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Racial/ethnic disparities in anticoagulation management are well established. Differences in warfarin monitoring can contribute to these disparities and should be measured.We assessed for differences in international normalized ratio (INR) monitoring by race/ethnicity and language preference across safety-net care systems serving predominantly low-income, ethnically diverse populations.Cross-sectional analysis of process and safety data shared from the Safety Promotion Action Research and Knowledge Network (SPARK-Net) initiative, a consortium of five California safety-net hospital systems.Eligible patients were at least 18 years old, received warfarin for at least 56 days during the measurement period from July 2015 to June 2017, and had INR testing in an ambulatory care setting at a participating healthcare system.We conducted a scaled Poisson regression for adjusted rate ratio of having at least one INR checked per 56-day time period for which a patient had a warfarin prescription. Adjusting for age, sex, healthcare system, and insurance status/type, we assessed for racial/ethnic and language disparities in INR monitoring.Of 8129 patients, 3615 (44%) were female; 1470 (18%), Black/African American; 3354 (41%), Hispanic/Latinx; 1210 (15%), Asian; 1643 (20%), White; and 452 (6%), other. Three thousand five hundred forty-nine (45%) were non-English preferring. We did not observe statistically significant disparities in the rate of appropriate INR monitoring by race/ethnicity or language; the primary source of variation was by healthcare network. Older age, female gender, and uninsured patients had a slightly higher rate of appropriate INR monitoring, but differences were not clinically significant.We did not find a race/ethnicity nor language disparity in INR monitoring; safety-net site was the main source of variation.

Background Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking. Research Question Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19? Study Design and Methods We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between January 2020 and August 2020 from two integrated health care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19. Results We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/μL. Interpretation Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19.

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen’s d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p

Queries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been used in hepatology due to the inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute‐on‐chronic liver failure (ACLF) models. Here, we describe a methodology to use EHR data to calculate rolling ACLF scores. We examined 239 patient admissions with end‐stage liver disease from July 2014 to June 2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses by chart review and calculated sensitivity, specificity, and Cohen’s kappa. Of 239 patient admissions analyzed, 37% were women, 46% were non‐Hispanic white, median age was 60 years, and the median Model for End‐Stage Liver Disease–Na score at admission was 25. Of the 239, 7% were diagnosed with ACLF as defined by the North American Consortium for the Study of End‐Stage Liver Disease (NACSELD) diagnostic criteria at admission, 27% during the hospitalization, and 9% at discharge. Forty percent were diagnosed with ACLF by the European Association for the Study of the Liver– Chronic Liver Failure Consortium (CLIF‐C) diagnostic criteria at admission, 51% during the hospitalization, and 34% at discharge. From the chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1‐4) were 92%‐97% and 76%‐95%, respectively; for severe HE (grades 3‐4), sensitivities and specificities were 100% and 78%‐98%, respectively. Cohen’s kappa between flowsheet and chart review of HE grades ranged from 0.55 to 0.72. Sensitivities and specificities for NACSELD‐ACLF diagnoses were 75%‐100% and 96%‐100%, respectively; for CLIF‐C‐ACLF diagnoses, these were 91%‐100% and 96‐100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission day. Conclusion: We developed an informatics‐based methodology to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such as big data methods, to develop electronic phenotypes for patients with ACLF., Queries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been utilized in hepatology due to previous inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute‐on‐chronic liver failure (ACLF) models. We describe a methodology to utilizing EHR data to calculate rolling ACLF scores.

Objectives This study analyzed changes in depressive symptoms in patients with heart failure and preserved ejection fraction (HFpEF) who were enrolled in the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Background There are limited longitudinal data for depressive symptoms in patients with HFpEF. Methods In patients enrolled in the United States and Canada (n = 1,431), depressive symptoms were measured using Patient Health Questionnaire-9 (PHQ-9). Clinically meaningful changes in PHQ-9 scores were defined as worse (≥3-point increase) or better (≥3-point decrease). Multivariate models were used to identify predictors of change in depressive symptoms. Cox proportional hazard models were used to determine the impact of symptom changes from baseline on subsequent incident cardiovascular events. Results At 12 months, 19% of patients experienced clinically worsening depressive symptoms, 31% better, and 49% unchanged. Independent predictors of clinically meaningful improvement in depressive symptoms included higher baseline PHQ-9 scores, male sex, lack of chronic obstructive pulmonary disease, and randomization to spironolactone. After data were adjusted for cardiovascular comorbidities, higher baseline PHQ-9 was associated with all-cause mortality (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.02 to 1.16; p = 0.011), whereas worsening depressive symptoms at 12 months were associated with cardiovascular death (HR: 2.47; 95% CI: 1.32 to 4.63; p = 0.005) and all-cause mortality (HR: 1.82; 95% CI: 1.13 to 2.93; p = 0.014). Randomization to spironolactone was associated with modest but statistically significant reduction in depressive symptoms over the course of the trial (p = 0.014). Conclusions Higher baseline depressive symptoms and worsening depressive symptoms were associated with all-cause mortality. Randomization to spironolactone was associated with modest reduction in depressive symptoms. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)

Objectives: To evaluate the safety of antimotility agents (AAs) in a population of patients with hematologic malignancies and concurrent Clostridioides difficile infection (CDI) and to describe the outcomes of AA use in a hospital setting. Patients and Methods: We used the electronic health record to identify patients who were hospitalized in the adult malignant hematology service who had 1 or more toxin-positive C difficile stool assay between April 1, 2012, and September 21, 2017. We reviewed medical charts to obtain information on the use of AAs and any subsequent gastrointestinal complications. Results: There were 339 patients who were stool toxin positive for CDI during the study period. Of those, 94 patients (27%) were prescribed AAs within 14 days of CDI diagnosis. All patients received CDI antimicrobial therapy within the first 24 hours. There were 2 adverse gastrointestinal events in the group that received AAs and 6 in the group that did not receive AAs. The risk of adverse events did not differ between patients who received AAs and those who did not (adjusted odds ratio, 0.36; 95% CI, 0.06 to 2.10). The mean age of the full cohort was 52.7±15.5 years, and the mean length of stay was 26.7±22.6 days. Early AA use (

Reverse left ventricular (LV) remodeling and recovery of LV function are associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction. A growing body of evidence suggests that even among patients who experience a complete normalization of LV ejection fraction, a significant proportion will develop recurrent LV dysfunction accompanied by recurrent heart failure events. This has led to intense interest in understanding how to manage patients with heart failure with recovered ejection fraction (HFrecEF). Because of the lack of a standard definition for HFrecEF, and the paucity of clinical data with respect to the natural history of HFrecEF patients, there are no current guidelines on how these patients should be followed up and managed. Accordingly, this JACC Scientific Expert Panel reviews the biology of reverse LV remodeling and the clinical course of patients with HFrecEF, as well as provides guidelines for defining, diagnosing, and managing patients with HFrecEF.

Background Studies have indicated differences between Asians and Whites in their propensity for stroke, coronary artery disease, heart failure, bleeding and thrombosis. We investigated whether Asian-Americans on durable left ventricular assist devices (LVADs) exhibit differential morbidity and mortality when compared to Whites. Methods We analysed prospectively collected data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database to compare the outcomes after LVAD implantation of Asians versus Whites. Results In total, 7,018 patients were included, 130 were identified as Asian-Americans. Asian-Americans were younger, had lower body mass index, higher serum bilirubin and lower albumin levels. In a multivariable regression model, there was no difference in survival between the two groups. Asian-Americans had lower incidence of device malfunction and after adjusting for multiple factors this remained lower. The adjusted risk of a major safety composite outcome, including major bleeding, major infection, stroke and device malfunction, revealed no difference between the two groups. Conclusions Although prior studies have reported worse cardiac surgery outcomes in Asians, in this INTERMACS analysis Asian-Americans appear to have similar survival and risk of adverse events as their White counterparts. The incidence of device malfunction was lower in the Asian-Americans, both in a univariate model and after adjusting for multiple clinical factors. Future, larger studies of Asian-Americans with end-stage heart failure and LVAD support are warranted to confirm these results.

BackgroundMen who have sex with men (MSM) are at risk for sexual transmission of enteric pathogens. The microbiology of gastroenteritis in MSM has not been examined since the advent of antiretroviral therapy and molecular diagnostics. Our objective was to assess the causes of gastroenteritis among MSM living with and without human immunodeficiency virus (HIV) coinfection in Seattle, Washington.MethodsWe conducted a retrospective cohort study of 235 MSM who underwent multiplex stool polymerase chain reaction (PCR) testing between 1 January 2017 and 1 June 2018. We abstracted clinical and laboratory data from electronic medical records. Parallel or reflexive culture and susceptibility testing were performed when PCR detected cultivable pathogens.ResultsAmong 235 MSM tested (268 episodes), 131 had 151 episodes with positive test results. 148 (63.0%) individuals were living with HIV. Among positive tests, 88.7% detected a bacterial pathogen, 26% a virus, and 40% a parasite. Diarrheagenic Escherichia coli (enteroaggretative, enteropathogenic), Shigella, and Campylobacter were the most commonly detected bacteria (33.1%, 30.5%, and 17.2% of positive samples, respectively). Forty-three percent of positive specimens had ≥2 pathogens. Etiologies and clinical presentations were similar between men living with and without HIV. Cultured Shigella and Campylobacter isolates were frequently resistant to multiple antibiotics.ConclusionsMSM present with gastroenteritis from varied pathogens, including some not detected by conventional stool culture. High levels of antibiotic resistance are consistent with frequent antibiotic exposure in this population and the transmission of multiresistant strains. New approaches are needed to detect, treat, and prevent enteric infections in MSM.

Importance Older adults who live alone are at risk for poor health outcomes. Whether social support mitigates the risk of living alone, particularly when facing a sudden change in health, has not been adequately reported. Objective To assess if identifiable support buffers the vulnerability of a health shock while living alone. Design, setting, and participants In this longitudinal, prospective, nationally representative cohort study from the Health and Retirement Study (enrollment March 2006 to April 2015), 4772 community-dwelling older adults 65 years or older who lived alone in the community and could complete activities of daily living (ADLs) and instrumental ADLs independently were followed up biennially through April 2018. Statistical analysis was completed from May 2020 to March 2021. Exposures Identifiable support (ie, can the participant identify a relative/friend who could help with personal care if needed), health shock (ie, hospitalization, new diagnosis of cancer, stroke, heart attack), and interaction (multiplicative and additive) between the 2 exposures. Main outcomes and measures The primary outcomes were incident ADL dependency, prolonged nursing home stay (≥30 days), and death. Results Of 4772 older adults (median [IQR] age, 73 [68-81] years; 3398 [71%] women) who lived alone, at baseline, 1813 (38%) could not identify support, and 3013 (63%) experienced a health shock during the study. Support was associated with a lower risk of a prolonged nursing home stay at 2 years (predicted probability, 6.7% vs 5.2%; P = .002). Absent a health shock, support was not associated with a prolonged nursing home stay (predicted probability over 2 years, 1.9% vs 1.4%; P = .21). However, in the presence of a health shock, support was associated with a lower risk of a prolonged nursing home stay (predicted probability over 2 years, 14.2% vs 10.9%; P = .002). Support was not associated with incident ADL dependence or death. Conclusions and relevance In this longitudinal cohort study among older adults who live alone, identifiable support was associated with a lower risk of a prolonged nursing home stay in the setting of a health shock.

Background: Polypharmacy is associated with a poor prognosis in the elderly, however, information on the association of polypharmacy with cardiovascular outcomes in heart failure with preserved ejection fraction is sparse. This study sought to investigate the relationship between polypharmacy and adverse cardiovascular events in patients with heart failure with preserved ejection fraction. Methods: Baseline total number of medications was determined in 1758 patients with heart failure with preserved ejection fraction enrolled in the Americas regions of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), by 3 categories: nonpolypharmacy ( Results: The proportion of patients taking 5 or more medications was 92.5% (inclusive of polypharmacy [38.7%] and hyper-polypharmacy [53.8%]). Over a 2.9-year median follow-up, compared with patients with polypharmacy, hyper-polypharmacy was associated with an increased risk for the primary outcome, hospitalization for any reason and any serious adverse events in the univariable analysis, but not significantly associated with mortality. After multivariable adjustment for demographic and comorbidities, hyper-polypharmacy remained significantly associated with an increased risk for hospitalization for any reason (hazard ratio, 1.22 [95% CI, 1.05–1.41]; P =0.009) and any serious adverse events (hazard ratio, 1.23 [95% CI, 1.07–1.42]; P =0.005), whereas the primary outcome was no longer statistically significant. Conclusions: Hyper-polypharmacy was common and associated with an elevated risk of hospitalization for any reason and any serious adverse events in patients with heart failure with preserved ejection fraction. There were no significant associations between polypharmacy status and mortality.

Background Recent prospective multicenter data from patients with advanced heart failure demonstrated that left ventricular assist device (LVAD) support combined with standard heart failure medications, induced significant cardiac structural and functional improvement, leading to high rates of LVAD weaning in selected patients. We investigated whether preintervention myocardial and systemic inflammatory burden could help identify the subset of patients with advanced heart failure prone to LVAD‐mediated cardiac improvement to guide patient selection, treatment, and monitoring. Methods and Results Ninety‐three patients requiring durable LVAD were prospectively enrolled. Myocardial tissue and blood were acquired during LVAD implantation, for measurement of inflammatory markers. Cardiac structural and functional improvement was prospectively assessed via serial echocardiography. Eleven percent of the patients showed significant reverse remodeling following LVAD support (ie, responders). Circulating tumor necrosis factor alpha, interleukin (IL)‐4, IL‐5, IL‐6, IL‐7, IL‐13, and interferon gamma were lower in responders, compared with nonresponders ( P P =0.037). Guided by our tissue studies and a multivariable dichotomous regression analysis, we identified that low levels of circulating interferon gamma (odds ratio [OR], 0.06; 95% CI, 0.01–0.35) and tumor necrosis factor alpha (OR, 0.05; 95% CI, 0.00–0.43), independently predict cardiac improvement, creating a 2‐cytokine model effectively predicting responders (area under the curve, 0.903; P Conclusions Baseline myocardial and systemic inflammatory burden inversely correlates with cardiac improvement following LVAD support. A circulating 2‐cytokine model predicting significant reverse remodeling was identified, warranting further investigation as a practical preintervention tool in identifying patients prone to LVAD‐mediated cardiac improvement and device weaning.

Background The usefulness of right heart catherization (RHC) has long been debated, and thus, we aimed to study the real‐world impact of the use of RHC in cardiogenic shock. Methods and Results In the Nationwide Readmissions Database using International Classification of Diseases, Tenth Revision ( ICD‐1 0 ), we identified 236 156 patient hospitalizations with cardiogenic shock between 2016 and 2017. We sought to evaluate the impact of RHC during index hospitalization on management strategies, complications, and outcomes as well as on 30‐day readmission rate. A total 25 840 patients (9.6%) received RHC on index admission. The RHC group had significantly more comorbidities compared with the non‐RHC group. During the index admission, the RHC group had lower death (25.8% versus 39.5%, P P P =0.04) and death on readmission (7.9% versus 9.3%, P =0.03) were also lower in the RHC group. After adjustment, RHC was associated with lower index admission mortality (odds ratio, 0.69; 95% CI, 0.66–0.72), lower stroke rate (odds ratio, 0.81; 95% CI, 0.72–0.90), lower 30‐day readmission (odds ratio, 0.83; 95% CI, 0.78–0.88), and higher left ventricular assist device implantations/orthotopic heart transplants (odds ratio, 6.05; 95% CI, 4.43–8.28) during rehospitalization. Results were not meaningfully different after excluding patients with cardiac arrest. Conclusions RHC use in cardiogenic shock is associated with improved outcomes and increased use of downstream advanced heart failure therapies. Further blinded randomized studies are required to confirm our findings.

BackgroundExtrinsic control of cardiac contractility and ultrastructure via neurohormonal signaling is well established, but how other organs regulate cardiomyocyte metabolism is less well understood. Fibroblast growth factor-21 (FGF21) a hormonal regulator of metabolism mainly produced in the liver and adipose tissue, is a prime candidate for such signaling.MethodsTo investigate this further, we examined blood and tissue obtained from human subjects with heart failure with reduced ejection fraction (HFrEF) at the time of left ventricular assist device (LVAD) implantation, and correlated serum FGF21 levels with cardiac gene expression, immunohistochemistry, and clinical parameters.ResultsCirculating FGF21 levels were substantially elevated in HFrEF, compared to healthy subjects (HFrEF: 834.4 ± 101.8 pg/mL, n = 40; controls: 145.9 ± 28.6 pg/mL, n = 20, p = 5.5 × 10−8). There was clear FGF21 staining in diseased cardiomyocytes, and circulating FGF21 levels negatively correlated with the expression of cardiac genes involved in ketone metabolism, consistent with cardiac FGF21 signaling. FGF21 gene expression was low in failing and non-failing hearts, suggesting at least partial extracardiac production of the circulating hormone. Circulating FGF21 levels were correlated with BNP and total bilirubin, markers of chronic cardiac and hepatic congestion.ConclusionsCirculating FGF21 levels are elevated in HFrEF. The liver is likely the main extracardiac source, and congestive hepatopathy, common in HFrEF, was likely the proximate signal leading to FGF21 elevations. This supports a model of venous congestion from cardiomyopathy driving hepatic FGF21 communication to diseased cardiomyocytes, defining a potential cardio-hepatic signaling circuit in human heart failure.

Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown.We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02).Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation.

Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD. Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was −0.6 cm (interquartile range [IQR], −1.1 to −0.1 cm; nonresponders), −1.1 cm (IQR, −1.8 to −0.4 cm; partial responders), and −1.9 cm (IQR, −2.9 to −1.1 cm; responders). Similarly, the median change in LVEF was −2% (IQR, −6% to 1%), 9% (IQR, 6%–14%), and 27% (IQR, 23%–33%), respectively. Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.

Background Adequate colon preparation is a critical component of high quality colonoscopy especially for inpatients undergoing colonoscopy for acute indications. Inpatient colonoscopy has a high incidences of inadequate preparations. We report implementation of a multifaceted quality improvement intervention to improve inpatient colonoscopy preparations. Methods Bowel preparation quality from inpatient colonoscopies performed for the 12 months prior to the comprehensive intervention were compared to colonoscopies performed for 12 months following the intervention. The intervention had multiple components including: EMR-based colonoscopy preparation order set; Automated EMR alerts prompting nursing assessment of preparation progress; Standardized nursing charting processes for tracking preparation progress; Standardized education for nursing staff and ordering providers on adequate colon preparation, assessment of colon preparation quality, and use of the above processes; and print and video patient education materials. Results 238 inpatient colonoscopies were performed in the pre-intervention assessment period and 163 colonoscopies in the post-intervention period. Median pre-intervention Boston Bowel Preparation Score (BBPS) was 6 and 26% of patients had inadequate colon preparation. Median postintervention BBPS was 8 with 16% inadequate colon preparation (p=0.016). The postintervention group had less ASA class I patients and used a lower dose of fentanyl than the preintervention group. There were no other significant differences between the pre- and postintervention groups. Conclusions Implementation of a comprehensive colon preparation quality intervention resulted in significantly improved inpatient colon preparation quality and decreased frequency of inadequate preparations. The intervention consisting of an EMR-based order-set, nursing alerts and charting process, and patient education materials is continually being refined.

Objectives This study sought to investigate the relationship between malnutrition and adverse cardiovascular (CV) events in heart failure with preserved ejection fraction (HFpEF). Background Malnutrition is associated with poor prognosis in a wide range of illnesses, however, the prognostic impact of malnutrition in HFpEF patients is not well known. Methods Baseline malnutrition risk was determined in 1,677 patients with HFpEF enrolled in the Americas regions of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial, according to 3 categories of the geriatric nutritional risk index (GNRI) as previously validated: moderate to severe, GNRI of Results Approximately one-third of patients were at risk for malnutrition (moderate to severe: 11%; low: 25%; and absence of risk: 64%). Over a median of 2.9-years’ follow-up, compared to those with absent risk for malnutrition, moderate to severe risk was associated with significantly increased risk for the primary outcome, CV death and all-cause death (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 1.02 to 1.76; HR: 2.06; 95% CI: 1.40 to 3.03; and HR: 1.79; 95% CI: 1.33 to 2.42, respectively) after multivariate adjustment for age, sex, history of CV diseases, and laboratory biomarkers. Conclusions Patients with HFpEF are at an elevated risk for malnutrition, which was associated with an increased risk for CV events in this population.

BACKGROUND Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic skin disorder. The genetic basis of familial (f)PLCA involves mutations in the oncostatin M receptor (OSMR) and interleukin-31 receptor A (IL31RA) genes, but the disease pathophysiology is not fully understood. AIM To investigate the OSMR mutation spectrum in patients with sporadic (s)PLCA/fPLCA, lichen/macular PLCA in mainland China. METHODS This study was carried out on 64 patients with sPLCA, along with 36 with fPLCA and 10 unaffected individuals collected from 23 unrelated Chinese families. Genomic DNA was extracted from peripheral blood samples. Mutation screening of 17 OSMR exons was performed by Sanger sequencing. RESULTS PLCA lesions are typically localized to the shins, forearm and back. Sequence analysis of OSMR exons demonstrated that the OSMR missense mutation rate in patients with fPLCA (63.89%) was significantly higher than that in patients with sPLCA (34.38%). The male/female ratio of patients carrying a homozygous OSMR mutation (0.29) was significantly lower than that of patients carrying a heterozygous OSMR mutation (1.08; P

Plasma volume expansion is clinically and prognostically relevant in individuals with heart failure. Prior cohorts either excluded or had limited representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between calculated plasma volume status (PVS) and outcomes in HFpEF.We included enrollees from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with available haematocrit and weight data (n = 3414). Plasma volume was derived from the Hakim formula and compared to estimates of ideal plasma volume to generate a relative PVS. Multivariable Cox proportional hazards models tested the association of PVS with clinical outcomes. The median PVS was -11.9% (25th-75th percentile: -17.2% to -6.4%) and the majority (91.1%) had PVS consistent with relative volume contraction (PVS ≤ 0%) as opposed to volume expansion (8.9%, PVS 0%). After multivariable adjustment, each 5% increment in PVS was associated with a ∼11%, 14%, and 12% higher risk for the primary composite endpoint, all-cause death, and heart failure hospitalization, respectively (P 0.002 for all), but not cardiovascular death (P = 0.051). After additional adjustment for natriuretic peptides, PVS only remained associated with heart failure hospitalization (HR 1.10, 95% confidence interval 1.001-1.21, P = 0.047). There were no significant interactions between spironolactone use and the PVS-risk relationship for any endpoint (P 0.1 for all).Higher calculated estimates of PVS were independently associated with a higher risk of long-term clinical outcomes in HFpEF, and particularly, heart failure hospitalization.

BACKGROUND Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF). The prognostic implications of spironolactone-associated WRF in HFpEF patients are not well understood.OBJECTIVES The purpose of this study was to investigate the association between WRF, spironolactone treatment, and clinical outcomes in patients with HFpEF.METHODS In 1,767 patients randomized to spironolactone or placebo in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial)-Americas study, we examined the incidence of WRF (doubling of serum creatinine) by treatment assignment. Associations between incident WRF and subsequent risk for the primary study endpoint of cardiovascular (CV) death, HFH, or aborted cardiac arrest and key secondary outcomes, including CV death, HFH, and all-cause mortality according to treatment assignment, were examined in time-updated Cox proportional hazards models with an interaction term.RESULTS WRF developed in 260 (14.7%) patients with higher rates in those assigned to spironolactone compared to placebo (17.8% vs. 11.6%; odds ratio: 1.66; 95% confidence interval: 1.27 to 2.17; p < 0.001). Regardless of treatment, incident WRF was associated with increased risk for the primary endpoint (hazard ratio: 2.04; 95% confidence interval: 1.52 to 2.72; p < 0.001) after multivariable adjustment. Although there was no statistical interaction between treatment assignment and WRF regarding the primary endpoint (interaction p = 0.11), spironolactone-associated WRF was associated with lower risk of CV death (interaction p = 0.003) and all-cause mortality (interaction p = 0.001) compared with placebo-associated WRF.CONCLUSIONS Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF. (c) 2021 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.

Background: Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction. Methods: EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF>0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z c ) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12. Results: In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, −3.0±0.8 mm Hg, P P c were greater in the sacubitril-valsartan group (−16±6 dyne×second/cm 5 , P =0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction P =0.036). With LVEFc were greater in the sacubitril-valsartan group (trough, −3±8 dyne×second/cm 5 versus post-dose, −17±8 dyne×second/cm 5 ; interaction P =0.024) with no sex difference (treatment×sex interaction, P =0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z c in women (women, −80±21 dyne×second/cm 5 versus men, −20±13 dyne×second/cm 5 ; interaction P =0.019). Conclusions: In prespecified analyses that include pre- and postdose assessments at 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Z c . In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z c in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02874794.

BACKGROUND: Differential opioid prescribing patterns have been reported in non-White patient populations. However, these disparities have not been well described among hospitalized medical inpatients. OBJECTIVE: To describe differences in opioid prescribing patterns among inpatients discharged from the general medicine service based on race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS: For this retrospective study, we performed a multivariable logistic regression for patient race/ethnicity and whether patients received an opioid prescription at discharge and a negative binomial regression for days of opioids prescribed at discharge. The study included all 10,953 inpatients discharged from the general medicine service from June 2012 to November 2018 at University of California San Francisco Medical Center who received opioids during the last 24 hours of their hospitalization. MAIN OUTCOMES AND MEASURES: We examined two primary outcomes: whether a patient received an opioid prescription at discharge, and, for patients prescribed opioids, the number of days dispensed. RESULTS: Compared with White patients, Black patients were less likely to receive an opioid prescription at discharge (predicted population rate of 47.6% vs 50.7%; average marginal effect [AME], −3.1%; 95% CI, −5.5% to −0.8%). Asian patients were more likely to receive an opioid prescription on discharge (predicted population rate, 55.6% vs 50.7%; AME, +4.9; 95% CI, 1.5%-8.3%). We also found that Black patients received a shorter duration of opioid days compared with White patients (predicted days of opioids on discharge, 15.7 days vs 17.8 days; AME, −2.1 days; 95% CI, −3.3 to −0.9). CONCLUSION: Black patients were less likely to receive opioids and received shorter courses at discharge compared with White patients, adjusting for covariates. Asian patients were the most likely to receive an opioid prescription.

Background: \ud In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%).\ud \ud Objectives: \ud The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.\ud \ud Methods: \ud Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.\ud \ud Results: \ud The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (≤22%) compared with the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF ≥33% (n = 1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.\ud \ud Conclusions: \ud In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug’s mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329)

Background and AimsQueries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been utilized in hepatology due to previous inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute-on-chronic liver failure (ACLF) models. Here, we describe a methodology to utilizing EHR data to calculate rolling ACLF scores.MethodsWe examined 239 patient-admissions with end-stage liver disease 7/2014-6/2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses via chart review; and calculated sensitivity, specificity, and Cohen’s kappa.ResultsOf 239 patient-admissions analyzed, 37% women, 46% non-Hispanic White, median age 60 years, median MELD-Na at admission. Of the 239, 7% were diagnosed with NACSELD-ACLF at admission, 27% during the hospitalization, and 9% at discharge. Forty percent diagnosed with CLIF-C-ACLF at admission, 51% during the hospitalization, and 34% at discharge.From chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1-4) were 92-97% and 76-95%, respectively; for severe HE (grades 3-4) were 100% and 78-98%, respectively. Cohen’s kappa between flowsheet and chart review HE grades ranged 0.55-0.72. Sensitivities and specificities for NACSELD-ACLF diagnoses were 75-100% and 96-100%, respectively; for CLIF-C-ACLF diagnoses were 91-100% and 96-100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission-day.ConclusionIn this study, we developed an informatics-based methodology for to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such big data methods to develop electronic phenotypes for ACLF patients.

BackgroundOlder adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability has not been previously characterized.MethodsWe performed a longitudinal, observational study in the nationally representative Health and Retirement Study (1992-2014). We included participants ≥65 years with Medicare claims who met incident AF diagnosis claims criteria. We examined the association of incident stroke with three functional outcomes: independence with activities of daily living (ADL) and instrumental activities of daily living (IADL) and community-dwelling. We fit separate logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimate the contribution of strokes to the overall population burden of functional impairment using the method of recycled predictions.ResultsAmong 3530 participants (median age 79 years, 53% women, median CHA2DS2-VASc 5), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for population comorbidities, annually, ADL dependence increased by 4.4%, IADL dependence increased by 3.9%, and nursing home residence increased by 1.2% (pConclusionOlder adults lose substantial function over time following AF diagnosis, independent of stroke. Stroke was associated with a significant decline in function and an increase in the likelihood of nursing home move, but stroke did not accelerate subsequent disability accrual. Because of the high background rate of functional loss, stroke was not the dominant determinant of population-level disability in older adults with AF.Impact statementWe certify that this work is novel. Little is known about long-term function (ADL, IADL, community-dwelling) among older adults with AF and the association with stroke. This nationally representative study finds a high rate of function loss independent of stroke, and among those who suffer a stroke, a dramatic and immediate decline in function. Because of the high rate of function loss independent of stroke and the relatively low rate of stroke, on a population level, stroke is not the dominant determinant of disability in older adults with AF.

Background Plaque erosion with subsequent coronary thrombosis is considered as an important cause of ST-segment elevation myocardial infarction (STEMI). Smoking is a major risk factor for acute coronary thrombosis. However, the relationship between current smoking status and plaque erosion has not been systematically investigated. Purpose The present study aimed to investigate predictors of plaque erosion in current smokers and non-current smokers with STEMI by using optical coherence tomography (OCT). Methods Between January 2015 to December 2017, a total of 1313 STEMI patients underwent pre-intervention OCT of culprit lesion were enrolled and divided into two groups based on current smoking status: current smoking group (n=713) and non-current smoking group (n=600). Using established criteria, quantitative and qualitative underlying plaque characteristics were assessed by OCT. Clinical, angiographic and OCT characteristics of all enrolled patients were recorded. Univariable and multivariable logistic regression analyses were used to identify predictors of plaque erosion in two groups. Results Plaque erosion were found in 30.9% (220/713) culprit lesions in current smoking group and 20.8% (125/600) of those in non-current smoking group detected by OCT. In multivariate regression analysis, the predictors that strongly related to plaque erosion in the current smoking group were nearby bifurcation (OR: 4.84; 95% CI:2.38–9.87; p Conclusions Predictors of plaque erosion causing STEMI onset are different between current smokers and non-current smoker, with nearby bifurcation and thicker minimal FCT both predicting plaque erosion in two groups of patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China, National Natural Science Foundation of China.

Aims The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and results Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N‐terminal pro‐B‐type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC‐HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure, Graphical representation of the GALACTIC‐HF trial design, enrolment and baseline characteristics. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor–neprilysin inhibitor; CRT, cardiac resynchronization therapy (biventricular pacemaker); CV, cardiovascular; EF, ejection fraction; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter defibrillator; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; NYHA, Hew York Heart Association; SBP, systolic blood pressure.

Background It has been reported that the lumen factors of the culprit lesions are related to Thrombolysis in Myocardial Infarction (TIMI) flow grade in ST-Segment–Elevation Myocardial Infarction (STEMI) patients, but the factors of reduced TIMI flow in plaque erosion have not been studied. Methods 329 STEMI patients with plaque erosion who underwent pre-intervention optical coherence tomography after thrombectomy were included and divided into 2 groups according to preprocedural TIMI flow grade [TIMI 0–1 (n=219) and TIMI 2–3 (n=110)]. Results The patients with older age (55.7±11.1yrs vs. 51.8±10.6yrs, P=0.003) and diabetes patients (18.3% vs. 8.2%, P=0.015) had poorer TIMI flow, and the patients with reduced TIMI flow grade have lower initial cTnI (1.2ng/mL vs. 2.1ng/mL, P=0.023). The lesion in the LAD had better blood flow than the lesion in RCA (P=0.003), and the patients in TIMI 0–1 grade had more lipid plaques (53.9% vs. 41.8%, P=0.039), more macrophage (59.8% vs. 41.8%, P=0.002), and more calcification (34.2% vs. 21.8%, P=0.020). There was no statistically significant difference in the descriptive indicators of lipid or lumen between the two groups. And In a multivariate logistic regression model, the independent correlation factors of reduced TIMI flow grade in erosion patients were age, diabetes mellitus, lesion vessel, and macrophage. Conclusions In STEMI patients with plaque erosion non-lumen factors greatly affect flow, which suggests that systemic treatment is as important as local treatment for plaque erosion. Flow Chart Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China (81827806, 81801861), National Key R&D Program of China (2016YFC1301100)

Background Plaque erosion is a frequent and important mechanism of acute coronary thrombosis only secondary to plaque rupture. Recent studies suggested plaque erosion with noncritical stenosis could be treated conservatively that distinct from those with critical stenosis. However, characteristics of plaque erosions with different coronary stenosis remain unknown. Purpose The present study aimed to investigate morphological features of plaque erosions with different coronary stenosis using optical coherence tomography (OCT). Methods Consecutive ST-segment elevated myocardial infarction (STEMI) patients with OCT images of culprit lesion between August 2014 and December 2017 were enrolled and 348 cases presented with plaque erosion identified by OCT. Based on the severity of lumen area stenosis [calculated by (1-minimal lumen area/reference lumen area) * 100%], all culprit plaque erosions were divided into three groups: Group A (area stenosis Results Of all 348 STEMI patients with plaque erosions, patients in Group A were youngest (p=0.008) and had the lowest frequency of hypertension (p=0.029) as compared with those in Group B and C. Angiographic analysis showed 72.0% of plaque erosions in Group A located in LAD, while 67.8% in Group B and 53.9% in Group C (p=0.039). OCT findings (Figure 1-A) showed the prevalence of fibrous plaque was significantly highest in Group A than those in Group B and C (82.0% vs. 54.8% vs. 34.9%, p Conclusion 56.3% plaque erosion in STEMI patients presented with noncritical stenosis, having distinct morphological features from erosion with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with the presence of noncritically stenotic plaque erosion, remaining a desire to tailor treatment therapy to individual patients. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Key R&D Program of China

Background Previous studies have suggested that Microchannel (MC) is associated with plaque progression and vulnerability. Optical coherence tomography (OCT) could provide a chance to directly visualize plaque neovascularization in vivo. Methods 1268 STEMI patients who underwent OCT examination of culprit lesion were included and divided into MC group (the culprit plaque with MC, n=560) and no-MC group (the culprit plaque without MC, n=708). MC was defined as a no-signal tubuloluminal structure on the cross-sectional optical coherence tomographic image. Clinical, angiography and other plaque morphological characteristics were compared between the two groups. Logistic regression analysis was used to identify independent predictors of MC in overall. In addition, the difference of predictors on MC was found in plaque rupture (PR) and plaque erosion (PE). Results Significant differences between MC group and no-MC group were found in the frequency of thin-cap fibroatheroma (74.6% vs 64.4%, p Conclusions MC in culprit plaque is associated with more lipid (especially cholesterol), higher Hb, hypertension, lesion location (compared with MLA) and the other vulnerable plaque morphological characteristics. The predictors of MC were different in plaque rupture and plaque erosion. Flow chart Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China (81827806, 81801861); National Key R&D Program of China (2016YFC1301100)

Background An elevated white blood cell count (WBC; >15 000/μL) is an established prognostic marker in patients with Clostridium difficile infection (CDI). Small observational studies have suggested that a markedly elevated WBC should prompt consideration of CDI. However, there is limited evidence correlating WBC elevation with the results of C. difficile nucleic acid amplification testing (NAAT). Methods Retrospective review of laboratory testing, outcomes, and treatment of 16 568 consecutive patients presenting to 4 hospitals over 4 years with NAAT and WBC testing on the same day. Results No significant relationship between C. difficile NAAT results and concurrent WBC in the inpatient setting was observed. Although an elevated WBC did predict NAAT results in the outpatient and emergency department populations (P 15 000/μL) in CDI was associated with a longer median hospital length of stay (15.5 vs 11.0 days; P Conclusions Although WBC is an important prognostic indicator in patients with CDI, an isolated WBC elevation has low sensitivity and specificity as a predictor of fecal C. difficile NAAT positivity in the inpatient setting. A high or rising WBC in isolation is not a sufficient indication for CDI testing.

Purpose Diabetes mellitus (DM) is prevalent among advanced heart failure (HF) patients, however its effect on the potential of left ventricular assist device (LVAD)-mediated cardiac recovery has not been described. Methods Consecutive advanced chronic HF patients (N=425) requiring durable continuous-flow LVAD were prospectively evaluated. After excluding patients with acute HF etiologies or post-LVAD follow up Results Baseline characteristics of the 2 groups are shown in the Table. Cardiac functional and structural improvement, as evidenced by relative LVEF and LVEDD changes, was more prominent in non-DM compared to DM patients, and in well- compared to not well-controlled DM patients (Figure). Overall, DM patients were less likely to experience cardiac recovery (8.4% vs 17.5%; p=0.032), while on LVAD support. This remained significant in a multivariate logistic regression after controlling for potential confounders. Conclusion The presence of DM, and notably not well-controlled DM, appears to negatively affect the potential for LVAD-induced myocardial recovery. Further research is needed to investigate the dynamic cardiac metabolism in HF with DM.

Purpose The complex anatomy and different contraction patterns of the different right ventricular (RV) wall segments has made it challenging to predict acute RV failure (ARVF) in patients receiving a left ventricular assist device (LVAD). We sought to improve the prediction of ARVF after LVAD by performing a comprehensive 18-segment strain (e) analysis of the RV. Methods Prospectively enrolled LVAD recipients had a right heart catheterization and echocardiogram prior to implant. From RV-focused views (Figure 1A), 18-segment e was performed and indexed to pulmonary arterial elastance (Ea [PV]). ARVF was defined as need for RVAD, inotropes for >14 days or pulmonary vasodilator for >48 hours post-LVAD. Logistic regression was used to identify associations between specific parameters and ARVF. Results ARVF occurred in 15 of 30 patients enrolled. Lower pulmonary artery pulsatility index (PAPi), TAPSE and basal free wall (FW) (basal anterior, lateral and posterior FW) segmental e/Ea (PV) were significantly associated with ARVF. Indexed basal FW segmental strain provided incremental predictive value over PAPi and TAPSE (Figure 1B). Conclusion Prediction of ARVF in LVAD candidates can be improved by adding comprehensive RV segmental strain analysis to traditional echocardiographic and hemodynamics parameters.

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.

A 51-year-old Spanish-speaking female with a history of diabetes mellitus and hypertension presented to the emergency department with dyspnea, pleuritic chest pain, night sweats, and fever. She noted 10 years of intermittent cough, productive of clear phlegm, that had worsened over the past year.

Background & Aims Familial clustering of eosinophilic esophagitis (EoE) has been described, and we report on the biopsy-assessed prevalence of esophageal eosinophilia (EE) in first-degree family members. The aim was to determine the prevalence of EE in first-degree adult relatives (FDRs) of EoE patients. METHODS: Index EoE patients diagnosed by EE (>15 eosinophils per high-power field) and proton pump inhibitor nonresponsiveness were identified and family trees were constructed. Adult FDRs were invited to undergo upper endoscopy with esophageal biopsies and to complete reflux, dysphagia, and allergy/atopy questionnaires. Questionnaire information was gathered only for those who responded as per institutional review board purview. Records from other children and adult FDRs with prior EoE diagnoses also were obtained when permission was obtained. Simple and multivariable logistic regression models were used to evaluate the unadjusted and odds ratios of EoE for demographic and clinical variables. Results A total of 239 FDRs from 37 index EoE patients were identified. Seventy-one of 239 adult (age, >18 y) FDRs completed endoscopy and questionnaires and 18 of 71 FDRs had EE. An additional 17 FDRs were confirmed to have EE after external medical record retrieval, resulting in a total of 35 of 239 (14.6%) FDRs with EE. Significantly more male FDRs had EE compared with female FDRs (P = .027). Proton pump inhibitors, dysphagia, gastroesophageal reflux disease, asthma, and reflux symptoms predicted EE in FDRs. FDRs who had EE reported hay fever, allergic eye symptoms, and food allergy more frequently than those without EE (P = .03, P = .001, and P = .02, respectively). Specifically, younger age, higher serum eosinophils, being male, and having food allergies all were associated with higher odds of EoE (P = .0211, P = .0031, P = .0362, and P = .0089, respectively). Conclusions The prevalence of esophageal eosinophilia is extremely high and male-predominant in first-degree relatives of EoE patients. Symptoms of hay fever, allergic eye symptoms, and food allergy were predictors of EE in FDRs. Dysphagia did not predict esophageal eosinophilia. Family members of EoE patients are at risk for EE, particularly those who have atopic symptoms.

BACKGROUND Atrial fibrillation (AF) significantly reduces health-related quality of life (HRQoL), previously measured in clinical trials using patient-reported outcomes (PROs). We examined AF PROs in clinical practice and their association with subsequent clinical management. METHODS The Utah My Evaluation (mEVAL) program collects the Toronto AF Symptom Severity Scale (AFSS) in AF outpatients at the University of Utah. Baseline factors associated with worse AF symptom score (range 0-35, higher is worse) were identified in univariate and multivariable analyses. Secondary outcomes included AF burden and AF healthcare utilization. We also compared subsequent clinical management at 6 months between patients with better versus worse AF HRQoL. RESULTS Overall, 1338 patients completed the AFSS symptom score, which varied by sex (mean 7.26 for males vs. 10.27 for females; p

Background: Significant improvements in myocardial structure and function have been reported in some patients with advanced heart failure (termed responders [R]) following left ventricular assist device (LVAD)–induced mechanical unloading. This therapeutic strategy may alter myocardial energy metabolism in a manner that reverses the deleterious metabolic adaptations of the failing heart. Specifically, our previous work demonstrated a post-LVAD dissociation of glycolysis and oxidative-phosphorylation characterized by induction of glycolysis without subsequent increase in pyruvate oxidation through the tricarboxylic acid cycle. The underlying mechanisms responsible for this dissociation are not well understood. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose-phosphate pathway and 1-carbon metabolism, which may mediate myocardial recovery in R. Methods: We prospectively obtained paired left ventricular apical myocardial tissue from nonfailing donor hearts as well as R and nonresponders at LVAD implantation (pre-LVAD) and transplantation (post-LVAD). We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy. Results: Western blot analysis shows significant increase in rate-limiting enzymes of pentose-phosphate pathway and 1-carbon metabolism in post-LVAD R (post-R) as compared with post-LVAD nonresponders (post-NR). The metabolite levels of these enzyme substrates, such as sedoheptulose-6-phosphate (pentose phosphate pathway) and serine and glycine (1-carbon metabolism) were also decreased in Post-R. Furthermore, post-R had significantly higher reduced nicotinamide adenine dinucleotide phosphate levels, reduced reactive oxygen species levels, improved mitochondrial density, and enhanced glycosylation of the extracellular matrix protein, α-dystroglycan, all consistent with enhanced pentose-phosphate pathway and 1-carbon metabolism that correlated with the observed myocardial recovery. Conclusions: The recovering heart appears to direct glycolytic metabolites into pentose-phosphate pathway and 1-carbon metabolism, which could contribute to cardioprotection by generating reduced nicotinamide adenine dinucleotide phosphate to enhance biosynthesis and by reducing oxidative stress. These findings provide further insights into mechanisms responsible for the beneficial effect of glycolysis induction during the recovery of failing human hearts after mechanical unloading.

BACKGROUND: Older adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability has not been previously characterized. METHODS: We performed a longitudinal, observational study in the nationally representative Health and Retirement Study (1992-2014). We included participants ≥65 years with Medicare claims who met incident AF diagnosis claims criteria. We examined the association of incident stroke with three functional outcomes: independence with activities of daily living (ADL) and instrumental activities of daily living (IADL) and community-dwelling. We fit separate logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimate the contribution of strokes to the overall population burden of functional impairment using the method of recycled predictions. RESULTS: Among 3530 participants (median age 79 years, 53% women, median CHA (2) DS (2) -VASc 5), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for population comorbidities, annually, ADL dependence increased by 4.4%, IADL dependence increased by 3.9%, and nursing home residence increased by 1.2% (p

Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography–mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. Results: In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51–0.61]; P P P P =0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated ( R =0.81, P Conclusions: Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.

This chapter reviews the most contemporary approach to hemodynamic assessment in heart failure.

AIMS The impact of frailty on outcomes in randomized heart failure with preserved ejection fraction (HFpEF) trials has not been previously reported. This analysis sought to characterize frailty in a large contemporary HFpEF clinical trial cohort and to evaluate its impact on patient relevant outcomes. METHODS AND RESULTS Using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, a frailty index (FI) was constructed at baseline using 39 clinical, laboratory, and self-reported variables. The relationship between frailty and outcomes and the role of frailty in modulating the benefits of spironolactone were examined in a subset of 1767 TOPCAT patients. For the cohort as a whole (mean age 71.5 years, 49% female), the mean FI at baseline was 0.37 ± 0.11. Four frailty classes were defined ranging from FI 0.21). Mean age was lowest for the most frail class (69 ± 9 years for Class 4; 73 ± 10 years for Class 1; P

Acute changes to left ventricular (LV) hemodynamics after transcatheter aortic valve replacement (TAVR) in humans have been sparsely investigated and informed largely by computer simulation of hypothetical pressure-volume (PV) loops. PV loops are the gold standard for evaluating mechanical

AIMS It is unclear whether spironolactone reduced heart failure (HF) hospitalizations in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial through potential diuretic or other effects. We examined the effects of spironolactone on weight, diuretic use, and renal function, and their subsequent impact on outcomes. METHODS AND RESULTS We analysed data from TOPCAT Americas (1767 patients with HF and preserved ejection fraction; 886 in spironolactone, 881 in placebo arm). We used mixed-effects models for serial data and shared frailty models to identify determinants of recurrent HF hospitalizations among baseline and serial parameters. There were 800 HF hospitalizations after a median of 3.0 years. Despite more weight loss with spironolactone initially, weight trajectories overlapped after 12 months. Daily furosemide dose (time-averaged Δ: -4.8% vs. +11.6%, P