Search

Objective The Patient-Centered Outcomes Research Institute (PCORI) uses a unique approach to Merit Review that includes patients and stakeholders as reviewers with scientists, and includes unique review criteria (patient-centeredness and active engagement of end users in the research). This study assessed the extent to which different reviewer types influence review scores and funding outcomes, the emphasis placed on technical merit compared to other criteria by a multistakeholder panel, and the impact of the in-person discussion on agreement among different reviewer types. Methods Cross-sectional analysis of administrative data from PCORI online and in-person Merit Review (N = 1312 applications from the five funding cycles from November 2013 to August 2015). Linear and logistic regression models were used to analyze the data. Results For all reviewer types, final review scores were associated with at least one review criterion score from each of the three reviewer types. The strongest predictor of final overall scores for all reviewer types was scientists’ prediscussion ratings of technical merit. All reviewers’ prediscussion ratings of the potential to improve health care and outcomes, and scientists’ ratings of technical merit and patient-centeredness, were associated with funding success. For each reviewer type, overall impact scores from the online scoring were changed on at least half of the applications at the in-person panel discussion. Score agreement across reviewer types was greater after panel discussion. Conclusions Scientist, patient, and stakeholder views all contribute to PCORI Merit Review of applications for research funding. Technical merit is critical to funding success but patient and stakeholder ratings of other criteria also influence application disposition.

Imagine a world where we are able to prevent and pre-empt the burden of cardiovascular, lung, and blood diseases, a world where we are able to capture the promise of personalized precision medicine, where each person receives the right treatment, tailored to his or her needs, at the right time. In

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC Eric R. Bates, MD, FACC Salvatore Costa, MD, FACC Lori Daniels, MD, FACC Akshay Desai, MD, FACC Douglas E. Drachman, MD, FACC Susan Fernandes, LPD, PA-C Rosario

Comparative effectiveness research (CER) aims to provide decision makers with the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart, Lung, and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address 8 clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER.

Over the past 50 years, we have seen dramatic changes in cardiovascular science and clinical care, accompanied by marked declines in the morbidity and mortality. Nonetheless, cardiovascular disease remains the leading cause of death and disability in the world, and its nature is changing as Americans become older, fatter, and ethnically more diverse. Instead of young or middle-aged men with ST-segment elevation myocardial infarction, the “typical” cardiac patient now presents with acute coronary syndrome or with complications related to chronic hypertension or ischemic heart disease, including heart failure, sudden death, and atrial fibrillation. Analogously, structural heart disease is now dominated by degenerative valve or congenital disease, far more common than rheumatic disease. The changing clinical scene presents cardiovascular scientists with a number of opportunities and challenges, including taking advantage of high-throughput technologies to elucidate complex disease mechanisms, accelerating development and implementation of evidence-based strategies, assessing evolving technologies of unclear value, addressing a global epidemic of cardiovascular disease, and maintaining high levels of innovation in a time of budgetary constraint and economic turmoil.

A few weeks ago Alberts et al published a PNAS Perspective with the attention-grabbing title “Rescuing US Biomedical Research From It Systematic Flaws.”(1) The authors noted that we suffer from “a severe imbalance between the dollars available for research and the still growing scientific community in United States.” At the National Institutes of Health (NIH), we are painfully aware of this, as over the past 10 years we have seen a steady decline in purchasing power, while the number of grant applications has increased and success rates have decreased. In 2000, while the NIH-doubling was still underway, 32% of R01 grant applications were funded; in 2013, that proportion had fallen to 17%.(2)

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 …

Alice K. Jacobs, MD, FACC, FAHA, Chair, 2009–2011 Sidney C. Smith, Jr, MD, FACC, FAHA, Immediate Past Chair, 2006–2008 [⁎⁎⁎][1] Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect Nancy Albert, PhD, CCNS, CCRN Christopher E. Buller, MD, FACC[⁎⁎⁎][1] Mark A. Creager, MD, FACC

In July of 2008, the National Heart, Lung, and Blood Institute convened experts in noninvasive cardiovascular imaging, outcomes research, statistics, and clinical trials to develop recommendations for future randomized controlled trials of the use of imaging in: 1) screening the asymptomatic patient for coronary artery disease; 2) assessment of patients with stable angina; 3) identification of acute coronary syndromes in the emergency room; and 4) assessment of heart failure patients with chronic coronary artery disease with reduced left ventricular ejection fraction. This study highlights several possible trial designs for each clinical situation.

Background Abnormal microvolt T-wave alternans (MTWA) and low peak oxygen consumption (VO 2 ) both predict poor outcome in heart failure. However, their independent predictive properties have not been assessed in large-scale cohorts. Methods This was an observational prospective cohort study of 303 consecutive patients referred for metabolic stress testing. All had an ejection fraction ≤ 40% and were considered candidates for transplantation. The exercise laboratory did not collect MTWA data from patients with implanted pacemakers or defibrillators. The primary end point was a composite of all-cause death or United Network for Organ Sharing status 1 transplantation. Results During a 2.8-year period, there were 34 deaths and 17 transplantations. Patients with abnormal MTWA had a higher event rate of 23% (31 of 136) vs 12% (20 of 167), with an unadjusted hazard ratio (HR) of 1.90 (95% confidence interval [CI], 1.90–3.33; p = 0.03). The association remained significant after adjustment for 3 clinical variables (HR, 1.89; 95% CI, 1.05–3.39; p = 0.03). After adding peak VO 2 to the model, the association was no longer significant (adjusted HR, 1.18; 95% CI, 0.64–2.17, p = 0.60). After accounting for peak VO 2 and 28 other confounders in a matched propensity analysis, MTWA was not predictive (propensity-matched HR, 0.79; 95% CI, 0.37–1.66; p = 0.53). Conclusions These results confirm the association of abnormal MTWA with poor outcome amongst patients with impaired left ventricular systolic function. However, this association is markedly attenuated after accounting for peak VO 2 .

ObjectivesWe sought to examine the short- and long-term outcomes of blood transfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI).BackgroundThe short- and long-term consequences of blood transfusion in anemic patients with recent STEMI remain controversial.MethodsWe evaluated 30-day, 6-month, and 1-year all-cause mortality among 4,131 STEMI patients enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial. Patients were categorized according to whether they received a blood transfusion during hospitalization. Cox proportional hazards survival models with transfusion as a time-dependent covariate were conducted for the whole and for the propensity-matched groups. Additionally, a series of sensitivity analyses assessed the magnitude of hidden bias that would need to be present to explain the associations actually observed.ResultsDeath at 30 days (13.7% vs. 5.5%), 6 months (19.7% vs. 6.9%), and 1 year (21.8% vs. 8.7%) was significantly higher for transfused patients than for nontransfused patients, respectively. After adjusting for over 25 baseline characteristics, nadir hemoglobin, and propensity score for transfusion, and using transfusion as a time-dependent covariate, transfusion remained significantly associated with increased risk of mortality at 30 days (hazard ratio [HR]: 3.89, 95% confidence interval [CI]: 2.66 to 5.68, p < 0.001), 6 months (HR: 3.63, 95% CI: 2.67 to 4.95, p < 0.001), and 1 year (HR: 3.03, 95% CI: 2.25 to 4.08, p < 0.001). Similar results were observed in the propensity-matched patients.ConclusionsBlood transfusion is associated with increased short- and long-term mortality in the setting of STEMI.

The International Classification of Diseases, Tenth Revision, defines sudden cardiac death (SCD) as death due to any cardiac disease that occurs out of hospital, in an emergency department, or in an individual reported dead on arrival at a hospital. In addition, death must have occurred within 1

Meta-analyses showed that exercise training decreased mortality in patients after myocardial infarction, but no single adequately powered trial has shown this benefit. The purpose of this study was to evaluate the effect of cardiac rehabilitative exercise training on prognostic variables derived from the exercise tolerance test and whether these changes had an effect on predicted cardiovascular and all-cause mortality using externally validated risk scores. Two hundred ten consecutive patients who completed a 12-week cardiac rehabilitation program were analyzed. Peak MET level, heart rate recovery, chronotropic index, Duke prognostic score, and Cleveland Clinic Foundation risk score obtained at program entry and exit were compared. All prognostic variables and risk score-derived predicted 5-year mortality rates improved significantly after cardiac rehabilitation. Exercise capacity increased by 32% (6.6 +/- 2.7 to 8.7 +/- 2.9 METS; p0.0001), heart rate recovery increased by 20% (15 +/- 9 to 18 +/- 10 beats/min; p0.0001), and chronotropic index increased by 11% (56 +/- 22% to 62 +/- 22%; p0.0001). Duke prognostic score 5-year predicted cardiovascular mortality rate decreased by 33% (6 +/- 4% to 4 +/- 2%; p0.0001), and Cleveland Clinic Foundation risk score 5-year predicted total mortality rate decreased by 40% (5 +/- 7% to 3 +/- 5%; p0.0001). These improvements remained significant in high-risk subgroups. When controlled for age, gender, diabetes, MET level achieved, ejection fraction, and beta-blocker use, changes remained significant (p0.0001) for each outcome measure. In conclusion, exercise training in supervised cardiac rehabilitation programs significantly improved exercise capacity, measures of chronotropic dynamics, and prognostic risk scores. These differences translate into a decrease in predicted mortality.

ObjectivesThe purpose of this study was to externally validate the prognostic value of age- and gender-based nomograms and categorical definitions of impaired exercise capacity (EC).BackgroundExercise capacity predicts death, but its use in routine clinical practice is hampered by its close correlation with age and gender.MethodsFor a median of 5 years, we followed 22,275 patients without known heart disease who underwent symptom-limited stress testing. Models for predicted or impaired EC were identified by literature search. Gender-specific multivariable proportional hazards models were constructed. Four methods were used to assess validity: Akaike Information Criterion (AIC), right-censored c-index in 100 out-of-bootstrap samples, the Nagelkerke Index R2, and calculation of calibration error in 100 bootstrap samples.ResultsThere were 646 and 430 deaths in 13,098 men and 9,177 women, respectively. Of the 7 models tested in men, a model based on a Veterans Affairs cohort (predicted metabolic equivalents [METs] = 18 − [0.15 × age]) had the highest AIC and R2. In women, a model based on the St. James Take Heart Project (predicted METs = 14.7 − [0.13 × age]) performed best. Categorical definitions of fitness performed less well. Even after accounting for age and gender, there was still an important interaction with age, whereby predicted EC was a weaker predictor in older subjects (p for interaction

Although peak oxygen consumption (VO(2)) during exercise is frequently used to help predict optimal timing for heart transplantation, its long-term prognostic value in women is not known. We followed 2,105 adult patients with heart failure (HF) and with impaired left ventricular (LV) systolic function for 5 years, including 525 women (25%) who underwent metabolic stress testing between January 1995 and December 2002. Multivariable proportional hazards modeling related VO(2) to survival with adjustments for30 confounders and with transplantation considered as a time-dependent covariate. During follow-up, 129 women (26%) died, as did 572 men (36%). There were 175 transplants, including 34 women. Women and men were similar in age (54 vs 55 years), but women were less likely to have coronary artery disease (28% vs 58%). Peak VO(2) was strongly predictive of time to death in women (adjusted hazard ratio [HR] for peak VO(2) decreasing from 15 to 14 ml/kg/min, 1.11, 95% confidence interval [CI] 1.05 to 1.18, p0.0001) and in men (adjusted HR 1.12, 95% CI 1.08 to 1.16, p0.0001). There was no gender interaction with peak VO(2) (p = 0.80), but for any given peak VO(2) women were at lower risk (adjusted HR for men compared with women 2.22, 95% CI 1.58 to 3.10, p0.0001). A significant interaction was found between gender and presence of coronary artery disease (p for interaction 0.02); in women, those with ischemic cardiomyopathy had a worse survival for any given peak VO(2). In conclusion, in this large cohort, peak VO(2) predicted survival in women and men whether or not coronary artery disease was present, but an interaction was noted between coronary artery, gender, and survival.

ObjectivesThe aim of this work was to determine whether mitral valve (MV) annuloplasty benefits patients with moderate/severe (3+/4+) functional ischemic mitral regurgitation (MR) who undergo coronary artery bypass grafting (CABG).BackgroundMitral regurgitation is a strong predictor of poor outcomes in patients with ischemic cardiomyopathy; whether correcting it at the time of CABG improves outcomes is less certain.MethodsFrom 1991 to 2003, 390 patients with 3+/4+ ischemic MR had CABG with (n = 290) or without (n = 100) MV annuloplasty. Groups were propensity-matched using demographics, extent of coronary disease, regional wall motion, and quantitative electrocardiography. Survival, echocardiographic severity of MR, and New York Heart Association (NYHA) functional class were compared.ResultsOne-, 5-, and 10-year survival was 88%, 75%, and 47% after CABG alone and 92%, 74%, and 39% after CABG + MV annuloplasty (p = 0.6). Mortality was increased in patients with severe lateral wall motion abnormalities (p = 0.05), ST-segment elevation in lateral leads (p < 0.004), and higher QRS voltage sum (p < 0.0001). Patients undergoing CABG alone were more likely to have 3+/4+ postoperative MR than those undergoing CABG + MV annuloplasty (48% vs. 12% at 1 year, p < 0.0001). The NYHA functional class substantially improved in both groups (p < 0.001) and remained improved; at 5 years, 23% of patients having CABG + mitral annuloplasty and 25% having CABG alone were in NYHA functional class III/IV.ConclusionsAlthough CABG + MV annuloplasty reduces postoperative MR and improves early symptoms compared with CABG alone, it does not improve long-term functional status or survival in patients with severe functional ischemic MR. The MV annuloplasty in this setting, without addressing fundamental ventricular pathology, is insufficient to improve long-term clinical outcomes.

Objectives We examined the safety and efficacy of nonculprit multivessel compared with culprit-only stenting in patients with multivessel disease presenting with unstable angina or non–ST-segment elevation myocardial infarction (non–ST-segment elevation acute coronary syndromes [NSTE-ACS]). Background In patients presenting with NSTE-ACS, multivessel coronary artery disease (CAD) is associated with adverse outcome. Methods Patients with multivessel CAD and NSTE-ACS that underwent percutaneous coronary intervention were included. The culprit lesion was defined by reviewing each patient’s angiographic report, electrocardiogram, echocardiogram and, if available, nuclear stress test. All patients had at least 2 vessels with ≥50% stenosis, and the angiographic severity of CAD was assessed using the Duke Prognostic Angiographic Score. Patients with coronary bypass grafts, chronic total occlusions, and those with uncertain culprit lesions were excluded. Our end point was the composite of death, myocardial infarction, or any target vessel revascularization. Results From January 1995 to June 2005, 1,240 patients with ACS and multivessel CAD underwent percutaneous coronary intervention with bare-metal stenting and met our study criteria. Of these, 479 underwent multivessel and 761 underwent culprit-only stenting. There were 442 events during a median follow-up of 2.3 years. Multivessel intervention was associated with lower death, myocardial infarction, or revascularization after both adjusting for baseline and angiographic characteristics (hazard ratio 0.80; 95% confidence interval 0.64 to 0.99; p = 0.04) and propensity matched analysis (hazard ratio 0.67; 95% confidence interval 0.51 to 0.88; p = 0.004). Conclusions In patients with multivessel CAD presenting with NSTE-ACS, multivessel intervention was significantly associated with a lower revascularization rate, which translated to a lower incidence of the composite end point compared with culprit-only stenting.

Preamble......379 Introduction......380 Consensus Statement Method......380 Introduction to CAC Measurement......381 Role of Risk Assessment in Cardiovascular Medicine......381 Matching Intensity of Intervention With Severity of Risk......382 Current Approaches to Global Risk Assessment and to

OBJECTIVES The purpose of this study was to develop 30-day and 1-year risk stratification models for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients that incorporate quantitative ST-segment depression and novel biomarkers. BACKGROUND Several novel biomarkers have changed the risk profile of ACS; thus, the reassessment of traditional indicators such as ST-segment depression in this new context is warranted. METHODS Multivariable logistic regression was used to identify significant predictors of 30-day death and death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded Arteries-IV ACS) trial between 1998 and 2000. RESULTS Among all other predictors, the degree of ST-segment depression had the highest prognostic value for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C-reactive protein was only predictive of long-term death. In contrast to mortality, the contribution of TnT to predicting 30-day death/MI increased, whereas NT-proBNP's role was attenuated. The discriminatory power was excellent (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day death/MI]; 0.81 [1-year]). CONCLUSIONS In this large contemporary study of NSTE-ACS patients, novel insights into risk stratification were observed-in particular, the utility of quantitative ST-segment depression and multiple biomarkers. Collection of these indicators in future NSTE-ACS populations is recommended to evaluate generalizability and clinical application of these findings.

Objectives: Exercise-induced QT/RR hysteresis exists when, for a given R-R interval, the QT interval duration is shorter during recovery after exercise than during exercise. We sought to assess the association between QT/RR hysteresis and imaging evidence of myocardial ischemia.Background: Because ischemia induces cellular disturbances known to decrease membrane action potential duration, we hypothesized a correlation between QT/RR and myocardial ischemia.Methods: We digitally analyzed 4-second samples of QT duration and R-R–interval duration in 260 patients referred for treadmill exercise stress and rest single photon emission computed tomography myocardial perfusion imaging; a cool-down period was used after exercise. None of the patients were in atrial fibrillation or used digoxin, and none had marked baseline electrocardiographic abnormalities. Stress and rest myocardial perfusion images were analyzed visually and quantitatively to define the extent and severity of stress-induced ischemia. QT/RR hysteresis was calculated using a computerized algorithm.Results: There were 82 patients (32%) who manifested myocardial ischemia by single photon emission computed tomography myocardial perfusion imaging. The likelihood of ischemia increased with increasing QT/RR hysteresis, with prevalence according to quartiles of 20%, 30%, 26%, and 49% (P = .003 for trend). In analyses adjusting for ST-segment changes, exercise capacity, heart rate recovery, and other confounders, QT/RR hysteresis was independently predictive of presence of myocardial ischemia (adjusted odds ratio for 100-point increase of QT/RR hysteresis, 1.61; 95% confidence interval, 1.22-2.12; P = .0008). QT/RR hysteresis was also predictive of severe ischemia.Conclusion: Exercise-induced QT/RR hysteresis is a strong and independent predictor of myocardial ischemia and provides additional information beyond that afforded by standard ST-segment measures.

Chronotropic incompetence, or an inability to increase heart rate during exercise, independently predicts death in patients not taking beta blockers. Whether it predicts death in patients taking beta blockers is not known. Consecutive patients (n = 3,736; mean age 58 +/- 11 years; 68% men), who were taking either metoprolol tartrate or atenolol and were referred for symptom-limited exercise testing from 1990 to 2002 at a major academic medical center, formed the prospective study cohort. None had heart failure, pacemakers, atrial fibrillation, or any electrocardiographic abnormalities. Patients were followed for a median of 4.5 years for all-cause mortality. Chronotropic response was defined as the percentage of heart rate reserve used. A value ofor =62%, which was noted in 813 patients (22%), was considered abnormal, meaning that chronotropic incompetence was present. There were 173 deaths. After adjusting for age, gender, heart rate at rest, standard risk factors, other medications, Duke treadmill score, and heart rate recovery, chronotropic incompetence predicted death (adjusted hazard ratio 1.94, 95% confidence interval 1.43 to 2.64, p0.0001). The association of chronotropic incompetence with death was present, irrespective of which drug was taken or the number of half-lives that had elapsed since the last dose. In conclusion, in patients taking beta blockers, chronotropic incompetence is independently predictive of death.

Objective The aim of the study was to derive and externally validate a mortality prediction rule for patients undergoing exercise testing. Background The prognostic value of exercise testing is increasingly appreciated. However, global prognosis estimates ideally should account for numerous routinely obtained variables, including demographics, risk factors, resting electrocardiogram, and multiple exercise test measures. Methods A prediction rule was derived by parametric hazards modeling on a derivation set of 46047 Cleveland Clinic patients (age 55 ± 11 years, 67% male) who had no history of heart failure, valve disease, or atrial fibrillation. Twenty-two variables covering demographics, risk factors, exercise hemodynamics, and electrocardiogram findings at rest and during exercise were considered. The resulting model included 16 variables and was tested on 4981 patients (age 50 ± 12 years, 55% male) who underwent exercise testing at West Virginia University. Results In the derivation cohort there were 3173 deaths during a mean of 7 years of follow-up, whereas in the validation cohort there were 180 deaths during a mean of 5 years of follow-up. Comparisons of predicted and observed death rates showed very good agreement among all patients across all spectrums of risk, as well as among prespecified high-risk subgroups. Model discrimination was also good, with c statistic of c = 0.79 in the derivation group and c = 0.81 in the validation cohort. Conclusions We have externally validated a mortality prediction rule for patients undergoing exercise testing and confirmed its accuracy among a wide spectrum of patients.

Background Although practice guidelines do not recommend routine exercise testing of patients after coronary stenting, several small studies have suggested that stress myocardial perfusion imaging can provide prognostic information about future adverse cardiac events. We sought to determine if exercise nuclear testing provides independent prognostic information in patients after coronary stenting. Methods We analyzed the outcomes of 370 patients who underwent dual isotope exercise nuclear scintigraphy at least 1 month after coronary stenting and had testing between April 1996 and May 2002. Patients were classified according to presence or absence of any ischemia. The primary endpoint was all-cause mortality or myocardial infarction (MI) during a median of 30 months (range 6-59) of follow-up. Results There were 86 patients (23%) who had ischemia. Major events—death or MI—occurred in 62 patients including 22 deaths. Among patients with no ischemia, the 30-month event rate was 9.1%, whereas among patients with ischemia, the event rate was 17.0% ( P = .001). After adjusting for age, sex, standard cardiac risk factors, cardiac history, left ventricular ejection fraction, angiographic findings, procedural variables, exercise capacity, and heart-rate dynamics, the presence of scintigraphic evidence of ischemia predicted death or MI (adjusted hazard ratio 2.08, 95% CI 1.21-3.56, P = .008). The presence of ischemia similarly predicted events in asymptomatic patients (adjusted hazard ratio 2.19, 95% CI 1.17-4.11, P = .015). Conclusions In patients with recent coronary stent placement, reversible nuclear perfusion defects independently predicted risk of death or MI.

Outcomes have improved significantly in pediatric cardiovascular disease in recent decades. The challenge now is to sustain these advances through innovative clinical trials, fundamental molecular investigations, genetics and genomics, and outreach to families, emphasizing the importance of participating in research. We describe several such efforts and provide a vision of the future for pediatric cardiovascular research.

Purpose Chest symptoms, along with standard cardiovascular risk factors, are commonly factored into pretest risk stratification of patients who are referred for stress testing. We sought to determine the independent prognostic value of chest symptoms. Methods We studied the outcomes of 10,870 patients referred for symptom-limited exercise testing who had no history of myocardial revascularization, heart failure, or arrhythmias. Chest symptoms were prospectively characterized according to prespecified definitions. Propensity analysis was used to account for differences in baseline and exercise characteristics. Results Typical angina was present in 635 patients (6%), atypical angina in 3408 (33%), nonanginal chest pain in 1805 (17%), and dyspnea in 841 (8%). The remaining 4181 patients (38%) were asymptomatic. During a mean follow-up of 4.3 years, there were 381 deaths. After propensity matching patients who had typical angina with asymptomatic patients, symptoms were not predictive of mortality (adjusted hazard ratio [HR] = 0.8; 95% confidence interval [CI]: 0.6 to 1.3; P = 0.4). Among patients who had chest pain, typical angina was associated with a highly significant risk of mortality as compared with nonanginal chest pain (HR = 2.7; 95% CI: 1.4 to 5.1; P = 0.002), but not compared with atypical angina (HR = 1.3; 95% CI: 0.9 to 2.1; P = 0.21). Conclusion After accounting for baseline and exercise characteristics, the presence of symptoms was not independently associated with increased mortality among patients undergoing testing for known or suspected coronary disease. Among patients who actually had chest pain, typical angina carried a higher mortality risk.

doi:10.1016/j.jtcvs.2004.03.039 N omori and colleagues demonstrate the relationship between contrast ratio derived from F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in cT1 N0 M0 lung adenocarcinoma and pathologic TNM classification, carcinoembryonic antigen levels, lymphatic and vascular invasion, pleural involvement, and tumor differentiation. These observations constitute the scientific merit of the study. Quite properly, the authors go on to ask what the findings mean and, in particular, what clinical inferences they suggest. Based on what appears to be 100% sensitivity of the imaging test, they conclude that if the contrast ratio is less than 0.5, “limited lung resection could be indicated, lymph node dissection or mediastinoscopy could be reduced, or both.” At the heart of these seemingly logically derived clinical inferences lies treachery. We must be quick to state that these same or similar inferences would be drawn by more than 90% of the readership, not just in this context but also in the general context of interpreting the accuracy of any diagnostic test; the authors are well within the mainstream. It is the rare reader who knows that the lid has been blown off many diagnostic tests, particularly the ones cardiologists and cardiac surgeons have come to rely on in ischemic heart disease. Heretofore, our training and backgrounds have been deficient in interpreting the accuracy of diagnostic testing. We have been misled by our ignorance. The data have not been false, but the interpretation and inferences have been.

Heart rate recovery (HRR) after exercise correlates with decreased vagal tone and mortality. Patients with COPD may have altered autonomic tone. We sought to determine the association of HRR with spirometry measures of pulmonary function.We analyzed 627 patients (mean [+/- SD] age, 58 +/- 12 years; 65% men; mean FEV(1), 2.6 +/- 0.9 L, 80 +/- 20% predicted; patients receiving inhaled beta(2) agonist therapy, 10%; patients receiving inhaled anticholinergic therapy, 3%; patients receiving inhaled steroids, 5%; patients receiving oral prednisone, 4%) who had undergone maximal exercise testing and had undergone pulmonary function tests1 year apart. Patients with heart failure, pacemakers, and atrial fibrillation were excluded. Abnormal HRR was defined as a fall in heart rate during the first minute after exercise ofor= 12 beats/min (or= 18 beats/min with stress echocardiography). Patients were divided into quartiles based on FEV(1) percent predicted.An abnormal HRR was seen in 229 patients (36%). The mean FEV(1) values broken into quartiles 1 to 4 were 54 +/- 11% predicted, 74 +/- 3% predicted, 87 +/- 4% predicted, and 106 +/- 10% predicted. In smokers and nonsmokers, a worsening FEV(1) percent predicted was associated with an abnormal HRR. In a multivariable model accounting for confounding factors including medications and functional capacity, the predictors of an abnormal HRR included FEV(1) percent predicted (adjusted odds ratio for 1 SD decrease, 1.32; 95% confidence interval, 1.07 to 1.65; p = 0.0004), impaired functional capacity, male gender, and age.Abnormalities found on spirometry are associated with abnormal HRR, which may reflect an altered autonomic tone associated with pulmonary dysfunction, either obstructive or restrictive in nature.

An attenuated systolic blood pressure recovery after exercise has been associated with the severity of atherosclerotic heart disease.For 6 years, we observed 12,379 patients who underwent symptom-limited exercise testing. We excluded patients receiving antihypertensive medication and patients with valvular disease, emphysema, end-stage renal disease, heart failure, left ventricular systolic dysfunction, and atrial fibrillation. Blood pressure recovery ratio was defined as the ratio of systolic blood pressure at 3 minutes into recovery to systolic blood pressure at peak exercise; this has been shown to correlate with angiographic severity of coronary disease.The blood pressure recovery ratios ranged from 0.36 to 1.62, with values for increasing quartiles of 0.72 +/- 0.05, 0.82 +/- 0.02, 0.88 +/- 0.02, and 0.99 +/- 0.07. During follow-up, there were 430 deaths (3%). Five-year Kaplan Meier survival rates were 0.975, 0.974, 0.969, and 0.966 in quartiles 1 to 4, respectively. Compared with patients in the lowest quartile of blood pressure recovery ratio, patients in the highest quartile were at somewhat increased risk (hazard ratio, 1.71; 95% CI, 1.31-2.24; P.001). However, after adjusting for age, sex, body mass index, resting heart rate and blood pressure, peak systolic blood pressure, heart rate recovery, exercise chronotropic response, cardiac history, and standard risk factors, this association was no longer present (adjusted hazard ratio, 1.05; 95% CI, 0.8-1.38; P =.74).In this low-risk population, abnormal systolic blood pressure recovery after exercise was not independently predictive of mortality after correcting for differences in baseline and exercise characteristics.

Background The prevalence of left ventricular systolic dysfunction (LVSD) among individuals at risk for heart failure (HF) and the feasibility of screening have not been clearly defined. This study determined the prevalence of LVSD with the use of a limited screening echocardiogram among patients with risk factors for HF but no prior HF. Methods General medicine patients ≥60 years of age with hypertension, diabetes, coronary artery disease, or previous myocardial infarction (MI) but no history of HF or reduced left ventricular ejection fraction (LVEF) were eligible. Medical history and symptoms of breathlessness were determined by interview and chart review; consenting patients underwent electrocardiography and echocardiography. The outcome was LVEF ≤45%, based on visual estimation from the echocardiogram. Results Of the 482 patients who completed the study, only 1 patient could not have the LVEF visually estimated. A total of 7.9% of patients had LVEF ≤45%. The prevalence was 15.4% among those with a prior MI and 6.7% among those without prior MI. In multivariate analysis, prior MI (adjusted odds ratio, 2.75; 95% CI, 1.14 to 6.64) and probable or definite left ventricular hypertrophy by electrocardiography (adjusted odds ratio, 3.57; 95% CI, 1.22 to 10.48) were the strongest predictors of LVEF ≤45%. Conclusions Screening for LVSD among high-risk patients is feasible and has substantial yield, even among patients without prior MI. In light of the low cost of screening and the available therapies to prevent progression of LVSD to overt HF, controlled clinical trials of screening high-risk subgroups appear to be justified.

We sought to determine whether abnormal heart rate recovery predicts mortality independent of the angiographic severity of coronary disease.An attenuated decrease in heart rate after exercise, or heart rate recovery (HRR), has been shown to predict mortality. There are few data on its prognostic significance once the angiographic severity of coronary artery disease (CAD) is ascertained.For six years we followed 2,935 consecutive patients who underwent symptom-limited exercise testing for suspected CAD and then had a coronary angiogram within 90 days. The HRR was abnormal ifor =12 beats/min during the first minute after exercise, except among patients undergoing stress echocardiography, in whom the cutoff wasor =18 beats/min. Angiographic CAD was considered severe if the Duke CAD Prognostic Severity Index wasor =42 (on a scale of 0 to 100), which corresponds to a level of CAD where revascularization is associated with better long-term survival.Severe CAD was present in 421 patients (14%), whereas abnormal HRR was noted in 838 patients (29%). There were 336 deaths (11%). Mortality was predicted by abnormal HRR (hazard ratio [HR] 2.5, 95% confidence interval [CI] 2.0 to 3.1; p0.0001) and by severe CAD (HR 2.0, 95% CI 1.6 to 2.6; p0.0001); both variables provided additive prognostic information. After adjusting for age, gender, standard risk factors, medications, exercise capacity, and left ventricular function, abnormal HRR remained predictive of death (adjusted HR 1.6, 95% CI 1.2 to 2.0; p0.0001); severe CAD was also predictive (adjusted HR 1.4, 95% CI 1.1 to 1.9; p = 0.008).Even after taking into account the angiographic severity of CAD, left ventricular function, and exercise capacity, HRR is independently predictive of mortality.

In the U.S., an estimated 40 million noninvasive cardiac tests are performed annually, and this rate has been increasing by as much as 20% per year [(1)][1]. This growth is part of a larger trend of progressive annual increases in total U.S. spending on medical care, which has accelerated over the

About 25 years ago, a group of researchers demonstrated that there is no such thing as the "hot hand" in professional basketball. When a player hits 5 or 7 shots in a row (or misses 10 in a row), what's at work is random variation, nothing more. However, random causes do not stop players, coaches, fans, and media from talking about and acting on "hot hands," telling stories and making choices that ultimately are based on randomness. The same phenomenon is true in medicine. Some clinical trials with small numbers of events yielded positive findings, which in turn led clinicians, academics, and government officials to talk, telling stories and sometimes making choices that were later shown to be based on randomness. I provide some cardiovascular examples, such as the use of angiotensin receptor blockers for chronic heart failure, nesiritide for acute heart failure, and cytochrome P-450 (CYP) 2C19 genotyping for the acute coronary syndromes. I also review the more general "decline effect," by which drugs appear to yield a lower effect size over time. The decline effect is due at least in part to over interpretation of small studies, which are more likely to be noticed because of publication bias. As funders of research, we at the National Heart, Lung, and Blood Institute seek to support projects that will yield robust, credible evidence that will affect practice and policy in the right way. We must be alert to the risks of small numbers.

Background Low-molecular-weight heparin (LMWH) has a more predictable anticoagulant effect than unfractionated heparin (UFH), is easier to administer, and does not require monitoring. Minimal data are available on LMWH combined with platelet glycoprotein (GP) IIb/IIIa inhibitors. Methods In the Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B (PARAGON B) trial, patients with an acute coronary syndrome were randomized to receive the IIb/IIIa inhibitor lamifiban or a placebo. To rigorously explore the potential benefits of LWMH and GP IIb/IIIa inhibition, we analyzed the rates of ischemic complications and safety outcomes in PARAGON B. Results Approximately one fifth of the patients received LMWH (805 vs 4395 UFH). For the overall cohort, the incidence of death/myocardial infarction (MI)/severe recurrent ischemia (SRI) was 12.2%, and this composite end point was numerically lowest in the lamifiban with LMWH group (10.2%). Similarly, the incidence of death/MI was 11.0% for the entire cohort and lowest in the lamifiban and LMWH group (9.0%). The lower event rate for patients taking LMWH in the lamifiban group was sustained at 6 months, with a lower revascularization rate (51.5% vs 42.8%) and a lower composite of death/MI (13.8% vs 11.9%). Bleeding was comparable in the 2 heparin groups (1.4% with UFH vs 0.9% with LMWH). The propensity adjusted odds ratio for 30-day revascularization was significantly lower with LMWH (odds ratio 0.67, 95% CI 0.57−0.79, P P =.465), death/MI at 30 days ( P =.264), and stroke at 30 days with the type of heparin use ( P =.201) after propensity risk adjustment. Conclusions In the PARAGON B trial, use of LMWH in conjunction with a GP IIb/IIIa inhibitor was safe and associated with a lower revascularization rate. These findings support the rationale and promise for combining GP IIb/IIIa blockers and LMWH for future management of acute coronary syndrome. (Am Heart J 2002;144:995-1002.)

OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival. BACKGROUND: The optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient < or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group. RESULTS: Despite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival.

Peak oxygen consumption, as measured by direct gas exchange analysis during exercise testing, is well established as a powerful and independent predictor of risk for death among patients with chronic, but stable, heart failure. Although there is still some debate about whether peak oxygen consumption should be indexed against a predicted value and what the best cut-off point may be, most authorities agree that peak oxygen consumption is such a powerful predictor of outcome that it routinely should be incorporated into the evaluation of all ambulatory heart transplant candidates. A few recent studies have demonstrated that a hyperventilatory response to exercise, as measured by the VE/VCO2 slope, also may be a powerful and independent predictor of death; however, more large studies, with large numbers of end-points, will be needed before this measure can deservedly take a place alongside peak oxygen consumption as a primary component of the heart failure staging process.

Exercise stress testing has traditionally been thought of as a means of diagnosing hemodynamically significant obstructive coronary artery disease (CAD), with primary attention paid to the behavior of the ST segment during and immediately after exercise. 19 Although extensive literature has demonstrated that exercise testing has some value for diagnostic purposes, particularly in patients with an intermediate pretest likelihood for having disease, 16,19 recent work has drawn attention to three serious limitations of exercise testing as a diagnostic modality. First, when compared to results of coronary angiography, ST-segment changes have only a modest sensitivity and specificity for detecting or excluding obstructive coronary lesions. 18 Second, almost every study done has suffered from sequential work-up bias, or verification bias, by which the performance of the gold standard coronary angiogram is at least in part determined by the results of the exercise test. This verification bias leads to overestimation of sensitivity and underestimation of specificity. 7,52 Indeed, a large recent study reported that the true sensitivity of exercise testing in a population free of work-up bias was only 40% to 50%. 17 Third, the gold standard itself, namely coronary angiography, suffers from its own inherent deficiencies, limiting its usefulness for accurately assessing severity of disease. 60 Over the past 10 to 15 years, increasing attention has been focused on the exercise test as a prognostic modality. As reviewed by Hlatky, 28 relatively few studies of prognosis have been reported because of the need for large sample sizes and long follow-up periods. Nonetheless, a number of groups have successfully followed large cohorts of patients who have undergone stress testing in a variety of settings and have been able to identify powerful markers of risk. 1,20,34,38,42,46,47,48,62 This review will focus on three measures that are routinely available in the vast majority of stress tests: the Duke exercise treadmill score, 41,42 the chronotropic response to exercise, 35,38 and heart rate recovery immediately after exercise. 8,9,47

Objectives: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. Methods: A total of 722 patients (67% men; age, 61 ± 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (≤5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. Results: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. Conclusion: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided. (J Thorac Cardiovasc Surg 2001;121:894-901)

OBJECTIVES The goal of this study was to determine the value of thallium201single photon emission computed tomography (SPECT) imaging for prediction of all-cause mortality when considered along with functional capacity and heart rate recovery. BACKGROUND Myocardial perfusion defects identified by thallium201SPECT imaging are predictive of cardiac events. Functional capacity and heart rate recovery are exercise measures that also have prognostic implications. METHODS We followed 7,163 consecutive adults referred for symptom-limited exercise thallium SPECT (mean age 60 ± 10, 25% women) for 6.7 years. Using information theory, we identified a probable best model relating nuclear findings to outcome to calculate a prognostic nuclear score. RESULTS There were 855 deaths. Intermediate- and high-risk prognostic nuclear scores were noted in 28% and 10% of patients. Compared with those with low-risk scans, patients with an intermediate-risk score were at increased risk for death (14% vs. 9%, hazard ratio: 1.67, 95% confidence interval [CI]: 1.44 to 1.95, p < 0.0001), while those with high-risk scores were at greater risk (24%, hazard ratio: 2.98, 95% CI: 2.49 to 3.56, p < 0.0001). In multivariable analyses that adjusted for clinical characteristics, functional capacity and heart rate recovery, an intermediate-risk nuclear score remained predictive of death (adjusted hazard ratio: 1.50, 95% CI: 1.28 to 1.76, p < 0.0001), as did a high-risk score (adjusted hazard ratio: 2.76, 95% CI: 2.13 to 2.56, p < 0.0001). Impaired functional capacity and decreased heart rate recovery provided additional prognostic information. CONCLUSIONS Myocardial perfusion defects detected by thallium SPECT imaging are independently predictive of long-term all-cause death, even after accounting for exercise capacity, heart rate recovery and other potential confounders.

Lipid-lowering agents are known to reduce long-term mortality in patients with stable coronary disease or significant risk factors. However, the effect of lipid-lowering therapy on short-term mortality immediately after an acute coronary syndrome has not been determined. We did an observational study using data from two randomised trials to investigate this issue.We used data from the GUSTO IIb and PURSUIT trials to compare all-cause mortality among patients with acute coronary syndromes who were discharged on lipid-lowering agents (n=3653) with those who were not (n=17,156). A propensity analysis was done to adjust for presumed selection biases in the prescription of lipid-lowering agents.Lipid-lowering therapy was associated with a smaller proportion of deaths at 30 days (17 [0.5%] vs 179 [1.0%], hazard ratio 0.44 [95% CI 0.27-0.73], p=0.001) and at 6 months (63 [1.7%] vs 605 [3.5%], 0.48 [0.37-0.63], p0.0001). After adjustment for the propensity to be prescribed lipid-lowering agents and other potential confounders, prescription of a lipid-lowering agent at discharge remained associated with a reduced risk of death at 6 months (0.67 [0.48-0.95], p=0.023).Prescription of a lipid-lowering drug at hospital discharge was independently associated with reduced short-term mortality among patients after an acute coronary syndrome.

Although it is well established that cigarette smoking causes excess mortality, the extent of the increased risk has been challenged because self-selection biases and confounding factors may not have been adequately accounted for in prior studies. We therefore performed a propensity analysis on a population-based cohort. A logistic regression model was used to generate a propensity score for current smoking in 6,099 adults (mean age 46 years, 54% men, 36% current smokers) participating in the National Heart Lung and Blood Institute’s (NHLBI) Lipid Research Clinic Prevalence Study. During 12 years of follow-up, 513 subjects (8%) died. After adjusting for age, current smoking was strongly associated with death (compared with never and former smokers, relative risk [RR] 2.69, 95% confidence interval [CI] 1.98 to 0.64, p

Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease. Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting. We sought to determine, using propensity analysis, whether the benefit of eptifibatide, a IIb/IIIa inhibitor, in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin. By trial design, patients were randomized to either eptifibatide or placebo, whereas use of intravenous heparin was left to the discretion of treating physicians. The effect of eptifibatide on the 30-day composite end point of death or myocardial infarction was studied in patients who received heparin and those who did not. Propensity analysis methods were used to control for confounding and presumed selection biases. Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered, eptifibatide was associated with a reduced composite end point rate (13%) compared with that of placebo (14.5% vs 16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving heparin, there was no difference in 30-day event rates with eptifibatide compared with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of heparin was developed, however, use of heparin did not affect the reduced risk associated with eptifibatide (adjusted relative risk [RR] for heparin-eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p > 0.5), but the propensity for heparin use was a strong predictor of events (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of eptifibatide independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to 0.93, p = 0.04). Thus, the apparent positive impact of heparin on the benefits of eptifibatide therapy was largely due to confounding and bias.

On February 17, 2009, the President signed into law the American Recovery and Reinvestment Act (ARRA). Designed to stimulate the ailing economy, the $787 billion legislation included a $10.4 billion allocation to the National Institutes of Health (NIH). These monies were intended to support

The case for screening asymptomatic adults for coronary artery disease seems to be, on the surface, obvious. Coronary disease is common and serious and involves a prolonged asymptomatic phase. Frequently the first clinical presentation causes serious morbidity or even death. Because of remarkable

Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.