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Objective To examine the effect of objectively measured exercise capacity (EC) on early mortality (EM) after a first myocardial infarction (MI). Patients and Methods This retrospective cohort study included 2061 patients without a history of MI (mean age, 62±12 years; 38% [n=790] women; 56% [n=1153] white) who underwent clinical treadmill stress testing in the Henry Ford Health System from January 1, 1991, through May 31, 2009, and suffered MI during follow-up (MI event proportion, 3.4%; mean time from the exercise test to MI, 6.1±4.3 years). Exercise capacity was categorized on the basis of peak metabolic equivalents (METs) achieved: less than 6, 6 to 9, 10 to 11, and 12 or more METs. Early mortality was defined as all-cause mortality within 28, 90, or 365 days of MI. Multivariable logistic regression models were used to assess the effect of EC on the risk of mortality at each time point post-MI adjusting for baseline demographic characteristics, cardiovascular risk factors, medication use, indication for stress testing, and year of MI. Results The 28-day EM rate was 10.6% overall, and 13.9%, 10.7%, 6.9%, and 6.0% in the less than 6, 6 to 9, 10 to 11, and 12 or more METs categories, respectively ( P P P =.006; 90 days: OR, 0.90; 95% CI, 0.86-0.95; P P Conclusion Higher baseline EC was independently associated with a lower risk of early death after a first MI.

Objective Given the aging population and prevalence of sedentary behaviour in the USA, we investigated the impact of differences in exercise capacity associated with age on long-term outcomes. We derived fitness-associated ‘biologic age’ as a tool to encourage positive lifestyle changes. Methods This retrospective cohort study included 57 085 patients without established coronary artery disease or heart failure (median age 53 years, 49% women, 29% black) who underwent clinically-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were followed for 10.4±5 and 5.4±4 years for all-cause mortality and myocardial infarction (MI), respectively. We calculated hazard ratios associated with exercise capacity by age deciles using Cox regression models, adjusting for demographic and haemodynamic data, medical history, and medication use. Fitness-associated ‘biologic age’ was derived as the chronologic age with equivalent mortality or MI risk. Results There were 6356 deaths and 1646 MIs during follow-up. Exercise capacity declined with increasing age. Higher exercise capacity was strongly associated with greater survival, with per-MET HR ranging from 0.82 (95% CI 0.78 to 0.86) in patients under 40 years of age, to 0.88 (95% CI 0.87 to 0.90) in those over 70 years of age. Biologic age varied markedly—up to three decades—within each age decile, and was a stronger predictor of mortality (C-statistic 0.81 vs 0.77) and MI (C-statistic 0.72 vs 0.68) than chronologic age. Conclusions Higher exercise capacity remained a powerful predictor of survival despite lower average exercise capacity at older ages, reinforcing its importance in patients of all ages. Fitness-associated biologic age was a stronger predictor of survival than chronologic age, and may be a useful clinical tool for facilitating patient discussions regarding the impact of exercise capacity on long-term risk.

Decreases in systolic blood pressure during exercise may predispose to arrhythmias such as atrial fibrillation (AF) because of underlying abnormal autonomic tone. We examined the association between systolic blood pressure response and incident AF in 57,442 (mean age 54 ± 13 years, 47% women, and 29% black) patients free of baseline AF who underwent exercise treadmill stress testing from the Henry Ford ExercIse Testing project. Exercise systolic blood pressure response was examined as a categorical variable across clinically relevant categories (>20 mm Hg: referent; 1 to 20 mm Hg, and ≤0 mm Hg) and per 1-SD decrease. Cox regression, adjusting for demographics, cardiovascular risk factors, medications, history of coronary heart disease, history of heart failure, and metabolic equivalent of task achieved, was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between systolic blood pressure response and incident AF. Over a median follow-up of 5.0 years, a total of 3,381 cases (5.9%) of AF were identified. An increased risk of AF was observed with decreasing systolic blood pressure response (>20 mm Hg: HR 1.0, referent; 1 to 20 mm Hg: HR 1.09, 95% CI 0.99, 1.20; ≤0 mm Hg: HR 1.22, 95% CI 1.06 to 1.40). Similar results were obtained per 1-SD decrease in systolic blood pressure response (HR 1.08, 95% CI 1.04 to 1.12). The results were consistent when stratified by age, sex, race, hypertension, and coronary heart disease. In conclusion, our results suggest that a decreased systolic blood pressure response during exercise may identify subjects who are at risk for developing AF.

Background: Cardiorespiratory fitness (CRF) is associated with a reduction in both cancer- and cardiovascular-specific mortality. In men however, little is known about the impact of pre-diagnostic CRF on mortality after prostate cancer. We hypothesized that among men with prostate cancer, low levels of CRF, measured prior to diagnosis, are associated with a higher risk of all-cause mortality. Methods: From the Henry Ford FIT Project, a cohort of 37,730 men who underwent clinically-indicated exercise stress test from 1991 through 2009, we identified 1,440 men who developed prostate cancer after stress test. CRF was measured in peak metabolic equivalents of task (METs) and categorized as less than 6, 6 to 9, 10 to 11, and at least 12 (reference). Multivariable Cox proportional hazard models were developed to evaluate the association between CRF, measured prior to prostate cancer diagnosis, and all-cause mortality. Models were adjusted for age at prostate cancer diagnosis (baseline), race, BMI, current aspirin and statin use, smoking history, hypertension, diabetes, prior cardiovascular disease (myocardial infarction and heart failure), time from stress test to prostate cancer diagnosis, and cancer stage (local, regional, distant) at diagnosis. Results: Mean age at time of stress test was 61 +/- 9 yr (57% white, 39% black), with 7 (+/-4) yrs of follow up after prostate cancer diagnosis. 81% of men were diagnosed with localized prostate cancer; 15% with regional disease, and 2% with distant metastatic disease. Mean time from stress test to diagnosis was 6 +/- 5 yrs. Mean METs achieved was 9 (+/- 3). Patients with low fitness (METs less than 6) before diagnosis had 2.6 times the risk of all-cause mortality (95% CI 1.6-4.2) compared to those with high fitness (METS at least 12). Those with CRF of 6-9 METs had 1.9 times the risk (95% CI 1.2-3.0). The risk of mortality was not different between the two highest fitness groups (P= 0.71; P for trend across all fitness groups less than 0.01). Results were similar when stratified by race. Conclusion: Low CRF prior to the diagnosis of prostate cancer in men is associated with a higher risk of all-cause mortality. This study highlights the prognostic importance of fitness even before a cancer diagnosis. Citation Format: Cara Reiter-Brennan, Omar Dzaye, Mouaz H. Al-Mallah, Zeina Dardari, Clinton A. Brawner, Lois E. Lamerato, Steven J. Keteyian, Jonathan K. Ehrman, Kala Visvanathan, Michael J. Blaha, Catherine Handy Marshall. Cardiorespiratory fitness levels in men who develop prostate cancer and its association with all-cause mortality [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4348.

Background: High levels of cardiorespiratory fitness (CRF) have been associated with a decreased risk of many cancers, but the association with prostate cancer (PCa) is less clear. A possible explanation for the lack of consistency is that prostate specific antigen (PSA) screening and in turn prostate cancer detection is more frequent in men with higher fitness although the relationship between fitness and PSA screening is not established. Methods: The Henry Ford (HF) FIT Project is a retrospective cohort study of 69,894 consecutive patients who underwent physician-referred exercise stress testing from 1991 through 2009. Cancer diagnosis was identified through linkage to the HF tumor registry. We included men aged 40-70 yr who had CRF testing beginning in 1995 (when PSA screening became widespread), without prevalent cancer, followed at least 3 yrs and up to 10 years, who never develop prostate cancer (n=12,442). CRF was measured in metabolic equivalents of task (METs) and categorized as less than 6 (ref), 6-9, 10-11, and at least 12. PSA values were abstracted from the HF electronic medical record between 1995 and 2010. Individuals with at least 3 screening PSA tests were categorized as high screeners. Logistic regression was used to evaluate the relationship between CRF and high PSA screeners, adjusted for age at stress test and race. Results: Participants had a mean age of 54 ± 8 yrs (67% white; 25% black) and mean follow-up was 7±2 yrs. Compared to individuals with low fitness (less than 6 METs, reference), those with higher fitness (6-9, 10-11, at least 12 METs) had higher odds of being a high PSA screener (Table). When stratified by race, the OR for black patients were not statistically different than white patients (Table). Results were similar among those with comorbidities (myocardial infarction, heart failure, or diabetes) at baseline. Odds ratio of being a high screener (at least 3 PSA tests) in individuals followed 3-10 yearsMETs categoryAll (n=12,442Whites (n=8,356Blacks (n=3,049)Patients w/comorbidities (n=3,924)=122.4 (2.1-2.9)2.5(2.0-3.1)2.1(1.6-2.8)3.2(2.5-4.0) Conclusion: High CRF is associated with more frequent PSA screening. This points towards a healthy screening bias and should be accounted for in studies looking at fitness and incident prostate cancer. Citation Format: Cara Reiter-Brennan, Omar Dzaye, Mouaz H. Al-Mallah, Zeina Dardari, Clinton A. Brawner, Lois E. Lamerato, Steven J. Keteyian, Jonathan K. Ehrman, Kala Visvanathan, Michael J. Blaha, Catherine Handy Marshall. Cardiorespiratory fitness and PSA screening patterns in the Henry Ford FIT Project [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5773.

7060 Background: The obesity paradox –i.e. inverse associations between body mass index (BMI) and mortality – has been reported in patients with cancer, heart failure, and diabetes. However, the influence of cardiorespiratory fitness (CRF) on this relationship is not well established. This study assesses the association of BMI and CRF with all-cause mortality among cancer patients. Methods: The Henry Ford (HF) FIT Project is a retrospective cohort study of 69,885 consecutive patients who underwent physician-referred exercise stress testing from 1991 through 2009. Cancer diagnosis was identified through linkage to the HF tumor registry. We included patients 40-70 years old, with BMI recorded, at time of exercise test, with a history of cancer > 6 months prior. BMI was categorized as normal (18.5-24.9kg/m2), overweight (25-29.9kg/m2), or obese ( > = 30kg/m2). All-cause mortality was obtained from the National Death Index. Because of a significant interaction between BMI and cancer type, patients with breast or prostate cancer were excluded. Multivariable adjusted Cox proportional hazard models were used to evaluate the association of CRF andBMI with all-cause mortality; adjusted for age at exercise test, sex, diabetes, smoking, cancer stage, and time from cancer diagnosis to exercise test. Results: Included were 676 patients with a mean age of 58 years (SD 7.5), 51% female, 70% White, 25% Black, with a median of 4.8 years from diagnosis to exercise test and median follow up time of 10.3 years. Among patients achieving < 10 METs, those who are overweight and obese had a lower risk of mortality HR 0.47 (95% CI 0.25,0.86) and HR 0.44 (95% CI 0.26, 0.74, respectively), compared to those with normal BMI. Among patients with METs > = 10, those who were overweight had the lowest risk of all-cause mortality (HR 0.23, 95% CI 0.09-0.62) compared to normal weight, while no statistically significant different risk of mortality was observed when comparing those who are obese to normal weight (HR 0.37, 95% CI 0.13-1.06). In an analysis combining BMI and fitness groups (four categories), those with BMI > = 25 and METs > = 10 had the lowest risk of all-cause mortality (Table). Conclusions: In non-breast/non-prostate cancer patients, increased BMI is associated with improved overall survival in those with METs < 10, while a U-shaped relationship between BMI and all-cause mortality exists among those with METs > = 10. [Table: see text]

Heart failure (HF) is a morbid condition associated with impaired exercise capacity. Exercise training is an effective strategy to improve functional capacity and quality of life. However, response to exercise training is highly variable and whether there are genetic factors that may impact response

BACKGROUND: Exercise capacity is associated with survival in the general population. Whether this applies to patients with treated depression is not clear. HYPOTHESIS: High exercise capacity remains associated with lower risk of all‐cause mortality (ACM) and nonfatal myocardial infraction (MI) among patients with treated depression. METHODS: We included 5128 patients on antidepressant medications who completed a clinically indicated exercise stress test between 1991 and 2009. Patients were followed for a median duration of 9.4 years for ACM and 4.5 years for MI. Exercise capacity was estimated in metabolic equivalents of tasks (METs). Cox proportional hazards regression models were used. RESULTS: Patients with treated depression who achieved ≥12 METs (vs those achieving

Advanced Exercise Physiology: Essential Concepts and Applications builds upon foundational topics and looks further into key physiological components to help advanced students gain a deeper level of understanding. Authors Jonathan K. Ehrman, Dennis J. Kerrigan, and Steven J. Keteyian address a wide range of complex topics with evidence-based information and a focused, targeted style. The first five chapters offer a detailed examination of the various body systems. The next two chapters focus on exercise testing and training principles, as well as training adaptations as they relate to aerobic power, anaerobic power, range of motion, and resistance training of healthy individuals and competitive athletes. The remaining chapters focus on a variety of topics, including athletic performance, body composition and weight management, and environmental influences of exercise physiology. The final two chapters bring a unique perspective to the book with a review of the relationship between exercise physiology and public health and a look at recent and emerging topics in the field, including genomics and pharmacology. Enhancing the content are learning aids, more than 140 images and illustrations, and practical examples from among clinical patients, healthy individuals, and competitive athletes. Key terms and their definitions appear at the end of each chapter; these help students understand key concepts and serve as a useful reference for practitioners. The appendixes contain information related to topics such as efficiency and energy expenditure, metabolic equivalent (MET) values of common activities, and the professionalization of exercise physiology.

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).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.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.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 levels3.5 METs identifies patients that might benefit from closer clinical surveillance and reinforced adherence to medical and lifestyle preventive strategies.

OBJECTIVE Prior evidence has linked higher cardiorespiratory fitness with a lower risk of diabetes in ambulatory populations. Using a demographically diverse study sample, we examined the association of fitness with incident diabetes in 46,979 patients from The Henry Ford ExercIse Testing (FIT) Project without diabetes at baseline. RESEARCH DESIGN AND METHODS Fitness was measured during a clinician-referred treadmill stress test performed between 1991 and 2009. Incident diabetes was defined as a new diagnosis of diabetes on three separate consecutive encounters derived from electronic medical records or administrative claims files. Analyses were performed with Cox proportional hazards models and were adjusted for diabetes risk factors. RESULTS The mean age was 53 years with 48% women and 27% black patients. Mean metabolic equivalents (METs) achieved was 9.5 (SD 3.0). During a median follow-up period of 5.2 years (interquartile range 2.6–8.3 years), there were 6,851 new diabetes cases (14.6%). After adjustment, patients achieving ≥12 METs had a 54% lower risk of incident diabetes compared with patients achieving CONCLUSIONS These data demonstrate that higher fitness is associated with a lower risk of incident diabetes regardless of demographic characteristics and baseline risk factors. Future studies should examine the association between change in fitness over time and incident diabetes.

Objectives This study examined the effects of a cardiac rehabilitation (CR) program on functional capacity and health status (HS) in patients with newly implanted left ventricular assist devices (LVADs). Background Reduced functional capacity and HS are independent predictors of mortality in patients with heart failure. CR improves both, and is related to improved outcomes in patients with heart failure; however, there is a paucity of data that describe the effects of CR in patients with LVADs. Methods Enrolled subjects (n = 26; 7 women; age 55 ± 13 years; ejection fraction 21 ± 8%) completed a symptom-limited cardiopulmonary exercise test, the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 6-min walk test (6MW), and single-leg isokinetic strength test before 2:1 randomization to CR versus usual care. Subjects in the CR group underwent 18 visits of aerobic exercise at 60% to 80% of heart rate reserve. Within-group changes from baseline to follow-up were analyzed with a paired t-test, whereas an independent t-test was used to determine differences in the change between groups. Results Within-group improvements were observed in the CR group for peak oxygen uptake (10%), treadmill time (3.1 min), KCCQ score (14.4 points), 6MW distance (52.3 m), and leg strength (17%). Significant differences among groups were observed for KCCQ, leg strength, and total treadmill time. Conclusions Indicators of functional capacity and HS are improved in patients with continuous-flow LVADs who attend CR. Future trials should examine the mechanisms responsible for these improvements, and if such improvements translate into improved clinical outcomes. (Cardiac Rehabilitation in Patients With Continuous Flow Left Ventricular Assist Devices:Rehab VAD Trial [RehabVAD]; NCT01584895 )

High exercise capacity (EC) has been associated with a lower risk of incident diabetes, whereas statin therapy has been associated with a higher risk. We sought to investigate whether the association between EC and diabetes risk is modified by statin therapy. This retrospective cohort study included 47,337 patients without diabetes or coronary artery disease at baseline (age 53 ± 13 years, 48% women, 66% white) who underwent clinical treadmill stress testing within the Henry Ford Health System from January 1, 1991, to May 31, 2009. The patients were stratified by baseline statin use and estimated peak METs achieved during exercise testing. Hazard ratios for incident diabetes were calculated using Cox proportional hazards models adjusted for demographic characteristics, co-morbidities, pertinent medications, and stress test indication. We observed 6,921 new diabetes cases (14.6%) over a median follow-up period of 5.1 years (interquartile interval of 2.6 to 8.2 years). Compared with the statin group, the no-statin group achieved higher mean METs (8.9 ± 2.7 vs 9.6 ± 3.0, respectively; p 0.001). After adjustment for covariates, a higher EC was associated with a lower risk of incident diabetes, irrespective of statin use (p-interaction = 0.15). Each 1-MET increment was associated with an 8%, 8%, and 6% relative risk reduction in the total cohort, the no-statin, and the statin groups, respectively (95% confidence interval, 0.91 to 0.93, 0.91 to 0.93, and 0.91 to 0.96, respectively; p 0.001 for all). We conclude that a higher EC is associated with a lower risk of incident diabetes regardless of statin use.

PURPOSE: We tested the hypothesis that higher-intensity interval training (HIIT) could be deployed into a standard cardiac rehabilitation (CR) setting and would result in a greater increase in cardiorespiratory fitness (ie, peak oxygen uptake, ) versus moderate-intensity continuous training (MCT). METHODS: Thirty-nine patients participating in a standard phase 2 CR program were randomized to HIIT or MCT; 15 patients and 13 patients in the HIIT and MCT groups, respectively, completed CR and baseline and followup cardiopulmonary exercise testing. RESULTS: No patients in either study group experienced an event that required hospitalization during or within 3 hours after exercise. The changes in resting heart rate and blood pressure at followup testing were similar for both HIIT and MCT. at ventilatory-derived anaerobic threshold increased more (P < .05) with HIIT (3.0 +/- 2.8 mL[middle dot]kg[middle dot]-1min-1) versus MCT (0.7 +/- 2.2 mL[middle dot]kg[middle dot]-1min-1). During followup testing, submaximal heart rate at the end of stage 2 of the exercise test was significantly lower within both the HIIT and MCT groups, with no difference noted between groups. Peak V[spacing dot above]o2 improved more after CR in patients in HIIT versus MCT (3.6 +/- 3.1 mL[middle dot]kg.-1[middle dot]min-1 vs 1.7 +/- 1.7 mL[middle dot]kg.-1[middle dot]min-1; P < .05). CONCLUSIONS: Among patients with stable coronary heart disease on evidence-based therapy, HIIT was successfully integrated into a standard CR setting and, when compared to MCT, resulted in greater improvement in peak exercise capacity and submaximal endurance.

The Making Effective Nutritional Choices Generation Y (MENU GenY) study is a web-based intervention trial aimed at improving food choices in those aged 21-30 years. We report baseline levels of the 5-2-1-0 healthy lifestyle patterns to predict a body mass index (BMI) ≥30 vs 3 daily servings of fruits/vegetables (odds ratio, OR = 0.90, 95% confidence interval, CI = 0.81, 0.99), and reporting >2.5 hours/week of vigorous physical activity (OR = 0.93, 95% CI = 0.89-0.96, P < 0.001) was associated with a BMI

Cardiorespiratory fitness (CRF) is a strong predictor of mortality and coronary heart disease. This study further examines the association between CRF and incident stroke types. We studied a retrospective cohort of 67,707 patients referred for treadmill stress testing in the Henry Ford Health

Traditional cardiovascular disease (CVD) risk factors have a decreased predictive strength with increasing age. We sought to determine if fitness could improve risk stratification among older adults at the extremes of CVD risk factor burden. We studied 6,509 patients ≥70 years of age without CVD

Background— Outpatient cardiac rehabilitation (CR) decreases mortality rates but is underutilized. Current median time from hospital discharge to enrollment is 35 days. We hypothesized that an appointment within 10 days would improve attendance at CR orientation. Methods and Results— At hospital discharge, 148 patients with a nonsurgical qualifying diagnosis for CR were randomized to receive a CR orientation appointment either within 10 days (early) or at 35 days (standard). The primary end point was attendance at CR orientation. Secondary outcome measures were attendance at ≥1 exercise session, the total number of exercise sessions attended, completion of CR, and change in exercise training workload while in CR. Average age was 60±12 years; 56% of participants were male and 49% were black, with balanced baseline characteristics between groups. Median time (95% confidence interval) to orientation was 8.5 (7–13) versus 42 (35 to NA [not applicable]) days for the early and standard appointment groups, respectively ( P P =0.022). The number needed to treat was 5.7. There was no difference ( P >0.05) in any of the secondary outcome measures, but statistical power for these end points was low. Safety analysis demonstrated no difference between groups in CR-related adverse events. Conclusions— Early appointments for CR significantly improve attendance at orientation. This simple technique could potentially increase initial CR participation nationwide. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01596036.

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.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.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 achieving6 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.Our analysis demonstrates that higher level of fitness is associated with a lower incidence of HF independent of HF risk factors.

PURPOSE There is an inverse relationship between phase 2 cardiac rehabilitation (CR) visits and all-cause mortality. Phase 3 CR is a maintenance exercise program for which clinical outcomes are uncertain. This retrospective study describes the association between phase 3 CR participation and clinical events among patients with ischemic heart disease after completion of phase 2 CR. METHODS Patients who completed 12 visits of phase 2 CR as provided by their health insurance were categorized on the basis of their frequency of participation (ie, none, irregular, and regular) in phase 3 CR during the 8 weeks after phase 2 CR. Cox regression analysis was used to evaluate the association between phase 3 CR participation and risk for a composite outcome that included all-cause mortality, nonfatal myocardial infarction, or heart failure hospitalization. RESULTS Among 2039 patients (32% women; age = 59 ± 10 years) who completed phase 2 CR, 101 were regular and 129 were irregular participants of phase 3 CR. Over a median followup of 5.6 years, 556 (27%) patients experienced the outcome. Neither irregular nor regular participation in phase 3 CR was significantly associated with risk for the outcome in unadjusted (P = .671 and P = .396, respectively) or adjusted (P = .737 and P = .890, respectively) analyses. CONCLUSIONS We did not observe an incremental clinical benefit from weekly participation in Phase 3 CR after completion of phase 2 CR among patients with ischemic heart disease. Additional research addressing the dose-response relationship between phase 2 and 3 CR and clinical outcomes is needed.

To describe the relationship between change in maximal exercise capacity (MEC) over time and risk of all-cause mortality separately in men and women.Consecutive patients (n=10,854; mean ± SD age, 54±11 years; 43% women; 30% nonwhite) who completed 2 physician-referred exercise tests between January 2, 1991, and May 28, 2009, were identified from the Henry Ford Exercise Testing (FIT) Project. The MEC was quantified in metabolic equivalents of task (METs) calculated from peak workload on a treadmill and adjusted to the equivalent for a 50-year-old man. Multivariable Cox proportional hazards regression was performed to assess risk of all-cause mortality associated with change in MEC based on (1) change from age-/sex-adjusted low fitness (8 METs) to intermediate or high fitness and (2) an absolute change in METs.Relative to patients with low fitness at both tests, increasing from low to intermediate or high fitness was associated with lower risk of all-cause mortality (adjusted hazard ratio [aHR] = 0.63 [95% CI, 0.45-0.87] in men and 0.56 [95% CI, 0.34-0.91] in women). Each 1-MET increase in age-/sex-adjusted MEC between baseline and follow-up was associated with an aHR of 0.87 (95% CI, 0.84-0.91) in men and 0.84 (95% CI, 0.79-0.89) in women, with no significant interaction by sex (P=.995). Similar aHRs were observed in a subgroup with intermediate fitness at baseline.In men and women referred for an exercise stress test, change in MEC over time is inversely related to risk of all-cause mortality.

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 (VO 2 ), percent predicted maximum oxygen uptake (ppMVO 2 ), minute ventilation to carbon dioxide production slope (V E /VCO 2 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 β-blockade therapy, ppMVO 2 was the strongest predictor of the end point (Wald χ 2 = 15.0, hazard ratio per 10%, P 2 (Wald χ 2 = 11.8, P = .001). V E /VCO 2 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 VO 2 and ppMVO 2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients.

Background Clinical trialists involved in projects aimed at assessing the impact of a device or therapy on exercise capacity must select an end point that can detect a therapy-derived change and do so in a manner that is both sensitive to the change and valid. Using baseline data from the Prospective Evaluation of Elastic Restraint to Lessen the Effects of Heart Failure (PEERLESS-HF) trial, we describe the coefficient of variation (CV) for peak oxygen uptake ( o 2 ) and other parameters measured during a cardiopulmonary exercise (CPX) test. Methods Prior to conducting CPX testing, a CPX core laboratory conducted training with testing staff at each site, and a standardized quality assurance protocol was completed. During screening, subjects performed two symptom-limited CPX tests (CPX-0 and CPX-1) within 14 days. Results The CVs for peak o 2 , ventilatory efficiency, and ventilatory-derived anaerobic threshold were 5.9%, 4.8%, and 6.8%, respectively. During CPX-0, the percentage of subjects with a respiratory exchange ratio (RER) o 2 by ≥ 6% during CPX-1 was 47%, compared with 12% of subjects also with an RER o 2 ≥ 6%. Conclusions In a multisite clinical trial setting, we showed that the achieved test-retest reproducibility for peak o 2 can be acceptable, as evidenced by a CV at 5.9%. Until more data are available to identify patients who may demonstrate greater test-retest variance and to avoid repeat testing in all subjects at baseline, clinical trialists might consider repeating tests when RER Trial registration clinicaltrials.gov ; Identifier: NCT00382863

1502Background: Cardiorespiratory fitness (CRF), an objective measure of exercise tolerance, is a strong predictor of cardiovascular disease and mortality yet its relationship with cancer incidence...

It is unknown if contemporary preventive treatments such as statins or primary percutaneous coronary intervention in patients with coronary heart disease (CHD) have rendered obsolete the use of measured exercise capacity for assessment of future risk and prognosis. Using a sample of patients from 2 clinical sites, most of whom were taking beta-blockade, antiplatelet, and statin therapy, we hypothesized that peak oxygen consumption (Vo(2)) would remain a strong and independent predictor of all-cause and cardiovascular-specific mortality in men and women with CHD.We studied 2,812 patients with CHD between 1996 and 2004. All-cause and cardiovascular disease-specific mortality served as end points.In all men and women and in a subgroup of patients following evidence-based care, peak Vo(2) remained a strong predictor of all-cause death, with every 1 mL x kg(-1) x min(-1) increase in peak Vo(2) associated with an approximate 15% decrease in risk of death. Among men, a peak Vo(2) (mL x kg(-1) x min(-1)) below approximately 15 was associated with the highest risk, whereas a peak Vo(2) above approximately 19 was associated with a low rate and risk for annual all-cause mortality. Among women, a peak Vo(2) below approximately 12 was associated with the highest risk, whereas a peak Vo(2) above approximately 16.5 was associated with the lowest rate and risk for annual all-cause mortality.In men and women with CHD, peak Vo(2) remains an independent predictor of all-cause and cardiovascular-specific mortality.

Background: Chronic kidney disease (CKD) is associated with high morbidity and mortality. We tested the hypothesis that cardiorespiratory fitness (CRF) retains incremental prognostic value over renal function, as measured by estimated glomerular filtration rate (eGFR). Methods: Our analysis included 50,121 patients (mean age 55 ± 12.6 years and 47.5% females) from The Henry Ford Exercise Testing Project (FIT project), who underwent exercise stress testing between 1991 and 2009. Patients with heart failure or missing relevant covariate data were excluded. The mean duration between stress testing and creatinine measurement was 30 days and eGFR was estimated using the Modification of Diet in Renal Disease equation. Treadmill stress testing used the standard Bruce protocol and CRF was estimated using metabolic equivalent of task units (MET). Patients were followed-up for all-cause mortality. Multiple nested Cox models were used to determine the incremental prognostic value of CRF over eGFR. Results: The magnitude of renal dysfunction was inversely associated with (level of CRF (mean METs achieved 9.1, 9.0, 7.5, 5.5 METS for Stage I, II, III and more than III CKD respectively, p Conclusion: Regardless of renal function, CRF is an independent predictor of mortality. Fitness adds incremental prognostic value over renal function in this large diverse clinical cohort.

Background: Cardiorespiratory fitness (CRF) is inversely related to all-cause mortality and cardiovascular-related morbidity and mortality. However, there is limited data describing whether change in CRF is associated with improved outcomes. Hypothesis: Change in CRF between two clinical exercise stress tests is related to risk of all-cause mortality. Methods: In this retrospective, observational study, we identified 14,305 patients (age = 55 ± 11 y; 39% women; 30% non-white) who completed two clinically-indicated exercise tests that were at least 12 mo apart between 1991 and 2009 within the Henry Ford Health System. CRF was quantified in metabolic equivalents of task (METs) estimated from peak treadmill speed and grade. All-cause mortality was identified through April 2013 using the Social Security Death Index. Cox regression analysis was used to evaluate the risk of mortality associated with change in CRF between tests 1 and 2. Change in CRF was analyzed as the change in categorization between Poor Fitness ( Results: The mean time between test 1 and 2 was 4.3 ± 2.8 y. During 9.4 ± 3.9 y of follow-up after test 2, there were 1,980 (14%) deaths. Adjusted Cox regression results are shown in the Table. Among all patients, each 1 MET increase in CRF at test 2 was associated with a 5% lower risk of mortality (hazard ratio 95% confidence interval 0.94, 0.97; p < 0.001). Conclusions: Among men and women referred for a clinical exercise test, change in CRF from Poor Fitness to Fit is associated with a 38% lower risk of all-cause mortality relative to patients who remain Unfit. These data support the importance of improving CRF and the clinical utility of serial assessments of CRF in risk assessment.

Background: Cardiorespiratory fitness (CRF) and chronotropic incompetence (CI) have both been associated with increased all - cause mortality. We tested the hypothesis that the association of CI with all - cause mortality is modified by a CRF level above and below 10 metabolic equivalents of task (METs). Methods: We included 43,402 patients who completed a clinical exercise stress test between 1991 and 2009. Patients on AV nodal blocking agents, antiarrhythmics and with known coronary artery disease/heart failure were excluded. Patients were followed-up for a mean duration of 11.5±5.2 years for all-cause mortality ascertained by a search of the social security death index in April 2013. CRF was estimated in metabolic equivalents of task (METs). Cox proportional hazards regression models were used to assess the risk of all - cause mortality associated with CI with adjustments for confounders. Results: Compared to no CI, patients with CI were older (51±12 vs. 54±13 years), less often white (68% vs. 58%), dyslipidemic (41% vs. 37%) and more likely to be hypertensive (46% vs. 60%), diabetic (15% vs. 22%), and smoke (40% vs. 51%). On average, patients with CI had lower CRF (9.8±2.8 vs. 7.4±3.0, p Conclusions: This study demonstrates that CRF attenuates the mortality risk associated with CI. In addition, patients with CI in the presence of CRF ≥ 10 METs have a much lower risk than patients with CI and lower CRF.

BackgroundData 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.ObjectivesThe 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).MethodsAmong 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.ResultsOver 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 5.3ml·kg(-1)·min(-1) in women.ConclusionsPeak 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).

To examine the effect of objectively measured exercise capacity (EC) on early mortality (EM) after a first myocardial infarction (MI).This retrospective cohort study included 2061 patients without a history of MI (mean age, 62±12 years; 38% [n=790] women; 56% [n=1153] white) who underwent clinical treadmill stress testing in the Henry Ford Health System from January 1, 1991, through May 31, 2009, and suffered MI during follow-up (MI event proportion, 3.4%; mean time from the exercise test to MI, 6.1±4.3 years). Exercise capacity was categorized on the basis of peak metabolic equivalents (METs) achieved: less than 6, 6 to 9, 10 to 11, and 12 or more METs. Early mortality was defined as all-cause mortality within 28, 90, or 365 days of MI. Multivariable logistic regression models were used to assess the effect of EC on the risk of mortality at each time point post-MI adjusting for baseline demographic characteristics, cardiovascular risk factors, medication use, indication for stress testing, and year of MI.The 28-day EM rate was 10.6% overall, and 13.9%, 10.7%, 6.9%, and 6.0% in the less than 6, 6 to 9, 10 to 11, and 12 or more METs categories, respectively (P.001). Patients who died were more likely to be older, be less fit, be nonobese, have treated hypertension, and have a longer duration from baseline to incident MI (P.05). Adjusted regression analyses revealed a decreased risk of EM with increasing EC categories. A 1-MET higher EC was associated with an 8% to 10% lower risk of mortality across all time points (28 days: odds ratio [OR], 0.92; 95% CI, 0.87-0.98; P=.006; 90 days: OR, 0.90; 95% CI, 0.86-0.95; P.001; 365 days: OR, 0.91; 95% CI, 0.87-0.94; P.001).Higher baseline EC was independently associated with a lower risk of early death after a first MI.

AIM: To describe the effect of the duration of the data averaging interval on the calculated peak oxygen uptake (VO2) reported from a symptom-limited maximal exercise test in patients with heart failure. METHODS: Maximal exercise test results from 275 patients diagnosed with stable heart failure due to left ventricular systolic dysfunction (ejection fraction1.05 to be +0.8±0.7mL/kg/min higher than those who had not achieved RER values>1.05; similar findings, +0.8±0.7mL/kg/min, were seen in those patients achieving RER>1.10 versus those who did not. CONCLUSIONS: Sampling rate method has a significant effect on calculated peak VO2 and RER. We suggest that laboratories standardize their sampling rate method to ensure consistency.

Background— Symptom-limited treadmill testing is commonly performed on entry to cardiac rehabilitation (CR) for its prognostic value and to design a safe and effective exercise program. Normative values for this evaluation are not available. The primary goals of this study were to establish normative values for peak aerobic capacity (peak V̇ o 2 ) for patients entering CR and to create nomograms for conversion of peak V̇ o 2 to a percentage of predicted exercise capacity, stratified by age, gender, and diagnosis. Methods and Results— Peak V̇ o 2 was measured in 2896 patients entering CR from 1996 to 2004. Peak V̇ o 2 was higher in men than in women: 19.3±6.1 mL · kg −1 · min −1 (range, 5.2 to 49.7 mL · kg −1 · min −1 ) versus 14.5±3.9 mL · kg −1 · min −1 (range, 3.8 to 29.8 mL · kg −1 · min −1 ) ( P o 2 decreased steadily with age with a greater rate of decline in men than women (−0.242 versus −0.116 mL · kg −1 · min −1 per year) ( P o 2 include coronary artery bypass grafting (CABG), angina at stress testing, hypertension, and, in women, β-blocking medications. Nomograms are presented for individual values to be compared with mean values by age, gender, and cardiac diagnosis. These include a nomogram to convert estimated maximal metabolic equivalents to actual peak V̇ o 2 for patients who do not undergo direct measurement of peak V̇ o 2 . Conclusions— Values of peak V̇ o 2 on entry to CR are extremely low, particularly in women, approaching values seen with severe chronic heart failure. This underscores the importance of CR after a major cardiac event to improve physical function and long-term prognosis.

PURPOSE Increasing caloric expenditure through physical activity is associated with reduced mortality. On the basis of observational studies, previous authors have suggested that at least 1000 kcal per week and possibly 1500 kcal per week of physical activity is necessary for health benefits. The authors have previously reported that patients in maintenance cardiac rehabilitation accumulate approximately 230 kcal per exercise session, suggesting that additional activity outside of cardiac rehabilitation is needed to achieve the goal of 1500 kcal per week. The authors estimated the amount of energy expenditure performed each week by patients in cardiac rehabilitation during both program participation and leisure time. METHODS For this study, 104 patients enrolled in a supervised maintenance cardiac rehabilitation program at both tertiary care and community settings for at least 6 months completed a self-administered physical activity questionnaire. Energy expenditure in cardiac rehabilitation and leisure time activity was measured in kilocalories. Total caloric expenditure was determined by adding up the number of kilocalories expended by the patients each week climbing stairs, walking, participating in cardiac rehabilitation, and engaging in sports. RESULTS Patients in cardiac rehabilitation expended weekly, on the average, 1504 +/- 830 kcal in physical activity, 830 +/- 428 kcal in cardiac rehabilitation, and 675 +/- 659 kcal in leisure time activity. There was a significant difference in caloric expenditure between men and women, between those with a body mass index (BMI) less than 30 and those with a BMI of 30 or more, and between those younger than 70 years and those 70 years or older. There was no difference between races. Whereas 43% of the patients accumulated 1500 kcal, 57% did not. CONCLUSIONS The findings showed that 72% of the patients in cardiac rehabilitation accumulated at least 1000 kcal of energy expenditure per week and met public health guidelines. Also, 43% of the patients in cardiac rehabilitation accumulated more than 1500 kcal of energy expenditure per week, a level identified as necessary to reduce all-cause mortality. Women of either race, patients with a BMI of 30 or more, and patients age 70 years or older are the groups least likely to achieve 1500 kcal of energy expenditure per week. The authors recommend incorporating weekly kilocalories of energy expenditure in the exercise prescription of patients to ensure achievement of maximum health benefits.

BRAWNER, C. A., S. J. KETEYIAN, and J. K. EHRMAN. The relationship of heart rate reserve to VO2 reserve in patients with heart disease. Med. Sci. Sports Exerc., Vol. 34, No. 3, pp. 418–422, 2002. Recent reports indicate that among healthy adults, % heart rate reserve (HRR) is more closely related t

Machine learning is becoming a popular and important approach in the field of medical research. In this study, we investigate the relative performance of various machine learning methods such as Decision Tree, Naïve Bayes, Logistic Regression, Logistic Model Tree and Random Forests for predicting incident diabetes using medical records of cardiorespiratory fitness. In addition, we apply different techniques to uncover potential predictors of diabetes. This FIT project study used data of 32,555 patients who are free of any 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 5-year follow-up. At the completion of the fifth year, 5,099 of those patients have developed diabetes. The dataset contained 62 attributes classified into four categories: demographic characteristics, disease history, medication use history, and stress test vital signs. We developed an Ensembling-based predictive model using 13 attributes that were selected based on their clinical importance, Multiple Linear Regression, and Information Gain Ranking methods. The negative effect of the imbalance class of the constructed model was handled by Synthetic Minority Oversampling Technique (SMOTE). The overall performance of the predictive model classifier was improved by the Ensemble machine learning approach using the Vote method with three Decision Trees (Naïve Bayes Tree, Random Forest, and Logistic Model Tree) and achieved high accuracy of prediction (AUC = 0.92). The study shows the potential of ensembling and SMOTE approaches for predicting incident diabetes using cardiorespiratory fitness data.

Background: Chronotropic incompetence (CI) has been associated with cardiovascular mortality. However, its relationship with long-term risk of heart failure (HF) is not well studied. Methods: We included 43,098 participants (mean age 51.7±12.3 years, 47.5% females, 66.6% white) of the 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 technique that classifies the data into predetermined categories. The aim of the analysis

Many studies have reported the prognostic significance of peak oxygen consumption (VO 2 ) and V E -VCO 2 slope in patients with heart failure (HF). However, there are limited data stratifying risk based on a combination of these measures and how to best use them. Purpose: Describe 1 and 3-y event rates for the composite endpoint of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT) based on the combined evaluation of peak VO 2 and V E -VCO 2 slope in patients with HF with reduced ejection fraction (≤ 40%; HFrEF). Methods: Patients (n= 1,116; 33% female; age= 54 ± 13 y) with a cardiopulmonary exercise test between 1997 and 2010 and confirmed HFrEF were identified. Endpoint data was obtained through 2011. Patients were grouped based on peak VO 2 (< 12, 12 to18, and > 18 mL/kg/min) and (V E -VCO 2 slope ≥ 34 or < 34). Cumulative events were identified from life tables. Cox regression with adjustment for age, gender, ejection fraction, and beta-blocker therapy was used to calculate the hazard ratio for V E -VCO 2 slope ≥ 34 within each peak VO 2 group. Results: The 1 and 3-y event rates are shown in the Table. Among patients with a peak VO 2 < 12, 1 and 3-y events were 23% and 44%, respectively. Within this group, V E -VCO 2 slope ≥ 34 represented more than twice the risk at both 1 y (HR 2.42, 95% CI 1.09, 5.38) and 3 y (HR 2.32, 95% CI 1.33, 4.05). Among patients with a peak VO 2 12 to 18, 1 and 3-y events were 14% and 30%, respectively. Within this group, a V E -VCO 2 slope ≥ 34 was associated with increased risk at both 1 y (HR 1.80, 95% CI 1.13, 2.87) and 3 y (HR 1.80, 95% CI 1.30, 2.50). Among patients with peak VO 2 > 18, 1 and 3-y events were 2% and 10%, respectively, and V E -VCO 2 slope was not statistically associated with increased risk. Conclusion: Among patients with a peak VO 2 ≤ 18, V E -VCO 2 slope ≥ 34 further refines the risk for a composite endpoint of mortality, LVAD, or CT at both 1 and 3 y.

The prognostic utility of cardiopulmonary exercise testing (CPX) in patients with heart failure and reduced ejection fraction (HFrEF) has received much attention. However, there are limited data on the value of CPX in patients with HF and preserved EF (HFpEF). Purpose: Among patients with HFpEF, describe the association between select CPX measures and prognosis for the composite endpoint of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT). Methods: Patients with a CPX between 1997 and 2010 and confirmed HFrEF (EF ≤ 40%; n= 1,201) or HFpEF (EF ≥ 50%; n= 192) were identified. Patients with HFpEF (n= 189, age= 54 ± 14 y, 43% female, EF = 56 ± 5%) were matched (propensity score) to patients with HFrEF (n= 189, age= 54 ± 13 y, 43% female, EF = 22 ± 9%) based on age, gender, history of coronary artery disease, and body mass index. Endpoint data was obtained through 2011. The association between select CPX measures and the endpoint was assessed using Cox regression with adjustment for age, gender, EF, and beta-blocker therapy. Results: There were 53 events (28%; median follow-up = 5.1 y) among the HFpEF group and 88 events (47%; median follow-up = 3.6 y) among the HFrEF group. Results from the Cox regression analyses are shown in the Table. Percent predicted peak VO 2 was one of the best predictors of the endpoint in both HFpEF and HFrEF with similar hazard ratios. Although significantly related to the endpoint among HFrEF, V E -VCO 2 slope and peak P ET CO 2 were not significant among HFpEF. Conclusions: These data support the use of % predicted peak VO 2 to risk stratify patients with HFpEF and suggest that the prognostic utility of some CPX measures developed in HFrEF may not be relevant in HFpEF. Additional research is needed to define the association between CPX measures and prognosis specifically for patients with HFpEF.

Introduction: Numerous metrics derived from the cardiopulmonary exercise test (CPX) are associated with outcomes among patients with heart failure with reduced ejection fraction (HFrEF). However few studies have examined the independent prognostic value of all variables assessed simultaneously. Purpose: Retrospective analysis to describe the relationship between all CPX measures and the composite outcome of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT). Methods: Patients (n= 1,201; 33% female; age= 55 ± 13 y) with a CPX between 1997 and 2010 and confirmed HFrEF (ejection fraction [EF] < 40%) were identified. Death data through 2011 was obtained from the National Death Index. The association with the composite endpoint was evaluated separately for 30 CPX measures with adjustment for age, gender, EF, and beta-blocker therapy using Cox regression. Forward stepwise Cox regression was performed to identify which of the CPX variables contribute the most to outcome prediction. Results: During a median follow-up of 3.75 years there were 576 (48%) events. When tested separately, nearly all CPX variables (except heart rate reserve/metabolic reserve and peak respiratory exchange ratio) were associated (p2 , Wald= 76.1), ventilatory power (peak systolic blood pressure/V E -VCO 2 slope, Wald= 58.0), and EF (Wald= 27.0) independently predicted outcomes. Conclusion: When considering all variables measured during a CPX test, % predicted peak VO 2 was the variable with the strongest independent association to outcomes in this cohort of patients with HFrEF. The % predicted peak VO 2 may represent a key variable in determining when to consider a patient for an LVAD or CT.

Introduction: Numerous metrics from the cardiopulmonary exercise test (CPX) are associated with outcomes among patients with heart failure with reduced ejection fraction (HFrEF). Among patients with HFrEF, mortality rates differ by race; however, the influence of race on the association between common measures obtained during CPX and mortality has not been fully described. Purpose: Retrospective analysis to describe the relationship between key CPX measures and the composite endpoint of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT) in white and black men with HFrEF. Methods: Self-identified white and black male patients (n= 761; age= 55 ± 12 y; BMI= 30.6±6.6) with a CPX between 1997 and 2010 and confirmed HFrEF (ejection fraction [EF] ≤ 40%) were identified. Endpoint data was obtained through 2011. The association with the composite endpoint was evaluated separately for 7 key CPX measures with adjustment for age, hypertension, beta-blocker therapy, EF, and ischemic etiology using Cox regression stratified by race. Results: During a median follow-up of 3.5 y there were 195 (54%) and 193 (48%) events for white and black patients, respectively. All CPX variables were associated (p2 ) at 76.2, and among black patients it was ventilatory efficiency (V E -VCO 2 slope) at 90.8. Conclusion: Among white and black male patients, % predicted peak VO 2 and V E -VCO 2 slope, respectively, were most strongly associated with the combined end point of mortality, LVAD or CT. These data suggest that risk stratification using CPX variables may differ by race. Further research is needed to determine if race-specific methods of CPX-based risk stratification are needed.

Many studies have shown a strong association between numerous variables from a cardiopulmonary exercise (CPX) test and prognosis in patients with heart failure with reduced ejection fraction (HFrEF). However, few studies have compared the prognostic value of a majority of these variables simultaneously, so controversy remains regarding optimal interpretation.This was a retrospective analysis of patients with HFrEF (n = 1,201; age = 55 ± 13 y; 33% female) and a CPX test from 1997 to 2010. Thirty variables from a CPX test were considered in separate adjusted Cox regression analyses to describe the strength of the relation of each to a composite end point of all-cause mortality, left ventricular assist device implantation, or heart transplantation. During a median follow-up of 3.8 years, there were 577 (48.0%) events. The majority of variables were highly significant (P.001). Among these, percentage of predicted maximum V˙O2 (ppMV˙O2; Wald = 203; P.001; C-index = 0.73) was similar to VE-VCO2 slope (Wald = 201; P.001; C = 0.72) and peak V˙O2 (Wald = 161; P.001; C = 0.72). In addition, there was no significant interaction observed for peak respiratory exchange ratio1 vs ≥1.Consistent with prior studies, many CPX test variables were strongly associated with prognosis in patients with HFrEF. The choice of which variable to use is up to the clinician. Renewed attention should be given to ppMV˙O2, which appears to be highly predictive of survival in these patients.

This study examined the effects of a cardiac rehabilitation (CR) program on functional capacity and health status (HS) in patients with newly implanted left ventricular assist devices (LVADs).Reduced functional capacity and HS are independent predictors of mortality in patients with heart failure. CR improves both, and is related to improved outcomes in patients with heart failure; however, there is a paucity of data that describe the effects of CR in patients with LVADs.Enrolled subjects (n = 26; 7 women; age 55 ± 13 years; ejection fraction 21 ± 8%) completed a symptom-limited cardiopulmonary exercise test, the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 6-min walk test (6MW), and single-leg isokinetic strength test before 2:1 randomization to CR versus usual care. Subjects in the CR group underwent 18 visits of aerobic exercise at 60% to 80% of heart rate reserve. Within-group changes from baseline to follow-up were analyzed with a paired t-test, whereas an independent t-test was used to determine differences in the change between groups.Within-group improvements were observed in the CR group for peak oxygen uptake (10%), treadmill time (3.1 min), KCCQ score (14.4 points), 6MW distance (52.3 m), and leg strength (17%). Significant differences among groups were observed for KCCQ, leg strength, and total treadmill time.Indicators of functional capacity and HS are improved in patients with continuous-flow LVADs who attend CR. Future trials should examine the mechanisms responsible for these improvements, and if such improvements translate into improved clinical outcomes. (Cardiac Rehabilitation in Patients With Continuous Flow Left Ventricular Assist Devices:Rehab VAD Trial [RehabVAD]; NCT01584895).

INTRODUCTION: Patient health status (PHS) and peak oxygen uptake ( O2) are important predictors of clinical outcomes in individuals with heart failure. Preliminary studies of individuals with left ventricular assist devices (LVADs) show improvements in both PHS and peak O2. However, the relationship between peak O2 and PHS in this population is not well described. Likewise, data regarding muscular strength are also lacking in this population. We sought to describe the association between peak O2, muscular strength, and PHS in patients with continuous-flow LVADs. METHODS: Subjects (n = 26; 7 women) completed a symptom-limited graded exercise test within an average of 82 days (range, 33-167 days) of LVAD implant. In addition, subjects underwent a 6-Minute Walk Test and an isokinetic knee extension strength test and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). Spearman correlation coefficients were performed, adjusting for body weight and gender, to examine relationships between variables. RESULTS: Muscular strength, as measured by peak torque, and peak O2 were both moderately associated with the KCCQ (r = 0.58, P = .006; r = 0.51, P = .019). A subanalysis revealed that muscular strength and peak O2 were related to different domains within the KCCQ. CONCLUSIONS: Leg muscle strength and peak O2 appear to be important factors related to PHS in patients with continuous-flow LVADs. This is likely partially a result of deconditioning due to recent hospitalization, as well as persistent heart failure-related peripheral maladaptations in skeletal muscle. Incorporating both a cardiovascular as well as strength training program before and after LVAD implant surgery may be beneficial.

Background The combined influence of fitness and fatness on mortality risk in diverse populations has not been adequately explored. Our aim was to assess the relative impact of exercise capacity and body mass index (BMI) on all-cause mortality. Methods We included 29,257 men and women (mean age 53 years; 27% African American) from The Henry Ford Exercise Testing (FIT) Project without cardiovascular disease and diabetes mellitus at baseline. All patients completed a symptom-limited maximal treadmill stress test between 1991 and 2009. Patients were grouped for analysis by exercise capacity (≥10 metabolic equivalents of task [METs] and 2 and 2 ), forming 4 subgroups. Independent and joint associations of BMI and exercise capacity with all-cause mortality were assessed using Cox proportional hazard models. Results During a mean follow-up of 10.8 years, 1898 patients (6.5%) died. We observed a strong inverse association between exercise capacity (per 1 MET unit) and all-cause mortality (hazard ratio [95% confidence interval], 0.86 [0.85-0.88]). Body mass index (per 1 BMI unit) was inversely related to mortality (hazard ratio [95% confidence interval], 0.98 [0.97-0.99]). In joint analysis, the highest mortality risk was in the 2 subgroup. Conclusions Reduced exercise capacity was a strong independent risk factor for all-cause mortality in this racially diverse population. Given the comparatively limited impact of BMI, more emphasis should be placed on measuring exercise capacity and developing strategies for its improvement in cardiovascular disease prevention programs.

Background In the general population, the exercise treadmill testing variables of lower resting heart rate, higher peak heart rate, and greater fitness have favorable prognosis for mortality. Patients with obstructive lung disease have increased mortality risk. Furthermore, some pulmonary medications (ie, beta2-agonists) can influence heart rate. We determined whether exercise treadmill test parameters carry the same prognostic value in patients who are using versus not using pulmonary medications. Methods We analyzed data on 69,855 patients (mean age, 55 years) who completed a clinically indicated exercise treadmill test. Patients were defined as having "lung disease" if they were taking medications routinely used to treat obstructive lung disease (n = 6145, 9%). International Classification of Diseases, 9th Revision codes regarding the type of lung disease were not available. Multivariate-adjusted Cox models were used to determine the risk of mortality, major adverse cardiac events, and myocardial infarction over a mean of 11 years follow-up. Results Higher resting heart rate was associated with increased mortality risk, and higher peak heart rate and fitness were associated with decreased risk. No significant interaction for lung disease status was seen for the heart rate variables, but a slightly stronger protective effect was observed for higher fitness among patients with lung disease ( P interaction = .032). The results were similar for major adverse cardiac events and myocardial infarction. Conclusions Heart rate parameters achieved on exercise treadmill tests are equally prognostic among patients using versus not using pulmonary medications. Higher fitness was associated with improved clinical outcomes for both; however, the relative benefit of fitness on survival was even greater in patients using pulmonary medications compared with those not using them.

We thank the readers for the interest in our article1 and for their insightful comments. One such reader, Dr Maylar, comments that the 6-month data from the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) study do not justify a firm conclusion in favor of supervised exercise (SE). We note that the study was designed with a peak-walking-time, 6-month primary outcome end point; using this prespecified end point, SE provided a superior outcome to stent revascularization. However, high-quality comparative effectiveness research is always best designed to permit >1 clinical end point over relevant timeframes. In this context, we note that primary care and vascular specialty clinicians will evaluate both 6- and 18-month time points and the full range of outcomes achieved. As Dr Maylar points out, patient-centered outcomes were not as strongly positive for SE as the treadmill outcomes. The finding of more improvement in treadmill walking by SE participants but more symptom improvement in stent revascularization participants needs to be understood. We also agree that SE requires more commitment on the part of patients (but note that exercise would ideally be done …