Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

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.

Improved cardiorespiratory fitness is associated with lower incident ischemic stroke risk: Henry Ford FIT project.

BACKGROUND: Change in cardiorespiratory fitness (CRF) modulates vascular disease risk; however, it's unclear if this adds further prognostic information, particularly for ischemic stroke. The objective of this analysis is to describe the association between the change in CRF over time and subsequent incident ischemic stroke. METHODS: This is a retrospective, longitudinal, observational cohort study of 9,646 patients (age=55±11 years; 41% women; 25% black) who completed 2 clinically indicated exercise tests (> 12 months apart) and were free of any stroke at the time of test 2. CRF was expressed as metabolic-equivalents-of-task (METs). Incident ischemic stroke was identified using ICD codes. The adjusted hazard ratio (aHR) was determined for risk of ischemic stroke associated with change in CRF. RESULTS: Mean time between tests was 3.7 years (IQR, 2.2, 6.0). During a median of 5.0 years (IQR, 2.7, 7.6 y) of follow-up, there were 873 (9.1%) ischemic stroke events. Each 1 MET increase between tests was associated with a 9% lower ischemic stroke risk (aHR 0.91 [0.88-0.94]; n = 9.646). There was an interaction effect by baseline CRF category, but not for sex or race. A sensitivity analysis which removed those who experienced an incident diagnosis known to be associated with an increased risk of ischemic vascular disease, validated our primary findings (aHR 0.91 [0.88, 0.95]; n= 6,943). CONCLUSIONS: Improvement in CRF over time is independently and inversely associated with a lower risk of ischemic stroke. Encouragement of regular exercise focused on improving CRF may reduce ischemic stroke risk.

The HEART Camp Exercise Intervention Improves Exercise Adherence, Physical Function, and Patient-Reported Outcomes in Adults With Preserved Ejection Fraction Heart Failure.

BACKGROUND: Despite exercise being one of few strategies to improve outcomes for individuals with heart failure with preserved ejection fraction (HFpEF), exercise clinical trials in HFpEF are plagued by poor interventional adherence. Over the last 2 decades, our research team has developed, tested, and refined Heart failure Exercise And Resistance Training (HEART) Camp, a multicomponent behavioral intervention to promote adherence to exercise in HF. We evaluated the effects of this intervention designed to promote adherence to exercise in HF focusing on subgroups of participants with HFpEF and heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: This randomized controlled trial included 204 adults with stable, chronic HF. Of those enrolled, 59 had HFpEF and 145 had HFrEF. We tested adherence to exercise (defined as ≥120 minutes of moderate-intensity [40%-80% of heart rate reserve] exercise per week validated with a heart rate monitor) at 6, 12, and 18 months. We also tested intervention effects on symptoms (Patient-Reported Outcomes Measurement Information System-29 and dyspnea-fatigue index), HF-related health status (Kansas City Cardiomyopathy Questionnaire), and physical function (6-minute walk test). Participants with HFpEF (n = 59) were a mean of 64.6 ± 9.3 years old, 54% male, and 46% non-White with a mean ejection fraction of 55 ± 6%. Participants with HFpEF in the HEART Camp intervention group had significantly greater adherence compared with enhanced usual care at both 12 (43% vs 14%, phi = 0.32, medium effect) and 18 months (56% vs 0%, phi = 0.67, large effect). HEART Camp significantly improved walking distance on the 6-minute walk test (η2 = 0.13, large effect) and the Kansas City Cardiomyopathy Questionnaire overall (η2 = 0.09, medium effect), clinical summary (η2 = 0.16, large effect), and total symptom (η2 = 0.14, large effect) scores. In the HFrEF subgroup, only patient-reported anxiety improved significantly in the intervention group. CONCLUSIONS: A multicomponent, behavioral intervention is associated with improvements in long-term adherence to exercise, physical function, and patient-reported outcomes in adults with HFpEF and anxiety in HFrEF. Our results provide a strong rationale for a large HFpEF clinical trial to validate these findings and examine interventional mechanisms and delivery modes that may further promote adherence and improve clinical outcomes in this population. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/. Unique identifier: NCT01658670.

Fitness and prostate cancer screening, incidence, and mortality: Results from the Henry Ford Exercise Testing (FIT) Project.

BACKGROUND: The relation between cardiorespiratory fitness (CRF) and prostate cancer is not well established. The objective of this study was to determine whether CRF is associated with prostate cancer screening, incidence, or mortality. METHODS: The Henry Ford Exercise Testing Project is a retrospective cohort study of men aged 40 to 70 years without cancer who underwent physician-referred exercise stress testing from 1995 to 2009. CRF was quantified in metabolic equivalents of task (METs) (<6 [reference], 6-9, 10-11, and ≥12 METs), estimated from the peak workload achieved during a symptom-limited, maximal exercise stress test. Prostate-specific antigen (PSA) testing, incident prostate cancer, and all-cause mortality were analyzed with multivariable adjusted Poisson regression and Cox proportional hazard models. RESULTS: In total, 22,827 men were included, of whom 739 developed prostate cancer, with a median follow-up of 7.5 years. Men who had high fitness (≥12 METs) had an 28% higher risk of PSA screening (95% CI, 1.2-1.3) compared with those who had low fitness (<6 METs. After adjusting for PSA screening, fitness was associated with higher prostate cancer incidence (men aged <55 years, P = .02; men aged >55 years, P ≤ .01), but not with advanced prostate cancer. Among the men who were diagnosed with prostate cancer, high fitness was associated with a 60% lower risk of all-cause mortality (95% CI, 0.2-0.9). CONCLUSIONS: Although men with high fitness are more likely to undergo PSA screening, this does not fully account for the increased incidence of prostate cancer seen among these individuals. However, men with high fitness have a lower risk of death after a prostate cancer diagnosis, suggesting that the cancers identified may be low-risk with little impact on long-term outcomes.

Home-Based Cardiac Rehabilitation: A Scientific Statement From the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology.

Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary prevention outcomes in patients with cardiovascular disease. CR programs reduce morbidity and mortality rates in adults with ischemic heart disease, heart failure, or cardiac surgery but are significantly underused, with only a minority of eligible patients participating in CR in the United States. New delivery strategies are urgently needed to improve participation. One potential strategy is home-based CR (HBCR). In contrast to center-based CR services, which are provided in a medically supervised facility, HBCR relies on remote coaching with indirect exercise supervision and is provided mostly or entirely outside of the traditional center-based setting. Although HBCR has been successfully deployed in the United Kingdom, Canada, and other countries, most US healthcare organizations have little to no experience with such programs. The purpose of this scientific statement is to identify the core components, efficacy, strengths, limitations, evidence gaps, and research necessary to guide the future delivery of HBCR in the United States. Previous randomized trials have generated low- to moderate-strength evidence that HBCR and center-based CR can achieve similar improvements in 3- to 12-month clinical outcomes. Although HBCR appears to hold promise in expanding the use of CR to eligible patients, additional research and demonstration projects are needed to clarify, strengthen, and extend the HBCR evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups. In the interim, we conclude that HBCR may be a reasonable option for selected clinically stable low- to moderate-risk patients who are eligible for CR but cannot attend a traditional center-based CR program.

Cardiorespiratory fitness and incident lung and colorectal cancer in men and women: Results from the Henry Ford Exercise Testing (FIT) cohort.

BACKGROUND: To the authors' knowledge, the relationship between cardiorespiratory fitness (CRF) and lung and colorectal cancer outcomes is not well established. METHODS: A retrospective cohort study was performed of 49,143 consecutive patients who underwent clinician-referred exercise stress testing from 1991 through 2009. The patients ranged in age from 40 to 70 years, were without cancer, and were treated within the Henry Ford Health System in Detroit, Michigan. CRF, measured in metabolic equivalents of task (METs), was categorized as <6 (reference), 6 to 9, 10 to 11, and ≥12. Incident cancer was obtained through linkage to the cancer registry and all-cause mortality from the National Death Index. RESULTS: Participants had a mean age of 54 ± 8 years. Approximately 46% were female, 64% were white, 29% were black, and 1% were Hispanic. The median follow-up was 7.7 years. Cox proportional hazard models, adjusted for age, race, sex, body mass index, smoking history, and diabetes, found that those in the highest fitness category (METs ≥12) had a 77% decreased risk of lung cancer (hazard ratio [HR], 0.23; 95% CI, 0.14-0.36) and a 61% decreased risk of incident colorectal cancer (HR, 0.39; 95% CI, 0.23-0.66; with additional adjustment for aspirin and statin use). Among those diagnosed with lung and colorectal cancer, those with high fitness had a decreased risk of subsequent death of 44% and 89%, respectively (HR, 0.56 [95% CI, 0.32-1.00] and HR, 0.11 [95% CI, 0.03-0.37], respectively). CONCLUSIONS: In what to the authors' knowledge is the largest study performed to date, higher CRF was associated with a lower risk of incident lung and colorectal cancer in men and women and a lower risk of all-cause mortality among those diagnosed with lung or colorectal cancer.

Exercise training workloads in cardiac rehabilitation are associated with clinical outcomes in patients with heart failure.

BACKGROUND: In patients with coronary heart disease, the exercise workload (i.e., metabolic equivalents of task, METs) at which patients exercise train upon entry and completion of cardiac rehabilitation (CR) are independently related to prognosis. Unknown is the association between exercise training workloads in CR and clinical outcomes in patients with heart failure (HF). METHODS: Patients with HF who participated in an early outpatient CR program were used in this retrospective analysis. Exercise workloads upon entry and completion of CR were converted to METs. The primary outcome was all-cause mortality and the secondary outcome was HF hospitalization. Cox regression analysis was used to assess the adjusted risk between MET levels in CR and clinical outcomes. RESULTS: Among 707 patients, the median exercise training workload at the start and end of CR was 2.5 METs (IQR 2.1 to 3.1 METs) and 3.2 METS (IQR 2.7 to 4.1 METs), respectively, for men and 2.2 METs (IQR 1.9 to 2.6 METs) and 2.9 METS (IQR 2.3 to 3.4 METs), respectively, for women. There were 242 deaths and 266 HF hospitalizations. METs achieved at the end of CR had the strongest independent association with all-cause mortality (adjusted HR, 95% CI: 0.58, 0.48-0.70) and HF hospitalization (adjusted HR, 95% CI: 0.62, 0.52-0.74). Each 1 MET higher work load at the end of CR was associated with a 42% and 38% lower adjusted risk for all-cause mortality and HF hospitalization, respectively. CONCLUSIONS: In a diverse cohort of patients with chronic HF our data suggests that an easily accessible measure of exercise capacity (i.e., METs) that is collected during CR is independently associated with the adjusted risk for both all-cause mortality and HF-specific hospitalization. Training at MET levels <3.5 METs identifies patients that might benefit from closer clinical surveillance and reinforced adherence to medical and lifestyle preventive strategies.

Cardiopulmonary Exercise Measures of Men and Women with HFrEF Differ in Their Relationship to Prognosis: The Henry Ford Hospital Cardiopulmonary Exercise Testing (FIT-CPX) Project.

BACKGROUND: This study evaluated if different prognostic characteristics exist for peak oxygen consumption (VO2), percent predicted peak VO2 (ppVO2), and the slope of the change in minute ventilation to volume of carbon dioxide produced (VE-VCO2) slope between men and women with heart failure and reduced ejection fraction (HFrEF). METHODS: Analysis of the Henry Ford Hospital Cardiopulmonary Exercise Testing database (n = 1085; 33% women, 55% black) of individuals with HFrEF who completed a physician-referred cardiopulmonary exercise testing (CPX) between 1997 and 2010. Primary outcome was a composite of all-cause death, left ventricular assist device placement, and orthotopic heart transplant . Logistic and Cox regressions were performed and Kaplan-Meier survival curves were developed to describe relationships of the CPX variables and the composite outcome within and between men and women. RESULTS: All patients were followed-up for a minimum of 5 years, during which there were 643 combined events (62%; 499 deaths, 64 left ventricular assist device implants, 80 orthotopic heart transplant). Each CPX variable was significantly related to event-free survival among both men and women. Log-rank assessment of Kaplan-Meier curves noted survival differences for peak VO2 and VE-VCO2 slope (p ≤ .002), but not ppVO2 (P = .32), between men and women. CONCLUSIONS: Prognostic values for peak VO2 and the VE-VCO2 slope might be considered separately for men and women, whereas the ppVO2 value corresponding to 1- and 3-year survival rates may not be different between the sexes.

Effects of the HEART Camp Trial on Adherence to Exercise in Patients With Heart Failure.

BACKGROUND: Few exercise training studies in patients with heart failure (HF) report adherence to guideline-recommended 150 minutes of moderate-intensity exercise per week, and no studies have focused on a primary outcome of adherence. METHODS AND RESULTS: This randomized controlled trial evaluated the effect of a multicomponent intervention, Heart Failure Exercise and Resistance Training (HEART) Camp, on adherence to exercise (after 6, 12, and 18 months) compared with an enhanced usual care (EUC) group. Patients (n = 204) were 55.4% male, overall average age was 60.4 years, and 47.5% were nonwhite. The HEART Camp group had significantly greater adherence at 12 (42%) and 18 (35%) months compared with the EUC group (28% and 19%, respectively). No significant difference (P > .05) was found at 6 months. The treatment effect did not differ based on patient's age, race, gender, marital status, type of HF (preserved or reduced ejection fraction) or New York Heart Association functional class. Left ventricular ejection fraction (LVEF) significantly moderated the treatment effect, with greater adherence at higher LVEF. CONCLUSIONS: The multicomponent HEART Camp intervention showed efficacy with significant effects at 12 months and 18 months. Adherence levels remained modest, indicating a need for additional research to address methods and strategies to promote adherence to exercise in patients with HF.

Accelerometer-Measured Daily Activity Levels and Related Factors in Patients With Heart Failure.

BACKGROUND: Few studies report objective accelerometer-measured daily physical activity levels in patients with heart failure (HF). OBJECTIVE: We examined baseline accelerometer-measured physical activity from the Heart Failure Exercise and Resistance Training Camp trial, a federally funded (R01-HL112979) 18-month intervention study to promote adherence to exercise in patients with HF. Factors associated with physical activity levels were also explored. METHODS: Patients with diagnosed HF (stage C chronic HF confirmed by echocardiography and clinical evaluation) were recruited from 2 urban medical centers. Physical activity energy expenditure and the number of minutes of moderate or vigorous physical activity (MVPA) were obtained from 7 full days of measurement with the accelerometer (Actigraph Model GT3X, Pensacola, Florida) for 182 subjects who met minimum valid wear time parameters. Additional measures of health-related factors were included to explore the association with physical activity levels. RESULTS: Subjects had 10.2 ± 10.5 minutes of MVPA per day. Total physical activity energy expenditure was 304 ± 173 kcal on average per day. There were 23 individuals (12.6%) who met the recommended goal of 150 minutes of MVPA per week. Men, whites, New York Heart Association class II, and subjects with better physical function had significantly higher levels of activity. CONCLUSIONS: Consistent with previous research, patients with HF are not meeting recommended guidelines for 150 minutes of MVPA per week.

Cardiorespiratory fitness and incident heart failure: The Henry Ford ExercIse Testing (FIT) Project.

BACKGROUND: Prior studies have demonstrated cardiorespiratory fitness (CRF) to be a strong marker of cardiovascular health. However, there are limited data investigating the association between CRF and risk of progression to heart failure (HF). The purpose of this study was to determine the relationship between CRF and incident HF. METHODS: We included 66,329 patients (53.8% men, mean age 55 years) free of HF who underwent exercise treadmill stress testing at Henry Ford Health Systems between 1991 and 2009. Incident HF was determined using International Classification of Diseases, Ninth Revision codes from electronic medical records or administrative claim files. Cox proportional hazards models were performed to determine the association between CRF and incident HF. RESULTS: A total of 4,652 patients developed HF after a median follow-up duration of 6.8 (±3) years. Patients with incident HF were older (63 vs 54 years, P<.001) and had higher prevalence of known coronary artery disease (42.3% vs 11%, P<.001). Peak metabolic equivalents (METs) of task were 6.3 (±2.9) and 9.1 (±3) in the HF and non-HF groups, respectively. After adjustment for potential confounders, patients able to achieve ≥12 METs had an 81% lower risk of incident HF compared with those achieving <6 METs (hazard ratio 0.19 [95% CI 0.14-0.29], P for trend < .001). Each 1 MET achieved was associated with a 16% lower risk (hazard ratio 0.84 [95% CI 0.82-0.86], P<.001) of incident HF. CONCLUSIONS: Our analysis demonstrates that higher level of fitness is associated with a lower incidence of HF independent of HF risk factors.

Socioeconomic and partner status in chronic heart failure: Relationship to exercise capacity, quality of life, and clinical outcomes.

BACKGROUND: Prognosis in patients with heart failure (HF) is commonly assessed based on clinical characteristics. The association between partner status and socioeconomic status (SES) and outcomes in chronic HF requires further study. METHODS: We performed a post hoc analysis of HF-ACTION, which randomized 2,331 HF patients with ejection fraction ≤35% to usual care ± aerobic exercise training. We examined baseline quality of life and functional capacity and outcomes (all-cause mortality/hospitalization) by partner status and SES using adjusted Cox models and explored an interaction with exercise training. Outcomes were examined based on partner status, education level, annual income, and employment. RESULTS: Having a partner, education beyond high school, an income >$25,000, and being employed were associated with better baseline functional capacity and quality of life. Over a median follow-up of 2.5 years, higher education, higher income, being employed, and having a partner were associated with lower all-cause mortality/hospitalization. After multivariable adjustment, lower mortality was seen associated with having a partner (hazard ratio 0.91, 95% CI 0.81-1.03, P=.15) and more than a high school education (hazard ratio 0.91, CI 0.80-1.02, P=.12), although these associations were not statistically significant. There was no interaction between any of these variables and exercise training on outcomes (all P>.5). CONCLUSIONS: Having a partner and higher SES were associated with greater functional capacity and quality of life at baseline but were not independent predictors of long-term clinical outcomes in patients with chronic HF. These findings provide information that may be considered as potential variables impacting outcomes.

Comparison of machine learning techniques to predict all-cause mortality using fitness data: the Henry ford exercIse testing (FIT) project.

BACKGROUND: Prior studies have demonstrated that cardiorespiratory fitness (CRF) is a strong marker of cardiovascular health. Machine learning (ML) can enhance the prediction of outcomes through classification techniques that classify the data into predetermined categories. The aim of this study is to present an evaluation and comparison of how machine learning techniques can be applied on medical records of cardiorespiratory fitness and how the various techniques differ in terms of capabilities of predicting medical outcomes (e.g. mortality). METHODS: We use data of 34,212 patients free of known coronary artery disease or heart failure who underwent clinician-referred exercise treadmill stress testing at Henry Ford Health Systems Between 1991 and 2009 and had a complete 10-year follow-up. Seven machine learning classification techniques were evaluated: Decision Tree (DT), Support Vector Machine (SVM), Artificial Neural Networks (ANN), Naïve Bayesian Classifier (BC), Bayesian Network (BN), K-Nearest Neighbor (KNN) and Random Forest (RF). In order to handle the imbalanced dataset used, the Synthetic Minority Over-Sampling Technique (SMOTE) is used. RESULTS: Two set of experiments have been conducted with and without the SMOTE sampling technique. On average over different evaluation metrics, SVM Classifier has shown the lowest performance while other models like BN, BC and DT performed better. The RF classifier has shown the best performance (AUC = 0.97) among all models trained using the SMOTE sampling. CONCLUSIONS: The results show that various ML techniques can significantly vary in terms of its performance for the different evaluation metrics. It is also not necessarily that the more complex the ML model, the more prediction accuracy can be achieved. The prediction performance of all models trained with SMOTE is much better than the performance of models trained without SMOTE. The study shows the potential of machine learning methods for predicting all-cause mortality using cardiorespiratory fitness data.

Cardiorespiratory Fitness and Risk of Incident Atrial Fibrillation: Results From the Henry Ford Exercise Testing (FIT) Project.

BACKGROUND: Poor cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between CRF and atrial fibrillation (AF) is less clear. The aim of this analysis was to investigate the association between CRF and incident AF in a large, multiracial cohort that underwent graded exercise treadmill testing. METHODS AND RESULTS: From 1991 to 2009, a total of 64 561 adults (mean age, 54.5±12.7 years; 46% female; 64% white) without AF underwent exercise treadmill testing at a tertiary care center. Baseline demographic and clinical variables were collected. Incident AF was ascertained by use of International Classification of Diseases, Ninth Revision code 427.31 and confirmed by linkage to medical claim files. Nested, multivariable Cox proportional hazards models were used to estimate the independent association of CRF with incident AF. During a median follow-up of 5.4 years (interquartile range, 3-9 years), 4616 new cases of AF were diagnosed. After adjustment for potential confounders, 1 higher metabolic equivalent achieved during treadmill testing was associated with a 7% lower risk of incident AF (hazard ratio, 0.93; 95% confidence interval, 0.92-0.94; P<0.001). This relationship remained significant after adjustment for incident coronary artery disease (hazard ratio, 0.92; 95% confidence interval, 0.91-0.93; P<0.001). The magnitude of the inverse association between CRF and incident AF was greater among obese compared with nonobese individuals (P for interaction=0.02). CONCLUSIONS: There is a graded, inverse relationship between cardiorespiratory fitness and incident AF, especially among obese patients. Future studies should examine whether changes in fitness increase or decrease risk of atrial fibrillation. This association was stronger for obese compared with nonobese, especially among obese patients.

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project.

BACKGROUND: Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. METHODS: This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. RESULTS: We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and ß-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. CONCLUSION: These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients.

Response to Exercise Training and Outcomes in Patients With Heart Failure and Diabetes Mellitus: Insights From the HF-ACTION Trial.

BACKGROUND: In HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), exercise training improved functional capacity in heart failure with reduced ejection fraction (HFrEF). Previous studies have suggested that diabetes mellitus (DM) may be associated with an attenuated response to exercise. We explored whether DM attenuated the improvement in functional capacity with exercise. METHODS AND RESULTS: HF-ACTION randomized 2331 patients with HFrEF to medical therapy with or without exercise training over a median follow-up of 2.5 years. We examined the interaction between DM and exercise response measured by change in 6-minute walk distance (6MWD) and peak VO2. We also examined outcomes by DM status. In HF-ACTION, 748 (32%) patients had DM. DM patients had lower functional capacity at baseline and had lower exercise volumes at 3 months. There was a significant interaction between DM status and exercise training for change in peak VO2 (interaction P = .02), but not 6MWD. In the exercise arm, DM patients had a smaller mean increase in peak VO2 than non-DM patients (P = .03). There was no interaction between DM and exercise on clinical outcomes. After risk adjustment, DM was associated with increased all-cause mortality/hospitalization (P = .03). CONCLUSIONS: In HF-ACTION, DM was associated with lower baseline functional capacity, an attenuated improvement in peak VO2, and increased hospitalizations.

Cardiorespiratory fitness attenuates risk for major adverse cardiac events in hyperlipidemic men and women independent of statin therapy: The Henry Ford ExercIse Testing Project.

AIMS: We sought to evaluate the effect of cardiorespiratory fitness (CRF) in predicting mortality, myocardial infarction (MI), and revascularization in patients with hyperlipidemia after stratification by gender and statin therapy. METHODS AND RESULTS: This retrospective cohort study included 33,204 patients with hyperlipidemia (57 ± 12 years old, 56% men, 25% black) who underwent physician-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were stratified by gender, baseline statin therapy, and estimated metabolic equivalents from stress testing. We computed hazard ratios using Cox regression models after adjusting for demographics, cardiac risk factors, comorbidities, pertinent medications, interaction terms, and indication for stress testing. RESULTS: There were 4,851 deaths, 1,962 MIs, and 2,686 revascularizations over a median follow-up of 10.3 years. In men and women not on statin therapy and men and women on statin therapy, each 1-metabolic equivalent increment in CRF was associated with hazard ratios of 0.86 (95% CI 0.85-0.88), 0.83 (95% CI 0.81-0.85), 0.85 (95% CI 0.83-0.87), and 0.84 (95% CI 0.81-0.87) for mortality; 0.93 (95% CI 0.90-0.96), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.86-0.92), and 0.90 (95% CI 0.86-0.95) for MI; and 0.91 (95% CI 0.88-0.93), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.87-0.92), and 0.90 (95% CI 0.86-0.94) for revascularization, respectively. No significant interactions were observed between CRF and statin therapy (P > .23). CONCLUSION: Higher CRF attenuated risk for mortality, MI, and revascularization independent of gender and statin therapy in patients with hyperlipidemia. These results reinforce the prognostic value of CRF and support greater promotion of CRF in this patient population.

Authorship in a multicenter clinical trial: The Heart Failure-A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) Authorship and Publication (HAP) scoring system results.

BACKGROUND: Few guidelines exist regarding authorship on manuscripts resulting from large multicenter trials. The HF-ACTION investigators devised a system to address assignment of authorship on trial publications and tested the outcomes in the course of conducting the large, multicenter, National Heart, Lung, and Blood Institute-funded trial (n = 2,331; 82 clinical sites; 3 countries). The HF-ACTION Authorship and Publication (HAP) scoring system was designed to enhance rate of dissemination, recognize investigator contributions to the successful conduct of the trial, and harness individual expertise in manuscript generation. METHODS: The HAP score was generated by assigning points based on investigators' participation in trial enrollment, follow-up, and adherence, as well as participation in committees and other trial activity. Overall publication rates, publication rates by author, publication rates by site, and correlation between site publication and HAP score using a Poisson regression model were examined. RESULTS: Fifty peer-reviewed, original manuscripts were published within 6.5 years after conclusion of study enrollment. In total, 137 different authors were named in at least 1 publication. Forty-five (55%) of the 82 sites had an author named to at least 1 article. A Poisson regression model examining incident rate ratios revealed that a higher HAP score resulted in a higher incidence of a manuscript, with a 100-point increase in site score corresponding to an approximately 32% increase in the incidence of a published article. CONCLUSIONS: Given the success in publishing a large number of manuscripts and widely distributing authorship, regular use of a transparent, objective authorship assignment system for publishing results from multicenter trials may be recommended to optimize fairness and dissemination of trial results.