Jerome L. Fleg

Efficacy and Safety of Exercise Training in Patients With Chronic Heart Failure: HF-ACTION Randomized Controlled Trial

CONTEXT Guidelines recommend that exercise training be considered for medically stable outpatients with heart failure. Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes. OBJECTIVE To test the efficacy and safety of exercise training among patients with heart failure. DESIGN, SETTING, AND PATIENTS Multicenter, randomized controlled trial of 2331 medically stable outpatients with heart failure and reduced ejection fraction. Participants in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) were randomized from April 2003 through February 2007 at 82 centers within the United States, Canada, and France; median follow-up was 30 months. INTERVENTIONS Usual care plus aerobic exercise training, consisting of 36 supervised sessions followed by home-based training, or usual care alone. MAIN OUTCOME MEASURES Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or heart failure hospitalization. RESULTS The median age was 59 years, 28% were women, and 37% had New York Heart Association class III or IV symptoms. Heart failure etiology was ischemic in 51%, and median left ventricular ejection fraction was 25%. Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12. A total of 759 patients (65%) in the exercise training group died or were hospitalized compared with 796 patients (68%) in the usual care group (hazard ratio [HR], 0.93 [95% confidence interval {CI}, 0.84-1.02]; P = .13). There were nonsignificant reductions in the exercise training group for mortality (189 patients [16%] in the exercise training group vs 198 patients [17%] in the usual care group; HR, 0.96 [95% CI, 0.79-1.17]; P = .70), cardiovascular mortality or cardiovascular hospitalization (632 [55%] in the exercise training group vs 677 [58%] in the usual care group; HR, 0.92 [95% CI, 0.83-1.03]; P = .14), and cardiovascular mortality or heart failure hospitalization (344 [30%] in the exercise training group vs 393 [34%] in the usual care group; HR, 0.87 [95% CI, 0.75-1.00]; P = .06). In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics, the HRs were 0.89 (95% CI, 0.81-0.99; P = .03) for all-cause mortality or hospitalization, 0.91 (95% CI, 0.82-1.01; P = .09) for cardiovascular mortality or cardiovascular hospitalization, and 0.85 (95% CI, 0.74-0.99; P = .03) for cardiovascular mortality or heart failure hospitalization. Other adverse events were similar between the groups. CONCLUSIONS In the protocol-specified primary analysis, exercise training resulted in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points. After adjustment for highly prognostic predictors of the primary end point, exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00047437.

Resistance Exercise in Individuals With and Without Cardiovascular Disease Benefits, Rationale, Safety, and Prescription An Advisory From the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association

Position paper endorsed by the American College of Sports Medicine Although exercise programs have traditionally emphasized dynamic lower-extremity exercise, research increasingly suggests that complementary resistance training, when appropriately prescribed and supervised, has favorable effects on muscular strength and endurance, cardiovascular function, metabolism, coronary risk factors, and psychosocial well-being. This advisory reviews the role of resistance training in persons with and without cardiovascular disease, with specific reference to health and fitness benefits, rationale, the complementary role of stretching, relevant physiological considerations, and safety. Participation criteria and prescriptive guidelines are also provided. Although resistance training has long been accepted as a means for developing and maintaining muscular strength, endurance, power, and muscle mass (hypertrophy),1 2 its beneficial relationship to health factors and chronic disease has been recognized only recently.3 4 5 Prior to 1990, resistance training was not a part of the recommended guidelines for exercise training and rehabilitation for either the American Heart Association or the American College of Sports Medicine (ACSM). In 1990, the ACSM first recognized resistance training as a significant component of a comprehensive fitness program for healthy adults of all ages.6 Both aerobic endurance exercise and resistance training can promote substantial benefits in physical fitness and health-related factors.3 5 Table 1⇓ summarizes these benefits and attempts to weigh them according to the current literature.3 Although both training modalities elicit benefits in most of the variables listed, the estimated weightings (ie, in terms of physiological benefits) are often substantially different. Aerobic endurance training weighs higher in the development of maximum oxygen uptake (Vo2max) and associated cardiopulmonary variables, and it more effectively modifies cardiovascular risk factors associated with the development of coronary artery disease. Resistance training offers greater development of muscular strength, endurance, and mass. It also assists in the …

Exercise and Heart Failure A Statement From the American Heart Association Committee on Exercise, Rehabilitation, and Prevention

Heart failure (HF) may be defined as the inability of the heart to meet the demands of the tissues, which results in symptoms of fatigue or dyspnea on exertion progressing to dyspnea at rest. The inability to perform exercise without discomfort may be one of the first symptoms experienced by patients with HF and is often the principal reason for seeking medical care. Therefore, exercise intolerance is inextricably linked to the diagnosis of HF. It might be expected that a tight relationship would exist between indices of resting ventricular function and exercise capacity. Data indicate, however, that indices of resting ventricular function (such as ejection fraction [EF]) are only weakly correlated to exercise tolerance.1 Exercise intolerance is defined as the reduced ability to perform activities that involve dynamic movement of large skeletal muscles because of symptoms of dyspnea or fatigue. Many investigators have sought mechanisms to explain the source of exercise intolerance. The aims of this position statement are to review (1) factors that affect exercise tolerance, with specific emphasis on chronic HF due to systolic dysfunction; (2) data that support the role of exercise training in chronic systolic HF, including the risks and benefits; (3) data on exercise training in patients with HF due to diastolic dysfunction; and finally (4) the subgroups of patients with HF for which data are lacking, and (5) the subgroups of patients who should not be included in exercise training programs. We anticipate this report will stimulate appropriate use of exercise training in patients with HF when indicated and encourage further studies in those areas in which data are lacking. ### Cardiovascular The capacity for performing aerobic exercise depends on the ability of the heart to augment its output to the exercising muscles and the ability of these muscles to utilize oxygen from the delivered …

Spironolactone for Heart Failure with Preserved Ejection Fraction

BACKGROUND Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate.

To assess the effect of age on cardiac volumes and function in the absence of overt or occult coronary disease, we performed serial gated blood pool scans at rest and during progressive upright bicycle exercise to exhaustion in 61 participants in the Baltimore Longitudinal Study of Aging. The subjects ranged in age from 25 to 79 years and were free of cardiac disease according to their histories and results of physical, resting and stress electrocardiographic, and stress thallium scintigraphic examinations. Absolute left ventricular volumes were obtained at each workload. There were no age-related changes in cardiac output, end-diastolic or end-systolic volumes, or ejection fraction at rest. During vigorous exercise (125 W), cardiac output was not related to age (cardiac output [1/min] = 16.02 + 0.03 [age]; r = .12, p = .46). However, there was an age-related increase in end-diastolic volume (end-diastolic volume [ml] = 86.30 + 1.48 [age]; r = .47, p = .003) and stroke volume (stroke volume [ml] = 85.52 + 0.80 [age]; r = .37, p = .02), and an age-related decrease in heart rate (heart rate [beats/min] = 184.66 - 0.70 [age]; r = -.50, p = .002). The dependence of the age-related increase in stroke volume on diastolic filling was emphasized by the fact that at this high workload end-systolic volume was higher (end-systolic volume [ml] = 3.09 + 0.65 [age]; r = .45, p = .003) and ejection fraction lower (ejection fraction = 88.48 - 0.18 [age]; r = -.33, p = .04) with increasing age. These findings indicate that although aging does not limit cardiac output per se in healthy community-dwelling subjects, the hemodynamic profile accompanying exercise is altered by age and can be explained by an age-related diminution in the cardiovascular response to beta-adrenergic stimulation.

Accelerated Longitudinal Decline of Aerobic Capacity in Healthy Older Adults

Background—The ability of older persons to function independently is dependent largely on the maintenance of sufficient aerobic capacity and strength to perform daily activities. Although peak aerobic capacity is widely recognized to decline with age, its rate of decline has been estimated primarily from cross-sectional studies that may provide misleading, overly optimistic estimates of aging changes. Methods and Results—To determine longitudinal rate of change in aerobic capacity and the influence of age, gender, and physical activity on these changes, we performed serial measurements of peak treadmill oxygen consumption (peak &OV0312;o2) in 375 women and 435 men ages 21 to 87 years from the Baltimore Longitudinal Study of Aging, a community-dwelling cohort free of clinical heart disease, over a median follow-up period of 7.9 years. A linear mixed-effects regression model was used to calculate the predicted longitudinal 10-year rate of change in peak &OV0312;o2, expressed in milliliters per minute, for each age decade from the 20s through the 70s after adjustment for self-reported leisure-time physical activity. A longitudinal decline in peak &OV0312;o2 was observed in each of the 6 age decades in both sexes; however, the rate of decline accelerated from 3% to 6% per 10 years in the 20s and 30s to >20% per 10 years in the 70s and beyond. The rate of decline for each decade was larger in men than in women from the 40s onward. Similar longitudinal rates of decline prevailed when peak &OV0312;o2 was indexed per kilogram of body weight or per kilogram of fat-free mass and in all quartiles of self-reported leisure-time physical activity. When the components of peak &OV0312;o2 were examined, the rate of longitudinal decline of the oxygen pulse (ie, the O2 utilization per heart beat) mirrored that of peak &OV0312;o2, whereas the longitudinal rate of heart rate decline averaged only 4% to 6% per 10 years, and accelerated only minimally with age. Conclusions—The longitudinal rate of decline in peak &OV0312;o2 in healthy adults is not constant across the age span in healthy persons, as assumed by cross-sectional studies, but accelerates markedly with each successive age decade, especially in men, regardless of physical activity habits. The accelerated rate of decline of peak aerobic capacity has substantial implications with regard to functional independence and quality of life, not only in healthy older persons, but particularly when disease-related deficits are superimposed.

Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain

BACKGROUND It is unclear whether an evaluation incorporating coronary computed tomographic angiography (CCTA) is more effective than standard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes. METHODS In this multicenter trial, we randomly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to standard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012. The primary end point was length of stay in the hospital. Secondary end points included rates of discharge from the emergency department, major adverse cardiovascular events at 28 days, and cumulative costs. Safety end points were undetected acute coronary syndromes. RESULTS The rate of acute coronary syndromes among 1000 patients with a mean (±SD) age of 54±8 years (47% women) was 8%. After early CCTA, as compared with standard evaluation, the mean length of stay in the hospital was reduced by 7.6 hours (P<0.001) and more patients were discharged directly from the emergency department (47% vs. 12%, P<0.001). There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days. After CCTA, there was more downstream testing and higher radiation exposure. The cumulative mean cost of care was similar in the CCTA group and the standard-evaluation group (

Exercise Standards for Testing and Training A Scientific Statement From the American Heart Association

4,289 and

Effects of Digoxin on Morbidity and Mortality in Diastolic Heart Failure The Ancillary Digitalis Investigation Group Trial

4,060, respectively; P=0.65). CONCLUSIONS In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating CCTA into a triage strategy improved the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department, but it resulted in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care. (Funded by the National Heart, Lung, and Blood Institute; ROMICAT-II ClinicalTrials.gov number, NCT01084239.).

Secondary Prevention of Coronary Heart Disease in the Elderly (With Emphasis on Patients ≥75 Years of Age) An American Heart Association Scientific Statement From the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention

The 2001 version of the exercise standards statement1 has served effectively to reflect the basic fundamentals of ECG–monitored exercise testing and training of both healthy subjects and patients with cardiovascular disease (CVD) and other disease states. These exercise standards are intended for use by physicians, nurses, exercise physiologists and specialists, technologists, and other healthcare professionals involved in exercise testing and training of these populations. Because of an abundance of new research in recent years, a revision of these exercise standards is appropriate. The revision deals with basic fundamentals of testing and training, with no attempt to duplicate or replace current clinical practice guidelines issued by the American Heart Association (AHA), the American College of Cardiology Foundation (ACCF), and other professional societies. It is acknowledged that the published evidence for some recommendations made herein is limited, but the depth of knowledge and experience of the writing group is believed to provide justification for certain …