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Abstract: Background: Heart failure is a leading cause of hospital admission and readmission in older adults. The new United States healthcare reform law has created provisions for financial penalties for hospitals with higher than expected 30-day all-cause readmission rates for hospitalized Medicare beneficiaries aged ≥65 years with heart failure. We examined the effect of digoxin on 30-day all-cause hospital admission in older patients with heart failure and reduced ejection fraction. Methods: In the main Digitalis Investigation Group trial, 6800 ambulatory patients with chronic heart failure (ejection fraction ≤45%) were randomly assigned to digoxin or placebo. Of these, 3405 were aged ≥65 years (mean age, 72 years; 25% were women; 11% were nonwhite). The main outcome in the current analysis was 30-day all-cause hospital admission. Results: In the first 30 days after randomization, all-cause hospitalization occurred in 5.4% (92/1693) and 8.1% (139/1712) of patients in the digoxin and placebo groups, respectively, (hazard ratio {HR} when digoxin was compared with placebo, 0.66; 95% confidence interval {CI}, 0.51-0.86; P=.002). Digoxin also reduced both 30-day cardiovascular (3.5% vs 6.5%; HR, 0.53; 95% CI, 0.38-0.72; P<.001) and heart failure (1.7 vs 4.2%; HR, 0.40; 95% CI, 0.26-0.62; P<.001) hospitalizations, with similar trends for 30-day all-cause mortality (0.7% vs 1.3%; HR, 0.55; 95% CI, 0.27-1.11; P=.096). Younger patients were at lower risk of events but obtained similar benefits from digoxin. Conclusions: Digoxin reduces 30-day all-cause hospital admission in ambulatory older patients with chronic systolic heart failure. Future studies need to examine its effect on 30-day all-cause hospital readmission in hospitalized patients with acute heart failure. [Copyright &y& Elsevier]

OBJECTIVES: To assess the ability of sedentary, frail subjects aged 80 and older to train in a community-based exercise program and to evaluate clinical factors that predict improvements in peak oxygen consumption (VO2 peak). DESIGN: Pretest, posttest. SETTING: Charlestown Retirement Community, Catonsville, Maryland PARTICIPANTS: Twenty-two (11 male, 11 female; mean age ± standard deviation = 84 ± 4.0, range 80–92) self-referred. INTERVENTION: Six months of moderate-intensity aerobic exercise training, two to three sessions/week, 20 to 30 minutes per session. Training modes included treadmill walking and/or stationary cycling. MEASUREMENTS: Baseline and follow-up maximal exercise treadmill tests (ETTs) with electrocardiogram monitoring and respiratory gas analysis. RESULTS: Six months of aerobic exercise training resulted in significant increases (mean ± standard deviation) in ETT duration (11.9 ± 3.3 vs 15.9 ± 4.3 minutes; P = .01), VO2 peak (1.23 ± 0.37 vs 1.31 ± 0.36 L/min; P = .04), and oxygen pulse (9.3 ± 2.8 vs 10.1 ± 3.2; P = .03). Mean heart rate was significantly lower during submaximal ETT stages 1 through 4 (P < .05), and resting systolic blood pressure decreased (146 ± 18 vs 133 ± 14 mmHg; P = .01) after training. Multiple regression analysis indicated that baseline VO2 peak (r = 0.75, P = .002) and the total amount of time spent in exercise training (r = 0.55, P = .008) were independent predictors of the training-related improvements in VO2 peak. CONCLUSION: Subjects aged 80 and older can increase aerobic capacity and reduce systolic blood pressure in a community-based exercise program of moderate intensity. The most important predictors of change in VO2 peak were baseline VO2 peak and the time spent in exercise training. Subjects with a lower baseline VO2 peak had the greatest improvements in VO2 peak... [ABSTRACT FROM AUTHOR]

OBJECTIVES: To compare the longitudinal changes in maximal aerobic capacity (VO2 max) in healthy middle aged and older athletes and sedentary men. DESIGN: A cohort study with mean follow-up of 8.7 years (range 4.0–12.8). SETTING: Outpatient research at a tertiary hospital. PARTICIPANTS: Forty-two healthy, middle aged, and older athletes (initial age 64 ± 1 year) and 47 healthy sedentary men of comparable age recruited for research studies. MEASUREMENTS: VO2 max during a maximal treadmill test. RESULTS: At baseline, the cross-sectional rates of decline in VO2 max with age (slope) were virtually identical in the athletes and sedentary men (-0.42 versus -0.43 mL·kg-1 · min-1 ·year-1 ). At follow-up, the VO2 max had declined by 11.9 ± 1.1 mL·kg-1 ·min-1 (22%) in the athletes, a crude average rate of -1.4 ± 0.14 mL·kg-1 ·min-1 ·year-1 . By comparison, the VO2 max declined by 4.4 ± 0.6 mL·kg-1 · min-1 (14%) in the sedentary men, a crude average rate of change of -0.48 ± 0.07 mL·kg-1 ·min-1 ·year-1 . Therefore, the observed absolute rate of longitudinal decline in VO2 max in the athletes was triple that of the sedentary men (P = .001) and significantly greater than the decline predicted by their baseline cross-sectional data (P = .001). Post hoc analyses of the longitudinal data in the athletes based on the training regimens over the follow-up period demonstrated that the seven individuals who continued to train vigorously (“high training”) had no significant decline in VO2 max (0.28% change in VO2 max per year). By contrast, the VO2 max declined by 2.6% per year in the “moderate training” group (N = 21),... [ABSTRACT FROM AUTHOR]

A major issue in evaluating the success of educational programs intended to improve public participation in physical activity is how to classify the intensity of activities performed. Currently, there are at least two approaches to estimating intensity of leisure time physical activity (LTPA), based on relative and absolute scales. We examined the impact of using relative versus absolute criteria on reaching physical activity goals set by the American College of Sports Medicine (ACSM; 2000) and the Surgeon General (United States Department of Health and Human Services, USDHHS, 1996). Subjects were healthy men (n = 619) and women (n = 497) aged 18-95 who were participants in the Baltimore Longitudinal Study of Aging. The percentage of subjects meeting the Surgeon General's recommendations for moderate and high intensity LTPA declined with age under the absolute classification system but increased with age when a relative intensity scale was used. Using ACSM recommendations, aging was associated with a decline in high absolute intensity LTPA. However, when a relative classification system was used, high relative intensity LTPA appeared to increase with age, inverting the relationship between high-intensity LTPA and cardiorespiratory fitness. The use of relative intensity LTPA criteria suggests that older subjects are meeting national standards for physical activity, raising questions about the appropriateness of such a scale to motivate older adults to improve their fitness. [ABSTRACT FROM AUTHOR]

Discusses the management of heart failure patients with normal systolic function in the United States. Determination of patterns of laboratory utilization and therapeutic interventions; Comparison of patient management among family practitioners, general internists, geriatricians and cardiologists.

Background: Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing.Objectives: In this post hoc analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness of Medical and Invasive Approaches-Chronic Kidney Disease), we compared outcomes of patients not listed versus those listed according to management strategy.Methods: In the ISCHEMIA-CKD trial (n = 777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction) and secondary (death, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed.Results: Compared with those not listed, listed patients were younger (60 years vs 65 years), were less likely to be of Asian race (15% vs 29%), were more likely to be on dialysis (83% vs 44%), had fewer anginal symptoms, and were more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios for the primary outcome were 0.91 (95% confidence interval [CI]: 0.54-1.54) and 1.03 (95% CI: 0.78-1.37) for those listed and not listed, respectively (pinteraction= 0.68). Adjusted hazard ratios for secondary outcomes were 0.89 (95% CI: 0.55-1.46) in listed and 1.17 (95% CI: 0.89-1.53) in those not listed (pinteraction = 0.35).Conclusions: In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant. (ISCHEMIA-Chronic Kidney Disease Trial [ISCHEMIA-CKD]; NCT01985360). [ABSTRACT FROM AUTHOR]

Background: Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables. Objectives: The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER). Methods: Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined. Results: Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3 ml·kg(-1)·min(-1) in women. Conclusions: Peak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437). [ABSTRACT FROM AUTHOR]

Objectives: Cardiovascular disease prevention for patients with type 2 diabetes is accomplished through hypertension and dyslipidemia management. Although studies have established strategies for lowering low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP), none have examined whether glycemia influences ability to achieve lipid and BP targets. This post hoc analysis from the Stop Atherosclerosis in Native Diabetics Study examines the role of baseline glycemia in achieving standard and aggressive targets and outcomes after 36 months.Methods: Diabetic individuals aged > 40 years with no cardiovascular events (n = 499) were randomized to aggressive versus standard targets for LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C) and systolic BP (SBP). Management algorithms were used for both groups. Carotid ultrasound and echocardiography were performed at baseline and after 36 months.Results: No differences were observed in baseline hemoglobin A1c between treatment groups nor any significant change in A1c after 36 months in either group. Baseline A1c, however, was significantly and negatively related to achieving LDL-C (P = .007), non-HDL-C (P = .03) and SBP targets (P = .007) and to changes in LDL-C (P = .007), non-HDL-C (P = .03) and SBP (P = .001) in both groups. Baseline A1c failed to predict progression of carotid intima medial thickness (CIMT) (P = .42) or left ventricular mass index (LVMI) (P = .10), nor was it related to the effects of lipid and BP lowering on CIMT and LVMI over 36 months.Conclusions: In diabetic adults with no cardiovascular disease events, A1c was negatively associated with ability to achieve LDL-C, non-HDL-C and SBP goals but was not independently related to treatment-associated changes in CIMT or LVMI over 36 months. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research., (Copyright © 2023 The American Heart Association , Inc. , and the American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Black women are disproportionately affected by cardiovascular disease with an excess burden of cardiovascular morbidity and mortality. In addition, the racialized structure of the United States shapes cardiovascular disease research and health care delivery for Black women. Given the indisputable evidence of the disparities in health care delivery, research, and cardiovascular outcomes, there is an urgent need to develop and implement effective and sustainable solutions to advance cardiovascular health equity for Black women while considering their ethnic diversity, regions of origin, and acculturation. Innovative and culturally tailored strategies that consider the differential impact of social determinants of health and the unique challenges that shape their health-seeking behaviors should be implemented. A patient-centered framework that involves collaboration among clinicians, health care systems, professional societies, and government agencies is required to improve cardiovascular outcomes for Black women. The time is "now" to achieve health equity for all Black women., Competing Interests: Funding Support and Author Disclosures Dr Ogunniyi has received institutional research grants from AstraZeneca, Boehringer Ingelheim, and Zoll; and has been an advisory board member for Pfizer. Dr Fatade is supported by the Stimulating Access to Research in Residency of the National Institutes of Health under award number R38AI140299. Dr Quesada is supported by the National Institutes of Health under award number K23 HL151867. Dr Mattina has received speaker fees from Zoll. Dr Ovbiagele is supported by research grants from the National Institutes of Health; and is a consultant and an advisory board member for AstraZeneca. The contents of this paper are solely the responsibility of the authors and do not necessarily represent official views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the U.S. Department of Health and Human Services. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. All rights reserved.)

Background: Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest., Objectives: Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up., Methods: In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models., Results: Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively., Conclusions: In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke., Condensed Abstract: In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively., (Copyright © 2020. Published by Elsevier Inc.)

Background and Aims: Total coronary artery calcium (CAC) burden is associated with an increased cardiovascular risk, while local CAC may represent stable plaques. We determined differences in relationship of total CAC with acute coronary syndrome (ACS) and local CAC with culprit lesions in patients with suspected ACS., Methods: We performed computed tomography (CT) for CAC and CT angiography to assess the presence of significant stenosis and high-risk plaque (positive remodeling, low CT attenuation, napkin-ring sign, spotty calcium) in 37 patients with ACS and 223 controls. Total and segmental Agatston scores were measured. Culprit lesions were assessed in subjects with ACS., Results: Patients (n = 260) with vs. without ACS had higher total CAC score (median 229, 25 th -75 th percentile 75-517 vs. 27, 25 th -75 th percentile 0-99, p<0.001), higher prevalence of significant stenosis (78% vs. 7%, p<0.001) and high-risk plaque (95% vs. 59%, p<0.001). In those with ACS, culprit (n = 41) vs. non-culprit (n = 200) lesions, had similar segmental CAC score (median 22, 25 th -75 th percentile 4-71 vs. 14, 25 th -75 th percentile 0-51; p=0.37), but higher prevalence of significant stenosis (81% vs. 11%, p<0.001) and high-risk plaque (76% vs. 51%, p=0.005). Significant stenosis (odds ratio 40.2, 95%CI 15.6-103.9, p<0.001) and high-risk plaque (odds ratio 3.4, 95%CI 1.3-9.1, p=0.02), but not segmental CAC score (odds ratio 1.0, 95%CI 1.0-1.0, p=0.47), were associated with culprit lesions of ACS., Conclusions: Total CAC burden was associated with ACS but segmental CAC was not associated with culprit lesions. Our findings suggest that total but not local CAC is a marker of ACS risk and support the hypothesis that extensive local CAC is a marker of plaque stability., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study sought to determine the multicenter reproducibility of magnetic resonance imaging (MRI) and the compatibility of different scanner platforms in assessing carotid plaque morphology and composition. A standardized multi-contrast MRI protocol was implemented at 16 imaging sites (GE: 8; Philips: 8). Sixty-eight subjects (61 ± 8 years; 52 males) were dispersedly recruited and scanned twice within 2 weeks on the same magnet. Images were reviewed centrally using a streamlined semiautomatic approach. Quantitative volumetric measurements on plaque morphology (lumen, wall, and outer wall) and plaque tissue composition [lipid-rich necrotic core (LRNC), calcification, and fibrous tissue] were obtained. Inter-scan reproducibility was summarized using the within-subject standard deviation, coefficient of variation (CV) and intraclass correlation coefficient (ICC). Good to excellent reproducibility was observed for both morphological (ICC range 0.98-0.99) and compositional (ICC range 0.88-0.96) measurements. Measurement precision was related to the size of structures (CV range 2.5-4.9 % for morphology, 36-44 % for LRNC and calcification). Comparable measurement variability was found between the two platforms on both plaque morphology and tissue composition. In conclusion, good to excellent inter-scan reproducibility of carotid MRI can be achieved in multicenter settings with comparable measurement precision between platforms, which may facilitate future multicenter endeavors that use serial MRI to monitor atherosclerotic plaque progression.

Background: In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients., Methods: In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin., Results: All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79)., Conclusions: In older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients., (Published by Elsevier Inc.)

Background: Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown., Methods: Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics., Results: Thirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction <45% (HR 0.63; 95% CI, 0.47-0.83), but not in those with ejection fraction ≥ 45% (HR 0.91; 95% CI, 0.60-1.37; P for interaction, .145), a difference that persisted throughout the first 12 months postdischarge (P for interaction, .019). HRs (95% CIs) for 12-month heart failure readmission and all-cause mortality were 0.72 (0.61-0.86) and 0.83 (0.70-0.98), respectively., Conclusions: In Medicare beneficiaries with systolic heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission, which was maintained at 12 months, and was not at the expense of higher mortality. Future randomized controlled trials are needed to confirm these findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Repeated failure in the Army Physical Fitness Test (APFT) is associated with lower fitness level, premature discharge, and significant career disruption, at high economic and health costs to the individual soldier and the U.S. Army. We used cost-effectiveness analysis to estimate the health and economic implications of two exercise interventions for Army National Guard (ARNG) soldiers who had failed the APFT, a traditional remediation program and a new pedometer-based program called Fitness for Life, involving individual counseling and follow-up telephone calls. Effectiveness of the interventions was analyzed in terms of APFT pass rates and calculated 10-year coronary heart disease risk. Costs were calculated based on tracking of resources used in the programs. APFT pass rates were 54.3% and 47.9%, respectively, for traditional and Fitness for Life programs, p = not significant. Neither program affected 10-year coronary heart disease risk. For assumed APFT pass rates up to 40% without any formal remediation, both the traditional remediation program and the ARNG Fitness for Life intervention had cost savings without significant group differences. Depending on the ARNG unit and personnel preference, although the Fitness for Life Program was more expensive and thus less cost-effective, either program could be cost-effective and of benefit to the military., (Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.)

Background: Anemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF., Hypothesis: Anemia is associated with cardiovascular events in patients with heart failure., Methods: The HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤ 35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes., Results: Hemoglobin was available at baseline in 1763 subjects (76% of total study population); their median age was 59.0 years, 73% were male, and 62% were Caucasian. The prevalence of anemia was 515/1763 (29%). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78% of those with anemia and 64% in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23% vs 15%, 67% vs 54%, and 44 vs 29%, respectively (P < 0.001). Heart failure hospitalizations occurred in 36% vs 22%, and urgent outpatient visits for HF exacerbations occurred in 67% and 55%, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95% CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95% CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95% CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95% CI: 1.06-1.51, P = 0.008)., Conclusions: Anemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints., (© 2013 Wiley Periodicals, Inc.)

Background: Treatment of Preserved Cardiac Function with an Aldosterone Antagonist (TOPCAT) is an ongoing randomized controlled trial of spironolactone versus placebo for heart failure with preserved ejection fraction (HFpEF). We sought to describe the baseline clinical characteristics of subjects enrolled in TOPCAT relative to other contemporary observational studies and randomized clinical trials of HFpEF., Methods and Results: Between August 2006 and January 2012, 3445 patients with symptomatic HFpEF from 270 sites in 6 countries were enrolled in TOPCAT. At the baseline study visit, all subjects provided a detailed medical history and underwent physical examination, electrocardiography, quality of life, and laboratory assessment. Key parameters were compared with other large, contemporary HFpEF studies. The mean age was 68.6±9.6 years with a slight female predominance (52%); mean body mass index was 32 kg/m2; and comorbidities were common. History of hypertension (91% prevalence in TOPCAT) exceeded all other major HFpEF clinical trials. However, baseline blood pressure was well controlled (129/76 mm Hg; systolic blood pressure 7-16 mm Hg lower than other similar trials). Other common comorbidities included coronary artery disease (57%), atrial fibrillation (35%), chronic kidney disease (38%) and diabetes mellitus (32%). Self-reported activity levels were low, quality of life scores were comparable with those reported for patients with end-stage renal disease, and the prevalence of moderate or greater depression was 27%., Conclusions: TOPCAT subjects share many common characteristics with contemporary HFpEF cohorts. Low activity level, significantly decreased quality of life, and depression were common at baseline in TOPCAT, underscoring the continued unmet need for evidence-based treatment strategies in HFpEF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00094302.

Background: The aim of this study was to investigate the clinical characteristics, exercise training response, β-blocker selectivity, and outcomes in patients with heart failure (HF) and chronic obstructive pulmonary disease (COPD)., Methods: We performed an analysis of HF-ACTION, which randomized 2,331 patients with HF having an ejection fraction of ≤35% to usual care with or without aerobic exercise training. We examined clinical characteristics and outcomes (mortality/hospitalization, mortality, cardiovascular [CV] mortality/CV hospitalization, and CV mortality/HF hospitalization) by physician-reported COPD status using adjusted Cox models and explored an interaction with exercise training. The interaction between β-blocker cardioselectivity and outcomes was investigated., Results: Of patients with COPD status documented (n = 2311), 11% (n = 249) had COPD. Patients with COPD were older, had more comorbidities, and had lower use of β-blockers compared with those without COPD. At baseline, patients with COPD had lower peak oxygen consumption and higher V(E)/V(CO)(2) slope. During a median follow-up of 2.5 years, COPD was associated with increased mortality/hospitalization, mortality, and CV mortality/HF hospitalization. After multivariable adjustment, the risk of CV mortality/HF hospitalization remained increased (hazard ratio [HR] 1.46, 95% CI 1.14-1.87), whereas mortality/hospitalization (HR 1.15, 95% CI 0.96-1.37) and mortality (HR 1.33, 95% CI 0.99-1.76) were not significantly increased. There was no interaction between COPD and exercise training on outcomes or between COPD and β-blocker selectivity on mortality/hospitalization (all P > .1)., Conclusions: Chronic obstructive pulmonary disease in patients with HF was associated with older age, more comorbidities, reduced exercise capacity, and increased CV mortality/HF hospitalization, but not a differential response to exercise training. β-Blocker selectivity was not associated with differences in outcome for patients with vs without COPD., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objectives: The goal of this study was to compare the prognostic efficacy of the 6-min walk (6MW) and cardiopulmonary exercise (CPX) tests in stable outpatients with chronic heart failure (HF)., Background: CPX and 6MW tests are commonly applied as prognostic gauges for systolic HF patients, but few direct comparisons have been conducted., Methods: Stable New York Heart Association (NYHA) functional class II and III systolic HF patients (ejection fraction ≤ 35%) from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were studied. 6MW distance (6MWD) and CPX indices (peak oxygen consumption [VO(2)] and ventilatory equivalents for exhaled carbon dioxide [VE/VCO(2)] slope) were compared as predictors of all-cause mortality/hospitalization and all-cause mortality over 2.5 years of mean follow-up., Results: A total of 2,054 HF-ACTION participants underwent both CPX and 6MW tests at baseline (median age 59 years; 71% male; 64% NYHA functional class II and 36% NYHA functional class III/IV). In unadjusted models and in models that included key clinical and demographic covariates, C-indices of 6MWD were 0.58 and 0.65 (unadjusted) and 0.62 and 0.72 (adjusted) in predicting all-cause mortality/hospitalization and all-cause mortality, respectively. C-indices for peak VO(2) were 0.61 and 0.68 (unadjusted) and 0.63 and 0.73 (adjusted). C-indices for VE/VCO(2) slope were 0.56 and 0.65 (unadjusted) and 0.61 and 0.71 (adjusted); combining peak VO(2) and VE/VCO(2) slope did not improve the C-indices. Overlapping 95% confidence intervals and modest integrated discrimination improvement values confirmed similar prognostic discrimination by 6MWD and CPX indices within adjusted models., Conclusions: In systolic HF outpatients, 6MWD and CPX indices demonstrated similar utility as univariate predictors for all-cause hospitalization/mortality and all-cause mortality. However, 6MWD or CPX indices added only modest prognostic discrimination to models that included important demographic and clinical covariates., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic ability of a single measurement of peak oxygen uptake (VO(2)) is well established in patients with chronic heart failure. The relation between a change in peak VO(2) and clinical outcomes is not well defined., Methods and Results: This investigation determined whether an increase in peak VO(2) was associated with a lower risk of the primary end point of time to all-cause mortality or all-cause hospitalization and 3 secondary end points. In Heart Failure and a Controlled Trial to Investigate Outcomes of Exercise Training, an exercise training trial for patients with systolic heart failure, cardiopulmonary exercise tests were performed at baseline and ≈3 months later in 1620 participants. Median peak VO(2) in the combined sample increased from 15.0 (11.9-18.0 Q1-Q3) to 15.4 (12.3-18.7 Q1-Q3) mL·kg(-1)·min(-1). Every 6% increase in peak VO(2,) adjusted for other significant predictors, was associated with a 5% lower risk of the primary end point (hazard ratio=0.95; CI=0.93-0.98; P<0.001); a 4% lower risk of the secondary end point of time to cardiovascular mortality or cardiovascular hospitalization (hazard ratio=0.96; CI=0.94-0.99; P<0.001); an 8% lower risk of cardiovascular mortality or heart failure hospitalization (hazard ratio=0.92; CI=0.88-0.96; P<0.001); and a 7% lower all-cause mortality (hazard ratio=0.93; CI=0.90-0.97; P<0.001)., Conclusions: Among patients with chronic systolic heart failure, a modest increase in peak VO(2) over 3 months was associated with a more favorable outcome. Monitoring the change in peak VO(2) for such patients may have benefit in assessing prognosis.

Background: The Stop Atherosclerosis in Native Diabetics Study (SANDS) reported cardiovascular benefit of aggressive versus standard treatment targets for both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) in diabetic individuals., Objective: In this analysis, we examined within trial cost-effectiveness of aggressive targets of LDL-C ≤70 mg/dL and systolic BP ≤115 mmHg versus standard targets of LDL-C ≤100 mg/dL and systolic BP ≤130 mmHg., Design: Randomized, open label blinded-to-endpoint 3-year trial., Data Sources: SANDS clinical trial database, Quality of Wellbeing survey, Centers for Medicare and Medicaid Services, Wholesale Drug Prices., Target Population: American Indians ≥ age 40 years with type 2 diabetes and no previous cardiovascular events., Time Horizon: April 2003 to July 2007., Perspective: Health payer., Interventions: Participants were randomized to aggressive versus standard groups with treatment algorithms defined for both., Outcome Measures: Incremental cost-effectiveness., Results of Base-Case Analysis: Compared with the standard group, the aggressive group had slightly lower costs of medical services (-$116) but a 54% greater cost for BP medication ($1,242) and a 116% greater cost for lipid-lowering medication ($2,863), resulting in an increased cost of $3,988 over 3 years. Those in the aggressively treated group gained 0.0480 quality-adjusted life-years (QALY) over the standard group. When a 3% discount rate for costs and outcomes was used, the resulting cost per QALY was $82,589., Results of Sensitivity Analysis: The use of a 25%, 50%, and 75% reduction in drug costs resulted in a cost per QALY of $61,329, $40,070, and $18,810, respectively., Limitations: This study was limited by use of a single ethnic group and by its 3-year duration., Conclusions: Within this 3-year study, treatment to lower BP and LDL-C below standard targets was not cost-effective because of the cost of the additional medications required to meet the lower targets. With the anticipated availability of generic versions of the BP and lipid-lowering drugs used in SANDS, the cost-effectiveness of this intervention should improve. Published by Elsevier Inc on behalf of the National Lipid Association.

The Stop Atherosclerosis in Native Diabetics Study (SANDS) was a randomized open-label clinical trial in type 2 diabetics designed to examine the effects of intensive reduction of blood pressure, aggressive vs standard goals (< or =115/75 mm Hg vs < or =130/80 mm Hg), and low-density lipoprotein (LDL) cholesterol on the composite outcome of change in carotid intimal-medial thickness and cardiovascular events. The study demonstrated that in conjunction with a lower LDL cholesterol target of 70 mg/dL, aggressive systolic blood pressure-lowering resulted in a reduction in carotid intimal-medial thickness and left ventricular mass without measurable differences in cardiovascular events. The blood pressure treatment algorithm included renin-angiotensin system blockade, with other agents added if necessary. The authors conclude that both standard and more aggressive systolic blood pressure reduction can be achieved with excellent safety and good tolerability in patients with type 2 diabetes mellitus.

An increased rate of cardiac symptoms at combat theater hospitals brings concerns about the predeployment health of Army National Guard (ARNG) soldiers on the basis of older age, lower fitness level, and sedentary lifestyle than active duty troops. The purpose of this study was to examine the association of physical fitness, reported physical activity (PA), and coronary risk factors to calculated 10-year hard coronary heart disease (CHD) risk in 136 ARNG soldiers, aged 18-53 years, who failed the 2-mile run of the Army Physical Fitness Test (APFT). The APFT score, derived from a composite of 2-mile run time, sit-ups, and push-ups, related inversely to 10-year CHD risk (r = -0.23, p < 0.01) but no relationship with CHD risk was observed for PA. APFT scores were positively associated with high-density lipoprotein (HDL) cholesterol and inversely with triglycerides, total cholesterol:HDL ratio, diastolic blood pressure, and body mass index (BMI). No relationship existed between PA and any of the CHD risk factors. We conclude that a higher APFT score is associated with a healthier CHD risk factor profile and is a predictor of better predeployment cardiovascular health.

We performed a retrospective follow-up study of 1926 women with heart failure who participated in the Digitalis Investigation Group trial. Adjusted hazard ratios and 95% confidence intervals for covariates that were significant independent predictors of all-cause mortality were age in years (1.02; 1.01-1.03; P<0.001), NYHA class IH-IV (1.56; 1.31-1.87), diabetes (1.63; 1.36-1.95), glomerular filtration rate in mL/min/1.73 m(2) (0.99; 0.98-4).996; P=0.001), pulmonary congestion by chest x-ray (1.57; 1.22-2.02), left ventricular ejection fraction (LVEF) (0.99; 0.98-0.993; P<0.001), and use of digoxin (1.20; 1.02-1.42). Covariates that were significant independent predictors of hospitalization due to worsening heart failure were: nonwhite race (1.28; 1.03-1.58), NYHA class III-IV (1.55; 1.30-1.84), diabetes (1.75; 1.47-2.09), glomerular filtration rate as mL/min/1.73 m(2) (0.99; 0.986-0.996; P<0.001), pulmonary congestion by chest x-ray (1.42; 1.12-1.81), and use of ACE inhibitors (0.67; 0.49-0.91). Longer duration of heart failure, higher NYHA classes, diabetes, chronic kidney disease, pulmonary congestion, and lower LVEF were significant independent predictors of all-cause mortality, all-cause hospitalization, and hospitalization for heart failure in women with heart failure.

Background: The Public Access Defibrillation (PAD) Trial found an overall doubling in the number of out-of-hospital cardiac arrest (CA) survivors when a lay responder team was equipped with an automated external defibrillator (AED), compared with cardiopulmonary resuscitation (CPR) alone., Objectives: To describe the types of facilities that participated in the trial and to report the incidence of CA and survival in these different types of facilities., Methods: In this post-hoc analysis of PAD Trial data, the physical characteristics of the participating facilities and the numbers of presumed CAs, treatable CAs, and survivors are reported for each category of facilities., Results: There were 625 presumed CAs at 1,260 participating facilities. Just under half (n = 291) of the presumed CAs were classified as treatable CAs. Treatable CAs occurred at a rate of 2.9 per 1,000 person-years of exposure; rates were highest in fitness centers (5.1) and golf courses (4.8) and lowest in office complexes (0.7) and hotels (0.7). Survival from treatable CA was highest in recreational complexes (0.5), public transportation sites (0.4), and fitness centers (0.4) and lowest in office complexes (0.1) and residential facilities (0.0)., Conclusions: During the PAD Trial, the exposure-adjusted rate of treatable CA was highest in fitness centers and golf courses, but the incidence per facility was low to moderate. Survival from treatable cardiac arrest was highest in recreational complexes, public transportation facilities, and fitness centers.