Effect of liraglutide on thigh muscle fat and muscle composition in adults with overweight or obesity: Results from a randomized clinical trial.

BACKGROUND: Excess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown. METHODS: This is a pre-specified secondary analysis of a randomized, double-blind, placebo-controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index ≥30 kg/m2 or ≥27 kg/m2 and metabolic syndrome. Participants were randomly assigned to a once-daily subcutaneous injection of liraglutide (target dose 3.0 mg) or matching placebo for 40 weeks. Body fat distribution and muscle composition was assessed by magnetic resonance imaging at baseline and 40-week follow-up. Muscle composition was described by the combination of thigh muscle fat and muscle volume. Treatment difference (95% confidence intervals [CI]) was calculated by least-square means adjusted for baseline thigh muscle fat. The association between changes in thigh muscle fat and changes in body weight were assessed using Spearman correlation coefficients. The effect of liraglutide versus placebo on adverse muscle composition, denoted by high thigh muscle fat and low thigh muscle volume, was explored. RESULTS: Among the 128 participants with follow-up imaging (92.2% women, 36.7% Black), median muscle fat at baseline was 7.8%. The mean percent change in thigh muscle fat over median follow-up of 36 weeks was -2.87% among participants randomized to liraglutide (n = 73) and 0.05% in the placebo group (absolute change: -0.23% vs. 0.01%). The estimated treatment difference adjusted for baseline thigh muscle fat was -0.24% (95% CI, -0.41 to -0.06, P-value 0.009). Longitudinal change in thigh muscle fat was significantly associated with change in body weight in the placebo group but not the liraglutide group. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow-up with liraglutide, but there was no change with placebo. CONCLUSIONS: In a cohort of predominantly women with overweight or obesity in the absence of diabetes, once-daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo. The contribution of muscle fat improvement to the cardiometabolic benefits of liraglutide requires further study.

Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease.

Highly bioavailable inorganic phosphate (Pi) is present in large quantities in the typical Western diet and represents a large fraction of total phosphate intake. Dietary Pi excess induces exercise intolerance and skeletal muscle mitochondrial dysfunction in normal mice. However, the relevance of this to humans remains unknown. The study was conducted on 13 individuals without a history of cardiopulmonary disease (46% female, 15% Black participants) enrolled in the pilot-phase of the Dallas Heart and Mind Study. Total dietary phosphate was estimated from 24-h dietary recall (ASA24). Muscle ATP synthesis was measured at rest, and phosphocreatinine (PCr) dynamics was measured during plantar flexion exercise using 7-T 31P magnetic resonance (MR) spectroscopy in the calf muscle. Correlation was assessed between dietary phosphate intake normalized to total caloric intake, resting ATP synthesis, and PCr depletion during exercise. Higher dietary phosphate intake was associated with lower resting ATP synthesis (r = -0.62, P = 0.03), and with higher levels of PCr depletion during plantar flexion exercise relative to the resting period (r = -0.72; P = 0.004). These associations remain significant after adjustment for age and estimated glomerular filtration rate (both P < 0.05). High dietary phosphate intake was also associated with lower serum Klotho levels, and Klotho levels are in turn associated with PCr depletion and higher ADP accumulation post exercise. Our study suggests that higher dietary phosphate is associated with reduced skeletal muscle mitochondrial function at rest and exercise in humans providing new insight into potential mechanisms linking the Western diet to impaired energy metabolism.NEW & NOTEWORTHY This is the first translational research study directly demonstrating the adverse effects of dietary phosphate on muscle energy metabolism in humans. Importantly, our data show that dietary phosphate is associated with impaired muscle ATP synthesis at rest and during exercise, independent of age and renal function. This is a new biologic paradigm with significant clinical dietary implications.

Association of global longitudinal strain by feature tracking cardiac magnetic resonance imaging with adverse outcomes among community-dwelling adults without cardiovascular disease: The Dallas Heart Study.

AIM: Left ventricular (LV) global longitudinal strain (GLS) may detect subtle abnormalities in myocardial contractility among individuals with normal LV ejection fraction (LVEF). However, the prognostic implications of GLS among healthy, community-dwelling adults is not well-established. METHODS AND RESULTS: Overall, 2234 community-dwelling adults (56% women, 47% Black) with LVEF ≥50% without a history of cardiovascular disease (CVD) from the Dallas Heart Study who underwent cardiac magnetic resonance (CMR) with GLS assessed by feature tracking CMR (FT-CMR) were included. The association of GLS with the risk of incident major adverse cardiovascular events (MACE; composite of incident myocardial infarction, incident heart failure [HF], hospitalization for atrial fibrillation, coronary revascularization, and all-cause death), and incident HF or death were assessed with adjusted Cox proportional hazards models. A total of 309 participants (13.8%) had MACE during a median follow-up duration of 17 years. Participants with the worst GLS (Q4) were more likely male and of the Black race with a history of tobacco use and diabetes with lower LVEF, higher LV end-diastolic volume, and higher LV mass index. Cumulative incidence of MACE was higher among participants with worse (Q4 vs. Q1) GLS (20.4% vs. 9.0%). In multivariable-adjusted Cox models that included clinical characteristics, cardiac biomarkers and baseline LVEF, worse GLS (Q4 vs. Q1) was associated with a significantly higher risk of MACE (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.07-2.24, p = 0.02) and incident HF or death (HR 1.57, 95% CI 1.03-2.38, p = 0.04). CONCLUSIONS: Impaired LV GLS assessed by FT-CMR among adults free of cardiovascular disease is associated with a higher risk of incident MACE and incident HF or death independent of cardiovascular risk factors, cardiac biomarkers and LVEF.

Trends and Outcomes Associated With Bariatric Surgery and Pharmacotherapies With Weight Loss Effects Among Patients With Heart Failure and Obesity.

BACKGROUND: Utilization patterns of bariatric surgery among older patients with heart failure (HF), and the associations with cardiovascular outcomes, are not well known. METHODS: Medicare beneficiaries with HF and at least class II obesity from 2013 to 2020 were identified with Medicare Provider Analysis and Review 100% inpatient files and Medicare 5% outpatient files. Patients who underwent bariatric surgery were matched to controls in a 1:2 ratio (matched on exact age, sex, race, body mass index, HF encounter year, and HF hospitalization rate pre-surgery/matched period). In an exploratory analysis, patients prescribed pharmacotherapies with weight loss effects (semaglutide, liraglutide, naltrexone-bupropion, or orlistat) were identified and matched to controls with a similar strategy in addition to HF medical therapy data. Cox models evaluated associations between weight loss therapies (as a time-varying covariate) and mortality risk and HF hospitalization rate (calculated as the rate of HF hospitalizations following index HF encounter per 100 person-months) during follow-up. RESULTS: Of 298 101 patients with HF and body mass index ≥35 kg/m2, 2594 (0.9%) underwent bariatric surgery (45% men; mean age, 56.2 years; mean body mass index, 51.5 kg/m2). In propensity-matched analyses over a median follow-up of 4.7 years, bariatric surgery was associated with lower risk of all-cause mortality (HR, 0.55 [95% CI, 0.49-0.63]; P<0.001), greater reduction in HF hospitalization rate (rate ratio, 0.72 [95% CI, 0.67-0.77]; P<0.001), and lower atrial fibrillation risk (HR, 0.78 [95% CI, 0.65-0.93]; P=0.006). Use of pharmacotherapies with weight loss effects was low (4.8%), with 96.3% prescribed GLP-1 (glucagon-like peptide-1) agonists (semaglutide, 23.6%; liraglutide, 72.7%). In propensity-matched analysis over a median follow-up of 2.8 years, patients receiving pharmacotherapies with weight loss effects (versus matched controls) had a lower risk of all-cause mortality (HR, 0.82 [95% CI, 0.71-0.95]; P=0.007) and HF hospitalization rate (rate ratio, 0.87 [95% CI, 0.77-0.99]; P=0.04). CONCLUSIONS: Bariatric surgery and pharmacotherapies with weight loss effects are associated with a lower risk of adverse outcomes among older patients with HF and obesity; however, overall utilization remains low.

Incident Heart Failure Risk Reclassification With Race-Independent Estimated Glomerular Filtration Rate: A National Heart, Lung, and Blood Institute Pooled Cohorts Analysis.

BACKGROUND: This study compared the predictive value of the race-independent creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) and the race-dependent creatinine-based eGFR (eGFRcr) for incident heart failure (HF). METHODS: This study combined the participant-level data from ARIC (Atherosclerosis Risk in Communities) (visit 4) and MESA (Multi-Ethnic Study of Atherosclerosis) (visit 1) to calculate eGFRcr-cys and eGFRcr. The primary outcome of the study was adjudicated incident HF over a follow-up period of 10 years. Multivariable Cox models were used to assess the risk of incident HF with the quartiles of eGFRcr-cys and eGFRcr. RESULTS: Among 15,615 individuals (median age: 62 [57-68] years; 55.0% females; 23.9% Black), the median eGFRcr-cys and eGFRcr were 91.4 (79.4, 102.0) mL/min/1.73m2 and 84.7 (72.0, 94.7) mL/min/1.73m2, respectively. Compared with the fourth quartile of eGFRcr-cys, the hazard ratio for incident HF was 1.02 (95% CI:0.80-1.30) in the third quartile, 1.02 (95% CI:0.80-1.30) in the second quartile, and 1.47 (95% CI:1.16-1.86) in the first quartile. Compared with the 4th quartile of the eGFRcr, the risk of incident HF was similar in the 3rd (HRadj:0.90 [95% CI:0.73-1.12]), 2nd (HRadj: 0.96 [95% CI:0.77-1.20]), and 1st (HRadj:1.15 [95% CI:0.93-1.44]) quartiles. C-statistics were similar for the multivariable-adjusted Cox models for incident HF using eGFRcr (0.80 [0.79-0.81]) and eGFRcr-cys (0.80 [0.79-0.82]). CONCLUSION: The eGFRcr and eGFRcr-cys had comparable predictive values for incident HF.

A Phenomapping Tool and Clinical Score to Identify Low Diuretic Efficiency in Acute Decompensated Heart Failure.

BACKGROUND: Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking. OBJECTIVES: The authors sought to develop and externally validate a machine learning-based phenomapping approach and integer-based diuresis score to identify patients with low diuretic efficiency. METHODS: Participants with ADHF from ROSE-AHF, CARRESS-HF, and ATHENA-HF were pooled in the derivation cohort (n = 794). Multivariable finite-mixture model-based phenomapping was performed to identify phenogroups based on diuretic efficiency (urine output over the first 72 hours per total intravenous furosemide equivalent loop diuretic dose). Phenogroups were externally validated in other pooled ADHF trials (DOSE/ESCAPE). An integer-based diuresis score (BAN-ADHF score: blood urea nitrogen, creatinine, natriuretic peptide levels, atrial fibrillation, diastolic blood pressure, hypertension and home diuretic, and heart failure hospitalization) was developed and validated based on predictors of the diuretic efficiency phenogroups to estimate the probability of low diuretic efficiency using the pooled ADHF trials described earlier. The associations of the BAN-ADHF score with markers and symptoms of congestion, length of stay, in-hospital mortality, and global well-being were assessed using adjusted regression models. RESULTS: Clustering identified 3 phenogroups based on diuretic efficiency: phenogroup 1 (n = 370; 47%) had lower diuretic efficiency (median: 13.1 mL/mg; Q1-Q3: 7.7-19.4 mL/mg) than phenogroups 2 (n = 290; 37%) and 3 (n = 134; 17%) (median: 17.8 mL/mg; Q1-Q3: 10.8-26.1 mL/mg and median: 35.3 mL/mg; Q1-Q3: 17.5-49.0 mL/mg, respectively) (P < 0.001). The median urine output difference in response to 80 mg intravenous twice-daily furosemide between the lowest and highest diuretic efficiency group (phenogroup 1 vs 3) was 3,520 mL/d. The BAN-ADHF score demonstrated good model performance for predicting the lowest diuretic efficiency phenogroup membership (C-index: 0.92 in DOSE/ESCAPE validation cohort) that was superior to measures of kidney function (creatinine or blood urea nitrogen), natriuretic peptide levels, or home diuretic dose (DeLong P < 0.001 for all). Net urine output in response to 80 mg intravenous twice-daily furosemide among patients with a low vs high (5 vs 20) BAN-ADHF score was 2,650 vs 660 mL per 24 hours, respectively. Participants with higher BAN-ADHF scores had significantly lower global well-being, higher natriuretic peptide levels on discharge, a longer in-hospital stay, and a higher risk of in-hospital mortality in both derivation and validation cohorts. CONCLUSIONS: The authors developed and validated a phenomapping strategy and diuresis score for individuals with ADHF and differential response to diuretic therapy, which was associated with length of stay and mortality.

Is There a Need for Palliative Care for Patients With Heart Failure With Preserved Ejection Fraction?

This Viewpoint discusses palliative care for patients with heart failure with preserved ejection fraction.

Palliative Care for Patients With Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) has become the leading form of heart failure worldwide, particularly among elderly patient populations. HFpEF is associated with significant morbidity and mortality that may benefit from incorporation of palliative care (PC). Patients with HFpEF have similarly high mortality rates to patients with heart failure with reduced ejection fraction. PC trials for heart failure have shown improvement in quality of life, quality of death, and health care utilization, although most trials defined heart failure clinically without differentiating between HFpEF and heart failure with reduced ejection fraction. As such, the timing and role of PC for HFpEF care remains uncertain, and PC referral rates for HFpEF are very low despite potential improvements in important patient-centered outcomes. Specific barriers to referral include limited data, prognostic uncertainty, provider misconceptions about PC, inadequate specialty PC workforce, complexities of treating multimorbidity, and limited home care options for patients with heart failure. While there are many barriers to integration of PC into HFpEF care, there are multiple potential benefits to patients with HFpEF throughout their disease course. As this population continues to grow, targeted efforts to study and implement PC interventions are needed to improve patient quality of life and death.

Frailty and heart failure: State-of-the-art review.

At least half of all patients with heart failure (HF) are affected by frailty, a syndrome that limits an individual ability to recover from acute stressors. While frailty affects up to 90% of patients with HF with preserved ejection fraction, it is also seen in ~30-60% of patients with HF with reduced ejection fraction, with ~26% higher prevalence in women compared with men. The relationship between frailty and HF is bidirectional, with both conditions exacerbating the other. Frailty is further complicated by a higher prevalence of sarcopenia (by ~20%) in HF patients compared with patients without HF, which negatively affects outcomes. Several frailty assessment methods have been employed historically including the Fried frailty phenotype and Rockwood Clinical Frailty Scale to classify HF patients based on the severity of frailty; however, a validated HF-specific frailty assessment tool does not currently exist. Frailty in HF is associated with a poor prognosis with a 1.5-fold to 2-fold higher risk of all-cause death and hospitalizations compared to non-frail patients. Frailty is also highly prevalent in patients with worsening HF, affecting >50% of patients hospitalized for HF. Such patients with multiple readmissions for decompensated HF have markedly poor outcomes compared to younger, non-frail cohorts, and it is hypothesized that it may be due to major physical and functional limitations that limit recovery from an acute episode of worsening HF, a care aspect that has not been addressed in HF guidelines. Frail patients are thought to confer less benefit from therapeutic interventions due to an increased risk of perceived harm, resulting in lower adherence to HF interventions, which may worsen outcomes. Multiple studies report that <40% of frail patients are on guideline-directed medical therapy for HF, of which most are on suboptimal doses of these medications. There is a lack of evidence generated from randomized trials in this incredibly vulnerable population, and most current practice is governed by post hoc analyses of trials, observational registry-based data and providers' clinical judgement. The current body of evidence suggests that the treatment effect of most guideline-based interventions, including medications, cardiac rehabilitation and device therapy, is consistent across all age groups and frailty subgroups and, in some cases, may be amplified in the older, more frail population. In this review, we discuss the characteristics, assessment tools, impact on prognosis and impact on therapeutic interventions of frailty in patients with HF.

Lifetime healthcare expenses across demographic and cardiovascular risk groups: The application of a novel modeling strategy in a large multiethnic cohort study.

Objective: To understand the burden of healthcare expenses over the lifetime of individuals and evaluate differences among those with cardiovascular risk factors and among disadvantaged groups based on race/ethnicity and sex. Methods: We linked data from the longitudinal multiethnic Dallas Heart Study, which recruited participants between 2000 and 2002, with inpatient and outpatient claims from all hospitals in the Dallas-Fort Worth metroplex through December 2018, capturing encounter expenses. Race/ethnicity and sex, as well as five risk factors, hypertension, diabetes, hyperlipidemia, smoking, and overweight/obesity, were defined at cohort enrollment. For each individual, expenses were indexed to age and cumulated between 40 and 80 years of age. Lifetime expenses across exposures were evaluated as interactions in generalized additive models. Results: A total of 2184 individuals (mean age, 45±10 years; 61% women, 53% Black) were followed between 2000 and 2018. The mean modeled lifetime cumulative healthcare expenses were $442,629 (IQR, $423,850 to $461,408). In models that included 5 risk factors, Black individuals had $21,306 higher lifetime healthcare spending compared with non-Black individuals (P < .001), and men had modestly higher expenses than women ($5987, P < .001). Across demographic groups, the presence of risk factors was associated with progressively higher lifetime expenses, with significant independent association of diabetes ($28,075, P < .001), overweight/obesity ($8816, P < .001), smoking ($3980, P = .009), and hypertension ($528, P = .02) with excess spending. Conclusion: Our study suggests Black individuals have higher lifetime healthcare expenses, exaggerated by the substantially higher prevalence of risk factors, with differences emerging in older age.

Social Determinants of Health and Racial Disparities in Cardiac Events in Breast Cancer.

BACKGROUND: Racial disparities have been reported for breast cancer and cardiovascular disease (CVD) outcomes. The determinants of racial disparities in CVD outcomes are not yet fully understood. We aimed to examine the impact of individual and neighborhood-level social determinants of health (SDOH) on the racial disparities in major adverse cardiovascular events (MACE; consisting of heart failure, acute coronary syndrome, atrial fibrillation, and ischemic stroke) among female patients with breast cancer. METHODS: This 10-year longitudinal retrospective study was based on a cancer informatics platform with electronic medical record supplementation. We included women aged ≥18 years diagnosed with breast cancer. SDOH were obtained from LexisNexis, and consisted of the domains of social and community context, neighborhood and built environment, education access and quality, and economic stability. Race-agnostic (overall data with race as a feature) and race-specific machine learning models were developed to account for and rank the SDOH impact in 2-year MACE. RESULTS: We included 4,309 patients (765 non-Hispanic Black [NHB]; 3,321 non-Hispanic white). In the race-agnostic model (C-index, 0.79; 95% CI, 0.78-0.80), the 5 most important adverse SDOH variables were neighborhood median household income (SHapley Additive exPlanations [SHAP] score [SS], 0.07), neighborhood crime index (SS = 0.06), number of transportation properties in the household (SS = 0.05), neighborhood burglary index (SS = 0.04), and neighborhood median home values (SS = 0.03). Race was not significantly associated with MACE when adverse SDOH were included as covariates (adjusted subdistribution hazard ratio, 1.22; 95% CI, 0.91-1.64). NHB patients were more likely to have unfavorable SDOH conditions for 8 of the 10 most important SDOH variables for the MACE prediction. CONCLUSIONS: Neighborhood and built environment variables are the most important SDOH predictors for 2-year MACE, and NHB patients were more likely to have unfavorable SDOH conditions. This finding reinforces that race is a social construct.

Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial.

BACKGROUND: Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established. OBJECTIVES: This study sought to evaluate the association between polypharmacy and odds of receiving optimal GDMT over time among patients with HFrEF. METHODS: The authors conducted a post hoc analysis of the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial. Polypharmacy was defined as receiving ≥5 medications (excluding HFrEF GDMT) at baseline. The outcome of interest was optimal triple therapy GDMT (concurrent administration of a renin-angiotensin-aldosterone blocker and beta-blocker at 50% of the target dose and a mineralocorticoid receptor antagonist at any dose) achieved over the 12-month follow-up. Multivariable adjusted mixed-effect logistic regression models with multiplicative interaction terms (time × polypharmacy) were constructed to evaluate how polypharmacy at baseline modified the odds of achieving optimal GDMT on follow-up. RESULTS: The study included 891 participants with HFrEF. The median number of non-GDMT medications at baseline was 4 (IQR: 3-6), with 414 (46.5%) prescribed ≥5 and identified as being on polypharmacy. The proportion of participants who achieved optimal GDMT at the end of the 12-month follow-up was lower with vs without polypharmacy at baseline (15% vs 19%, respectively). In adjusted mixed models, the odds of achieving optimal GDMT over time were modified by baseline polypharmacy status (P for interaction < 0.001). Patients without polypharmacy at baseline had increased odds of achieving GDMT (OR: 1.16 [95% CI: 1.12-1.21] per 1-month increase; P < 0.001) but not patients with polypharmacy (OR: 1.01 [95% CI: 0.96-1.06)] per 1-month increase). CONCLUSIONS: Patients with HFrEF who are on non-GDMT polypharmacy have lower odds of achieving optimal GDMT on follow-up.

Neighborhood-level Social Vulnerability and Prevalence of Cardiovascular Risk Factors and Coronary Heart Disease.

Social determinants of health are implicated in the geographic variation in cardiovascular diseases (CVDs). The social vulnerability index (SVI) is an estimate of a neighborhood's potential for deleterious outcomes when faced with natural disasters or disease outbreaks. We sought to investigate the association of the SVI with cardiovascular risk factors and the prevalence of coronary heart disease (CHD) in the United States at the census tract level. We linked census tract SVI with prevalence of census tract CVD risk factors (smoking, high cholesterol, diabetes, high blood pressure, low physical activity and obesity), and prevalence of CHD obtained from the behavioral risk factor surveillance system. We evaluated the association between SVI, its sub-scales, CVD risk factors and CHD prevalence using linear regression. Among 72,173 census tracts, prevalence of all cardiovascular risk factors increased linearly with SVI. A higher SVI was associated with a higher CHD prevalence (R2 = 0.17, P < 0.0001). The relationship between SVI and CHD was stronger when accounting for census-tract median age (R2 = 0.57, P < 0.0001). A multivariable linear regression model including 4 SVI themes separately explained considerably more variation in CHD prevalence than the composite SVI alone (50.0% vs 17.3%). Socioeconomic status and household composition and disability were the SVI themes most closely associated with cardiovascular risk factors and CHD prevalence. In the United States, social vulnerability can explain significant portion of geographic variation in CHD, and its risk factors. Neighborhoods with high social vulnerability are at disproportionately increased risk of CHD and its risk factors. Social determinants of health are implicated in the geographic variation in cardiovascular diseases (CVDs). We investigated the association of social vulnerability index (SVI) with cardiovascular risk factors and the prevalence of coronary heart disease (CHD) in the United States at the census tract level. We show that cardiovascular risk factors and CHD were more common with higher SVI. A multivariable linear regression model including 4 SVI themes separately explained considerably more variation in CHD prevalence than the composite SVI alone (50.0% vs 17.3%). Socioeconomic status and household composition and/or disability were the SVI themes most closely associated with cardiovascular risk factors and CHD prevalence.

Physical activity, cardiorespiratory fitness, and cardiovascular health: A clinical practice statement of the ASPC Part I: Bioenergetics, contemporary physical activity recommendations, benefits, risks, extreme exercise regimens, potential maladaptations.

Regular moderate-to-vigorous physical activity (PA) and increased levels of cardiorespiratory fitness (CRF) or aerobic capacity are widely promoted as cardioprotective measures in the primary and secondary prevention of atherosclerotic cardiovascular (CV) disease (CVD). Nevertheless, physical inactivity and sedentary behaviors remain a worldwide concern. The continuing coronavirus (COVID-19) pandemic has been especially devastating to patients with known or occult CVD since sitting time and recreational PA have been reported to increase and decrease by 28% and 33%, respectively. Herein, in this first of a 2-part series, we discuss foundational factors in exercise programming, with specific reference to energy metabolism, contemporary PA recommendations, the dose-response relationship of exercise as medicine, the benefits of regular exercise training, including the exercise preconditioning cardioprotective phenotype, as well as the CV risks of PA. Finally, we discuss the 'extreme exercise hypothesis,' specifically the potential maladaptations resulting from high-volume, high-intensity training programs, including accelerated coronary artery calcification and incident atrial fibrillation. The latter is commonly depicted by a reverse J-shaped or U-shaped curve. On the other hand, longevity data argue against this relationship, as elite endurance athletes live 3-6 years longer than the general population.

Ninety-Day Risk-Standardized Home Time as a Performance Metric for Cardiac Surgery Hospitals in the United States.

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.

Post-operative atrial fibrillation and risk of heart failure hospitalization.

AIMS: Post-operative atrial fibrillation (POAF) is associated with stroke and mortality. It is unknown if POAF is associated with subsequent heart failure (HF) hospitalization. This study aims to examine the association between POAF and incident HF hospitalization among patients undergoing cardiac and non-cardiac surgeries. METHODS AND RESULTS: A retrospective cohort study was conducted using all-payer administrative claims data that included all non-federal emergency department visits and acute care hospitalizations across 11 states in the USA. The study population included adults aged at least 18 years hospitalized for surgery without a prior diagnosis of HF. Cox proportional hazards regression models were used to examine the association between POAF and incident HF hospitalization after making adjustment for socio-demographics and comorbid conditions. Among 76 536 patients who underwent cardiac surgery, 14 365 (18.8%) developed incident POAF. In an adjusted Cox model, POAF was associated with incident HF hospitalization [hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.25-1.41]. In a sensitivity analysis excluding HF within 1 year of surgery, POAF remained associated with incident HF hospitalization (HR 1.15; 95% CI 1.01-1.31). Among 2 929 854 patients who underwent non-cardiac surgery, 23 763 (0.8%) developed incident POAF. In an adjusted Cox model, POAF was again associated with incident HF hospitalization (HR 2.02; 95% CI 1.94-2.10), including in a sensitivity analysis excluding HF within 1 year of surgery (HR 1.49; 95% CI 1.38-1.61). CONCLUSIONS: Post-operative atrial fibrillation is associated with incident HF hospitalization among patients without prior history of HF undergoing both cardiac and non-cardiac surgeries. These findings reinforce the adverse prognostic impact of POAF and suggest that POAF may be a marker for identifying patients with subclinical HF and those at elevated risk for HF.

Association Between Thigh Muscle Fat Infiltration and Incident Heart Failure: The Health ABC Study.

BACKGROUND: Excess adiposity is a well-known risk factor for heart failure (HF). Fat accumulation in and around the peripheral skeletal muscle may further inform risk for HF. OBJECTIVES: The purpose of this study was to evaluate the association between intramuscular and intermuscular fat deposition and incident HF in a longitudinal cohort of community-dwelling older adults. METHODS: The associations of intramuscular and intermuscular fat with incident HF were assessed using Cox models among 2,399 participants from the Health ABC (Health, Aging and Body Composition) study (70-79 years of age, 48% male, 40.2% Black) without baseline HF. Intramuscular fat was determined by bilateral thigh muscle density on computed tomography and intermuscular fat area was determined with computed tomography. RESULTS: After a median follow-up of 12.2 years, there were 485 incident HF events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with HF risk. After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was associated with higher risk for HF (HR: 1.34 [95% CI: 1.06-1.69]; P = 0.012, tertile 3 vs tertile 1). This association remained significant after additional adjustment for body mass index (HR: 1.32 [95% CI: 1.03-1.69]), total percent fat (HR: 1.33 [95% CI: 1.03-1.72]), visceral fat (HR: 1.30 [95% CI: 1.01-1.65]), and indexed thigh muscle strength (HR: 1.30 [95% CI: 1.03-1.64]). The association between higher intramuscular fat and HF appeared specific to higher risk of incident HF with reduced ejection fraction (HR: 1.53 [95% CI: 1.03-2.29]), but not with HF with preserved ejection fraction (HR: 1.28 [95% CI: 0.82-1.98]). CONCLUSIONS: Intramuscular, but not intermuscular, thigh muscle fat is independently associated with HF after adjustment for cardiometabolic risk factors and other measurements of adiposity.

Long-Term Cardiovascular Outcomes After Bariatric Surgery in the Medicare Population.

BACKGROUND: The long-term effect of bariatric surgery on cardiovascular outcomes in the elderly population is not well studied. OBJECTIVES: The aim of this study was to evaluate the association between bariatric surgery and long-term cardiovascular outcomes in the Medicare population. METHODS: Medicare beneficiaries who underwent bariatric surgery from 2013 to 2019 were matched to a control group of patients with obesity with a 1:1 exact matching based on age, sex, body mass index, and propensity score matching on 87 clinical variables. The study outcomes included all-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke. An instrumental variable analysis was performed as a sensitivity analysis. RESULTS: The study cohort included 189,770 patients (94,885 matched patients in each group). By study design, the 2 groups had similar age (mean: 62.33 ± 10.62 years), sex (70% female), and degree of obesity (mean body mass index: 44.7 ± 7.3 kg/m2) and were well balanced on all clinical variables. After a median follow-up of 4.0 years (IQR: 2.4-5.7 years), bariatric surgery was associated with a lower risk of mortality (9.2 vs 14.7 per 1,000 person-years; HR: 0.63; 95% CI: 0.60-0.66), new-onset HF (HR: 0.46; 95% CI: 0.44-0.49), MI (HR: 0.63; 95% CI: 0.59-0.68), and stroke (HR: 0.71; 95%: CI: 0.65-0.79) (P < 0.001). The benefit of bariatric surgery was evident in patients who were 65 years and older. Using instrumental variable analysis, bariatric surgery was associated with a lower risk of mortality, HF, and MI. CONCLUSIONS: Among Medicare beneficiaries with obesity, bariatric surgery is associated with lower risk of mortality, new-onset HF, and MI.