Search

An Institute of Medicine report titled U.S. Health in International Perspective: Shorter Lives, Poorer Health documents the decline in the health status of Americans relative to people in other high-income countries, concluding that “Americans are dying and suffering from illness and injury at rates that are demonstrably unnecessary.”1 The report blames many factors, “adverse economic and social conditions” among them. In an editorial in Science discussing the findings of the Institute of Medicine report, Bayer et al2 call for a national commission on health “to address the social causes that have put the USA last among comparable nations.” Although mortality from cardiovascular disease (CVD) in the United States has been on a linear decline since the 1970s, the burden remains high. It accounted for 31.9% of deaths in 2010.3 There is general agreement that the decline is the result, in equal measure, of advances in prevention and advances in treatment. These advances in turn rest on dramatic successes in efforts to understand the biology of CVD that began in the late 1940s.4,5 It has been assumed that the steady downward trend in mortality will continue into the future as further breakthroughs in biological science lead to further advances in prevention and treatment. This view of the future may not be warranted. The prevalence of CVD in the United States is expected to rise 10% between 2010 and 2030.6 This change in the trajectory of cardiovascular burden is the result not only of an aging population but also of a dramatic rise over the past 25 years in obesity and the hypertension, diabetes mellitus, and physical inactivity that accompany weight gain. Although there is no consensus on the precise causes of the obesity epidemic, a dramatic change in the underlying biology of Americans is …

This document was developed by the American College of Cardiology Foundation (ACCF) Task Force on Clinical Expert Consensus Documents (ECDs) and cosponsored by the American College of Radiology (ACR), American Heart Association (AHA), American Society of Nuclear Cardiology (ASNC), North American

Thanks to the dedicated involvement of the communities it serves, the National Heart, Lung, and Blood Institute (NHLBI) completed development of a scientific working strategic plan in 2007 to guide its activities and initiatives over the next 5 to 10 years.1 The plan outlines a cross-cutting approach that identifies areas in which the NHLBI is well positioned to make major contributions through investigator-initiated research and through programs that enable and supplement investigator-initiated activities. Translational research—both from the bench to the bedside and from the bedside to the community—is strongly and specifically underscored throughout the plan. Here, we summarize NHLBI programs and efforts in translational research. Funding opportunities and early career advice for aspiring researchers have been presented previously in this series.2,3 The ultimate goal of biomedical research is to improve individual and public health by discovering new effective strategies for the maintenance of wellness and for the prevention and treatment of disease. The Institute of Medicine Clinical Research Roundtable identified 2 “translational blocks,” or obstacles, to the realization of tangible health benefits derived from original research.4 The first block, or T1, is “the transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans.” The second block, or T2, is “the translation of results from clinical studies into everyday clinical practice and health decision making.” Some authorities divide T2 into 2 components: T2 includes guideline development, meta-analyses, and systematic reviews, whereas T3 includes dissemination and implementation research.5 Some commentators have argued that the National Institutes of Health (NIH) disproportionately funds T1 compared with T2/T3 and that there is a need for increased national commitments to T2/T3 (from this point referred to as T2).5,6 A recent survey of >3000 …

This document details the procedures and recommendations of the Goals and Metrics Committee of the Strategic Planning Task Force of the American Heart Association, which developed the 2020 Impact Goals for the organization. The committee was charged with defining a new concept, cardiovascular health , and determining the metrics needed to monitor it over time. Ideal cardiovascular health, a concept well supported in the literature, is defined by the presence of both ideal health behaviors (nonsmoking, body mass index 2 , physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol

Thank you. The comments I am about to make are my own personal views. They are not the views of the National Heart, Lung, and Blood Institute or the US Department of Health and Human Services. I have no conflicts of interest to disclose. There once was a king who had 2 servants.1 One day, he asked the servants to take buckets down to the well, which was located just outside the palace. He told them to draw water into the buckets and bring them back to him. The loyal servants did exactly as they were told, but when they reached the well, they noticed something rather strange. The buckets the king had given them were porous, full of holes. The first servant said, “The king must have made a mistake. It makes absolutely no sense to me why I should draw water into a porous bucket. I won’t do it.” The second servant said, “I agree that it does not make sense, but nonetheless I will do as the king asked.” The servant drew water into the bucket, and sure enough within a few minutes all the water had drained out. When the servants returned to the king, he asked them whether they had carried out his orders. The first servant explained that he discovered holes in his bucket, and logic dictated to him that he should disobey the king’s order. The second servant admitted that he too felt that it logically made sense to disobey the king’s order, but he nonetheless drew water into the bucket as he was told. The king looked at the second servant and said to him, “You did right. You see, what I wanted was for you to clean my buckets.”1 This is a story that was told over 2000 years …

Background— Quantitative ECG measures of left ventricular mass and repolarization predict outcome in population-based cohorts and patients with hypertension. We assessed the prognostic value of preoperative quantitative electrocardiography in patients who underwent isolated coronary artery bypass grafting. Methods and Results— For 6 years we followed 8166 patients who underwent primary isolated coronary artery bypass grafting between 1990 and 2003, all of whom had routine preoperative ECGs. With use of specialized digital software, quantitative measures were recorded on ventricular rate, P duration, PR interval, QRS duration, QT interval, QRS axis, Sokolow-Lyon and Cornell voltages, and ST-segment depression and slope. There were 1516 deaths. After adjustment for age, gender, clinical characteristics, left ventricular ejection fraction, and other confounders, death was independently predicted by ventricular rate (adjusted hazard ratio [AHR] for 90 versus 60 beats per minute, 1.34; 95% confidence interval [CI], 1.21 to 1.50; P P P P P Conclusions— Quantitative ECG measures of left ventricular rate, mass, and repolarization are predictive of mortality among patients who underwent isolated coronary artery bypass grafting. These findings suggest that quantitative electrocardiography may be valuable for risk stratification in patients with severe coronary artery disease.

Exercise testing remains the most widely accessible and relatively inexpensive method for initial evaluation of suspected coronary disease and for evaluation of its severity.1–3 Clinical usefulness has been limited, however, by poor sensitivity of standard ST-segment depression criteria for assessment of anatomic and functional coronary disease severity and for prediction of risk.1,2,4–6 Recent data make it clear that symptomatic obstructive plaques that typically result in exercise-mediated ischemia may be less relevant to infarction and sudden death than less obstructive unstable plaques.7 These limitations mandate a rethinking of the exercise ECG along 2 distinct lines: First, is it possible to improve the diagnostic value of the exercise ECG? Second, separate from its ability to diagnose obstructive coronary artery lesions, can the exercise test be used as a prognostic tool that can encourage effective prevention of premature deaths or coronary events? Both goals take us beyond the ST segment. Reversible ST-segment depression is the characteristic finding associated with exercise-induced, demand-driven ischemia in patients with significant coronary obstruction but no flow limitation at rest. This process differs from the flow-limited acute coronary syndromes because exercise-related ischemia is generally limited to the subendocardium and is proportional to increases in myocardial oxygen demand. Ventricular waveforms of the ECG can be related to the net uncanceled transmural gradients between endocardial and epicardial myocardium, as extrapolated from the work of Holland and Brooks, among others.8–10 Accordingly, isoelectric TQ and ST segments in normal and in nonischemic patients can be related to comparable resting membrane and action potential plateau voltages in endocardial and epicardial action potentials. During exercise, progressive ischemia results in changing endocardial action potentials during both diastole and systole. Less negative endocardial cell resting membrane potential leads to current flow across the ischemic boundary during diastole, leading to elevation of the TQ …

Background— The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomography (PET) with fluorodeoxyglucose (FDG) imaging may identify patients for whom revascularization may lead to improved survival. We performed a propensity analysis to determine whether there might be a survival advantage from revascularization. Methods and Results— We analyzed the survival of 765 consecutive patients (age 64±11 years, 80% men) with advanced left ventricular systolic dysfunction (ejection fraction ≤35%) and without significant valvular heart disease who underwent PET/FDG study at the Cleveland Clinic between 1997 and 2002. Early intervention was defined as any cardiac intervention (surgical or percutaneous) within the first 6 months of the PET/FDG study. In the entire cohort, 230 patients (30%) underwent early intervention (188 [25%] had open heart surgery, most commonly coronary artery bypass grafting, and 42 [5%] had percutaneous revascularization); 535 (70%) were treated medically. Using 39 demographic, clinical and PET/FDG variables, we were able to propensity-match 153 of the 230 patients with 153 patients who did not undergo early intervention. Among the propensity-matched group, there were 84 deaths during a median of 3 years follow-up. Early intervention was associated with a markedly lower risk of death (3-year mortality rate of 15% versus 35%, propensity adjusted hazard ratio 0.52, 95% CI 0.33 to 0.81, P =0.0004). Conclusions— Among systolic heart failure patients referred for PET/FDG, early intervention may be associated with improved survival irrespective of the degree of viability.

Along with coronary artery calcium scanning, ankle-brachial index measurement, and carotid artery ultrasound, exercise electrocardiography has been proposed as a screening tool for asymptomatic subjects thought to be at intermediate risk for developing clinical coronary disease. A wealth of data indicate that exercise testing can be used to assess and refine prognosis, particularly when emphasis is placed on nonelectrocardiographic measures such as exercise capacity, chronotropic response, heart rate recovery, and ventricular ectopy. Nevertheless, randomized trial data on the clinical value of screening exercise testing are absent; that is, it is not known whether a strategy of routine screening exercise testing in selected subjects reduces the risk for premature mortality or major cardiac morbidity. The writing group believes that a large-scale randomized trial of such a strategy should be performed.

When he dedicated the new National Institutes of Health (NIH) Bethesda campus in October 1940, President Franklin D. Roosevelt declared, “We cannot be a strong nation unless we are a healthy nation. And so we must recruit knowledge and science in the service of national strength.”1 For more than 65 years, the National Heart, Lung, and Blood Institute’s (NHLBI’s) core mission has been, and continues to be, the generation and dissemination of knowledge and science with the goal of securing a healthy nation.2 Thirty-two years after Roosevelt’s NIH dedication, on July 26, 1972, Elliot Richardson, the Secretary of the US Department of Health, Education, and Welfare, announced the establishment of a “National Hypertension Program.”3 The program planned a 4-step approach to include agreement on standards and conditions for treatment, education of health workers, public dissemination of information, and research on the impact of the program on healthcare delivery. Richardson appointed 2 committees: one, the Hypertension Information and Education Advisory Committee, was to focus on the knowledge of hypertension and the communication of that knowledge, whereas the other, the Interagency Working Group, was to focus on exchange of information and coordination with the professional community. In 1977, the NHLBI issued the first of a number of clinical practice guidelines4 that would emerge from the National High Blood Pressure Education Program, as well as from other similar efforts such as the National Cholesterol Education Program. The NHLBI guidelines have covered a variety of topics, including, but not limited to, cholesterol, blood pressure, asthma, and von Willebrand disease.5 Over the years, these groundbreaking health education initiatives have successfully promoted marked increases in the public’s awareness of cardiovascular disease risk factors and contributed to the major reductions in coronary heart disease mortality observed during this period.6,7 …

Background— Although heart rate recovery (HRR) predicts mortality after exercise testing, its ability to identify patients likely to benefit after revascularization is unknown. We sought to determine whether HRR can identify patients likely to have improved survival after revascularization. Methods and Results— A total of 8861 patients undergoing treadmill nuclear or echocardiographic testing were divided into early revascularization (percutaneous coronary intervention or bypass surgery within 3 months) and non–early revascularization groups. Prespecified subgroup analysis was performed based on the presence or absence of ischemia, normal or impaired functional capacity, and normal or abnormal HRR. The primary end point was all-cause mortality. Early revascularization occurred in 552 patients. We propensity-matched 508 early revascularization patients to 508 non–early revascularization patients on the basis of 48 possible confounders. This constituted the present study cohort. During 8-year follow-up, 232 patients died. Overall, revascularization was associated with a slight but not significant decrease in mortality (hazard ratio [HR] 0.80, 95% CI 0.62 to 1.03). A significant decrease in mortality after revascularization was present in patients with imaging evidence of stress-induced ischemia (HR 0.62, 95% CI 0.44 to 0.87). Ischemic patients with normal HRR had significantly lower mortality with revascularization (HR 0.55, 95% CI 0.34 to 0.90), whereas ischemic patients with abnormal HRR did not (HR 0.78, 95% CI 0.47 to 1.29); however, the test for interaction between these 2 groups was not significant ( P =0.34). Conclusions— In patients with imaging evidence of myocardial ischemia, an abnormal HRR is associated with a nonsignificant trend toward blunting the survival improvement associated with early revascularization. HRR does not appear to identify patients likely to have a survival benefit.

Background— The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort. Methods and Results— CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9±1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5%) had AF. Compared with subjects in the first CRP quartile (3.41 mg/L) had more AF (7.4% versus 3.7%, adjusted OR 1.8, 95% CI 1.2 to 2.5; P =0.002). Of 5491 subjects without AF at baseline, 897 (16%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95% CI 1.08 to 1.58; P =0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95% CI 1.11 to 1.40; P Conclusions— CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.

In July 1984, Jim Fixx collapsed suddenly during a run, dying at 52 years of age of autopsy-proven coronary atherosclerosis. Fixx had popularized interest in the benefits of exercise, in part through his writings about his own self-transformation from a sedentary to a physically active life. In the wake of his sudden death, medical professionals and public followers were confused, and in some cases, dumbfounded. It can be argued that Fixx had beaten the odds by quitting smoking, losing weight, and becoming fit, thereby gaining years of life over what his genetic background foretold. Still, how was it possible that he should succumb to heart disease at a relatively young age, when, through his own hard work, he had realized the highest levels of physical fitness? Fixx and others had argued that physical activity and fitness were powerful promoters of good health and long life, and they had scientific data to back them up. Or so they thought. In one of the many newspaper articles that appeared after Fixx's death, Dr Robert Ascheim, a Cornell University cardiologist, admitted, “Does running benefit you? Nobody really has a clear answer.”1 Article see p 1377 In the 27 years since Fixx's death, scientists from many disciplines have published an enormous body of work on the physiological and metabolic effects of exercise. Higher levels of physical activity and exercise capacity are correlated with lower levels of blood pressure, heart rate, and tendency to thrombosis, and with higher levels of parasympathetic tone, cardiovascular reserve, endogenous thrombolysis, and endothelial function.2 Population-based and clinical epidemiological investigators have consistently observed a strong and inverse association between exercise capacity and adverse health outcomes.3 Scientists from the Cooper Clinic have been among the leaders in showing that men and women with greater exercise capacity have lower rates …

Background Recent studies have supported the hypothesis that calcific aortic stenosis is the product of an active inflammatory process, with similarities to atherosclerosis. We sought to determine whether therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) might slow the progression of aortic stenosis. Methods and Results A retrospective study of 174 patients (mean age 68±12 years) with mild to moderate calcific aortic stenosis was conducted. Patients required normal left ventricular function, ≤2+ aortic regurgitation, and ≥2 echocardiograms performed at least 12 months apart. Fifty-seven patients (33%) received treatment with a statin; the remaining 117 (67%) did not. The statin group was older and had a higher prevalence of hypertension, diabetes mellitus, and coronary disease. During a mean follow-up of 21 months, patients treated with statin had a smaller increase in peak and mean gradient and a smaller decrease in aortic valve area. When annualized, the decrease in aortic valve area for the nonstatin group was 0.11±0.18 cm 2 compared with 0.06±0.16 cm 2 for those treated with a statin ( P =0.03). In multivariate analysis, statin usage was a significant independent predictor of a smaller decrease in valve area ( P =0.01) and a lesser increase in peak gradient ( P =0.02). Conclusions Statin-treated patients, despite a higher risk profile for progression, had reduced aortic stenosis progression compared with those not treated with a statin. These data provide justification for a prospective randomized trial to substantiate whether statin therapy slows the progression of aortic stenosis.

Background An attenuated heart rate recovery after exercise has been shown to be predictive of mortality. In prior studies, recovery heart rates were measured while patients were exercising lightly, that is, during a cool-down period. It is not known whether heart rate recovery predicts mortality when measured in the absence of a cool-down period or after accounting for left ventricular systolic function. Methods and Results We followed 5438 consecutive patients without a history of heart failure or valvular disease referred for exercise echocardiography for 3 years. Heart rate recovery was defined as the difference in heart rate between peak exercise and 1 minute later; a value ≤18 beats per minute was considered abnormal. Patients assumed the left lateral decubitus position after exercise. An abnormal heart rate recovery was present in 805 patients (15%); during follow-up, 190 died. An abnormal heart rate recovery was predictive of death (9% versus 2%, hazard ratio [HR] 3.9, 95% CI 2.9 to 5.3, P P Conclusions Even in the absence of a cool-down period and even after accounting for left ventricular systolic function, heart rate recovery is a powerful and independent predictor of death.

Background —An abnormally low chronotropic response and an abnormally high ventilatory response (V̇ e /V̇ co 2 ) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. Methods and Results —Consecutive patients with heart failure referred for metabolic stress testing who were not taking β-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V̇ o 2 and V̇ e /V̇ co 2 were directly measured. Chronotropic index and peak V̇ o 2 were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V̇ e /V̇ co 2 was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high V̇ e /V̇ co 2 , low chronotropic index, low V̇ o 2 , low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V̇ e /V̇ co 2 and peak V̇ o 2 , it is possible to identify low, intermediate, and very high risk groups. In multivariate analyses, the only independent predictors of death were high V̇ e /V̇ co 2 (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P P =0.0009). Conclusions —The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.

The past 50 years have witnessed sea changes in cardiovascular medicine and research.1 We came to recognize untreated hypertension as a highly malignant disorder and to recognize that medical treatment of hypertension leads to marked reductions in risk of stroke, myocardial infarction, and premature death. We also came to recognize the power of the randomized trial for assessing candidate strategies for prevention and treatment. Indeed, mega-trials conducted by cardiovascular clinician scientists have played a critical role in defining nearly every major evidence-based intervention, from hypertension treatment to cholesterol reduction and use of aspirin.1

Background Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality. These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome. This investigation was designed to look at the prognostic implications of exercise heart rate response in a population-based sample. Methods and Results In this prospective cohort investigation, 1575 male participants (mean age, 43 years) in the Framingham Offspring Study who were free of coronary heart disease, who were not taking β-blockers, and who underwent submaximal treadmill exercise testing (Bruce protocol) were studied. Heart rate response was assessed in three ways: (1) failure to achieve 85% of the age-predicted maximum heart rate, which has been the traditional definition of chronotropic incompetence; (2) the actual increase in heart rate from rest to peak exercise; and (3) the ratio of heart rate to metabolic reserve used by stage 2 of exercise (“chronotropic response index”). Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up. Failure to achieve target heart rate occurred in 327 (21%) subjects. During follow-up there were 55 deaths (14 caused by coronary heart disease) and 95 cases of incident coronary heart disease. Failure to achieve target heart rate, a smaller increase in heart rate with exercise, and the chronotropic response index were predictive of total mortality and incident coronary heart disease ( P P =.02). After adjusting for the same factors, the increase in exercise heart rate remained inversely predictive of total mortality ( P =.04) and coronary heart disease incidence ( P =.0003). The chronotropic response index also was predictive of total mortality ( P =.05) and incident coronary heart disease ( P =.001) after adjusting for age and other risk factors. Conclusions An attenuated heart rate response to exercise, a manifestation of chronotropic incompetence, is predictive of increased mortality and coronary heart disease incidence.

Clinicians have long been aware that patients capable of high levels of physical exertion have a better prognosis than those with limited exercise capacity. Although the initial clinical encounter usually suffices to gain a qualitative appreciation of functional capacity, more precision can be obtained from formal graded exercise testing. In both asymptomatic subjects and patients with clinical coronary artery disease (CAD), exercise-based measures of functional capacity repeatedly have been shown to provide powerful independent prognostic information.1,2 Yet when decisions are made about the role and value of exercise testing in clinical cardiology, the focus is inevitably on measures believed to reflect the state of the coronary arterial circulation and the potential need for angiography and revascularization. The widespread tendency to ignore exercise capacity in clinical management seems to be a function of a general uncertainty about its therapeutic implications. Stress-induced ischemia may be less important prognostically, but its message seems clear: Fix the plumbing. See p 1554 In symptomatic CAD patients, exercise capacity typically is used to provide the context in which ischemic responses are interpreted.3 Thus, ischemia in the setting of poor exercise capacity means high risk, whereas in the setting of good exercise capacity, ischemia (even when measured with nuclear perfusion techniques) has little prognostic impact.4 In asymptomatic subjects, in whom evidence of ischemia is quite infrequent, the utility of exercise capacity has been more of a puzzle. In the American College of Cardiology/American Heart Association Exercise Testing Guidelines,5 exercise testing for routine screening of asymptomatic men and women was rated a Class III indication (ie, not useful). The use of exercise testing in asymptomatic persons with multiple risk factors as a guide to risk reduction therapy was rated a Class IIb indication (ie, usefulness not well established).6 These recommendations reflect concerns about …

It is essential that the medical profession play a central role in critically evaluating the evidence related to drugs, devices, and procedures for the detection, management, or prevention of disease. Properly applied, rigorous, expert analysis of the available data documenting absolute and relative benefits and risks of these therapies and procedures can improve the effectiveness of care, optimize patient outcomes, and favorably affect the cost of care by focusing resources on the most effective strategies. One important use of such data is the production of clinical practice guidelines that, in turn, can provide a foundation for a variety of other applications, such as performance measures, appropriate use criteria, clinical decision support tools, and quality improvement tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force) is charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, and the Task Force directs and oversees this effort. Writing committees are charged with assessing the evidence as an independent group of authors to develop, update, or revise recommendations for clinical practice. Experts in the subject under consideration have been selected from both organizations to examine subject-specific data and write guidelines in partnership with representatives from other medical practitioner and specialty groups. Writing committees are specifically charged to perform a formal literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and clinical outcomes constitute …

Background— Health-related quality-of-life instruments have become important measures of early health outcomes after cardiac surgery. The relationship between quality of life after recovery from surgery and subsequent long-term survival has not previously been explored. Our objective was to determine whether the Duke Activity Status Index (DASI) was predictive of subsequent time-related survival after recovery from cardiac surgery. Methods and Results— We examined survival status among 6305 patients who underwent isolated coronary artery bypass grafting with or without valve procedures or isolated valve procedure between May 1995 and June 1998 who had a preoperative baseline and follow-up DASI. The postoperative DASI was administered nominally at 6 and 12 months. Baseline and perioperative variables and postoperative morbid events were prospectively collected concurrently with patient care. The end point was all-cause mortality. The Social Security Death Index was queried for survival status. Cox proportional-hazards analysis was used to study the associations between DASI, a number of traditional risk factors, and survival. Median follow-up was 8.6 years. The “dose-response” relationship between baseline and follow-up DASI and risk of long-term death was established. Follow-up DASI was associated with risk-adjusted long-term survival hazard ratio of 0.98 per unit increase (confidence limits, 0.97 to 0.98; P P =0.0005). Conclusions— Poor health-related quality of life after recovery from cardiac surgery identifies patients who are at risk for reduced long-term survival.

Background— Peak oxygen uptake (peak V̇ o 2 ) is a strong predictor of mortality and is commonly used in the evaluation of patients for cardiac transplantation. β-Blockers reduce mortality in patients with heart failure, without influencing peak V̇ o 2 , raising the possibility that peak V̇ o 2 is no longer suitable as an indicator of prognosis in these patients. Methods and Results— We analyzed prospectively gathered data on 2105 patients referred for cardiopulmonary testing for all-cause mortality and for occurrence of death or transplantation. Patients receiving β-blockers were younger, more likely to have coronary disease, and had a greater mean ejection fraction but had a similar peak V̇ o 2 . There were 555 deaths (26%) and 194 (9%) transplants during a median follow-up of 3.5 years. Peak V̇ o 2 was a predictor of mortality irrespective of β-blocker use; a decrease of 1 mL · kg −1 · min −1 resulted in an adjusted hazard ratio (HR) of 1.13 (95% CI 1.09 to 1.17, P P o 2 values became very low (≈10 mL · kg −1 · min −1 ), at which level survival rates were equally poor. Conclusion— Peak V̇ o 2 is a determinant of survival in patients in heart failure even in the setting of β-blockade. Because of improved survival in patients treated with β-blockers, the cut point value of 14 mg · kg −1 · min −1 for referral for cardiac transplantation in these patients requires reevaluation, and a lower cut point may be more appropriate.

This article updates the 1994 American Heart Association scientific statement on cardiac rehabilitation. It provides a review of recommended components for an effective cardiac rehabilitation/secondary prevention program, alternative ways to deliver these services, recommended future research directions, and the rationale for each component of the rehabilitation/secondary prevention program, with emphasis on the exercise training component.

Background— Although most randomized clinical trials have suggested that long-term survival rates after percutaneous coronary intervention (PCI) or surgical multivessel coronary revascularization (CABG) are equivalent, some post hoc analyses in high-risk groups and adjustment for severity of coronary disease have suggested higher mortality after PCI. Methods and Results— We studied 6033 consecutive patients who underwent revascularization in the late 1990s. PCI was performed in 872 patients; 5161 underwent CABG. Half the patients had significant left ventricular dysfunction or diabetes. Propensity analysis to predict the probability of undergoing PCI according to 22 variables and their interactions was used. The C-statistic for this model was 0.90, indicating excellent discrimination between treatments. There were 931 deaths during 5 years of follow-up. The 1- and 5-year unadjusted mortality rates were 5% and 16% for PCI and 4% and 14% for CABG (unadjusted hazard ratio, 1.13; 95% CI, 1.0 to 1.4; P =0.07). PCI was associated with an increased risk of death (propensity-adjusted hazard ratio, 2.3; 95% CI, 1.9 to 2.9; P P ≤0.01 for all) were renal dysfunction, age, diabetes mellitus, chronic lung disease, peripheral vascular disease, left main trunk stenosis, and extent of coronary disease (Duke angiographic score). Conclusions— In patients with multivessel coronary artery disease and many high-risk characteristics, CABG was associated with better survival than PCI after adjustment for risk profile.

Background — Logical Analysis of Data is a methodology of mathematical optimization on the basis of the systematic identification of patterns or “syndromes.” In this study, we used Logical Analysis of Data for risk stratification and compared it to regression techniques. Methods and Results — Using a cohort of 9454 patients referred for exercise testing, Logical Analysis of Data was applied to identify syndromes based on 20 variables. High-risk syndromes were patterns of up to 3 findings associated with >5-fold increase in risk of death, whereas low-risk syndromes were associated with >5-fold decrease. Syndromes were derived on a randomly derived training set of 4722 patients and validated in 4732 others. There were 15 high-risk and 26 low-risk syndromes. A risk score was derived based on the proportion of possible high risk and low risk syndromes present. A value ≥0, meaning the same or a greater proportion of high-risk syndromes, was noted in 979 patients (21%) in the validation set and was predictive of 5-year death (11% versus 1%, hazard ratio 8.3, 95% CI 5.9 to 11.6, P Conclusion — Using the Logical Analysis of Data method, we identified subsets of patients who had an increased risk and who also accounted for the majority of deaths. Future research is needed to determine how best to use this technique for risk stratification.

Background Established methods of risk assessment in percutaneous coronary intervention have focused on clinical and anatomical lesion characteristics. Emerging evidence indicates the substantial contribution of inflammatory processes to short-term and long-term outcomes in coronary artery disease. Methods and Results Within a single-center registry of contemporary percutaneous coronary revascularization strategies with postprocedural creatine kinase and clinical events routinely recorded, we assessed the association of baseline C-reactive protein with death or myocardial infarction within the first 30 days. Predictive usefulness of baseline C-reactive protein within the context of established clinical and angiographic predictors of risk was also examined. Among 727 consecutive patients, elevated baseline C-reactive protein before percutaneous coronary intervention was associated with progressive increase in death or myocardial infarction at 30 days (lowest quartile, 3.9%, versus highest quartile, 14.2%; P =0.002). Among clinical and procedural characteristics, baseline C-reactive protein remained independently predictive of adverse events, with the highest quartile of C-reactive protein associated with an odds ratio for excess 30-day death or myocardial infarction of 3.68 (95% CI, 1.51 to 8.99; P =0.004). A predictive model that included baseline C-reactive protein quartiles, American College of Cardiology/American Heart Association lesion score, acute coronary syndrome presentation, and coronary stenting appears strongly predictive of 30-day death or myocardial infarction within this population (C-statistic, 0.735) and among individual patients (Brier score, 0.006). Conclusions Elevated baseline C-reactive protein portends heightened risk of 30-day death or myocardial infarction after coronary intervention. Coupled anatomic, clinical, and inflammatory risk stratification demonstrates strong predictive utility among patients undergoing percutaneous coronary intervention and may be useful for guiding future strategies.

To the Editor: We read with great interest the article by Robbins et al1 describing how exercise-related ventilatory and heart rate responses better predict heart failure mortality than peak exercise oxygen consumption.2 Although Robbins et al1 correctly state that other investigators have shown that exercise-related ventilatory abnormalities can be useful in predicting mortality,3 they fail to acknowledge the fact that our group4 previously published similar findings, which demonstrated that ventilatory abnormalities were related to outcome in congestive heart failure. Importantly, we demonstrated that by combining ventilatory abnormalities and peak exercise oxygen consumption, patients at a particularly high …

Background —Although systolic blood pressure (SBP) response to exercise has been shown to predict subsequent hypertension in small samples of men, this association has not been studied in a large population-based sample of middle-aged men and women. The purpose of this study was to examine, in normotensive subjects, the relations of SBP and diastolic blood pressure (DBP) during the exercise and recovery periods of a graded treadmill test to the risk of developing new-onset hypertension. Methods and Results —BP data from exercise testing in 1026 men and 1284 women (mean age, 42±10 years; range, 20 to 69 years) from the Framingham Offspring Study who were normotensive at baseline were related to the incidence of hypertension 8 years later. New-onset hypertension, defined as an SBP ≥140 mm Hg or DBP ≥90 mm Hg or the initiation of antihypertensive drug treatment, occurred in 228 men (22%) and 207 women (16%). Exaggerated SBP (Ex-SBP 2) and DBP (Ex-DBP 2) response and delayed recovery of SBP (R-SBP 3) and DBP (R-DBP 3) were defined as an age-adjusted BP greater than the 95th percentile during the second stage of exercise and third minute of recovery, respectively. After multivariable adjustment, Ex-DBP 2 was highly predictive of incident hypertension in both men (OR, 4.16; 95% CI, 2.15, 8.05) and women (OR, 2.17; CI, 1.19, 3.96). R-SBP 3 was predictive of hypertension in men in a multivariable model that included exercise duration and peak exercise BP (OR, 1.92; CI, 1.00, 3.69). Baseline resting SBP (χ 2 , 23.4 in men and 34.7 in women) and DBP (χ 2 , 11.3 in men and 13.1 in women) had stronger associations with new-onset hypertension than exercise DBP (χ 2 , 16.4 in men and 6.1 in women) and recovery SBP (χ 2 , 6.5 in men and 2.1 in women) responses. Conclusions —An exaggerated DBP response to exercise was predictive of risk for new-onset hypertension in normotensive men and women. An elevated recovery SBP was predictive of hypertension in men. These findings may reflect subtle pathophysiological features in the preclinical stage of hypertension.

Background In this study, we sought to determine whether cigarette smoking is associated with chronotropic incompetence and to explore prognostic implications of this association. Methods and Results Members of the Framingham Offspring Study (1468 men and 1642 women) underwent graded exercise. Chronotropic incompetence was assessed in two ways: (1) failure to achieve an age-predicted target heart rate and (2) a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate, and physical fitness. Smokers were more likely to fail to reach target heart rate than were nonsmokers (men, 25% versus 15%, odds ratio [OR], 1.97; 95% confidence interval [CI], 1.51 to 2.56; women, 32% versus 18%; OR, 2.10; 95% CI, 1.63 to 2.61) and were more likely to have a low chronotropic index (men, 17% versus 12%; OR, 1.50; 95% CI, 1.12 to 2.03; women, 17% versus 8%; OR, 2.28; 95% CI, 1.68 to 3.09). These associations persisted after adjustment for age, cardiovascular risk factors, pulmonary function, and ST-segment response to graded exercise. During 8 years of follow-up, there were 48 deaths and 90 incident coronary heart disease events among the men. After adjustment for the same confounders, men who were smokers and failed to achieve target heart rate were at particularly high risk for death (adjusted relative risk [RR], 2.45; 95% CI, 1.14 to 5.24) and for coronary heart disease (adjusted RR, 4.92; 95% CI, 2.84 to 8.53). There were too few end points in women for analysis. Conclusions In this population-based cohort, cigarette smoking was predictive of chronotropic incompetence. Male smokers who manifested chronotropic incompetence were at particularly high risk for death and coronary heart disease events.

In this issue of Circulation , Khan and colleagues present the results of an elegantly performed meta-analysis of the prognostic implications of elevated levels of troponin T and I among asymptomatic patients with end-stage renal disease.1 After systematically collating the results of 28 cohort studies involving 3931 patients, they noted that an elevated troponin T level identified a group of end-stage renal disease patients with high mortality risk. Although elevated troponin I was also associated with increased risk, the exact effect size was difficult to assess because of a lack of standardization of current assays. The authors noted that despite the consistent association between elevated troponin T and mortality, the effect might be overestimated because of publication bias and study heterogeneity. Nonetheless, this meta-analysis, along with the specific reports of the largest published cohort studies,2,3 provides robust evidence that troponin T elevation in the setting of end-stage renal disease is ominous. Article p 3088 The development of troponin measurement in the absence of end-stage renal disease is an excellent paradigm for the modern evolution of clinical tests. Troponin T and troponin I are both integral parts of the cardiac muscle infrastructure and play critical roles in excitation-contraction coupling.4 The diagnostic importance of troponin elevation stems from its release into the bloodstream when there is some type of damage to cardiac myocyte cell-wall integrity.5 The high sensitivity of troponin for detecting even small myocardial infarctions has led to widespread recommendations for its routine measurement for the diagnosis of myocardial infarction.6 It could be argued, though, that were elevated troponin to diagnose myocardial infarctions that were of little prognostic …

Background Heart rate (HR) response to exercise plays an important role in the diagnosis of coronary artery disease (CAD). Adjustment of ST-segment depression for the change in HR with exercise increases the accuracy of the exercise ECG in the detection of CAD. In addition, an attenuated HR response to exercise, a manifestation of chronotropic incompetence, may have independent diagnostic value for CAD. Methods and Results The diagnostic value of adjusting the magnitude of ST-segment depression, the ST-segment (ST)/HR index, and the ST/HR slope for chronotropic response to exercise was assessed in 283 control subjects and 337 patients with CAD by dividing each ST measurement by the fraction of HR reserve achieved. At a matched specificity of 96%, ST-segment depression of >160 μV identified CAD with a sensitivity of 52%, an ST/HR index of >1.69 μV/bpm identified CAD with a sensitivity of 90%, and an ST/HR slope of >2.96 μV/bpm identified CAD with a sensitivity of 88%. Adjustment for HR reserve improved the sensitivity of each method: adjusted ST-segment depression of >176 had a sensitivity of 87% ( P 2.14 had a sensitivity of 94% ( P =.005), and an adjusted ST/HR slope of >3.47 had a sensitivity of 93% ( P =.0001). In addition, the 94% and 93% sensitivities of the adjusted ST/HR index and ST/HR slope were significantly greater than the 87% sensitivity of adjusted ST-segment depression ( P Conclusions Correction for an attenuated HR response to exercise improves performance of the simple and HR-adjusted ST-segment depression criteria for the identification of CAD. These findings support assessment of the degree of chronotropic reserve in routine evaluation of the exercise ECG.