A New Era in Cardiac Rehabilitation Delivery: Research Gaps, Questions, Strategies, and Priorities.

Cardiac rehabilitation (CR) is a guideline-recommended, multidisciplinary program of exercise training, risk factor management, and psychosocial counseling for people with cardiovascular disease (CVD) that is beneficial but underused and with substantial disparities in referral, access, and participation. The emergence of new virtual and remote delivery models has the potential to improve access to and participation in CR and ultimately improve outcomes for people with CVD. Although data suggest that new delivery models for CR have safety and efficacy similar to traditional in-person CR, questions remain regarding which participants are most likely to benefit from these models, how and where such programs should be delivered, and their effect on outcomes in diverse populations. In this review, we describe important gaps in evidence, identify relevant research questions, and propose strategies for addressing them. We highlight 4 research priorities: (1) including diverse populations in all CR research; (2) leveraging implementation methodologies to enhance equitable delivery of CR; (3) clarifying which populations are most likely to benefit from virtual and remote CR; and (4) comparing traditional in-person CR with virtual and remote CR in diverse populations using multicenter studies of important clinical, psychosocial, and cost-effectiveness outcomes that are relevant to patients, caregivers, providers, health systems, and payors. By framing these important questions, we hope to advance toward a goal of delivering high-quality CR to as many people as possible to improve outcomes in those with CVD.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

BACKGROUND: The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. METHODS: We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. RESULTS: In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). CONCLUSIONS: Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

Impact of the COVID-19 Pandemic on the Provision of Dialysis Service and Mortality in Veterans Receiving Maintenance Hemodialysis in the VA: An Interrupted Time-Series Analysis.

INTRODUCTION: According to the US Renal Data System (USRDS), patients with end-stage kidney disease (ESKD) on maintenance dialysis had higher mortality during early COVID-19 pandemic. Less is known about the effect of the pandemic on the delivery of outpatient maintenance hemodialysis and its impact on death. We examined the effect of pandemic-related disruption on the delivery of dialysis treatment and mortality in patients with ESKD receiving maintenance hemodialysis in the Veterans Health Administration (VHA) facilities, the largest integrated national healthcare system in the USA. METHODS: Using national VHA electronic health records data, we identified 7,302 Veterans with ESKD who received outpatient maintenance hemodialysis in VHA healthcare facilities during the COVID-19 pandemic (February 1, 2020, to December 31, 2021). We estimated the average change in the number of hemodialysis treatments received and deaths per 1,000 patients per month during the pandemic by conducting interrupted time-series analyses. We used seasonal autoregressive moving average (SARMA) models, in which February 2020 was used as the conditional intercept and months thereafter as conditional slope. The models were adjusted for seasonal variations and trends in rates during the pre-pandemic period (January 1, 2007, to January 31, 2020). RESULTS: The number (95% CI) of hemodialysis treatments received per 1,000 patients per month during the pre-pandemic and pandemic periods were 12,670 (12,525-12,796) and 12,865 (12,729-13,002), respectively. Respective all-cause mortality rates (95% CI) were 17.1 (16.7-17.5) and 19.6 (18.5-20.7) per 1,000 patients per month. Findings from SARMA models demonstrate that there was no reduction in the dialysis treatments delivered during the pandemic (rate ratio: 0.999; 95% CI: 0.998-1.001), but there was a 2.3% (95% CI: 1.5-3.1%) increase in mortality. During the pandemic, the non-COVID hospitalization rate was 146 (95% CI: 143-149) per 1,000 patients per month, which was lower than the pre-pandemic rate of 175 (95% CI: 173-176). In contrast, there was evidence of higher use of telephone encounters during the pandemic (3,023; 95% CI: 2,957-3,089), compared with the pre-pandemic rate (1,282; 95% CI: 1,241-1,324). CONCLUSIONS: We found no evidence that there was a disruption in the delivery of outpatient maintenance hemodialysis treatment in VHA facilities during the COVID-19 pandemic and that the modest rise in deaths during the pandemic is unlikely to be due to missed dialysis.

Prevalence of Comorbid Depression and Insomnia Among Veterans Hospitalized for Heart Failure with Alzheimer Disease and Related Disorders.

OBJECTIVE: To examine prevalence of Alzheimer Disease and related dementias (ADRD) and patient characteristics as a function of comorbid insomnia and/or depression among heart failure (HF) patients discharged from hospitals. DESIGN: Retrospective cohort descriptive epidemiology study. SETTING: VA Hospitals. PARTICIPANTS: N = 373,897 Veterans hospitalized with heart failure from October 1, 2011 until September 30, 2020. MEASUREMENTS: We examined VA and Center for Medicare & Medicaid Services (CMS) coding in the year prior to admission using published ICD-9/10 codes for dementia, insomnia, and depression. The primary outcome was the prevalence of ADRD and the secondary outcomes were 30-day and 365-day mortality. RESULTS: The cohort were predominantly older adults (mean age = 72 years, SD = 11), male (97%), and White (73%). Dementia prevalence in participants without insomnia or depression was 12%. In those with both insomnia and depression, dementia prevalence was 34%. For insomnia alone and depression alone, dementia prevalence was 21% and 24%, respectively. Mortality followed a similar pattern with highest 30-day and 365-day mortality higher in those with both insomnia and depression. CONCLUSIONS: These results suggest that persons with both insomnia and depression are at an increased risk of ADRD and mortality compared to persons with one or neither condition. Screening for both insomnia and depression, especially in patients with other ADRD risk factors, could lead to earlier identification of ADRD. Understanding comorbid conditions which may represent earlier signs of ADRD may be critical in the identification of ADRD risk.

Physical Function Assessment of Older Veterans With Serious Mental Illness.

OBJECTIVE: To characterize the physical function of older veterans with serious mental illness (SMI) across endurance, strength, and mobility domains. DESIGN: Retrospective analysis of clinical performance data. SETTING: Gerofit program, a national outpatient supervised exercise program for older veterans, delivered in Veterans Health Administration sites. PARTICIPANTS: Older veterans aged 60 and older (n = 166 with SMI, n = 1,441 without SMI) enrolled across eight national Gerofit sites between 2010 and 2019. MEASUREMENTS: Performance measures of physical function covering endurance (6-minute walk test), strength (chair stands, arm curls), and mobility (10-m walk, 8-foot-up-and-go), were administered at Gerofit enrollment. Baseline data from these measures were analyzed to characterize the functional profiles of older veterans with SMI. One sample t tests were examined to compare functional performance of older veterans with SMI to age- and sex-based reference scores. Propensity score matching (1:3) and linear mixed effects models were used to evaluate differences in function between veterans with and without SMI. RESULTS: Older veterans with SMI performed worse on all measures of function (chair stands, arm curls, 10-m walk, 6-minute walk test, 8-foot-up-and-go) compared to age- and sex-based reference scores with statistically significant differences present in the male sample. Functional performance of those with SMI was also worse compared to propensity-score matched older veterans without SMI with statistically significant differences on chair stands, 6-minute walk test, and 10-m walk. CONCLUSION: Older veterans with SMI have compromised strength, mobility, and endurance. Physical function should be a core component of screening and treatment for this population.

Prenatal exposure to famine and the development of diabetes later in life: an age-period-cohort analysis of the China health and nutrition survey (CHNS) from 1997 to 2015.

PURPOSE: Prenatal exposure to famine has been linked to increased diabetes risk in adulthood. However, one fundamental issue to be addressed is that the reported famine-diabetes relation may be confounded by the age differences between the exposed and non-exposed groups. We aimed to determine the association between prenatal exposure to the Chinese famine of 1959-1962 and risk of diabetes by applying age well-controlled strategies. METHODS: Among 20,535 individuals born in 1955-1966 who participated in the China Health and Nutrition Survey from 1997 to 2015, we constructed age-matched exposed vs. non-exposed groups to investigate the role of prenatal exposure to the Chinese famine of 1959-1962 in relation to diabetes. We also built a hierarchical age-period-cohort (HAPC) model to specifically examine the relation of famine to diabetes risk independent of age. RESULTS: Compared to the age-balanced men in the non-exposed group, the exposed men born in 1961 had a 154% increased risk of diabetes [odds ratio (OR) 2.54 (95% CI 1.07-6.03), P = 0.04). In the HAPC analysis, the predicted probabilities of diabetes peaked in the 1961-birth cohort of men [3.4% (95% CI 2.4%-5.0%)], as compared to the average probability of diabetes (reference) of 1.8% for men overall. Neither analytical strategy revealed any strong relation between famine exposure and diabetes risk in women. CONCLUSION: Among the pre-defined Chinese famine period of 1959-1962, early-life exposure to famine was associated with increased diabetes risk in men but not in women, and these relations were independent of age.

Hostility and prevalent diabetes among black adults: The Jackson Heart Study.

BACKGROUND AND AIMS: The relationship between hostility and the prevalence of diabetes mellitus (DM) among black adults was investigated using the Jackson Heart Study (JHS) cohort. We hypothesized that Cook-Medley Hostility scores will be positively related with the prevalence of DM. METHODS AND RESULTS: A total of 3232 black adults who completed at least one question for each of the three subscales of the Cook-Medley Hostility Scale and had data available regarding DM status were included. Using multivariate logistic regression, we studied the cross-sectional relationship between the overall Total Cook-Medley Hostility scores and individual subscales, hostile affect (n = 3232), aggression (n = 3119) and cynical distrust (n = 3085), with prevalent DM, adjusting for known DM confounders. Our population was 36% male with a mean age of 53.5 ± 0.9 years. In risk-factor adjusted models, each point higher in the overall Total Cook-Medley Hostility scores was associated with increased odds of having DM [Adjusted OR 1.02, 95%CI 1.00-1.04, P = 0.03]. Higher scores of cynicism were independently associated with prevalent DM [Adjusted OR 1.04, 95%CI 1.01-1.07, p = 0.021]. CONCLUSIONS: There was a positive relationship between overall hostility levels and prevalent DM. Future studies should investigate the extent to which additional social determinants may impact the relationship between hostile affect and prevalent DM.

A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P < 0.05) in the joint meta-analysis with the HGI (Ncases = 44,820; Ncontrols = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.

Mindfulness-Based Interventions for Patients with Cardiovascular Disease: A Focused Review for Practicing Clinicians.

PURPOSE OF REVIEW: With growing scientific and public interest in the health benefits of mindfulness, clinicians increasingly face questions and solicitations for advice from patients about the efficacy of mindfulness-based interventions (MBIs) for cardiovascular disease (CVD). In this clinician-focused review, we aim to revisit empirical studies on MBIs for CVD with the purpose of informing clinicians' decisions on how to provide recommendations consistent with updated scientific findings to patients interested in MBIs. RECENT FINDINGS: We start by defining MBIs and identifying the possible physiological, psychological, behavioral, and cognitive mechanisms underlying the potentially positive effects of MBIs for CVD. Potential mechanisms include the reduction of sympathetic nervous system activity, improved vagal control, and biological markers (physiological); psychological distress and cardiovascular health behaviors (psychological and behavioral); and executive function, memory, and attention (cognitive). Then, we summarize the extant evidence to identify gaps and limitations in MBI research for the purpose of informing future directions for cardiovascular and behavioral medicine researchers. We conclude with practical recommendations for clinicians communicating with patients with CVD who are interested in MBIs.

Biological and psychological predictors of heart rate patterns during physical activity.

Objective: Latent class modeling (LCM) offers a promising approach for examining correlates of heart rate (HR) patterns over multiple exercise sessions. This research examined biological and psychological variables associated with different patterns of HR response to physical activity (PA). Methods: In a three-arm randomized controlled trial (exercise video games vs. standard exercise vs. non-exercise control), HR was recorded during PA sessions over a 12-week period. LCM identified three patterns of HR during PA across 189 participants in active arms: 1) high HR across sessions with low variability within sessions, 2) linear increase in HR across sessions with low variability within sessions, and 3) high variability in HR across all sessions. Associations with biological (resting heart rate, blood pressure, BMI, age, cholesterol, triglycerides, HbA1c) and psychological (depression, motivations for PA, PA-induced feelings) predictors of latent class membership were iteratively tested. Results: Psychological variables played as important a role in the final model as biological variables for predicting latent class membership. Few differences were found between LC1 and LC2, but LC3 differed from the other two groups in that participants were likelier to report that feel revitalized after PA (vs. LC1 and LC2), to be less motivated for PA (vs. LC1), reported greater depression (vs. LC1 and LC2), and were younger (vs. LC1). Conclusions: These findings demonstrate the potential of LCM to identify biological and psychological factors associated with chronotropic responses to PA, and advance understanding of the role of psychological factors in chronotropic PA outcomes.

Association of Serum Aldosterone and Plasma Renin Activity With Ambulatory Blood Pressure in African Americans: The Jackson Heart Study.

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<0.05). A higher log-aldosterone was associated with higher clinic, awake, and asleep DBP (all P<0.05). A 1-unit higher log-PRA was associated with lower odds of daytime hypertension (odds ratio [OR] 0.59 [95% CI, 0.49-0.71]), nocturnal hypertension (OR, 0.68 [95% CI, 0.58-0.79]), daytime and nocturnal hypertension (OR, 0.59 [95% CI, 0.48-0.71]), sustained hypertension (OR, 0.52 [95% CI, 0.39-0.70]), and masked hypertension (OR 0.75 [95% CI, 0.62-0.90]). A 1-unit higher log-aldosterone was associated with higher odds of nocturnal hypertension (OR, 1.38 [95% CI, 1.05-1.81]). Neither PRA nor aldosterone was associated with percent dipping, nondipping BP pattern, or white-coat hypertension. Patterns for aldosterone:renin ratio were similar to patterns for PRA. 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.

Variation in statin prescription among veterans with HIV and known atherosclerotic cardiovascular disease.

BACKGROUND: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. OBJECTIVE: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. METHODS: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. RESULTS: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. CONCLUSION: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.

Glaucoma Genetic Risk Scores in the Million Veteran Program.

PURPOSE: Primary open-angle glaucoma (POAG) is a degenerative eye disease for which early treatment is critical to mitigate visual impairment and irreversible blindness. POAG-associated loci individually confer incremental risk. Genetic risk score(s) (GRS) could enable POAG risk stratification. Despite significantly higher POAG burden among individuals of African ancestry (AFR), GRS are limited in this population. A recent large-scale, multi-ancestry meta-analysis identified 127 POAG-associated loci and calculated cross-ancestry and ancestry-specific effect estimates, including in European ancestry (EUR) and AFR individuals. We assessed the utility of the 127-variant GRS for POAG risk stratification in EUR and AFR Veterans in the Million Veteran Program (MVP). We also explored the association between GRS and documented invasive glaucoma surgery (IGS). DESIGN: Cross-sectional study. PARTICIPANTS: MVP Veterans with imputed genetic data, including 5830 POAG cases (445 with IGS documented in the electronic health record) and 64 476 controls. METHODS: We tested unweighted and weighted GRS of 127 published risk variants in EUR (3382 cases and 58 811 controls) and AFR (2448 cases and 5665 controls) Veterans in the MVP. Weighted GRS were calculated using effect estimates from the most recently published report of cross-ancestry and ancestry-specific meta-analyses. We also evaluated GRS in POAG cases with documented IGS. MAIN OUTCOME MEASURES: Performance of 127-variant GRS in EUR and AFR Veterans for POAG risk stratification and association with documented IGS. RESULTS: GRS were significantly associated with POAG (P < 5 × 10-5) in both groups; a higher proportion of EUR compared with AFR were consistently categorized in the top GRS decile (21.9%-23.6% and 12.9%-14.5%, respectively). Only GRS weighted by ancestry-specific effect estimates were associated with IGS documentation in AFR cases; all GRS types were associated with IGS in EUR cases. CONCLUSIONS: Varied performance of the GRS for POAG risk stratification and documented IGS association in EUR and AFR Veterans highlights (1) the complex risk architecture of POAG, (2) the importance of diverse representation in genomics studies that inform GRS construction and evaluation, and (3) the necessity of expanding diverse POAG-related genomic data so that GRS can equitably aid in screening individuals at high risk of POAG and who may require more aggressive treatment.

Right Ventricular Ejection Fraction and Beta-Blocker Effect in Heart Failure With Reduced Ejection Fraction.

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.

New Antipsychotic Prescribing Continued into Skilled Nursing Facilities Following a Heart Failure Hospitalization: a Retrospective Cohort Study.

BACKGROUND: Multimorbidity and polypharmacy are common among individuals hospitalized for heart failure (HF). Initiating high-risk medications such as antipsychotics may increase the risk of poor clinical outcomes, especially if these medications are continued unnecessarily into skilled nursing facilities (SNFs) after hospital discharge. OBJECTIVE: Examine how often older adults hospitalized with HF were initiated on antipsychotics and characteristics associated with antipsychotic continuation into SNFs after hospital discharge. DESIGN: Retrospective cohort. PARTICIPANTS: Veterans without prior outpatient antipsychotic use, who were hospitalized with HF between October 1, 2010, and September 30, 2015, and were subsequently discharged to a SNF. MAIN MEASURES: Demographics, clinical conditions, prior healthcare utilization, and antipsychotic use data were ascertained from Veterans Administration records, Minimum Data Set assessments, and Medicare claims. The outcome of interest was continuation of antipsychotics into SNFs after hospital discharge. KEY RESULTS: Among 18,008 Veterans, antipsychotics were newly prescribed for 1931 (10.7%) Veterans during the index hospitalization. Among new antipsychotic users, 415 (21.5%) continued antipsychotics in skilled nursing facilities after discharge. Dementia (adjusted OR (aOR) 1.48, 95% CI 1.11-1.98), psychosis (aOR 1.62, 95% CI 1.11-2.38), proportion of inpatient days with antipsychotic use (aOR 1.08, 95% CI 1.07-1.09, per 10% increase), inpatient use of only typical (aOR 0.47, 95% CI 0.30-0.72) or parenteral antipsychotics (aOR 0.39, 95% CI 0.20-0.78), and the day of hospital admission that antipsychotics were started (day 0-4 aOR 0.36, 95% CI 0.23-0.56; day 5-7 aOR 0.54, 95% CI 0.35-0.84 (reference: day > 7 of hospital admission)) were significant predictors of continuing antipsychotics into SNFs after hospital discharge. CONCLUSIONS: Antipsychotics are initiated fairly often during HF admissions and are commonly continued into SNFs after discharge. Hospital providers should review antipsychotic indications and doses throughout admission and communicate a clear plan to SNFs if antipsychotics are continued after discharge.

Implementation of supervised exercise therapy in a veteran population with symptomatic claudication.

BACKGROUND: Real-world implementation of supervised exercise therapy (SET) referral for symptomatic intermittent claudication has been limited by poor provider awareness around reimbursement and low patient adherence owing to factors including limited center availability and long travel distances to sites. METHODS: In this study, 76 of 77 consecutive male veteran patients with intermittent claudication managed at a single-center vascular specialty clinic were referred to SET prior to revascularization. Pre- and post-SET submaximal exercise treadmill testing was performed for assessment of exercise capacity in metabolic equivalents (METs). RESULTS: In the 48.7% of subjects who completed 36 sessions of SET (n = 37), the average improvement in METs was 60.3%, reflecting improvement from baseline average of 3.4 METs to 5.5 METs after SET. Another 14 patients pursued self-guided exercise therapy and 25 patients declined any participation in exercise therapy. Reasons for declining participation in SET included inadequate transportation, cost of copayment, and interference with full-time work schedules. There was a nonsignificant numeric trend toward improved change in ankle-brachial index in the combined SET and self-guided exercise groups compared to those that declined exercise therapy (0.011 ± 0.124 vs -0.040 ± 0.105, p = 0.156). CONCLUSION: High acceptance of referral to SET is possible, despite the limitations to implementation. Incorporation of novel pre- and post-SET submaximal exercise treadmill testing allows for assessment of change in exercise capacity and aids in risk stratification and management of intermittent claudication symptoms.

Ledipasvir/sofosbuvir for HCV genotype 1, 2, 4-6 infection: Real-world evidence from a nationwide registry in Taiwan.

BACKGROUND/PURPOSE: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. METHODS: Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common. CONCLUSION: LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.

Women's participation in stress management interventions for chronic heart failure: a meta-analysis of randomized controlled trials.

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; I2 = 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 R2 = 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.

Racial/Ethnic Differences in 30-Day Mortality for Heart Failure and Pneumonia in the Veterans Health Administration Using Claims-based, Clinical, and Social Risk-adjustment Variables.

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.

Evaluating the Effectiveness of Diabetes Shared Medical Appointments (SMAs) as Implemented in Five Veterans Affairs Health Systems: a Multi-site Cluster Randomized Pragmatic Trial.

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 < .001), and those who attended at least half of scheduled SMAs achieved reductions 0.53 % points greater (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.