last 2 decades in the United States. Stratification by race, ethnicity, urbanization, and census region showed ethnoracial and regional disparities that will require further evaluation and remedy.