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Stress management interventions (SMIs) can alleviate the psychosocial stress often experienced by women with heart failure. The purpose of this meta-analysis was to summarize women's participation rates, and predictors of participation, in SMIs for the management of psychosocial distress in women with chronic HF. Studies were retrieved from bibliographic databases, reference sections of relevant papers, and research registries. Included studies (a) evaluated a SMI approach for the management of chronic HF, (b) sampled chronic HF patients, and (c) used a randomized controlled trial (RCT) design. Independent coders extracted the relevant data. Thirty-five RCTs met inclusion criteria (N = 3,649; mean age = 63.5 ± 7.0 years). All studies sampled both men and women; the mean proportion of women who participated in the trials was 38.8% (95% confidence interval [CI] = 34.5-43.4; I 2 = 82.4, 95% CI = 81.0-83.6). Women's participation rates were higher in studies sampling more HF patients with hypertension (B = 1.01, SE = 0.45, P = .046) but fewer HF patients prescribed beta blockers (B = -1.10, SE = 0.33, P = .006), F (2,12) = 6.27, P = 0.014, adjusted R 2 = 61%. SMIs may offer women a complementary or integrative approach to standard treatment to help manage the psychological distress associated with HF. Future research should explore the potential benefits of offering stress management approaches to women as part of comprehensive HF care.

Background Home Based Cardiac Rehabilitation (HBCR) has been considered a reasonable alternative to Center-based Cardiac Rehabilitation (CBCR) in patients with established cardiovascular disease, especially in the midst of COVID-19 pandemic. However, the long-term cardiovascular outcomes of patients referred to HBCR remains unknown. Objectives To compare outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR). Methods We performed a retrospective study of 269 patients referred to HBCR at Providence Veterans Affairs Medical Center (PVAMC). From November 2017 to March 2020, 427 patients were eligible and referred for Cardiac Rehabilitation (CR) at PVAMC. Of total patients, 158 patients were referred to CBCR and 269 patients to HBCR based on patient and/or clinician preference. The analysis of outcomes was focused on HBCR patients. We compared outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR) from 3 to 12 months of the referral date. HBCR consisted of face-to-face entry exam with exercise prescription, weekly phone calls for education and exercise monitoring, with adjustments where applicable, for 12-weeks and an exit exam. Primary outcome was composite of all-cause mortality and hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: smoking, left ventricular ejection fraction and CABG status. Results A total of 269 patients (mean age: 72, 98% Male) were referred to HBCR, however, only 157 (58%) patients attended HBCR. The primary outcome occurred in 30 patients (19.1%) in the HBCR group and 30 patients (30%) in the Non-HBCR group (adjusted HR=0.56, CI 0.33-0.95, P=.03). All-cause mortality occurred in 6.4% of patients in the HBCR group and 13% patients in the Non-HBCR group 3 to 12 months after HBCR referral (adjusted HR=0.43, CI 0.18-1.0, P= .05). There was no difference in cardiovascular hospitalizations (HBCR: 5.7% vs Non-HBCR: 10%, adjusted HR 0.57, CI 0.22-1.4, P= .23) or all cause hospitalizations at 3 to 12 months between the groups (HBCR: 12.7% vs Non-HBCR: 21%, adjusted HR 0.53, CI 0.28-1.01, P= .05). Conclusion Completion of HBCR among referred patients was associated with a lower risk of the combined all-cause mortality and all-cause hospitalizations up to 12 months. Based on the outcomes, HBCR is a reasonable option that can improve access to CR for patients who are not candidates of or cannot attend CBCR. Randomized-controlled studies are needed to confirm these findings.

Background A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown. Methods and Results Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75–1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78–1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55–0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83–1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251). Conclusions The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.

The availability of electronic health record (EHR)-linked biobank data for research presents opportunities to better understand complex ocular diseases. Developing accurate computable phenotypes for ocular diseases for which gold standard diagnosis includes imaging remains inaccessible in most biobank-linked EHRs. The objective of this study was to develop and validate a computable phenotype to identify primary open-angle glaucoma (POAG) through accessing the Department of Veterans Affairs (VA) Computerized Patient Record System (CPRS) and Million Veteran Program (MVP) biobank. Accessing CPRS clinical ophthalmology data from VA Medical Center Eye Clinic (VAMCEC) patients, we developed and iteratively refined POAG case and control algorithms based on clinical, prescription, and structured diagnosis data (ICD-CM codes). Refinement was performed via detailed chart review, initially at a single VAMCEC (n = 200) and validated at two additional VAMCECs (n = 100 each). Positive and negative predictive values (PPV, NPV) were computed as the proportion of CPRS patients correctly classified with POAG or without POAG, respectively, by the algorithms, validated by ophthalmologists and optometrists with access to gold-standard clinical diagnosis data. The final algorithms performed better than previously reported approaches in assuring the accuracy and reproducibility of POAG classification (PPV >83% and NPV >97%) with consistent performance in Black or African American and in White Veterans. Applied to the MVP to identify cases and controls, genetic analysis of a known POAG-associated locus further validated the algorithms. We conclude that ours is a viable approach to use combined EHR-genetic data to study patients with complex diseases that require imaging confirmation.

Background: While an association between atherosclerosis and dementia has been identified, few studies have assessed the longitudinal relationship between aortic valve calcification (AVC) and cognitive impairment (CI). Objective: We sought to determine whether AVC derived from lung cancer screening CT (LCSCT) was associated with CI in a moderate-to-high atherosclerotic risk cohort. Methods: This was a single site, retrospective analysis of 1401 U.S. veterans (65 years [IQI: 61, 68] years; 97%male) who underwent quantification of AVC from LCSCT indicated for smoking history. The primary outcome was new diagnosis of CI identified by objective testing (Mini-Mental Status Exam or Montreal Cognitive Assessment) or by ICD coding. Time-to-event analysis was carried out using AVC as a continuous variable. Results: Over 5 years, 110 patients (8%) were diagnosed with CI. AVC was associated with new diagnosis of CI using 3 Models for adjustment: 1) age (HR: 1.104; CI: 1.023–1.191; p = 0.011); 2) Model 1 plus hypertension, hyperlipidemia, diabetes, CKD stage 3 or higher (glomerular filtration rate

Background/aims Direct‐acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)‐infected patients. The real‐world treatment outcome in Taiwanese patients on a nationwide basis is elusive. Methods The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end‐of‐treatment). Results A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype‐1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment‐naïve noncirrhotic, treatment‐naïve cirrhotic, treatment‐experienced noncirrhotic and treatment‐experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment‐experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment‐naïve noncirrhotic patients (94.8%) and treatment‐experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence

Aims Pre‐existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease‐2019 (COVID‐19) outcomes. However, data on outcomes of COVID‐19 among people with pre‐existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre‐existing HF with COVID‐19 outcomes. Methods and results A retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID‐19 diagnosis among Veterans with and without pre‐existing diagnosis of HF. Cox‐regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID‐19, 6148 had pre‐existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID‐19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61–2.17) and 1.79 (1.66–1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15–1.64) and 1.27 (1.16–1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants. Conclusions Patients with COVID‐19 and pre‐existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin‐converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.

Objective To examine whether diabetes shared medical appointments (SMAs) implemented as part of usual clinical practice in diverse health systems are more effective than usual care in improving and sustaining A1c improvements. Research Design and Methods A multi-site cluster randomized pragmatic trial examining implementation in clinical practice of diabetes SMAs in five Veterans Affairs (VA) health systems was conducted from 2016 to 2020 among 1537 adults with type 2 diabetes and elevated A1cs. Eligible patients were randomly assigned to either: (1) invitation to participate in a series of SMAs totaling 8–9 h; or (2) continuation of usual care. Relative change in A1c (primary outcome) and in systolic blood pressure, insulin starts, statin starts, and anti-hypertensive medication classes (secondary outcomes) were measured as part of usual clinical care at baseline, at 6 months and at 12 months (~7 months after conclusion of the final SMA in four of five sites). We examined outcomes in three samples of SMA participants: all those scheduled for a SMA, those attending at least one SMA, and those attending at least half of SMAs. Results Baseline mean A1c was 9.0%. Participants scheduled for an SMA achieved A1c reductions 0.35% points greater than the control group between baseline and 6-months follow up (p = .001). Those who attended at least one SMA achieved reductions 0.42 % points greater (p p < .001) than the control group. At 12-month follow-up, the three SMA analysis samples achieved reductions from baseline ranging from 0.16 % points (p = 0.12) to 0.29 % points (p = .06) greater than the control group. Conclusions Diabetes SMAs as implemented in real-life diverse clinical practices improve glycemic control more than usual care immediately after the SMAs, but relative gains are not maintained. Our findings suggest the need for further study of whether a longer term SMA model or other follow-up strategies would sustain relative clinical improvements associated with this intervention. Trial Registration ClinicalTrials.gov ID NCT02132676

Objectives This study sought to evaluate a decision algorithm for the estimation of left ventricular filling pressure (LVFP) in patients with mitral annular calcification (MAC). Background In a single center study, Abudiab et al evaluated echocardiographic parameters to estimate LVFP in patients with MAC against invasive hemodynamic measurements and developed a decision algorithm which demonstrated high predictive accuracy. Methods Retrospectively, 55 patients (mean age 68.5 ± 11.5) with MAC and a left heart catheterization within 24 hours of an echocardiogram were identified. The decision algorithm was applied using echo data to classify patients as having normal or elevated LVFP which was then compared with the invasively obtained LVFP. Results The algorithm performed poorly at predicting pre-A LVFP as normal or high (P = .182). Accuracy for the algorithm was 0.59 [0.46, 0.72] (mean [95% CI]), sensitivity was 0.45 [0.28, 0.62], specificity was 0.73 [0.54, 0.86], false positive rate was 0.27 [0.14, 0.46], and false negative rate was 0.55 [0.38, 0.72]. E/A ratio, IVRT, and E/e'ratio showed no significant relationship to actual patient LVFP. Conclusions The Abudiab et al algorithm failed to demonstrate comparable sensitivity, specificity, and accuracy in our sample. Additional study is necessary to refine this tool prior to more widespread use in clinical practice.

Background Adiponectin is a polypeptide hormone related to obesity, and a known modulator of pulmonary vascular remodeling. Association between plasma adiponectin levels and pulmonary hypertension (PH) has not been studied in African Americans (AAs) who are disproportionately affected by obesity. The relationship between adiponectin and heart failure (HF) and mortality, outcomes associated with PH, is unclear. Methods We performed cross-sectional and longitudinal analysis to examine if there is an association between plasma adiponectin and PH and associated clinical outcomes, in participants of Jackson Heart Study (JHS). JHS is a prospective observational cohort study of heart disease in AAs from Jackson, Mississippi. Results Of the 3161 participants included in the study, mean age (SD) was 56.38 (12.61) years, 1028 were men (32.5%), and mean (SD) BMI was 31.42 (7.05) kg/m 2 . Median (IQR) adiponectin was 4516.82 (2799.32–7065.85) ng/mL. After adjusting for potential confounders including BMI, higher adiponectin levels were associated with increased odds of PH (adjusted odds ratio per log increment in adiponectin, (1.81; 95% CI, 1.41–2.32). High adiponectin levels were also associated with associated HF admissions (adjusted hazard ratio [HR] per log increment in adiponectin, 1.63, 95% CI, 1.24–2.14) and mortality (adjusted HR per log increment in adiponectin, 1.20; 95% CI 1.02–1.41). Conclusions Elevated plasma adiponectin levels are associated with PH, HF admissions and mortality risk in AAs. High adiponectin levels may help identify an at-risk population that could be evaluated for targeted prevention and management strategies in future studies

Background Digoxin reduces the risk of heart failure hospitalization in patients with heart failure with reduced ejection fraction. Less is known about this association in patients with heart failure with preserved ejection fraction (HFpEF), the examination of which was the objective of the current study. Methods In the Medicare-linked OPTIMIZE-HF registry, 7374 patients hospitalized for HF had ejection fraction ≥50% and were not receiving digoxin prior to admission. Of these, 5675 had a heart rate ≥50 beats per minute, an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 or did not receive inpatient dialysis, and digoxin was initiated in 524 of these patients. Using propensity scores for digoxin initiation, calculated for each of the 5675 patients, we assembled a matched cohort of 513 pairs of patients initiated and not initiated on digoxin, balanced on 58 baseline characteristics (mean age, 80 years; 66% women; 8% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin initiation were estimated in the matched cohort. Results Among the 1026 matched patients with HFpEF, 30-day heart failure readmission occurred in 6% and 9% of patients initiated and not initiated on digoxin, respectively (HR 0.70; 95% CI, 0.45-1.10; P = .124). HRs (95% CIs) for 30-day all-cause readmission and all-cause mortality associated with digoxin initiation were 0.95 (0.73-1.23; P = .689) and 0.93 (0.55-1.56; P = .773), respectively. Digoxin initiation had no association with 6-year outcomes. Conclusion Digoxin initiation prior to hospital discharge was not associated with 30-day or 6-year outcomes in older hospitalized patients with HFpEF.

BACKGROUND AND AIMS: Calcific aortic valve disease is highly prevalent in patients with significant smoking history and is a marker of atherosclerosis. The aim of this study was to define the prognostic value of aortic valve calcification (AVC) derived from low dose, lung cancer screening computed tomography (LCSCT) for all-cause mortality in this higher risk population. METHODS: This is a single site, retrospective analysis of 1529 moderate-to-high atherosclerotic cardiovascular risk U.S. veterans (65 years [IQI: 61, 68] years; 96% male), who underwent clinically indicated LCSCT. CTs were scored for aortic valve calcification (AVC) and coronary artery calcification (CAC). The primary endpoint was all-cause mortality and secondary endpoints were nonfatal myocardial infarction (MI) and nonfatal cerebrovascular accident (CVA). RESULTS: Over 4-year follow-up, 227 patients (15%) died, 112 patients (7%) had nonfatal MI, and 52 patients (3%) had nonfatal CVA. AVC was predictive of all-cause mortality (HR per 100: 1.041 [1.030–1.052], p < 0.001), and this association remained significant after multivariate adjustment for traditional atherosclerotic risk factors, including CAC (1.021 [1.007–1.036], p = 0.003). After excluding patients with severe aortic stenosis (AS) or severe AVC (≥1274 AU in women and ≥2065 AU in men), in a subset of 765 patients who had echocardiograms, this association remained significant after multivariate analysis (HR per 100: 1.052 [1.010–1.095], p = 0.014). Despite controlling for CAC in the models, AVC was still associated with MI (HR per 100: 1.021 [1.004–1.039], p = 0.017) and with CVA (HR per 100: 1.027 [1.002–1.051], p = 0.032). CONCLUSIONS: Scoring AVC derived from LCSCT is predictive of mortality, nonfatal MI, and nonfatal CVA in patients at known risk for cardiovascular disease, independent of coronary calcification or severe aortic valve stenosis.

Background Smoking cessation is recommended for adults with heart failure (HF). The prevalence of e-cigarette use among adults with HF is unknown. Objective To determine prevalence of and reasons for e-cigarette use among adults with HF. Methods Data from the Population Assessment of Tobacco and Health Study (Wave 1) were examined. Results Of 484 respondents with HF, 1% (weighted) reported current e-cigarette use, and 5% (weighted) reported dual cigarette/e-cigarette use. Adults with HF had higher odds of dual use (OR = 1.76, 95% CI: 1.22–2.54) compared to those without HF, controlling for age, sex, race, and income. Dual users with HF reported using e-cigarettes because they may be less harmful to nearby people and to themselves than cigarettes. Conclusions E-cigarette use should be assessed and monitored to understand the safety and potential efficacy of e-cigarettes as a harm reduction approach for HF patients.

BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis. Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer (CRC). AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis. METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways. Patients were divided into two groups based on the methylation status of the six evaluated genes, namely, the < 3 aberrancy group and ≥ 3 aberrancy group. Various tumor stages were divided into two subgroups (local and advanced stages) on the basis of the pathological type of the following tissues: Tumor and adjacent normal tissues (matched normal). We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression (TTP) and overall survival. RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue. The 5-year TTP survival curves showed a significant difference between the ≥ 3 aberrancy group and the < 3 aberrancy group. Compared with the < 3 aberrancy group, a significantly shorter TTP was observed in the ≥ 3 aberrancy group. We further analyzed the interaction between CRC prognosis and different cancer stages (local and advanced) according to the methylation status of the selected genes in both types of tissues. There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages. We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues. CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC. We recommend using these novel markers to assist in clinical decision-making.

Background Prior studies have identified lower mortality in Black Veterans compared with White Veterans after hospitalization for common medical conditions, but these studies adjusted for comorbid conditions identified in administrative claims. Objectives The objectives of this study were to compare mortality for non-Hispanic White (hereafter, "White"), non-Hispanic Black (hereafter, "Black"), and Hispanic Veterans hospitalized for heart failure (HF) and pneumonia and determine whether observed mortality differences varied according to whether claims-based comorbid conditions and/or clinical variables were included in risk-adjustment models. Research design This was an observational study. Subjects The study cohort included 143,520 admissions for HF and 127,782 admissions for pneumonia for Veterans hospitalized in 132 Veterans Health Administration (VA) Medical Centers between January 2009 and September 2015. Measures The primary independent variable was racial/ethnic group (ie, Black, Hispanic, and non-Hispanic White), and the outcome was all-cause mortality 30 days following admission. To compare mortality by race/ethnicity, we used logistic regression models that included different combinations of claims-based, clinical, and sociodemographic variables. For each model, we estimated the average marginal effect (AME) for Black and Hispanic Veterans relative to White Veterans. Results Among the 143,520 (127,782) hospitalizations for HF (pneumonia), the average patient age was 71.6 (70.9) years and 98.4% (97.1%) were male. The unadjusted 30-day mortality rates for HF (pneumonia) were 7.2% (11.0%) for White, 4.1% (10.4%) for Black and 8.4% (16.9%) for Hispanic Veterans. Relative to White Veterans, when only claims-based variables were used for risk adjustment, the AME (95% confidence interval) for the HF [pneumonia] cohort was -2.17 (-2.45, -1.89) [0.08 (-0.41, 0.58)] for Black Veterans and 1.32 (0.49, 2.15) [4.51 (3.65, 5.38)] for Hispanic Veterans. When clinical variables were incorporated in addition to claims-based ones, the AME, relative to White Veterans, for the HF [pneumonia] cohort was -1.57 (-1.88, -1.27) [-0.83 (-1.31, -0.36)] for Black Veterans and 1.50 (0.71, 2.30) [3.30 (2.49, 4.11)] for Hispanic Veterans. Conclusions Compared with White Veterans, Black Veterans had lower mortality, and Hispanic Veterans had higher mortality for HF and pneumonia. The inclusion of clinical variables into risk-adjustment models impacted the magnitude of racial/ethnic differences in mortality following hospitalization. Future studies examining racial/ethnic disparities should consider including clinical variables for risk adjustment.

Background Studies have reported that people living with HIV have higher burden of subclinical cardiovascular disease, but the data are not adequately synthesized. We performed meta‐analyses of studies of coronary artery calcium and coronary plaque in people living with HIV. Methods and Results We performed systematic search in electronic databases, and data were abstracted in standardized forms. Study‐specific estimates were pooled using meta‐analysis. 43 reports representing 27 unique studies and involving 10 867 participants (6699 HIV positive, 4168 HIV negative, mean age 52 years, 86% men, 32% Black) were included. The HIV‐positive participants were younger (mean age 49 versus 57 years) and had lower Framingham Risk Score (mean score 6 versus 18) compared with the HIV‐negative participants. The pooled estimate of percentage with coronary artery calcium >0 was 45% (95% CI, 43%–47%) for HIV‐positive participants, and 52% (50%–53%) for HIV‐negative participants. This difference was no longer significant after adjusting for difference in Framingham Risk Score between the 2 groups. The odds ratio of coronary artery calcium progression for HIV‐positive versus ‐negative participants was 1.64 (95% CI, 0.91–2.37). The pooled estimate for prevalence of noncalcified plaque was 49% (95% CI, 47%–52%) versus 20% (95% CI, 17%–23%) for HIV‐positive versus HIV‐negative participants, respectively. Odds ratio for noncalcified plaque for HIV‐positive versus ‐negative participants was 1.23 (95% CI, 1.08–1.38). There was significant heterogeneity that was only partially explained by available study‐level characteristics. Conclusions People living with HIV have higher prevalence of noncalcified coronary plaques and similar prevalence of coronary artery calcium, compared with HIV‐negative individuals. Future studies on coronary artery calcium and plaque progression can further elucidate subclinical atherosclerosis in people living with HIV.

RationaleA commonMUC5Bgene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis, but its role in the SARS-CoV-2 infection and disease severity is unclear.ObjectivesTo assess whether rs35705950-T confers differential risk for clinical outcomes associated with COVID-19 infection among participants in the Million Veteran Program (MVP) and COVID-19 Host Genetics Initiative (HGI).MethodsMVP participants were examined for an association between the incidence or severity of COVID-19 and the presence of aMUC5Brs35705950-T allele. Comorbidities and clinical events were extracted from the electronic health records (EHR). The analysis was performed within each ancestry group in the MVP, adjusting for sex, age, age2,and first twenty principal components followed by a trans-ethnic meta-analysis. We then pursued replication and performed a meta-analysis with the trans-ethnic summary statistics from the HGI. A phenome-wide association study (PheWAS) of the rs35705950-T was conducted to explore associated pathophysiologic conditions.Measurements and Main ResultsA COVID-19 severity scale was modified from the World Health Organization criteria, and phenotypes derived from the International Classification of Disease-9/10 were extracted from EHR. Presence of rs35705950-T was associated with fewer hospitalizations (Ncases=25353, Ncontrols=631,024; OR=0.86 [0.80-0.93], p=7.4 × 10−5) in trans-ethnic meta-analysis within MVP and joint meta-analyses with the HGI (N=1641311; OR=0.89 [0.85-0.93], p =1.9 × 10−6). Moreover, individuals of European Ancestry with at least one copy of rs35705950-T had fewer post-COVID-19 pneumonia events (OR=0.85 [0.76-0.96], p =0.008). PheWAS exclusively revealed pulmonary involvement.ConclusionsTheMUC5Bvariant rs35705950-T is protective in COVID-19 infection.

Background/AimsThe study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan.MethodsThe Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3,144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). ResultsThe overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). ConclusionsThe results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

Background Although HIV is associated with increased risk of heart failure (HF), it is not known if people living with HIV develop HF at a younger age compared with individuals without HIV. Crude comparisons of age at diagnosis of HF between individuals with and without HIV does not account for differences in underlying age structures between the populations. Methods and Results We used Veterans Health Administration data to compare the age at HF diagnosis between veterans with and without HIV, with adjustment for difference in population age structure. Statistical weights, calculated for each 1‐year strata of veterans with HIV in each calendar year from 2000 to 2018, were applied to the veterans without HIV to standardize the age structure. We identified 5093 veterans with HIV (98% men, 34% White) with first HF episode recorded after HIV diagnosis (median age at incidence of HF, 58 years), and 1 425 987 veterans without HIV (98% men, 78% White) with HF (corresponding age, 72 years), with an absolute difference of 14 years. After accounting for difference in age structure, the adjusted median age at HF diagnosis for veterans without HIV was 63 years, 5 years difference with veterans with HIV ( P Conclusions Veterans with HIV are diagnosed with HF at a significantly younger age compared with veterans without HIV. These findings may have implications for HF prevention in individuals with HIV. Future studies are needed to make the findings more generalizable.

Background: Increasing evidence points to cardiac injury (CI) as a common coronavirus disease 2019 (COVID-19) related complication. The characteristics of early CI (occurred within 72 h of admission) and late CI (occurred after 72 h of admission) and its association with mortality in COVID-19 patients is unknown.Methods: This retrospective study analyzed patients confirmed with COVID-19 in Union Hospital (Wuhan, China) from Jan 29th to Mar 15th, 2020. Clinical outcomes (discharge, or death) were monitored to April 15, 2020, the latest date of follow-up. Demographic, clinical, laboratory, as well as treatment and prognosis were collected and analyzed in patients with early, late CI and without CI.Results: A total of 196 COVID-19 patients were included for analysis. The median age was 65 years [interquartile range (IQR) 56–73 years], and 112 (57.1%) were male. Of the 196 COVID-19 patients, 49 (25.0%) patients had early and 20 (10.2%) patients had late CI, 56.6% developed Acute-Respiratory-Distress-Syndrome (ARDS) and 43 (21.9%) patients died. Patients with any CI were more likely to have developed ARDS (87.0 vs. 40.2%) and had a higher in-hospital mortality than those without (52.2 vs. 5.5%, P < 0.001). Among CI subtypes, a significantly higher risk of in-hospital death was found in patients with early CI with recurrence [19/49 patients, adjusted odds ratio (OR) = 7.184, 95% CI 1.472–35.071] and patients with late CI (adjusted OR = 5.019, 95% CI 1.125–22.388) compared to patients with early CI but no recurrence.Conclusions: CI can occur early on or late after, the initial 72 h of admission and is associated with ARDS and an increased risk of in-hospital mortality. Both late CI and recurrent CI after the initial episode were associated with worse outcomes than patients with early CI alone. This study highlights the importance of early examination and periodical monitoring of cardiac biomarkers, especially for patients with early CI or at risk of clinical deterioration.

Background The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented. Objectives The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists. Methods Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled. Results Four-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778). Conclusions Among hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes.

PURPOSE The aim of this study was to determine participation rates and outcomes for patients with Takotsubo cardiomyopathy (TC) in a cardiac rehabilitation (CR) program. METHODS Patients at 2 academic medical centers with a discharge diagnosis of TC from January 2008 to March 2015 were retrospectively identified. Patients meeting the Mayo Clinic criteria for TC were cross-matched to the CR center affiliated with the hospitals to determine the referral rate and outcomes after completion of the program. RESULTS In total, 380 unique patients were identified who survived the index hospitalization. Eighteen patients (5%) were referred to CR, 15 enrolled, and of those enrolled, 10 patients (67%) completed the program. Patients undergoing percutaneous coronary intervention of a nonculprit vessel at the time of diagnosis was the only predictor for referral to CR (11% vs 1%, P = .01). The 10 patients who completed CR attended 33 ± 6 (range, 20-36) sessions. Weight and body mass index reduction were 2.8 ± 3.5 lb and 0.6 ± 0.7 kg/m (P = .04, both), respectively. Post-CR exercise duration was 37 ± 4 min/session, which improved by 13 ± 6 min/session from baseline (P < .01). Two patients entered the phase III maintenance program. One-year cardiac readmission rates were comparable among patients who completed CR and those who were referred but did not attend or complete CR (0% vs 13%, P = .47). CONCLUSIONS Referral for the TC population was low; however, enrollment and completion rates were adequate, with percutaneous coronary intervention in nonculprit vessel as the only predictor of CR referral. Limited data showed CR may help with weight reduction and improve exercise duration.

INTRODUCTION: Adults who engage in regular physical activity have lower rates of morbidity and mortality than those who do not. Exercise videogames may offer an attractive, sustainable alternative or supplement to traditional modes of exercise. This study compared exercise videogames with standard exercise modalities for improving uptake and maintenance of moderate to vigorous physical activity, and health risk indices. STUDY DESIGN: A three-arm clinical RCT including 12 weeks of supervised laboratory-based moderate to vigorous physical activity followed by 6 months follow-up. SETTING/PARTICIPANTS: This study was conducted at a university affiliated hospital research lab. Healthy, sedentary adults were eligible. INTERVENTIONS: This study compared a 12-week program of supervised exercise videogames versus standard exercise (e.g., treadmill) versus control. Data were collected from January 2012 to September 2017 and analyzed in 2018. MAIN OUTCOME MEASURES: The primary outcome was weekly minutes of moderate to vigorous physical activity at end of treatment, assessed at 3 and 6 months post-intervention by using self-report and accelerometer data. Health risk indices (e.g., HbA1c, lipids) were also assessed. RESULTS: Participants (N=283) had an average age of 46.2 ±13.5 years; 79% were female. At end of treatment, those in the exercise videogame arm engaged in 30 minutes/week more moderate to vigorous physical activity compared with standard exercise and 85 more minutes/week than controls (all p

Purpose One unexplored mechanism for poor outcomes in cardiovascular and pulmonary rehabilitation (CVPR) is fear about aerobic exercise. Patients in CVPR may tend to avoid aerobic exercise because of the fear of physical sensations associated with exertion. This study examined fear about exercise in patients enrolled in outpatient CVPR and practitioner beliefs and behaviors related to fear associated with exercise. Methods Survey data were collected from patients (n = 117) enrolled in cardiac rehabilitation (n = 69) and pulmonary rehabilitation (n = 48) and practitioners (n = 16) who were exercise physiologists and nurses working in CVPR. Results Fears about exercise and avoidance behaviors were common among patients. In pulmonary rehabilitation, fears and avoidance of exercise were correlated with higher levels of anxiety and depression (r values = 0.27-0.54), lower forced expiratory volume in the first second of expiration/forced vital capacity (r values = -0.13 to -0.39), lower health-related quality of life (r values = -0.13 to -0.62), and stronger beliefs about utility of anxiety treatment (r values = 0.21-0.36). In cardiac rehabilitation, fears about exercise were correlated with higher levels of anxiety (r values = 0.19-0.38), lower mental health quality of life (r values = -0.25 to -0.27), and stronger beliefs about utility of anxiety treatment (r values = 0.30-0.40), and avoidance of exercise was correlated with lower exercise tolerance and poorer physical health quality of life (r values = -0.22 to -0.24). Practitioners estimated that an average of 47 ± 20% of patients experience fear associated with exercise and reported low feelings of preparedness to address patient anxiety and fear. Conclusions It may be beneficial to provide practitioners with skills to recognize and address anxiety and fear in their patients as it relates to exercise.

Objective To synthesize existing epidemiological data on cardiac dysfunction in HIV. Background Data on the burden and risk of human immunodeficiency virus (HIV) infection-associated cardiac dysfunction have not been adequately synthesized. We performed meta-analyses of extant literature on the frequency of several subtypes of cardiac dysfunction among people living with HIV. Methods We searched electronic databases and reference lists of review articles and combined the study-specific estimates using random-effects model meta-analyses. Heterogeneity was explored using subgroup analyses and meta-regressions. Results We included 63 reports from 54 studies comprising up to 125,382 adults with HIV infection and 12,655 cases of various cardiac dysfunctions. The pooled prevalence (95% confidence interval) was 12.3% (6.4% to 19.7%; 26 studies) for left ventricular systolic dysfunction (LVSD); 12.0% (7.6% to 17.2%; 17 studies) for dilated cardiomyopathy; 29.3% (22.6% to 36.5%; 20 studies) for grades I to III diastolic dysfunction; and 11.7% (8.5% to 15.3%; 11 studies) for grades II to III diastolic dysfunction. The pooled incidence and prevalence of clinical heart failure were 0.9 per 100 person-years (0.4 to 2.1 per 100 person-years; 4 studies) and 6.5% (4.4% to 9.6%; 8 studies), respectively. The combined prevalence of pulmonary hypertension and right ventricular dysfunction were 11.5% (5.5% to 19.2%; 14 studies) and 8.0% (5.2% to 11.2%; 10 studies), respectively. Significant heterogeneity was observed across studies for all the outcomes analyzed (I2 > 70%, p Conclusions Cardiac dysfunction is frequent in people living with HIV. Additional prospective studies are needed to better understand the burden and risk of various forms of cardiac dysfunction related to HIV and the associated mechanisms. (Cardiac dysfunction in people living with HIV–a systematic review and meta-analysis; CRD42018095374)

PURPOSE Depression is indicative of poor prognosis in cardiac patients. Reductions in depression have been observed following cardiac rehabilitation (CR). Whether similar improvements in positive and negative affect occur is unknown. Greater understanding of depressive symptom and affect change is needed to enhance facilitators of emotional improvement after a cardiac event. METHODS Cardiac rehabilitation attendees (n = 637) completed measures of depressive symptoms, affect, health status, and social support at CR intake and discharge. Body mass index, metabolic equivalents, and blood pressure were also measured. Relationships between changes in psychosocial and physical health indicators and depressive symptoms, positive affect, and negative affect were examined. RESULTS From intake to discharge, depressive symptoms (d = 0.40, P < .001) and negative affect (d = 0.26, P < .001) decreased. Positive affect increased (d = 0.34, P < .001). In multivariate regression, predictors of depressive symptom reduction were increased vitality (β = -.26) and decreased bodily pain (β = -.08). Predictors of positive affect increase were increased vitality (β = .25), social support (β = .16), and physical role functioning (β = .09). Predictors of negative affect reduction were increased vitality (β = -.23) and social support (β = -.10). Changes in indicators of physical health were not related to depressive symptom or affect change. CONCLUSIONS Depressive symptom and affect improvements following CR were observed and most strongly associated with improvements in vitality and social support. Future research should explore how enhancement of these mechanisms may further improve depressive symptom and affect during CR.

Key Points Question Is delirium associated with 30-day functional recovery in patients discharged to skilled nursing facilities after heart failure hospitalization? Findings In this cohort study of 20 495 patients from the US Department of Veterans Affairs health system discharged to skilled nursing facilities after heart failure hospitalization, delirium was associated with poor functional recovery. The baseline Activities of Daily Living score on admission to a skilled nursing facility was significantly worse among patients with delirium; patients with delirium also had significantly lower Activities of Daily Living improvement from baseline to follow-up assessments. Meaning Study results suggest that delirium on admission to skilled nursing facilities after heart failure hospitalization was associated with poor functional recovery., Importance A substantial number of patients discharged to skilled nursing facilities (SNFs) after heart failure (HF) hospitalization experience regression in function or do not improve. Delirium is one of few modifiable risk factors in this patient population. Therefore, understanding the role of delirium in functional recovery may be useful for improving outcomes. Objective To assess the association of delirium with 30-day functional improvement in patients discharged to SNFs after HF hospitalization. Design, Setting, and Participants This retrospective cohort study included patients hospitalized for HF in 129 US Department of Veterans Affairs hospitals who were discharged to SNFs from October 1, 2010, to September 30, 2015. Data were analyzed from June 14 to December 18, 2020. Exposures Delirium, as determined by the Minimum Data Set (MDS) 3.0 Confusion Assessment Method, with dementia as a covariate, determined via International Classification of Diseases, Ninth Revision (ICD-9) coding. Main Outcomes and Measures The difference between admission and 30-day MDS 3.0 Activities of Daily Living (ADL) scores. Results A total of 20 495 patients (mean [SD] age, 78 [10.3] years; 78.9% White; and 97% male) were included in the analysis. Of the total sample, 882 patients (4.3%) had delirium on an SNF admission. The mean (SD) baseline ADL score on admission to SNF was significantly worse among patients with delirium than without (18.3 [4.7] vs 16.1 [5.2]; P, This cohort study assesses the association between delirium and functional recovery for patients recently discharged to skilled nursing facilities after heart failure hospitalization.

PURPOSE The conceptual utility of home-based cardiac rehabilitation (HBCR) is widely acknowledged. However, data substantiating its effectiveness and safety are limited. This study evaluated effectiveness and safety of the Veterans Affairs (VA) national HBCR program. METHODS Veterans completed a 12-wk HBCR program over 18 mo at 25 geographically dispersed VA hospitals. Pre- to post-changes were compared using paired t tests. Patient satisfaction and adverse events were also summarized descriptively. RESULTS Of the 923 Veterans with a mean age of 67.3 ± 10.6 yr enrolled in the HBCR program, 572 (62%) completed it. Findings included significant improvements in exercise capacity (6-min walk test distance: 355 vs 398 m; P < .05; Duke Activity Status Index: 27.1 vs 33.5; P < .05; self-reported steps/d: 3150 vs 4166; P < .05); depression measured by Patient Health Questionnaire (6.4 vs 4.9; P < .0001); cardiac self-efficacy (33.1 vs 39.2; P < .0001); body mass index (31.5 vs 31.1 kg/m2; P = .0001); and eating habits measured by Rate Your Plate, Heart (47.2 vs 51.1; P < .05). No safety issues were related to HBCR participation. Participants were highly satisfied. CONCLUSIONS The VA HBCR program demonstrates strong evidence of effectiveness and safety to a wide range of patients, including those with high clinical complexity and risk. HBCR provides an adjunct to site-based programs and access to cardiac rehabilitation. Additional research is needed to assess long-term effects, cost-effectiveness, and sustainability of the model.

Background: The renin-angiotensin-aldosterone system (RAAS) is an important driver of blood pressure (BP), but the association of the RAAS with ambulatory BP (ABP) and ABP monitoring phenotypes among African Americans has not been assessed. Methods: ABP and ABP monitoring phenotypes were assessed in 912 Jackson Heart Study participants with aldosterone and plasma renin activity (PRA). Multivariable linear and logistic regression analyses were used to analyze the association of aldosterone and PRA with clinic, awake, and asleep systolic BP and diastolic BP (DBP) and ABP monitoring phenotypes, adjusting for important confounders. Results: The mean age of participants was 59±11 years and 69% were female. In fully adjusted models, lower log-PRA was associated with higher clinic, awake, and asleep systolic BP and DBP (all P P Conclusions: Suppressed renin activity and higher aldosterone:renin ratios were associated with higher systolic BP and DBP in the office and during the awake and asleep periods as evidenced by ABP monitoring. Higher aldosterone levels were associated with higher DBP, but not systolic BP, in the clinic and during the awake and asleep periods. Further clinical investigation of novel and approved medications that target low renin physiology such as epithelial sodium channel inhibitors and mineralocorticoid receptor antagonists may be paramount in improving hypertension control in African Americans.