Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID-19.

Background Venous thromboembolism (VTE) contributes significantly to COVID-19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID-19. Whether suPAR levels identify patients with COVID-19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID-19 with suPAR and D-dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine-Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D-dimer levels. There was a positive association between suPAR and D-dimer (ß=7.34; P=0.002). Adjusted for clinical covariables, including D-dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51-4.75]; P<0.001). Findings were consistent when stratified by D-dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D-dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D-dimer in patients hospitalized for COVID-19. Combining suPAR and D-dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

Clinical outcomes of COVID-19 infection in patients with pre-existing cardiovascular disease.

Introduction: Patients with pre-existing cardiovascular disease may carry a higher risk for mortality from COVID-19. This study examined the association between individuals with pre-existing cardiovascular disease admitted for COVID-19 and their clinical outcomes. Methods: A retrospective cohort study was conducted on patients admitted with COVID-19 to Rush University System for Health (RUSH) to identify cardiovascular risk factors associated with increased mortality and major adverse cardiovascular events (MACE; a composite of cardiovascular death, stroke, myocardial injury, and heart failure exacerbation). Multivariable logistic regression was used to adjust for demographic data and comorbid conditions. Results: Of the 1682 patients who met inclusion criteria, the median age was 59. Patients were predominantly African American (34.4 %) and male (54.5 %). Overall, 202 (12 %) patients suffered 60-day mortality. In the multivariable model that assessed risk factors for 60-day mortality, age 60-74 (adjusted odds ratio [aOR] 3.30 [CI: 1.23-10.62]; p < 0.05) and age 75-100 (aOR 4.52 [CI: 1.46-16.15]; p < 0.05) were significant predictors when compared to those aged 19 to 39. This model also showed that those with past medical histories of atrial fibrillation (aOR 2.47 [CI: 1.38-4.38]; p < 0.01) and venous thromboembolism (aOR 2.00 [CI: 1.12-3.50]; p < 0.05) were at higher risk of 60-day mortality. Conclusion: In this cohort, patients over 60 years old with a pre-existing history of atrial fibrillation and venous thromboembolism were at increased risk of mortality from COVID-19.

Hyperdynamic left ventricular ejection fraction is associated with higher mortality in COVID-19 patients.

Study objective: To compare the characteristics and outcomes of COVID-19 patients with a hyperdynamic LVEF (HDLVEF) to those with a normal or reduced LVEF. Design: Retrospective study. Setting: Rush University Medical Center. Participants: Of the 1682 adult patients hospitalized with COVID-19, 419 had a transthoracic echocardiogram (TTE) during admission and met study inclusion criteria. Interventions: Participants were divided into reduced (LVEF < 50%), normal (≥50% and <70%), and hyperdynamic (≥70%) LVEF groups. Main outcome measures: LVEF was assessed as a predictor of 60-day mortality. Logistic regression was used to adjust for age and BMI. Results: There was no difference in 60-day mortality between patients in the reduced LVEF and normal LVEF groups (adjusted odds ratio [aOR] 0.87, p = 0.68). However, patients with an HDLVEF were more likely to die by 60 days compared to patients in the normal LVEF group (aOR 2.63 [CI: 1.36-5.05]; p < 0.01). The HDLVEF group was also at higher risk for 60-day mortality than the reduced LVEF group (aOR 3.34 [CI: 1.39-8.42]; p < 0.01). Conclusion: The presence of hyperdynamic LVEF during a COVID-19 hospitalization was associated with an increased risk of 60-day mortality, the requirement for mechanical ventilation, vasopressors, and intensive care unit.

Prognostic value of H2FPEF score in COVID-19.

STUDY OBJECTIVE: This study sought to assess the predictive value of H2FPEF score in patients with COVID-19. DESIGN: Retrospective study. SETTING: Rush University Medical Center. PARTICIPANTS: A total of 1682 patients had an echocardiogram in the year preceding their COVID-19 admission with a preserved ejection fraction (≥50%). A total of 156 patients met inclusion criteria. INTERVENTIONS: Patients were divided into H2FPEF into low (0-2), intermediate (3-5), and high (6-9) score H2FPEF groups and outcomes were compared. MAIN OUTCOME MEASURES: Adjusted multivariable logistic regression models evaluated the association between H2FPEF score group and a composite outcome for severe COVID-19 infection consisting of (1) 60-day mortality or illness requiring (2) intensive care unit, (3) intubation, or (4) non-invasive positive pressure ventilation. RESULTS: High H2FPEF scores were at increased risk for severe COVID-19 infection when compared intermediate to H2FPEF score groups (OR 2.18 [CI: 1.01-4.80]; p = 0.049) and low H2FPEF score groups (OR 2.99 [CI: 1.22-7.61]; p < 0.05). There was no difference in outcome between intermediate H2FPEF scores (OR 1.34 [CI: 0.59-3.16]; p = 0.489) and low H2FPEF score. CONCLUSIONS: Patients with a high H2FPEF score were at increased risk for severe COVID-19 infection when compared to patients with an intermediate or low H2FPEF score regardless of regardless of coronary artery disease and chronic kidney disease.

Cardiac CT angiography in current practice: An American society for preventive cardiology clinical practice statement✰.

In this clinical practice statement, we represent a summary of the current evidence and clinical applications of cardiac computed tomography (CT) in evaluation of coronary artery disease (CAD), from an expert panel organized by the American Society for Preventive Cardiology (ASPC), and appraises the current use and indications of cardiac CT in clinical practice. Cardiac CT is emerging as a front line non-invasive diagnostic test for CAD, with evidence supporting the clinical utility of cardiac CT in diagnosis and prevention. CCTA offers several advantages beyond other testing modalities, due to its ability to identify and characterize coronary stenosis severity and pathophysiological changes in coronary atherosclerosis and stenosis, aiding in early diagnosis, prognosis and management of CAD. This document further explores the emerging applications of CCTA based on functional assessment using CT derived fractional flow reserve, peri­coronary inflammation and artificial intelligence (AI) that can provide personalized risk assessment and guide targeted treatment. We sought to provide an expert consensus based on the latest evidence and best available clinical practice guidelines regarding the role of CCTA as an essential tool in cardiovascular prevention - applicable to risk assessment and early diagnosis and management, noting potential areas for future investigation.

Controversial Dietary Patterns: A High Yield Primer for Clinicians.

In cardiology clinic visits, the discussion of optimal dietary patterns for prevention and management of cardiovascular disease is usually very limited. Herein, we explore the benefits and risks of various dietary patterns, including intermittent fasting, low carbohydrate, Paleolithic, whole food plant-based diet, and Mediterranean dietary patterns within the context of cardiovascular disease to empower clinicians with the evidence and information they need to maximally benefit their patients.

Socioeconomics of coronary artery calcium: Is it scored or ignored?

IMPORTANCE: Chicago is one of the most racially segregated cities in the US, with the largest mortality gap between neighborhoods. Computed tomographic coronary artery calcium scoring (CACS) is an excellent risk stratification tool, but costs about $200 out-of-pocket, making it inaccessible to some. OBJECTIVE: To determine whether this ACC/AHA guideline-recommended screening tool is accessible to all populations and neighborhoods, we evaluated the price and availability of CACS in Chicago area hospitals. DESIGN: We used the Illinois Department of Public Health list of area hospitals to inquire about CACS availability and price. We compared these results to US Census Bureau data for each hospital's service area's demographic, ethnic and socioeconomic population characteristics. RESULTS: Out of the 40 hospitals in Chicagoland, 30 offered CACS. The 10 hospitals without CACS were smaller hospitals in zip codes with a higher population density (p â€‹< â€‹0.01), higher poverty rates (22% vs. 13%, p â€‹< â€‹0.01), lower percentage of white population (p â€‹< â€‹0.02), lower frequency of higher education (35% vs. 51%, p â€‹< â€‹0.05), and a trend toward more black residents (p â€‹< â€‹0.10). Life expectancy was greater in areas with CACS available (78 vs. 75 years, p â€‹< â€‹0.05). Even in areas with CACS, there was wide price variation, with higher prices in poorer areas (r â€‹= â€‹0.57, p â€‹< â€‹0.01). The highest vs. lowest quintile of income had higher education, larger white population (80% vs. 14%, p â€‹< â€‹0.0001), and longer life expectancy (81 vs. 72 years, p â€‹< â€‹0.0002), but tended to have a lower price of CACS ($86 vs. $487, p â€‹< â€‹0.08). CONCLUSIONS AND RELEVANCE: CACS is a powerful, evidenced-based clinical tool, but the availability and price vary widely in Chicagoland, and directly correlate with the socioeconomic and health care disparities that are known to exist. Removing these barriers to coronary artery disease screening may be one method to improve the poor cardiovascular outcomes in these areas.

Trending Nutrition Controversies #3: Top Controversies in 2021.

Each year, patients are bombarded with diverging and even contradictory reports concerning the impact of certain additives, foods, and nutrients on cardiovascular health and its risk factors. Accordingly, this third review of nutrition controversies examines the impact of artificial sweeteners, cacao, soy, plant-based meats, nitrates, and meats from grass compared to grain-fed animals on cardiovascular and other health outcomes with the goal of optimizing clinician-led diet counseling.

Oral anticoagulants and relative risk of acute kidney injury in patients with atrial fibrillation: A systematic review and network meta-analysis.

Study objective: Oral anticoagulants (direct oral anticoagulants [DOACs] or warfarin) prevent stroke in patients with atrial fibrillation (AF), but their use may be associated with acute kidney injury (AKI). We aimed to compare AKI risk across individual oral anticoagulants in patients with AF. Design: Systematic review and network meta-analysis. Setting: Randomized trials and population-based studies. Participants: Patients with AF. Interventions: Oral anticoagulants. Main outcome measures: AKI. Results: A systematic literature search in Medline and Embase databases performed on December 17, 2021 identified ten randomized trials and eight population-based longitudinal studies based on prespecified inclusion criteria for systematic review. Clinical trials had short follow-ups and reported only low event rates of serious AKI. Retrospective longitudinal studies were assessed to be at higher risk for bias from confounding and outcome ascertainment, but follow-up was longer (1.5 to 8 years), with AKI incidence ranging from 2 to 29/100 person-years. Eight longitudinal studies that met transitivity assumption were included in a random-effects network meta-analysis within a Bayesian framework. All DOACs were associated with significantly lower risk of AKI compared to warfarin. Dabigatran was associated with lower risk of AKI compared to apixaban (hazard ratio [HR] = 0.82; 95% confidence interval [CI]: 0.68-0.99), rivaroxaban (HR = 0.84; 95%CI: 0.72-0.98), and warfarin (HR = 0.68; 95%CI: 0.59-0.77). Effect size estimates varied by chronic kidney disease status and study geographic locations. Conclusion: Apixaban, rivaroxaban, and dabigatran were associated with lower long-term risk of AKI compared to warfarin among patients with AF, with dabigatran potentially associated with the lowest risk.

Cardiovascular findings on chest computed tomography associated with COVID-19 adverse clinical outcomes.

STUDY OBJECTIVE: Chest computed tomography (chest CT) is routinely obtained to assess disease severity in COVID-19. While pulmonary findings are well-described in COVID-19, the implications of cardiovascular findings are less well understood. We evaluated the impact of cardiovascular findings on chest CT on the adverse composite outcome (ACO) of hospitalized COVID-19 patients. SETTING/PARTICIPANTS: 245 COVID-19 patients who underwent chest CT at Rush University Health System were included. DESIGN: Cardiovascular findings, including coronary artery calcification (CAC), aortic calcification, signs of right ventricular strain [right ventricular to left ventricular diameter ratio, pulmonary artery to aorta diameter ratio, interventricular septal position, and inferior vena cava (IVC) reflux], were measured by trained physicians. INTERVENTIONS/MAIN OUTCOME MEASURES: These findings, along with pulmonary findings, were analyzed using univariable logistic analysis to determine the risk of ACO defined as intensive care admission, need for non-invasive positive pressure ventilation, intubation, in-hospital and 60-day mortality. Secondary endpoints included individual components of the ACO. RESULTS: Aortic calcification was independently associated with an increased risk of the ACO (odds ratio 1.86, 95% confidence interval (1.11-3.17) p < 0.05). Aortic calcification, CAC, abnormal septal position, or IVC reflux of contrast were all significantly associated with 60-day mortality and major adverse cardiovascular events. IVC reflux was associated with in-hospital mortality (p = 0.005). CONCLUSION: Incidental cardiovascular findings on chest CT are clinically important imaging markers in COVID-19. It is important to ascertain and routinely report cardiovascular findings on CT imaging of COVID-19 patients as they have potential to identify high risk patients.

The prognostic value of cardiac troponin for 60 day mortality and major adverse events in COVID-19 patients.

BACKGROUND: The variability of coronavirus disease 2019 (COVID-19) illness severity has puzzled clinicians and has sparked efforts to better predict who would benefit from rapid intervention. One promising biomarker for in-hospital morbidity and mortality is cardiac troponin (cTn). METHODS: A retrospective study of 1331 adult patients with COVID-19 admitted to the Rush University System in Illinois, USA was performed. Patients without cTn measurement during their admission or a history of end stage renal disease or stage 5 chronic kidney disease were excluded. Using logistic regression adjusted for baseline characteristics, pre-existing comorbidities, and other laboratory markers of inflammation, cTn was assessed as a predictor of 60-day mortality and severe COVID-19 infection, consisting of a composite of 60-day mortality, need for intensive care unit, or requiring non-invasive positive pressure ventilation or intubation. RESULTS: A total of 772 patients met inclusion criteria. Of these, 69 (8.9%) had mild cTn elevation (> 1 to < 2x upper limit of normal (ULN)) and 46 (6.0%) had severe cTn elevation (≥ 2x ULN). Regardless of baseline characteristics, comorbidities, and initial c-reactive protein, lactate dehydrogenase, and ferritin, when compared to the normal cTn group, mild cTn elevation and severe cTn elevation were predictors of severe COVID-19 infection (adjusted OR [aOR] aOR 3.00 [CI: 1.51 - 6.29], P < 0.01; aOR 9.96 [CI: 2.75 - 64.23], P < 0.01, respectively); severe cTn elevation was a predictor of in-hospital mortality (aOR 2.42 [CI: 1.10 - 5.21], P < 0.05) and 60-day mortality (aOR 2.45 [CI: 1.13 - 5.25], P < 0.05). CONCLUSION: In our cohort, both mild and severe initial cTn elevation were predictors of severe COVID-19 infection, while only severe cTn elevation was predictive of 60-day mortality. First cTn value on hospitalization is a valuable longitudinal prognosticator for COVID-19 disease severity and mortality.

Sex Differences in COVID-19 Hospitalization and Mortality.

Background: To investigate sex differences in coronavirus disease 2019 (COVID-19) outcomes in a large Illinois-based cohort. Methods: A multicenter retrospective cohort study compared males versus females with COVID-19 infections from March 1, 2020, to June 21, 2020, in the Rush University System. We analyzed sex differences in rates of hospitalization, intensive care unit (ICU) admission, vasopressor use, endotracheal intubation, and death in this cohort. A multivariable model correcting for age and sum of comorbidities was used to explore associations between sex and COVID-19-related outcomes. Results: There were 8108 positive COVID-19 patients-4300 (53.0%) females and 3808 (47.0%) males. Males had higher rates of hospitalization (19% vs. 13%; p < 0.001), ICU transfer (8% vs. 4%; p < 0.001), vasopressor support (4% vs. 2%; p < 0.001), and endotracheal intubation (5% vs. 2%; p < 0.001). Of those who died, 92 were males and 64 were females (2% vs. 1%; p = 0.003). A multivariable model correcting for age and sum of comorbidities showed a significant association between male sex and mortality in the total cohort (odds ratio, 1.96; 95% confidence interval, 1.34-2.90; p = 0.001). Conclusion: Male sex was independently associated with death, hospitalization, ICU admissions, and need for vasopressors or endotracheal intubation, after correction for important covariates.

Association of Outpatient Practice-Level Socioeconomic Disadvantage With Quality of Care and Outcomes Among Older Adults With Coronary Artery Disease: Implications for Value-Based Payment.

BACKGROUND: Medicare patients with coronary artery disease (CAD) have been a significant focus of value-based payment programs for outpatient practices. Physicians and policymakers, however, have voiced concern that value-based payment programs may penalize practices that serve vulnerable populations. This study evaluated whether outpatient practices that serve socioeconomically disadvantaged populations have worse CAD outcomes, and if this reflects the delivery of lower-quality care or rather, patient and community factors beyond the care provided by physician practices. METHODS AND RESULTS: Retrospective cohort study of Medicare fee-for-service patients ≥65 years with CAD at outpatient practices participating in the the Practice Innovation and Clinical Excellence registry from January 1, 2010 to January 1, 2015. Outpatient practices were stratified into quintiles by the proportion of most disadvantaged patients-defined by an area deprivation score in the highest 20% nationally-served at each practice site. Prescription of guideline recommended therapies for CAD as well as clinical outcomes (emergency department presentation for chest pain, hospital admission for unstable angina or acute myocardial infarction [AMI], 30-day readmission after AMI, and 30-day mortality after AMI) were evaluated by practice-level socioeconomic disadvantage with hierarchical logistic regression models, using practices serving the fewest socioeconomically disadvantaged patients as a reference. The study included 453 783 Medicare fee-for-service patients ≥65 years of age with CAD (mean [SD] age, 75.3 [7.7] years; 39.7% female) cared for at 271 outpatient practices. At practices serving the highest proportion of socioeconomically disadvantaged patients (group 5), compared with practices serving the lowest proportion (group 1), there was no significant difference in the likelihood of prescription of antiplatelet therapy (odds ratio [OR], 0.94 [95% CI, 0.69-1.27]), ß-blocker therapy if prior myocardial infarction or left ventricular ejection fraction <40% (OR, 0.97 [95% CI, 0.69-1.35]), ACE (angiotensin-converting enzyme) inhibitor or angiotensin receptor blocker if left ventricular ejection fraction <40% and/or diabetes mellitus (OR, 0.93 [95% CI, 0.74-1.19]), statin therapy (OR, 0.88 [95% CI, 0.68-1.14]), or cardiac rehabilitation (OR, 0.45 [95% CI, 0.20-1.00]). Patients cared for at the most disadvantaged-serving practices (group 5) were more likely to be admitted for unstable angina (adjusted OR, 1.46 [95% CI, 1.04-2.05]). There was no significant difference in the likelihood of emergency department presentation for chest pain or hospital admission for AMI between practices. Thirty day mortality rates after AMI were higher among patients at the most disadvantaged-serving practices (aOR, 1.31 [95% CI, 1.02-1.68]), but 30-day readmission rates did not differ. All associations were attenuated after additional adjustment for patient-level area deprivation index. CONCLUSIONS: Physician outpatient practices that serve the most socioeconomically disadvantaged patients with CAD perform worse on some clinical outcomes, despite providing similar guideline-recommended care as other practices, and consequently could fare poorly under value-based payment programs. Social factors beyond care provided by outpatient practices may partly explain worse outcomes. Policymakers should consider accounting for socioeconomic disadvantage in value-based payment programs initiatives that target outpatient practices.