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Patients with continuous flow destination therapy (DT) left ventricular assist devices (LVAD) comprise a heterogeneous population. We hypothesized that phenotypic clustering of individuals with DT LVADs by their implantation characteristics will be associated with different long-term risk profiles. We analyzed 5,999 patients with continuous flow DT LVADs in Interagency Registry for Mechanically Assisted Circulatory Support using 18 continuous variable baseline characteristics. We Z-transformed the variables and applied a Gaussian finite mixture model to perform unsupervised clustering resulting in identification of 4 phenogroups. Survival analyses considered the competing risk for cumulative incidence of transplant or the composite end point of death or heart transplant where appropriate. Phenogroup 1 (n = 1,163, 19%) was older (71 years) and primarily white (81%). Phenogroups 2 (n = 648, 11%) and 3 (n = 3,671, 61%) were of intermediate age (70 and 62 years), weight (85 and 87 kg), and ventricular size. Phenogroup 4 (n = 517, 9%) was younger (40 years), heavier (108 kg), and more racially diverse. The cumulative incidence of death, heart transplant, bleeding, LVAD malfunction, and LVAD thrombosis differed among phenogroups. The highest incidence of death and the lowest rate of heart transplant was seen in phenogroup 1 (p <0.001). For adverse outcomes, phenogroup 4 had the lowest incidence of bleeding, whereas LVAD device thrombosis and malfunction were lowest in phenogroup 1 (p <0.001 for all). Finally, the incidence of stroke, infection, and renal dysfunction were not statistically different. In conclusion, the present unsupervised machine learning analysis identified 4 phenogroups with different rates of adverse outcomes and these findings underscore the influence of phenotypic heterogeneity on post-LVAD implantation outcomes., Competing Interests: Disclosures Dr. Grodin receives grant support from Texas Health Resources. Dr. Grodin reports relations with Pfizer Inc that includes consulting or advisory. Dr. Grodin reports relations with Alnylam Pharmaceuticals Inc that includes consulting or advisory. Dr. Grodin reports relations with Eidos Therapeutics that includes consulting or advisory and funding grants. Dr. Grodin reports relations with Sarepta Therapeutics Inc that includes consulting or advisory. Dr. Pandey receives a grant support from Texas Health Resources. Dr. Drazner receives grant support from James M. Wooten Chair in Cardiology. Dr. Grodin reports consulting fees from Pfizer, Eidos, Alnylam, and Sarepta. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Cardiovascular (CV) mortality has declined for more than 3 decades in the US. However, differences in declines among residents at a US county level are not well characterized., Objective: To identify unique county-level trajectories of CV mortality in the US during a 35-year study period and explore county-level factors that are associated with CV mortality trajectories., Design, Setting, and Participants: This longitudinal cross-sectional analysis of CV mortality trends used data from 3133 US counties from 1980 to 2014. County-level demographic, socioeconomic, environmental, and health-related risk factors were compiled. Data were analyzed from December 2019 to September 2021., Exposures: County-level characteristics, collected from 5 county-level data sets., Main Outcomes and Measures: Cardiovascular mortality data were obtained for 3133 US counties from 1980 to 2014 using age-standardized county-level mortality rates from the Global Burden of Disease study. The longitudinal K-means approach was used to identify 3 distinct clusters based on underlying mortality trajectory. Multinomial logistic regression models were constructed to evaluate associations between county characteristics and cluster membership., Results: Among 3133 US counties (median, 49.5% [IQR, 48.9%-50.5%] men; 30.7% [IQR, 27.1%-34.4%] older than 55 years; 9.9% [IQR, 4.5%-22.7%] racial minority group [individuals self-identifying as Black or African American, American Indian or Alaska Native, Asian, Native Hawaiian, Pacific Islander, other, or multiple races/ethnicities]), CV mortality declined by 45.5% overall and by 38.4% in high-mortality strata (694 counties), by 45.0% in intermediate-mortality strata (1382 counties), and by 48.3% in low-mortality strata (1057 counties). Counties with the highest mortality in 1980 continued to demonstrate the highest mortality in 2014. Trajectory groups were regionally distributed, with high-mortality trajectory counties focused in the South and in portions of Appalachia. Low- vs high-mortality groups varied significantly in demographic (racial minority group proportion, 7.6% [IQR, 4.1%-14.5%]) vs 23.9% [IQR, 6.5%-40.8%]) and socioeconomic characteristics such as high-school education (9.4% [IQR, 7.3%-12.6%] vs 20.1% [IQR, 16.1%-23.2%]), poverty rates (11.4% [IQR, 8.8%-14.6%] vs 20.6% [IQR, 17.1%-24.4%]), and violent crime rates (161.5 [IQR, 89.0-262.4] vs 272.8 [IQR, 155.3-431.3] per 100 000 population). In multinomial logistic regression, a model incorporating demographic, socioeconomic, environmental, and health characteristics accounted for 60% of the variance in the CV mortality trajectory (R2 = 0.60). Sociodemographic factors such as racial minority group proportion (odds ratio [OR], 1.70 [95% CI, 1.35-2.14]) and educational attainment (OR, 6.17 [95% CI, 4.55-8.36]) and health behaviors such as smoking (OR for high vs low, 2.04 [95% CI, 1.58-2.64]) and physical inactivity (OR, 3.74 [95% CI, 2.83-4.93]) were associated with the high-mortality trajectory., Conclusions and Relevance: Cardiovascular mortality declined in all subgroups during the 35-year study period; however, disparities remained unchanged during that time. Disparate trajectories were associated with social and behavioral risks. Health policy efforts across multiple domains, including structural and public health targets, may be needed to reduce existing county-level cardiovascular mortality disparities.

Background: Whether the volume of coronavirus disease 2019 (COVID-19) hospitalizations is associated with outcomes has important implications for the organization of hospital care both during this pandemic and future novel and rapidly evolving high-volume conditions., Methods: We identified COVID-19 hospitalizations at US hospitals in the American Heart Association COVID-19 Cardiovascular Disease Registry with ≥10 cases between January and August 2020. We evaluated the association of COVID-19 hospitalization volume and weekly case growth indexed to hospital bed capacity, with hospital risk-standardized in-hospital case-fatality rate (rsCFR)., Results: There were 85 hospitals with 15,329 COVID-19 hospitalizations, with a median hospital case volume was 118 (interquartile range, 57, 252) and median growth rate of 2 cases per 100 beds per week but varied widely (interquartile range: 0.9 to 4.5). There was no significant association between overall hospital COVID-19 case volume and rsCFR (rho, 0.18, P = .09). However, hospitals with more rapid COVID-19 case-growth had higher rsCFR (rho, 0.22, P = 0.047), increasing across case growth quartiles (P trend = .03). Although there were no differences in medical treatments or intensive care unit therapies (mechanical ventilation, vasopressors), the highest case growth quartile had 4-fold higher odds of above median rsCFR, compared with the lowest quartile (odds ratio, 4.00; 1.15 to 13.8, P = .03)., Conclusions: An accelerated case growth trajectory is a marker of hospitals at risk of poor COVID-19 outcomes, identifying sites that may be targets for influx of additional resources or triage strategies. Early identification of such hospital signatures is essential as our health system prepares for future health challenges., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Thirty-day home time, defined as time spent alive and out of a hospital or facility, is a novel, patient-centered performance metric that incorporates readmission and mortality., Objectives: To characterize risk-adjusted 30-day home time in patients discharged with heart failure (HF) as a hospital-level quality metric and evaluate its association with the 30-day risk-standardized readmission rate (RSRR), 30-day risk-standardized mortality rate (RSMR), and 1-year RSMR., Design, Setting, and Participants: This hospital-level cohort study retrospectively analyzed 100% of Medicare claims data from 2 968 341 patients from 3134 facilities from January 1, 2012, to November 30, 2017., Exposures: Home time, defined as time spent alive and out of a short-term hospital, skilled nursing facility, or intermediate/long-term facility 30 days after discharge., Main Outcomes and Measures: For each hospital, a risk-adjusted 30-day home time for HF was calculated similar to the Centers for Medicare & Medicaid Services risk-adjustment models for 30-day RSRR and RSMR. Hospitals were categorized into quartiles (lowest to highest risk-adjusted home time). The correlations between hospital rates of risk-adjusted 30-day home time and 30-day RSRR, 30-day RSMR, and 1-year RSMR were estimated using the Pearson correlation coefficient. Distribution of days lost from a perfect 30-day home time were calculated. Reclassification of hospital performance using 30-day home time vs 30-day RSRR was also evaluated., Results: Overall, 2 968 341 patients (mean [SD] age, 81.0 [8.3] years; 53.6% female) from 3134 hospitals were included in this study. The median hospital risk-adjusted 30-day home time for patients with HF was 21.77 days (range, 8.22-28.41 days). Hospitals in the highest quartile of risk-adjusted 30-day home time (best-performing hospitals) were larger (mean [SD] number of beds, 285 [275]), with a higher volume of patients with HF (median, 797 patients; interquartile range, 395-1484) and were more likely academic hospitals (59.9%) with availability of cardiac surgery (51.1%) and cardiac rehabilitation (68.8%). A total of 72% of home time lost was attributable to stays in an intermediate- or long-term care facility (mean [SD], 2.65 [6.44] days) or skilled nursing facility (mean [SD], 3.96 [9.04] days), 13% was attributable to short-term readmissions (mean [SD], 1.25 [3.25] days), and 15% was attributable to death (mean [SD], 1.37 [6.04] days). Among 30-day outcomes, the 30-day RSRR and 30-day RSMR decreased in a graded fashion across increasing 30-day home time categories (correlation coefficients: 30-day RSRR and 30-day home time, -0.23, P < .001; 30-day RSMR and 30-day home time, -0.31, P < .001). Similar patterns of association were also noted for 1-year RSMR and 30-day home time (correlation coefficient, -0.35, P < .001). Thirty-day home time meaningfully reclassified hospital performance in 30% of the hospitals compared with 30-day RSRR and in 25% of hospitals compared with 30-day RSMR., Conclusions and Relevance: In this study, 30-day home time among patients discharged after a hospitalization for HF was objectively assessed as a hospital-level quality metric using Medicare claims data and was associated with readmission and mortality outcomes and with reclassification of hospital performance compared with 30-day RSRR and 30-day RSMR.

Importance: Heart failure (HF) incidence is declining among Medicare beneficiaries. However, the epidemiological mechanisms underlying this decline are not well understood., Objective: To evaluate trends in HF incidence across risk factor strata., Design, Setting, and Participants: Retrospective, national cohort study of 5% of all fee-for-service Medicare beneficiaries with no prior HF followed up from 2011 to 2016. The study examined annual trends in HF incidence among groups with and without primary HF risk factors (hypertension, diabetes, and obesity) and predisposing cardiovascular conditions (acute myocardial infarction [MI] and atrial fibrillation [AF])., Exposures: The presence of comorbid HF risk factors including hypertension, diabetes, obesity, acute MI, and AF identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes., Main Outcomes and Measures: Incident HF, defined using at least 1 inpatient HF claim or at least 2 outpatient HF claims among those without a previous diagnosis of HF., Results: Of 1 799 027 unique Medicare beneficiaries at risk for HF (median age, 73 years [interquartile range, 68-79 years]; 56% female [805 060-796 253 participants during the study period]), 249 832 had a new diagnosis of HF. The prevalence of all 5 risk factors increased over time (0.8% mean increase in hypertension per year, 1.9% increase in diabetes, 2.9% increase in obesity, 0.2% increase in acute MI, and 0.4% increase in AF). Heart failure incidence declined from 35.7 cases per 1000 beneficiaries in 2011 to 26.5 cases per 1000 beneficiaries in 2016, consistent across subgroups based on sex and race/ethnicity. A greater decline in HF incidence was observed among patients with prevalent hypertension (relative excess decline, 12%), diabetes (relative excess decline, 3%), and obesity (relative excess decline, 16%) compared with those without corresponding risk factors. In contrast, there was a relative increase in HF incidence among individuals with acute MI (26% vs no acute MI) and AF (22% vs no AF)., Conclusions and Relevance: Findings of this study suggest that the temporal decline in HF incidence among Medicare beneficiaries reflects a decrease in HF incidence among those with primary HF risk factors. The increase in HF incidence among those with acute MI and those with AF highlights potential targets for future HF prevention strategies.

Aims: Plasma volume expansion is clinically and prognostically relevant in individuals with heart failure. Prior cohorts either excluded or had limited representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between calculated plasma volume status (PVS) and outcomes in HFpEF., Methods and Results: We included enrollees from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with available haematocrit and weight data (n = 3414). Plasma volume was derived from the Hakim formula and compared to estimates of ideal plasma volume to generate a relative PVS. Multivariable Cox proportional hazards models tested the association of PVS with clinical outcomes. The median PVS was -11.9% (25th-75th percentile: -17.2% to -6.4%) and the majority (91.1%) had PVS consistent with relative volume contraction (PVS ≤ 0%) as opposed to volume expansion (8.9%, PVS > 0%). After multivariable adjustment, each 5% increment in PVS was associated with a ∼11%, 14%, and 12% higher risk for the primary composite endpoint, all-cause death, and heart failure hospitalization, respectively (P < 0.002 for all), but not cardiovascular death (P = 0.051). After additional adjustment for natriuretic peptides, PVS only remained associated with heart failure hospitalization (HR 1.10, 95% confidence interval 1.001-1.21, P = 0.047). There were no significant interactions between spironolactone use and the PVS-risk relationship for any endpoint (P > 0.1 for all)., Conclusion: Higher calculated estimates of PVS were independently associated with a higher risk of long-term clinical outcomes in HFpEF, and particularly, heart failure hospitalization., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

BACKGROUND: The contemporary measures of hospital performance for heart failure hospitalization and 30-day risk-standardized readmission rate (RSRR) and risk-standardized mortality rate (RSMR) are estimated using the same risk adjustment model and overall event rate for all patients. Thus, these measures are mainly driven by the care quality and outcomes for the majority racial and ethnic group, and may not adequately represent the hospital performance for patients of Black and other races. METHODS: Fee-for-service Medicare beneficiaries from January 2014 to December 2019 hospitalized with heart failure were identified. Hospital-level 30-day RSRR and RSMR were estimated using the traditional race-agnostic models and the race-specific approach. The composite race-specific performance metric was calculated as the average of the RSRR/RMSR measures derived separately for each race and ethnicity group. Correlation and concordance in hospital performance for all patients and patients of Black and other races were assessed using the composite race-specific and race-agnostic metrics. RESULTS: The study included 1 903 232 patients (75.7% White [n=1 439 958]; 14.5% Black [n=276 684]; and 9.8% other races [n=186 590]) with heart failure from 1860 hospitals. There was a modest correlation between hospital-level 30-day performance metrics for patients of White versus Black race (Pearson correlation coefficient: RSRR=0.42; RSMR=0.26). Compared with the race-agnostic RSRR and RSMR, composite race-specific metrics for all patients demonstrated stronger correlation with RSRR (correlation coefficient: 0.60 versus 0.74) and RSMR (correlation coefficient: 0.44 versus 0.51) for Black patients. Concordance in hospital performance for all patients and patients of Black race was also higher with race-specific (versus race-agnostic) metrics (RSRR=64% versus 53% concordantly high-performing; 61% versus 51% concordantly low-performing). Race-specific RSRR and RSMR metrics (versus race-agnostic) led to reclassification in performance ranking of 35.8% and 39.2% of hospitals, respectively, with better 30-day and 1-year outcomes for patients of all race groups at hospitals reclassified as high-performing. CONCLUSIONS: Among patients hospitalized with heart failure, race-specific 30-day RSMR and RSRR are more equitable in representing hospital performance for patients of Black and other races.

OBJECTIVES: In this study, we sought to evaluate the association of frailty with the use of optimal guideline-directed medical therapy (GDMT) and outcomes in heart failure with reduced ejection fraction (HFrEF). BACKGROUND: The burden of frailty in HFrEF is high, and the patterns of GDMT use according to frailty status have not been studied previously. METHODS: A post hoc analysis of patients with HFrEF enrolled in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial was conducted. Frailty was assessed with the use of a frailty index (FI) using a 38-variable deficit model, and participants were categorized into 3 groups: class 1: nonfrail, FI 0.31). Multivariate-adjusted Cox models were used to study the association of frailty status with clinical outcomes. Use of optimal GDMT over time (beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists) across frailty strata was assessed with the use of adjusted linear and logistic mixed-effect models. RESULTS: The study included 879 participants, of which 56.3% had high frailty burden (class 3 FI). A higher frailty burden was associated with a significantly higher risk of HF hospitalization or death in adjusted Cox models: high frailty vs nonfrail HR: 1.76, 95% CI: 1.20-2.58. On follow-up, participants with high frailty burden also had a significantly lower likelihood of achieving optimal GDMT: high frailty vs non-frail GDMT triple therapy use at study end: 17.7% vs 28.4%; P interaction, frailty class × time

BackgroundSocioeconomic disadvantage is a strong determinant of adverse outcomes in patients with heart failure. However, the contribution of community-level economic distress to adverse outcomes in heart failure may differ across races and ethnicities.MethodsPatients of self-reported Black, White, and Hispanic race and ethnicity hospitalized with heart failure between 2014 and 2019 were identified from the Medicare MedPAR Part A 100% Files. We used patient-level residential ZIP code to quantify community-level economic distress on the basis of the Distressed Community Index (quintile 5: economically distressed versus quintiles 1-4: nondistressed). The association of continuous and categorical measures (distressed versus nondistressed) of Distressed Community Index with 30-day, 6-month, and 1-year risk-adjusted mortality, readmission burden, and home time were assessed separately by race and ethnicity groups.ResultsThe study included 1 611 586 White (13.2% economically distressed), 205 840 Black (50.6% economically distressed), and 89 199 Hispanic (27.3% economically distressed) patients. Among White patients, living in economically distressed (versus nondistressed) communities was significantly associated with a higher risk of adverse outcomes at 30-day and 1-year follow-up. Among Black and Hispanic patients, the risk of adverse outcomes associated with living in distressed versus nondistressed communities was not meaningfully different at 30 days and became more prominent by 1-year follow-up. Similarly, in the restricted cubic spline analysis, a stronger and more graded association was observed between Distressed Community Index score and risk of adverse outcomes in White patients (versus Black and Hispanic patients). Furthermore, the association between community-level economic distress and risk of adverse outcomes for Black patients differed in rural versus urban areas. Living in economically distressed communities was significantly associated with a higher risk of mortality and lower home time at 1-year follow-up in rural areas but not urban areas.ConclusionsThe association between community-level economic distress and risk of adverse outcomes differs across race and ethnic groups, with a stronger association noted in White patients at short- and long-term follow-up. Among Black patients, the association of community-level economic distress with a higher risk of adverse outcomes is less evident in the short term and is more robust and significant in the long-term follow-up and rural areas.

BackgroundThe burden of amyloidosis among hospitalized patients is increasing over time. However, amyloidosis remains an underdiagnosed cause of heart failure (HF) hospitalization among older adults.ObjectivesWe investigated the prevalence and prognostic implications of amyloidosis among patients hospitalized with HF.MethodsAll hospitalizations for primary diagnosis of HF between January 1, 2010, and August 31, 2015, identified in the Nationwide Readmissions Database were categorized into those with and without a secondary diagnosis of amyloidosis. HF hospitalizations with amyloidosis were then matched in a 3:1 fashion to HF hospitalizations without amyloidosis using the year of admission, discharge quarter, age, sex, and Charlson comorbidity index. Primary outcomes were inpatient mortality and 30-day readmission. Multivariable logistic regression was used to estimate the association between HF with amyloidosis and clinical outcomes.ResultsOf 1,593,360 HF hospitalizations that met inclusion criteria, 2,846 (0.18%) had HF with a secondary diagnosis of amyloidosis and were matched to 8,515 hospitalizations for HF without amyloidosis. Hospitalizations for HF with amyloidosis were associated with higher prevalence of kidney disease (56% vs. 45%), malignancy (20% vs. 4%), and higher inpatient mortality (6% vs. 3%) as compared with HF without amyloidosis. In adjusted analyses, HF with amyloidosis was associated with higher odds of in-hospital mortality (odds ratio: 1.46; 95% confidence interval [CI]: 1.17 to 1.82), 30-day readmission (odds ratio: 1.17; 95% CI: 1.05 to 1.31), and longer mean length of stay (least-squares mean difference: 1.46; 95% CI: 1.12 to 1.80).ConclusionsIn patients hospitalized with decompensated HF, presence of amyloidosis was associated with higher risk of inpatient mortality and 30-day readmission.

Aims Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). Methods and results This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12–2.12) and 1.37 (1.04–1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17–2.97) increased rate of CVD mortality and an 81% (1.45–2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07–2.65), per 10-fold increase in total KB]. Conclusion The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment. [ABSTRACT FROM AUTHOR]

Background: Housing instability is a key social determinant of health and has been linked to adverse short- and long-term health. Eviction reflects a severe form of housing instability and disproportionately affects minority and women residents in the USA; however, its relationship with mortality has not previously been described. Objective: To evaluate the independent association of county-level eviction rates with all-cause mortality in the USA after adjustment for county demographic, socioeconomic, and health-related characteristics. Design: Cross-sectional. Participants: Six hundred eighty-six US counties with available 2016 county-level eviction and mortality data. Exposure: 2016 US county-level eviction rate. Outcome: 2016 US county-level age-adjusted all-cause mortality. Key Results: Among 686 counties (66.1 million residents, 50.5% [49.7–51.2] women, 2% [0.5–11.1] Black race) with available eviction and mortality data in 2016, we observed a significant and graded relationship between county-level eviction rate and all-cause mortality. Counties in the highest eviction tertile demonstrated a greater proportion of residents of Black race and women and a higher prevalence of poverty and comorbid health conditions. After adjustment for county-level sociodemographic traits and prevalent comorbid health conditions, age-adjusted all-cause mortality was highest among counties in the highest eviction tertile (Tertile 3 vs 1 (per 100,000 people) 33.57: 95% CI: 10.5–56.6 p=.004). Consistent results were observed in continuous analysis of eviction, with all-cause mortality increasing by 9.32 deaths per 100,000 people (4.77, 13.89, p<.0001) for every 1% increase in eviction rates. Significant interaction in the relationship between eviction and all-cause mortality was observed by the proportion of Black and women residents. Conclusions: In this cross-sectional analysis, county-level eviction rates were significantly associated with all-cause mortality with the strongest effects observed among counties with the highest proportion of Black and women residents. State and federal protections from evictions may help to reduce the health consequences of housing instability and address disparities in health outcomes. [ABSTRACT FROM AUTHOR]

Background: Supervised aerobic exercise training (ET) is recommended for stable outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Frailty, a syndrome characterized by increased vulnerability and decreased physiologic reserve, is common in patients with HFrEF and associated with a higher risk of adverse outcomes. The effect modification of baseline frailty on the efficacy of aerobic ET in HFrEF is not known.Methods: Stable outpatients with HFrEF randomized to aerobic ET versus usual care in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were included. Baseline frailty was estimated using the Rockwood frailty index (FI), a deficit accumulation-based model of frailty assessment; participants with FI scores >0.21 were identified as frail. Multivariable Cox proportional hazard models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether frailty modified the treatment effect of aerobic ET on the primary composite end point (all-cause hospitalization or mortality), secondary end points (composite of cardiovascular death or cardiovascular hospitalization, and cardiovascular death or HF hospitalization), and Kansas City Cardiomyopathy Questionnaire score. Separate models were constructed for continuous (FI) and categorical (frail versus not frail) measures of frailty.Results: Among 2130 study participants (age, 59±13 years; 28% women), 1266 (59%) were characterized as frail (FI>0.21). Baseline frailty burden significantly modified the treatment effect of aerobic ET (P interaction: FI × treatment arm=0.02; frail status [frail versus nonfrail] × treatment arm=0.04) with a lower risk of primary end point in frail (hazard ratio [HR], 0.83 [95% CI, 0.72-0.95]) but not nonfrail (HR, 1.04 [95% CI, 0.87-1.25]) participants. The favorable effect of aerobic ET among frail participants was driven by a significant reduction in the risk of all-cause hospitalization (HR, 0.84 [95% CI, 0.72-0.99]). The treatment effect of aerobic ET on all-cause mortality and other secondary endpoints was not different between frail and nonfrail patients (P interaction>0.1 for each). Aerobic ET was associated with a nominally greater improvement in Kansas City Cardiomyopathy Questionnaire scores at 3 months among frail versus nonfrail participants without a significant treatment interaction by frailty status (P interaction>0.2).Conclusions: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of aerobic ET with a greater reduction in the risk of all-cause hospitalization but not mortality. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) are closely interrelated in the setting of heart failure (HF). Here we investigate the prevalence and prognostic significance of AF in patients with acute decompensated HF (ADHF) stratified by MR severity.Methods and Results: The Atherosclerosis Risk in Communities Study investigated ADHF hospitalizations in residents greater than or equal to 55 years of age in 4 US communities. ADHF cases were stratified by MR severity (none/mild or moderate/severe) and HF subtype (HF with reduced [HFrEF] or preserved [HFpEF] ejection fraction). The odds of AF in patients with increasing MR severity was estimated using multivariable logistic regression, adjusting for age, race, sex, diabetes, hypertension, coronary artery disease, hemodialysis, stroke, and anemia. Cox regression models were used to assess the association of AF with 1-year mortality in patients with HFpEF and HFrEF, stratified by MR severity and adjusted as described, also adjusting for the year of hospitalization. From 2005 to 2014, there were 3,878 ADHF hospitalizations (17,931 weighted). AF was more likely in those with higher MR severity regardless of HF subtype; more so in HFpEF (odds ratio [OR] 1.38, 95% confidence interval [CI], 1.31-1.45) than in HFrEF (OR, 1.19, 95% CI, 1.13-1.25) (interaction P [by HF subtype] < .01). When stratified by HF type, association between AF and 1-year mortality was noted in patients with HFpEF (OR, 1.28, 95% CI 1.04-1.56) but not HFrEF (OR 0.96, 95% CI 0.79-1.16) (interaction by EF subtype, P = .02).Conclusions: In patients with ADHF, AF prevalence increased with MR severity and this effect was more pronounced in HFpEF compared with HFrEF. AF was associated with an increased 1-year mortality only in patients with HFpEF and concomitant moderate/severe MR.Registration: NCT00005131, https://clinicaltrials.gov/ct2/show/NCT00005131. [ABSTRACT FROM AUTHOR]

Aims: Hospitalization for heart failure (HF) constitutes a major healthcare and economic burden. Trends and characteristics of hospitalizations for HF for the recent years are not clear. We sought to determine the trends and characteristics of hospitalization for HF in the United States. Method and results: A retrospective analysis of the National Inpatient Sample weighted data between 1 January 2004 and 31 December 2018, which included hospitalized adults ≥ 18 years with primary discharge diagnosis of HF using International Classification of Diseases‐9/10 administrative codes. Main outcomes were trends in hospitalizations for HF (per 1000 person) and inpatient mortality (%) between 2004 and 2018. Conclusions: Hospitalizations for HF have been increasing across both sexes and age groups since 2013, whereas inpatient mortality has been decreasing over the study period. Blacks have the highest risk of hospitalization for HF, and Whites have the highest in‐hospital mortality. There are significant racial and geographic disparities related to hospitalizations for HF. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established.Methods: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files.Results: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P<0.0001) and men (5.20 versus 4.82; P<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF. [ABSTRACT FROM AUTHOR]

Background: The utility of 30-day risk-standardized readmission rate (RSRR) as a hospital performance metric has been a matter of debate. Home time is a patient-centered outcome measure that accounts for rehospitalization, mortality, and postdischarge care. We aim to characterize risk-adjusted 30-day home time in patients with acute myocardial infarction (AMI) as a hospital-level performance metric and to evaluate associations with 30-day RSRR, 30-day risk-standardized mortality rate (RSMR), and 1-year RSMR.Methods: The study included 984 612 patients with AMI hospitalization across 2379 hospitals between 2009 and 2015 derived from 100% Medicare claims data. Home time was defined as the number of days alive and spent outside of a hospital, skilled nursing facility, or intermediate-/long-term acute care facility 30 days after discharge. Correlations between hospital-level risk-adjusted 30-day home time and 30-day RSRR, 30-day RSMR, and 1-year RSMR were estimated with the Pearson correlation. Reclassification in hospital performance using 30-day home time versus 30-day RSRR and 30-day RSMR was also evaluated.Results: Median hospital-level risk-adjusted 30-day home time was 24.0 days (range, 15.3-29.0 days). Hospitals with higher home time were more commonly academic centers, had available cardiac surgery and rehabilitation services, and had higher AMI volume and percutaneous coronary intervention use during the AMI hospitalization. Of the mean 30-day home time days lost, 58% were to intermediate-/long-term care or skilled nursing facility stays (4.7 days), 30% to death (2.5 days), and 12% to readmission (1.0 days). Hospital-level risk-adjusted 30-day home time was inversely correlated with 30-day RSMR (r=-0.22, P<0.0001) and 30-day RSRR (r=-0.25, P<0.0001). Patients admitted to hospitals with higher risk-adjusted 30-day home time had lower 30-day readmission (quartile 1 versus 4, 21% versus 17%), 30-day mortality rate (5% versus 3%), and 1-year mortality rate (18% versus 12%). Furthermore, 30-day home time reclassified hospital performance status in ≈30% of hospitals versus 30-day RSRR and 30-day RSMR.Conclusions: Thirty-day home time for patients with AMI can be assessed as a hospital-level performance metric with the use of Medicare claims data. It varies across hospitals, is associated with postdischarge readmission and mortality outcomes, and meaningfully reclassifies hospital performance compared with the 30-day RSRR and 30-day RSMR metrics. [ABSTRACT FROM AUTHOR]

Aims: Total occlusion (TO) of the culprit artery usually presents with ST-elevation myocardial infarction. A subset of patients with TO present as non-ST segment elevation myocardial infarction (NSTEMI) without classic ST-elevation on the electrocardiogram. This may lead to delay in identification of these patients and further management. We performed a meta-analysis to estimate the difference in outcomes between totally occluded and non-occluded culprit arteries in patients with NSTEMI. Methods and results: Our literature search yielded seven studies with 40 777 patients. The outcomes assessed were clinical presentation (Killip class), left ventricular ejection fraction, time to angiography, major cardiac adverse events (MACE) and allcause mortality. The generic inverse or Mantel-Haenszel method was used to pool relevant outcomes and the mean difference (MD) or relative risk (RR) was calculated. A total of 10 415 (25.5%) patients had an occluded culprit artery with a predominant infero-lateral distribution (40% right coronary and 33% left circumflex artery). There was an increased risk of both MACE (short-term RR: 1.41; CI: 1.17, 1.70; P = 0.0003; I² = 26%; medium- to long-term RR: 1.32; CI: 1.11, 1.56; P = 0.001; I² = 25%) and all-cause mortality (short-term RR: 1.67; CI: 1.31, 2.13; P < 0.0001; I² = 41%; medium to long-term RR: 1.42; CI: 1.08, 1.86; P = 0.01; I² = 32%) with TO of the culprit artery. Conclusion: Our meta-analysis suggests that patients with NSTEMI who demonstrate a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events. Better risk stratification tools are needed to identify such high-risk acute coronary syndrome patients to facilitate earlier revascularization and potentially to improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking. Methods: Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21–30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups. Results: Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HRadj], 1.75 [1.23–2.47]) females had the highest risk of death followed by non-Hispanic White females (HRadj, 1.15 [1.07–1.25]; P interaction=0.02). Hispanic (HRadj, 0.60 [0.40–0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HRadj, 0.76 [0.67–0.86]), and non-Hispanic White females (HRadj, 0.88 [0.80–0.96]) compared with their male counterparts (P interaction<0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HRadj, 1.32 [1.18–1.48]) had the highest risk of death (P interaction=0.01). The risk of death (P interaction=0.44) and cumulative incidence of heart transplantation (P interaction=0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups. Conclusions: Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups. [ABSTRACT FROM AUTHOR]

Background: Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization. Methods: The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression. Results: From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28–0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44–0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04–1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28–1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02–1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14–1.51]). Conclusions: Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population. [ABSTRACT FROM AUTHOR]

Background and Objectives: Racial differences in stroke outcomes have major health policy implications. There is paucity of contemporary data on racial differences in clinical outcomes and resource utilization in acute ischemic stroke hospitalizations in the United States.Methods: We used the 2011-2012 National Inpatient Sample to identify hospitalizations with a primary diagnosis of acute ischemic stroke. Primary outcomes were in-hospital mortality, utilization of thrombolysis, and endovascular mechanical thrombectomy (EMT). Secondary outcomes were length of stay (LOS) and average inflation-adjusted charges.Results: A total of 173,910 hospitalizations representing 835,811 hospitalizations nationwide were included in the study. Mean age was 70.9 years and 52.3% were women. Blacks (adjusted OR .71, 95% CI .64-.78, P < .001) and Asian or Pacific Islanders (adjusted OR .80, 95% CI .66-.97, P = .02) had a lower in-hospital mortality compared to Whites. Blacks were less likely to be treated with thrombolysis (adjusted OR .84, 95% CI .76-.92, P < .001) and EMT (OR .73, 95% CI .58-.91, P = .01). Average LOS and inflation-adjusted charges were significantly higher for racial minorities compared to Whites.Conclusions: Blacks and Asians hospitalized for ischemic stroke are less likely to die in the hospital compared to Whites. Hospitalization for stroke in Blacks is associated with lower rates of reperfusion therapy, longer lengths of stay, and higher costs compared to Whites. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend surgical revascularization (coronary artery bypass graft [CABG]) over percutaneous coronary intervention (PCI) in patients with diabetes mellitus and multivessel coronary artery disease. Few data are available describing revascularization patterns among these patients in the setting of non-ST-segment-elevation myocardial infarction.Methods and Results: Using Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines (ACTION Registry-GWTG), we compared the in-hospital use of different revascularization strategies (PCI versus CABG versus no revascularization) in diabetes mellitus patients with non-ST-segment-elevation myocardial infarction who had angiography, demonstrating multivessel coronary artery disease between July 2008 and December 2014. Factors associated with use of CABG versus PCI were identified using logistic multivariable regression analyses. A total of 29 769 patients from 539 hospitals were included in the study, of which 10 852 (36.4%) were treated with CABG, 13 760 (46.2%) were treated with PCI, and 5157 (17.3%) were treated without revascularization. The overall use of revascularization increased over the study period with an increase in the proportion undergoing PCI (45% to 48.9%; Ptrend=0.0002) and no change in the proportion undergoing CABG (36.1% to 34.7%; ptrend=0.88). There was significant variability between participating hospitals in the use of PCI and CABG (range: 22%-100%; 0%-78%, respectively; P value <0.0001 for both). Patient-level, but not hospital-level, characteristics were statistically associated with the use of PCI versus CABG, including anatomic severity of the disease, early treatment of adenosine diphosphate receptor antagonists at presentation, older age, female sex, and history of heart failure.Conclusions: Among patients with diabetes mellitus and multivessel coronary artery disease presenting with non-ST-segment-elevation myocardial infarction, only one third undergo CABG during the index admission. Furthermore, the use of PCI, but not CABG, increased modestly over the past 6 years. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Bedside evaluation of congestion is a mainstay of heart failure (HF) management. Whether detected physical examination signs have changed over time as obesity prevalence has increased in HF populations, or if the associated prognosis differs for HF with reduced or preserved ejection fraction (HFrEF or HFpEF) is uncertain. Methods: From 2005 to 2014, the ARIC study (Atherosclerosis Risk in Communities) conducted adjudicated hospital surveillance of acute decompensated HF. We analyzed trends in physical examination findings, imaging signs, and symptoms related to congestion, both over time and by obesity class, and associated 28-day mortality risks. Results: Of 24 937 weighted hospitalizations for acute decompensated HF (mean age 75 years, 53% women, 32% Black), 47% had HFpEF. The prevalence of obesity increased from 2005 to 2014 for both HF types. With increasing obesity category, detected edema increased, while jugular venous distension decreased, and rales remained stable. Detected edema also increased over time, for both HF types. Associations between 28-day mortality and individual signs and symptoms of congestion were similar for HFpEF and HFrEF; however, the adjusted mortality risk with all 3 (edema, rales, and jugular venous distension) versus <3 physical examination findings was higher for patients with HFpEF (odds ratio, 2.41 [95% CI, 1.53–3.79]) than HFrEF (odds ratio, 1.30 [95% CI, 0.87–1.93]); P for interaction by HF type =0.02. Conclusions: In patients hospitalized with acute decompensated HF, detected physical examination findings differ both temporally and by obesity. Combined findings from the physical examination are more prognostic of 28-day mortality for patients with HFpEF than HFrEF. [ABSTRACT FROM AUTHOR]

Background: Assessing hospital performance for cardiac surgery necessitates consistent and valid care quality metrics. The association of hospital-level risk-standardized home time for cardiac surgeries with other performance metrics such as mortality rate, readmission rate, and annual surgical volume has not been evaluated previously.Methods: The study included Medicare beneficiaries who underwent isolated or concomitant coronary artery bypass graft, aortic valve, or mitral valve surgery from January 1, 2013, to October 1, 2019. Hospital-level performance metrics of annual surgical volume, 90-day risk-standardized mortality rate, 90-day risk-standardized readmission rate, and 90-day risk-standardized home time were estimated starting from the day of surgery using generalized linear mixed models with a random intercept for the hospital. Correlations between the performance metrics were assessed using the Pearson correlation coefficient. Patient-level clinical outcomes were also compared across hospital quartiles by 90-day risk-standardized home time. Last, the temporal stability of performance metrics for each hospital during the study years was also assessed.Results: Overall, 919 698 patients (age 74.2±5.8 years, 32% women) were included from 1179 hospitals. Median 90-day risk-standardized home time was 71.2 days (25th-75th percentile, 66.5-75.6), 90-day risk-standardized readmission rate was 26.0% (19.5%-35.7%), and 90-day risk-standardized mortality rate was 6.0% (4.0%-8.8%). Across 90-day home time quartiles, a graded decline was observed in the rates of in-hospital, 90-day, and 1-year mortality, and 90-day and 1-year readmission. Ninety-day home time had a significant positive correlation with annual surgical volume (r=0.31; P<0.001) and inverse correlation with 90-day risk-standardized readmission rate (r=-0.40; P <0.001) and 90-day risk-standardized mortality rate (r=-0.60; P <0.001). Use of 90-day home time as a performance metric resulted in a meaningful reclassification in performance ranking of 22.8% hospitals compared with annual surgical volume, 11.6% compared with 90-day risk-standardized mortality rate, and 19.9% compared with 90-day risk-standardized readmission rate. Across the 7 years of the study period, 90-day home time demonstrated the most temporal stability of the hospital performance metrics.Conclusions: Ninety-day risk-standardized home time is a feasible, comprehensive, patient-centered metric to assess hospital-level performance in cardiac surgery with greater temporal stability than mortality and readmission measures. [ABSTRACT FROM AUTHOR]

Background: Patient-centric measures of hospital performance for transcatheter aortic valve replacement (TAVR) are needed.Objectives: This study evaluated 30-day, risk-adjusted home time as a hospital performance metric for patients who underwent TAVR.Methods: This study identified 160,792 Medicare beneficiaries who underwent elective TAVR from 2015 to 2019. Home time was calculated for each patient as the number of days alive and spent outside the hospital, skilled nursing facility (SNF), and long-term acute care facility for 30 days after the TAVR procedure date. Correlations between risk-adjusted, 30-day home time and other metrics (30-day, risk-adjusted readmission rate [RSRR], 30-day, risk-adjusted mortality rate [RSMR], and annual TAVR volume) were estimated using Pearson's correlation. Meaningful upward or downward reclassification (≥2 quartile ranks) in hospital performance based on quartiles of risk-adjusted, 30-day home time compared with quartiles of other measures were assessed.Results: Median risk-adjusted, 30-day home time was 27.4 days (interquartile range [IQR]: 26.3-28.5 days). The largest proportion of days lost from 30-day home time was hospital stay after TAVR and SNF stay. An inverse correlation was observed between hospital-level, risk-adjusted, 30-day home time and 30-day RSRR (r = -0.465; P < 0.001) and 30-day RSMR (r = -0.3996; P < 0.001). The use of the 30-day, risk-adjusted home time was associated with reclassification in hospital performance rank hospitals compared with other metrics (9.1% up-classified, 11.2% down-classified vs RSRR; 9.1% up-classified, 10.3% down-classified vs RSMR; and 20.1% up-classified, 19.3% down-classified vs annual TAVR volume).Conclusions: Risk-adjusted, 30-day home time represents a novel patient-centered performance metric for TAVR hospitals that may provide a complimentary assessment to currently used metrics. [ABSTRACT FROM AUTHOR]

The article discusses the sedentary behavior of chronic subclinical myocardial injury. Topics mention including the effects of a higher level of physical activity on troponin levels, association of increase sedentary time with increase cause of mortality and connection of chronic myocardial injury with increase sedentary time.