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The heart-liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3 years. We found that higher Fib-4 was associated with reduction in the MPRI (β [SE] - 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart-liver disease.

IntroductionEarly reports highlighted racial/ethnic disparities in the severity of COVID-19 seen across the USA; the extent to which these disparities have persisted over time remains unclear. Our research objective was to understand temporal trends in racial/ethnic variation in severity of COVID-19 illness presenting over time.MethodsWe conducted a retrospective cohort analysis using longitudinal data from Cedars-Sinai Medical Center, a high-volume health system in Southern California. We studied patients admitted to the hospital with COVID-19 illness from 4 March 2020 through 5 December 2020. Our primary outcome was COVID-19 severity of illness among hospitalised patients, assessed by racial/ethnic group status. We defined overall illness severity as an ordinal outcome: hospitalisation but no intensive care unit (ICU) admission; admission to the ICU but no intubation; and intubation or death.ResultsA total of 1584 patients with COVID-19 with available demographic and clinical data were included. Hispanic/Latinx compared with non-Hispanic white patients had higher odds of experiencing more severe illness among hospitalised patients (OR 2.28, 95% CI 1.62 to 3.22) and this disparity persisted over time. During the initial 2 months of the pandemic, non-Hispanic blacks were more likely to suffer severe illness than non-Hispanic whites (OR 2.02, 95% CI 1.07 to 3.78); this disparity improved by May, only to return later in the pandemic.ConclusionIn our patient sample, the severity of observed COVID-19 illness declined steadily over time, but these clinical improvements were not seen evenly across racial/ethnic groups; greater illness severity continues to be experienced among Hispanic/Latinx patients.

Background Immune-inflammatory myocardial disease contributes to multiple chronic cardiac processes, but access to non-invasive screening is limited. We have previously developed a method of echocardiographic texture analysis, called the high-spectrum signal intensity coefficient (HS-SIC) which assesses myocardial microstructure and previously associated with myocardial fibrosis. We aimed to determine whether this echocardiographic texture analysis of cardiac microstructure can identify inflammatory cardiac disease in the clinical setting. Methods We conducted a retrospective case-control study of 318 patients with distinct clinical myocardial pathologies and 20 healthy controls. Populations included myocarditis, atypical chest pain/palpitations, STEMI, severe aortic stenosis, acute COVID infection, amyloidosis, and cardiac transplantation with acute rejection, without current rejection but with prior rejection, and with no history of rejection. We assessed the HS-SIC’s ability to differentiate between a broader diversity of clinical groups and healthy controls. We used Kruskal-Wallis tests to compare HS-SIC values measured in each of the clinical populations with those in the healthy control group and compared HS-SIC values between the subgroups of cardiac transplantation rejection status. Results For the total sample of N = 338, the mean age was 49.6 ± 20.9 years and 50% were women. The mean ± standard error of the mean of HS-SIC were: 0.668 ± 0.074 for controls, 0.552 ± 0.049 for atypical chest pain/palpitations, 0.425 ± 0.058 for myocarditis, 0.881 ± 0.129 for STEMI, 1.116 ± 0.196 for severe aortic stenosis, 0.904 ± 0.116 for acute COVID, and 0.698 ± 0.103 for amyloidosis. Among cardiac transplant recipients, HS-SIC values were 0.478 ± 0.999 for active rejection, 0.594 ± 0.091 for prior rejection, and 1.191 ± 0.442 for never rejection. We observed significant differences in HS-SIC between controls and myocarditis (P = 0.0014), active rejection (P = 0.0076), and atypical chest pain or palpitations (P = 0.0014); as well as between transplant patients with active rejection and those without current or prior rejection (P = 0.031). Conclusions An echocardiographic method can be used to characterize tissue signatures of microstructural changes across a spectrum of cardiac disease including immune-inflammatory conditions.

ObjectiveWe sought to determine the extent of SARS-CoV-2 seroprevalence and the factors associated with seroprevalence across a diverse cohort of healthcare workers.DesignObservational cohort study of healthcare workers, including SARS-CoV-2 serology testing and participant questionnaires.SettingsA multisite healthcare delivery system located in Los Angeles County.ParticipantsA diverse and unselected population of adults (n=6062) employed in a multisite healthcare delivery system located in Los Angeles County, including individuals with direct patient contact and others with non-patient-oriented work functions.Main outcomesUsing Bayesian and multivariate analyses, we estimated seroprevalence and factors associated with seropositivity and antibody levels, including pre-existing demographic and clinical characteristics; potential COVID-19 illness-related exposures; and symptoms consistent with COVID-19 infection.ResultsWe observed a seroprevalence rate of 4.1%, with anosmia as the most prominently associated self-reported symptom (OR 11.04, pConclusion and relevanceThe demographic factors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace. The size and diversity of our study population, combined with robust survey and modelling techniques, provide a vibrant picture of the demographic factors, exposures and symptoms that can identify individuals with susceptibility as well as potential to mount an immune response to COVID-19.

ObjectivesWe sought to understand the demographic and clinical factors associated with variations in longitudinal antibody response following completion of two-dose regiment of BNT162b2 vaccination.DesignThis study is a 10-month longitudinal cohort study of healthcare workers and serially measured anti-spike protein IgG (IgG-S) antibody levels using mixed linear models to examine their associations with participant characteristics.SettingA large, multisite academic medical centre in Southern California, USA.ParticipantsA total of 843 healthcare workers met inclusion criteria including completion of an initial two-dose course of BNT162b2 vaccination, complete clinical history and at least two blood samples for analysis. Patients had an average age of 45±13 years, were 70% female and 7% with prior SARS-CoV-2 infection.ResultsVaccine-induced IgG-S levels remained in the positive range for 99.6% of individuals up to 10 months after initial two-dose vaccination. Prior SARS-CoV-2 infection was the primary correlate of sustained higher postvaccination IgG-S levels (partial R2=0.133), with a 1.74±0.11 SD higher IgG-S response (pConclusionsWhile the IgG-S antibody response remains in the positive range for up to 10 months following initial mRNA vaccination in most adults, determinants of sustained higher antibody levels include prior SARS-CoV-2 infection, female sex, younger age and absence of hypertension. Certain determinants of the longitudinal antibody response appear significantly modified by prior infection status. These findings offer insights regarding factors that may influence the ‘hybrid’ immunity conferred by natural infection combined with vaccination.

Background: Takotsubo syndrome (TTS) has been increasingly recognized in the United States. Since its initial description in 1990, diagnosed cases of TTS have been rising over time and the extent to which this trend differs by sex and across age is unclear. Methods: Using the National Inpatient Sample (NIS) data from 2006 to 2014, we identified hospitalizations with either a primary or secondary diagnosis of TTS. We analyzed these data stratified by sex and by age groups: =75 years. For the trend measurements, the sampling effects were accounted for by applying NIS survey weights using the SAS PROC SURVEYMEANS procedure. Results: We identified a total of N=18,051 TTS cases over the study period, most of which were experienced by women (89.1%). The frequency of diagnosed TTS cases progressively increased from 2006 to 2014 in both women and men, across all age groups. However, the frequency of diagnosed TTS cases increased at a markedly more rapid rate in women compared to men (rate of change of 182.7 per million hospitalization per year in women vs 44.9 per million hospitalization per year in men, P Figure ). Conclusion: Our results demonstrate that while increasing recognition of TTS may be contributing to a steady rise of case diagnoses per annum in both sexes and across age groups, the rate of case diagnosis increase is particularly rapid in middle-aged and older women. Further research is needed to validate and investigate the potential determinants underlying our findings.

Background: Takotsubo syndrome (TTS) is an uncommon but increasingly recognized cause of myocardial infarction in both women and men across the age spectrum. Emerging data suggest that outcomes are worse in younger compared to older adults, and the extent to which this trend differs by sex is unclear. Methods: Using the National Inpatient Sample data from years 2006 to 2014, we identified hospitalizations with either a primary or secondary diagnosis of TTS. We analyzed these data stratified by age and sex. Outcomes measured include in-hospital mortality and in-hospital complications of cardiac arrest, cardiogenic shock, any type of shock, vasopressor use, intra-aortic balloon pump use, and mechanical ventilation. Results: We identified a total of N=18,051 TTS cases over the study period, most of which were experienced by women (89%). Despite the majority cases occurring in patients over age 50 years (89%), younger patients hospitalized with TTS were consistently more likely to suffer almost all major types of in-hospital complications except for in-hospital mortality ( Figure ). These apparently paradoxical age-based trends were observed in women more so than in men. Conclusion: Our results demonstrate that while individuals age 50 years and older continue to be more frequently hospitalized with TTS than younger patients, younger patients present with greater complications. This age-based finding is seen predominantly in women and much less so in men, potentially related to sex differences in sympathetic regulation of cardiovascular responses to stress. Further research is needed to validate and investigate the potential mechanisms underlying our findings.

Background: Home blood pressure monitoring (HBPM) devices can now be linked to electronic health records (EHR) systems in ways that could be used to facilitate blood pressure (BP) management; however, their potential feasibility and utility remain unclear. Methods: For our pilot study, we identified N=5 outpatients with uncontrolled hypertension and implemented use of a HBPM device with frequent monitoring and direct linkage to the EHR, whereby real-time data was made available to treating providers. We matched our intervention patients by age and sex with N=50 patients who also had uncontrolled hypertension and underwent standard-of-care treatment. We assessed change over time in BP measures for the intervention and standard-of-care groups. Results: In analyses accounting for differences in the timing and frequency of BP measurements, we observed that the intervention compared to the standard-of-care group had an average systolic BP at 8 weeks that was lower in percent change from baseline (β=-22 mm Hg, P=0.008). We also found a difference between baseline and 8-week systolic BP within the intervention group (mean difference -25.9 mm Hg, P=0.024). Conclusions: In our pilot, intensive remote HBPM appeared to improve BP levels over the short term. While unblinded and not controlled for factors beyond age and sex, this pilot demonstrates feasibility of an EHR-linked HBPM intervention and potential efficacy that may be related to increased patient as well as provider awareness translating to greater patient-provider engagement around hypertension management. More studies are needed to validate and expand from our findings.

ImportanceAntibody testing is important for understanding patterns of exposure and potential immunity to SARS-CoV-2. Prior data on seroprevalence have been subject to variations in selection of individuals and nature as well as timing of testing in relation to exposures.ObjectiveWe sought to determine the extent of SARS-CoV-2 seroprevalance and the factors associated with seroprevelance across a diverse cohort of healthcare workers.DesignObservational cohort study of healthcare workers, including SARS-CoV-2 serology testing and participant questionaires.ParticipantsA diverse and unselected population of adults (n=6,062) employed in a multi-site healthcare delivery system located in Los Angeles County, including individuals with direct patient contact and others with non-patient-oriented work functions.ExposureExposure and infection with the SARS-CoV-2 virus, as determined by seropositivity.Main OutcomesUsing Bayesian and multi-variate analyses, we estimated seroprevalence and factors associated with seropositivity and antibody titers, including pre-existing demographic and clinical characteristics; potential Covid-19 illness related exposures; and, symptoms consistent with Covid-19 infection.ResultsWe observed a seroprevalence rate of 4.1%, with anosmia as the most prominently associated self-reported symptom in addition to fever, dry cough, anorexia, and myalgias. After adjusting for potential confounders, pre-existing medical conditions were not associated with antibody positivity. However, seroprevalence was associated with younger age, Hispanic ethnicity, and African-American race, as well as presence of either a personal or household member having a prior diagnosis of Covid-19. Importantly, African American race and Hispanic ethnicity were associated with antibody positivity even after adjusting for personal Covid-19 diagnosis status, suggesting the contribution of unmeasured structural or societally factors. Notably, number of people, or children, in the home was not associated with antibody positivity.Conclusion and RelevanceThe demographic factors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace. The size and diversity of our study population, combined with robust survey and modeling techniques, provide a vibrant picture of the demographic factors, exposures, and symptoms that can identify individuals with susceptibility as well as potential to mount an immune response to Covid-19.Key PointsQuestionWhat is the SARS-CoV-2 IgG seroprevalence rate across a large and diverse healthcare worker population, and which clinical, envionrmental, and symptom-based measures are associated with seropositivity?FindingsWe observed a seroprevalence rate of 4.1%. Adjusting for potential confounders, seropositivity was associated with younger age, Hispanic ethnicity, African-American race, and the symptom of anosmia, while not significantly associated with any pre-existing medical conditions.MeaningFactors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace.

Of individuals with SARS-CoV-2 IgG antibody testing performed, those who contemporaneously experienced a cluster of Covid-19 relevant symptoms in the 1-2 months preceding the antibody assay were more likely to test positive whereas those who experienced the symptom clustering in the prior 3-6 months were more likely to test negative. These findings suggest that antibodies likely wane over a period of months, particularly in relation to the timing of symptoms.

We describe the rationale, design, and implementation of baseline enrollment for a longitudinal, observational cohort study of healthcare workers. The importance of workplace as a characteristic of interest in population-based studies has become increasingly apparent over time. Most adults spend a majority of their waking hours living in their workplace environment, which serves as a source of unique as well as shared exposures, stressors, and related determinants of health. A rapidly expanding segment of the working population includes those individuals who work in the fields of healthcare. The healthcare workforce, at large, represents an increasingly diverse subset of the population with broad exposures; some exposures are specific to the workplace and others are common to persons living in the community. Importantly, healthcare workers tend to have general interest and willingness to participate in research, in addition to stable employment and easy access to on-site clinical research assessment locations. Accordingly, from a population of individuals working at a large medical delivery network, we enrolled over 6300 healthcare workers into a cohort study involving survey data collection on medical history, work environment, and family and living situation; this information was linked to participant electronic health record data and collected biospecimens.

BackgroundEchocardiographic texture analysis using the signal intensity coefficient (SIC) can identify fibrosis-associated microstructural changes. This approach has not been tested in immune-inflammatory disease states such as myocarditis or transplant rejection.MethodsRetrospective pilot analysis using the SIC was performed in populations including myocarditis (n=5), acute left anterior descending coronary artery STEMI (n=6), severe aortic stenosis with normal ejection fraction (n=7), ATTR amyloidosis (n=6), and cardiac transplant patients undergoing biopsy including patients with active rejection on histopathology (n=22), patients with history of rejection but no current rejection (n=15), and patients without history of or current rejection (n=5), and a healthy control group (n=28).ResultsDecreased SIC was noted in the myocarditis and transplant rejection populations, with decreasing SIC by presence and history of rejection. Consistent with prior literature, the SIC was elevated in cardiac conditions associated with fibrosis.ConclusionsThe SIC may be able to capture microstructural changes associated with immune-inflammatory processes such as cardiac transplant rejection and myocarditis.

IntroductionEDs are often the first line of contact with individuals infected with COVID-19 and play a key role in triage. However, there is currently little specific guidance for deciding when patients with COVID-19 require hospitalisation and when they may be safely observed as an outpatient.MethodsIn this retrospective study, we characterised all patients with COVID-19 discharged home from EDs in our US multisite healthcare system from March 2020 to August 2020, focusing on individuals who returned within 2 weeks and required hospital admission. We restricted analyses to first-encounter data that do not depend on laboratory or imaging diagnostics in order to inform point-of-care assessments in resource-limited environments. Vitals and comorbidities were extracted from the electronic health record. We performed ordinal logistic regression analyses to identify predictors of inpatient admission, intensive care and intubation.ResultsOf n=923 patients who were COVID-19 positive discharged from the ED, n=107 (11.6%) returned within 2 weeks and were admitted. In a multivariable-adjusted model including n=788 patients with complete risk factor information, history of hypertension increased odds of hospitalisation and severe illness by 1.92-fold (95% CI 1.07 to 3.41), diabetes by 2.20-fold (1.18 to 4.02), chronic lung disease by 2.21-fold (1.22 to 3.92) and fever by 2.89-fold (1.71 to 4.82). Having at least two of these risk factors increased the odds of future hospitalisation by 6.68-fold (3.54 to 12.70). Patients with hypertension, diabetes, chronic lung disease or fever had significantly longer hospital stays (median 5.92 days, 3.08–10.95 vs 3.21, 1.10–5.75, pDiscussionPatients infected with COVID-19 may appear clinically safe for home convalescence. However, those with hypertension, diabetes, chronic lung disease and fever may in fact be only ‘pseudo-safe’ and are most at risk for subsequent hospitalisation with more severe illness and longer hospital stays.

BackgroundCertain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.MethodsWe studied N=442 patients who presented with laboratory confirmed Covid-19 illness to our U.S. metropolitan healthcare system. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation.ResultsOf all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, PinteractionConclusionsIn our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.

BACKGROUNDUse of electronic cigarettes (e-cigarettes) has increased substantially in recent years. Marketed as a safer alternative to conventional tobacco cigarettes, the safety profile of e-cigarettes is now being questioned. Importantly, the clinical consequences of e-cigarette use remain poorly characterized.METHODSUsing data from the electronic health record (EHR), we identified a cohort of e-cigarette users and never-smokers in the region of central Los Angeles. Using information extracted from the EHR, we assessed temporal trends in the demographic characteristics of e-cigarette users, including race/ethnicity and location of residence. We also used data on urgent medical visits (i.e. emergency department encounters and hospital admissions) occurring during the study period (January 2014 to January 2020) and employed a negative binomial regression model to compare healthcare utilization rates between e-cigarette users and never-smokers.RESULTSWe identified a total of 698 e-cigarette users, in addition to 999 never-smokers, with demographic, clinical, and outcomes data available over the duration of the study period. From the beginning to the end of the study period, e-cigarette use increased across all race/ethnicity groups and across all geographic regions of residence. Notably, e-cigarette users experienced a 4.96 higher rate of urgent medical visits when compared to never-smokers evaluated over the same study period.CONCLUSIONE-cigarettes use continues to expand, with evidence of racial/ethnic as well as geographic variation in uptake. Use of e-cigarette devices is associated with substantially higher rates of urgent healthcare utilization. These findings highlight the need for a more granular understanding of e-cigarette use and enhanced attention to the diversity as well as breadth of the population affected by this burgeoning health crisis.

BACKGROUNDElectronic (e-) cigarettes are marketed as a safer alternative to conventional tobacco cigarettes. Although e-cigarettes contain a lower level of nicotine, the delivery method involves delivering an aerosolized bolus of poorly-characterized ultrafine particles that have unknown cardiovascular effects.METHODSWe studied apparently adult volunteers, free of any chronic disease, including: non-smoking controls, chronic e-cigarette users, and chronic tobacco cigarette smokers. After overnight abstinence, we used myocardial contrast echocardiography to measure acute increases in myocardial blood flow (MBF)induced by ischemic rhythmic handgrip stress, which causes sympathetically-mediated increases in myocardial work and oxygen demand and, in turn, shear stress, nitric oxide production, and coronary endothelial-dependent vasodilation.RESULTSIn non-smoking controls, handgrip stress increased myocardial blood flow, reflecting normal endothelial function. Chronic tobacco cigarette smokers demonstrated stress-induced blunting in myocardial blood flow change, when compared to non-smoking controls. Chronic e-cigarette smokers demonstrated a decrease, rather than increase, in myocardial blood flow change.CONCLUSIONChronic e-cigarette users demonstrated substantially impaired coronary microvascular endothelial function, even more pronounced than that seen in chronic tobacco cigarette users. These findings suggest that chronic e-cigarette use leads to measurable and persistent adverse vascular effects that are not directly related to nicotine.

BackgroundIncidence of congestive heart failure is difficult to predict by standard methods. We have developed a method called the signal intensity coefficient that uses echocardiographic texture analysis to quantify microstructural changes which may occur in at-risk patients prior to development of a clinical heart failure syndrome.MethodsParticipants from the Framingham Offspring Cohort study who attended the 8th visit and received screening echocardiography were included. Participants were followed for a mean of 7.4 years for incident congestive heart failure. Cox proportional hazards modeling was used to assess the hazard ratio of signal intensity coefficient in the top quartile of values versus other quartiles in the total and sex-stratified population.Results2511 participants with interpretable echocardiography and no history of congestive heart failure, stroke, or myocardial infarction were included in this study. The top quartile signal intensity coefficient had a hazard ratio of 1.83 (p=0.0048) for incident heart failure. When additional clinical risk factors were added to the model, this became non-significant. Within women, an elevated hazard ratio was significant in multiple models including age and hypertensive medication use. Models were not significant in men.ConclusionsElevated signal intensity coefficient is associated with an increased risk of incident congestive heart failure. This trend remains significant in women after inclusion of age and hypertensive medication use. The signal intensity coefficient may be able to identify patients at risk of developing congestive heart failure using echocardiographic texture analysis.