Overcoming Pandemic-Related Challenges in Recruitment and Screening: Strategies and Representation of Older Women With Cardiovascular Disease for a Multidomain Lifestyle Trial to Prevent Cognitive Decline.

BACKGROUND: Recruiting participants with cardiovascular disease into research during the COVID-19 pandemic was challenging, particularly those at risk of health disparities. OBJECTIVE: During the pandemic, 12 cohorts of older women with cardiovascular disease were recruited from cardiology clinics into a lifestyle intervention trial to prevent cognitive decline. Objectives were to (a) describe the results of modified recruitment/screening strategies to overcome pandemic-related challenges and (b) evaluate differences in age, race, and ethnicity between patients recruited/randomized, recruited/not randomized (entered recruitment but not randomized because of being ineligible or not interested), and not recruited (clinic patients who met preliminary criteria but did not enter recruitment). METHODS: This was a cross-sectional descriptive analysis. In-person study strategies proposed before the COVID-19 pandemic were modified before study onset (September 2020). Women 65 years or older with cardiovascular disease were recruited from cardiology clinics by clinicians, posted flyers, and letters mailed to patients randomly selected from electronic health record data extractions. Patients were classified as recruited/randomized, recruited/not randomized, and not recruited. RESULTS: Of 5719 patients potentially eligible, 1689 patients entered recruitment via referral (49.1%), posted flyers (0.5%), or mailed letters (50.3%), and 253 patients were successfully recruited/randomized. Recruited/randomized participants were, on average, 72.4 years old (range, 65-90 years old), non-Hispanic White (54.2%), non-Hispanic Black (38.3%), Hispanic/Latinx (1.6%), and other/not reported (5.1%). The recruited/randomized group was significantly younger with fewer patients of Hispanic/Latinx ethnicity compared with those not recruited. CONCLUSIONS: During the pandemic, all recruitment/screening goals were met using modified strategies. Differences in sociodemographic representation indicate a need for tailored strategies.

Impact of the COVID-19 pandemic on cardiovascular disease mortality in a major metropolitan area.

Background: The mortality from COVID-19 alone cannot account for the impact of the pandemic. Cardiovascular disease (CVD) mortality has increased disproportionately in specific racial/ethnic populations. Objective: This study aimed to characterize how the COVID-19 pandemic impacted the association between CVD mortality and social and demographic factors as characterized by the Social Vulnerability Index (SVI). Methods: Medical Examiner Case Archive of Cook County, Illinois was utilized to identify CVD deaths in 2019 (pre-pandemic) and 2020 (pandemic). Rate ratios (RRs) were used to compare age-adjusted mortality rates (AAMRs). Addresses of deaths were geocoded to Chicago Community Areas. The Spearman's rank correlation coefficient (ρ) test was used to identify the association between SVI and CVD mortality. Results: AAMRs of CVD deaths significantly increased among non-Hispanic Black individuals (AAMRR, 1.1; 95 % CI, 1.1-1.2) and Hispanic individuals (AAMRR, 1.8; 95 % CI, 1.5-2.1) from 2019 to 2020. Among non-Hispanic White individuals, the AAMR did not significantly increase (AAMRR, 1.0; 95 % CI, 0.9-1.1). A significant positive association was observed between SVI and the percentage of non-Hispanic Black residents (ρ = 0.45; P < 0.05), while the inverse was observed with the percentage of non-Hispanic White residents (ρ = -0.77; P < 0.05). A significant positive association between SVI and CVD mortality rate increased (ρ = 0.24 and 0.28; P < 0.05). Conclusions: Significant association between SVI and CVD mortality was strengthened from 2019 to 2020, and CVD mortality increased among non-Hispanic Black and Hispanic populations. These findings demonstrate that the COVID-19 pandemic has led to an exacerbation of health inequities among different racial/ethnic populations resulting in increased CVD mortality.

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.

All-cause and in-hospital mortality after aspirin use in patients hospitalized with COVID-19: a systematic review and meta-analysis.

Background: With the results of the largest randomized controlled trial (RECOVERY) and the most extensive retrospective cohort study on coronavirus disease 2019 (COVID-19) recently published, we performed a meta-analysis on the association of aspirin with mortality of COVID-19. We aimed to investigate the role of aspirin in COVID-19 hospitalizations. Materials and Methods: We searched PubMed, EMBASE and Cochrane databases for studies from 1 January 2020 until 20 July 2022, that compared aspirin versus non-aspirin use in hospitalized COVID-19 patients. We excluded case reports, review articles and studies on non-hospitalized COVID-19 infections. We used the inverse variance method and random effects model to pool the individual studies. Results: Ten observational studies and one randomized controlled trial met the criteria for inclusion. There were 136 695 total patients, of which 27 168 were in the aspirin group and 109 527 were in the non-aspirin group. Aspirin use was associated with a 14% decrease in all-cause mortality compared with non-aspirin use in patients hospitalized with COVID-19 [relative risk (RR) 0.86, confidence interval (95% CI) 0.76-0.97; P = 0.002; I 2 =64%]. Among subgroups of studies reporting in-hospital mortality in COVID-19 hospitalizations, aspirin use was associated with a 16% decrease in in-hospital mortality compared with non-aspirin use (RR 0.84, 95% CI 0.71-0.99; P = 0.007; I 2 =64%). Conclusion: Our study shows that aspirin decreases in-hospital mortality in patients hospitalized with COVID-19. Further studies are needed to assess which COVID-19 patient populations benefit most, such as patients on aspirin for primary versus secondary prevention of atherosclerotic disease. In addition, significant bleeding also needs to be considered when assessing the risk-benefit of aspirin use.

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.

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.

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.

Leveraging virtual reality to train certified nursing assistants as essential dementia-care personnel in the age of COVID-19.

BACKGROUND: COVID-19 has placed an extraordinary and disproportionate level of responsibility and risk on certified nursing assistants (CNAs) caring for persons with dementia (PWD) relative to their training, resources, and compensation levels. Nearly one-quarter of COVID-19 deaths in the United States have been nursing home residents and staff. Despite providing the majority of direct care, CNAs are amongst the most under-resourced and under-trained frontline workers. Given their essentiality, it is critical to support CNAs during the COVID-19 pandemic. The purpose of this work is to provide CNAs with a space to strengthen their knowledge and confidence in caring for PWD. This pilot study applies a virtual reality (VR) curriculum to train CNAs regarding the lived experiences of PWD and their loved ones. The VR vignette portrays a Latinx woman, Beatriz, through progressive stages of Alzheimer's disease. METHOD: Chicago Methodist Senior Services (CMSS) CNAs were recruited (N=7; 86% female, 86% Black) for a seven-week online training program consisting of 1.5 hours per week. Each class included a didactic lecture and an Embodied Labs VR module depicting a first-person experience of dementia through a distributive model approach. The program concluded with two recorded focus groups. Participants completed the UCLA Geriatric Attitudes Scale, a dementia knowledge assessment, the Interpersonal Reactivity Index surveys, and a COVID-19 Impact questionnaire. Current analyses include qualitative content analysis for focus group data and descriptive, quantitative statistics for pre-and post-VR intervention surveys. RESULT: Preliminary results demonstrate that CNAs endorsed a positive change in attitudes toward older adults (p=0.069), a deepened understanding of dementia, and increased confidence in caregiving skills. Focus groups allowed CNAs to discuss changes in resident behavior and support one another through a virtual platform during a global pandemic. CONCLUSION: Combining traditional didactic lectures with VR-based curricula provided CNAs with foundational knowledge and first-hand experience of dementia pathology. Participants reported greater levels of insight and empathy for PWD. Future aims include expansion of training content to include end-of-life conversations, LGBTQIA aging, and Lewy body dementia.

Modifications in response to the COVID-19 pandemic in a multimodal intervention trial to prevent cognitive impairment in older women with cardiovascular disease

Background Cognitive impairment disproportionately affects women compared to men, and cardiovascular disease (CVD) increases risk. Physical activity and cognitive training may have synergistic effects on cognition when delivered together. However, no multimodal intervention has targeted older women (≥65) with CVD or has utilized a scalable lifestyle approach. Our study seeks to evaluate the efficacy of MindMoves, a 24-week multimodal intervention, on cognition and serum biomarkers in 254 older women with CVD. However, effects of the COVID-19 pandemic complicated implementation of our original in-person trial protocol. The purpose of this paper is to describe protocol modifications made by our interdisciplinary team in response to COVID-19, Method We employ a 2x2 factorial randomized controlled trial design to determine independent and combined efficacies of Mind (cognitive training with BrainHQ) and Move (lifestyle physical activity with goal self-monitoring and nurse-led group meetings) interventions. Outcome measures of cognition and serum biomarkers (brain-derived neurotrophic factor, vascular endothelial growth factor, insulin-like growth factor 1) are collected at baseline, 24, 48, and 72 weeks. Nurse scientists oversee interventions, cardiologists refer women ≥65 years with CVD and no cognitive impairment from clinics, and a cognitive neurologist and neuropsychologist oversee outcome measures. Pandemic-related protocol changes were implemented to maximize study integrity and participant/staff safety. Targeted mailings were added to in-person recruitment strategies. Screening activities shifted to phone. In-person data collection was modified for phone/virtual settings, including accelerometer mailing (device measure of physical activity), neurocognitive tests validated for phone use, and home-based participant-administered dried blood spot collection for serum biomarkers. Women are now provided and trained to use iPad tablets to complete intervention activities virtually (e.g., Move group meetings). Result The anticipated number of participants (19) in the first cohort was recruited without disruption, in the original timeline. Participants completed all phone-based questionnaires and mailed devices were returned. Randomization occurred as planned. Intervention activities are ongoing, including phone-based orientations and ≥90% attendance at virtual meetings. Conclusion The modified trial protocol is being successfully implemented during the COVID-19 pandemic. Results will demonstrate efficacy of pivoting from in-person to virtual delivery of a lifestyle-focused multimodal intervention in at-risk older women with CVD.

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.

Impact of pre-existing heart failure on 60-day outcomes in patients hospitalized with COVID-19.

BACKGROUND: In the coronavirus disease 2019 (COVID-19) global pandemic, patients with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. However, the relationship between COVID-19 and heart failure (HF) is unclear, specifically whether HF is an independent risk factor for severe infection or if other accompanying comorbidities are responsible for the increased risk. METHODS: This is a retrospective analysis of 1331 adult patients diagnosed with COVID-19 infection between March and June 2020 admitted at Rush University System for Health (RUSH) in metropolitan Chicago, Illinois, USA. Patients with history of HF were identified by International Classification of Disease, Tenth Revision (ICD-10) code assignments extracted from the electronic medical record. Propensity score matching was utilized to control for the numerous confounders, and univariable logistic regression was performed to assess the relationship between HF and 60-day morbidity and mortality outcomes. RESULTS: The propensity score matched cohort consisted of 188 patients in both the HF and no HF groups. HF patients did not have lower 60-day mortality (OR 0.81; p = 0.43) compared to patients without HF. However, those with HF were more likely to require readmission within 60 days (OR 2.88; p < 0.001) and sustain myocardial injury defined as troponin elevation within 60 days (OR 3.14; p < 0.05). CONCLUSIONS: This study highlights the complex network of confounders present between HF and COVID-19. When balanced for these numerous factors, those with HF appear to be at no higher risk of 60-day mortality from COVID-19 but are at increased risk for morbidity.