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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

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 .

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.

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.

Recent clinical trials found that, compared with an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker and neprilysin inhibitor combination therapy decreased cardiovascular morta...

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.

AIM: To examine the association of left ventricular hypertrophy (LVH) on admission electrocardiography with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 7443 non-ST-elevation ACS patients in Global Utilization of STrategies to Open occluded arteries (GUSTO) IV ACS trial had admission electrocardiograms analysed at a core laboratory. LVH [>or=20 mm Cornell voltage (LV voltage) (women) or >or=28 mm (men) plus strain patterns] was observed in 586 (7.9%) patients, and women accounted for 74%. LVH patients were also older and had more co-morbidities, ST-depression >or= 0.5 mm, elevated C-reactive protein and N-terminal pro-brain naturetic peptide (NT-proBNP), and lower troponin T. Invasive procedures occurred less often in LVH patients (cardiac catheterization: 31 vs. 38%, P = 0.001; percutaneous coronary intervention: 12 vs. 20%, P < 0.001). Mortality was significantly higher in patients with LVH (30 day: 5 vs. 3%, P = 0.046; 1 year: 14 vs. 7%, P < 0.001), whereas 30 day myocardial infarction (MI) and death/MI did not differ. After baseline adjustment including NT-proBNP, LVH remained associated with increased hazard of 1 year mortality in women, but not in men [P-interaction = 0.033; women: adjusted hazard ratio (LVH vs. no LVH): 1.42 (1.04-1.94), P = 0.029]. CONCLUSION: Electrocardiographic-LVH identifies an important subset of ACS patients with a higher risk of long-term mortality, particularly among women. These novel findings highlight opportunities to improve treatment and outcome among similar ACS patients. Udgivelsesdato: 2007-Sep

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.

An entity of patients with mixed physiology of constriction and restriction has been reported, however, the characteristics of these patients have not been well documented. We evaluated the clinical features and the outcome of these patients.Study subjects consisted of 38 patients (57+/-14 years, 8 females, 30 males) who were diagnosed as having mixed physiology based on transthoracic and/or transesophageal echocardiography, MRI (or CT), cardiac catheterization, endomyocardial biopsy and/or surgical findings. Prior radiation therapy was the most frequent (50%) cause of mixed physiology followed by coronary artery bypass graft without prior radiation (24%) and heart transplantation (8%). The respiratory variation of peak early diastolic transmitral flow velocity by pulsed Doppler transesophageal echocardiography was 10.7% in patients with sinus rhythm and 18.1% in patients with atrial arrhythmia. Pericardial thickening was noted adjacent to the right-sided chambers in 19 patients, left-sided chambers in 10 patients, or both in 9 patients. All-cause 5-year mortality was 40% and unrelated to age, etiology, left ventricular systolic function and therapeutic course. There was a statistically significant difference (p0.01) between the survival rates in patients with mixed physiology and in patients with pure constriction (n=125).Due to the high mortality in this disease, discrimination of the entity from the patients with pure constriction is mandatory. Transthoracic and transesophageal echocardiography are helpful noninvasive techniques in the diagnosis and the understanding of the physiology of patients with mixed constriction and restriction.

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

Background We previously demonstrated that cardiovascular (CV) trials funded by the National Heart, Lung, and Blood Institute ( NHLBI ) were more likely to be published in a timely manner and receive high raw citation counts if they focused on clinical endpoints. We did not examine the metrics of trial reports, and our citation measures were limited by failure to account for topic‐related citation behaviors. Methods and Results Of 244 CV trials completed between 2000 and 2011, we identified 184 whose main results were published by August 20, 2014. One investigator who was blinded to rapidity of publication and citation data read each publication and characterized it according to modified Delphi criteria. There were 46 trials (25%) that had Delphi scores of 8 or 9 (of a possible 9); these trials published faster (median time from trial completion to publication, 12.6 [interquartile range { IQR }, 6.7 to 23.3] vs. 21.8 [ IQR , 12.1 to 34.9] months; P IQR , 0.64 to 7.83] vs. 8.41 [ IQR , 1.80 to 24.75]; P =0.002). By random forest regression, we found that the 3 most important predictors of normalized citation percentile values were total costs, intention‐to‐treat analyses (as a modified Delphi quality measure), and focus on clinical (not surrogate) endpoints. Conclusions NHLBI CV trials were more likely to publish results quickly and yield higher topic‐normalized citation impact if they reported results according to well‐defined metrics, along with focus on clinical endpoints.

1.1 Document Development Process #### 1.1.1 Writing Committee Organization The writing committee was selected to represent the American College of Cardiology (ACC) and included a cardiovascular training program director, several active cardiovascular scientists and research methodology

Aims To determine whether the presence and severity of aortic atheroma predict long-term all-cause mortality among patients undergoing cardiac surgery. Methods and results We followed 8581 patients who underwent cardiac surgery and had routine intraoperative transoesophageal echocardiography for 2.8 years (range 0.06–6.0 years). Data regarding multiple potential confounders were prospectively collected and electronically recorded. There were 2878 (34%) patients with no atheroma; 4129 (48%) patients with mild atheroma; 1215 (14%) with moderate atheroma; and 359 (4%) with severe atheroma. There were 1000 deaths. Death rates were increased in patients with moderate [relative risk (RR) 3.29, 95% CI 2.50–4.32, P < 0.0001) and severe atheroma (RR 5.21, 95% CI 3.65–7.41, P < 0.0001). After adjusting for multiple other confounders, severe atheroma remained modestly predictive of risk (adjusted RR 1.46, 95% CI 1.07–2.00, P = 0.02); but moderate atheroma and mild atheroma were not predictive of increased risk. In a propensity analysis that matched patients with comparable range of variables, severe atheroma was no longer predictive of risk (adjusted RR 1.39, 95% CI 0.87–2.23, P = 0.17). Conclusion Our study shows that severe atheroma is associated with increased long-term mortality in patients undergoing cardiac surgery; however, the relationship is weak using propensity analysis, suggesting no causal association.

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 …

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.

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.

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.

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.

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.

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.

Recent studies have confirmed heart rate fall after treadmill exercise testing, or heart rate recovery, as a powerful predictor of mortality from heart disease. Heart rate recovery depends on central reactivation of vagal tone and decreased vagal activity is a risk factor for death. If heart rate recovery is defined as the fall in heart rate after 1 minute following peak exercise, then a heart rate recovery value of 12 beats per minute (bpm) or lower has been shown to be a good prognostic threshold for identifying patients at high risk. Although this finding establishes a simple, useful relationship between heart recovery and mortality, a working understanding of how heart rate recovery interacts with other characteristics of a patient in determining risk of death is still largely unexplored. Such knowledge, addressed in this article, could improve the prognostic value of the exercise test. Our analysis is based on over 23,000 patients who underwent exercise testing. A rich assortment of data was collecte...

In the current issue of Circulation Research , McCrory et al1 report on the association of heart rate recovery after simple orthostatic challenge—otherwise known as standing up—with all-cause mortality. The authors measured heart rate changes in the first 110 seconds after standing up in 4475 participants of an Irish population–based, cohort study. Immediately after standing, heart rate, as expected, increased but in most subjects started to fall toward resting levels within 10 seconds. The rate of decline between 10 and 20 seconds post orthostatic challenge—or heart rate recovery (HRR10–20)—was lower in older subjects and in subjects with a history of vascular disease. It was also an independent predictor of 4-year mortality: the lower the HRR10–20, the greater the mortality. Article, see p 666 To put these findings in perspective, we go back 28 years, when Schwartz et al2 published a report on a series of experiments that linked baroreceptor function with cardiac response to acute stress. The investigators produced an anterior myocardial infarction (MI) in 301 dogs and …

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.

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.

OBJECTIVE—Heart rate recovery (HRR) is an independent prognostic indicator for cardiovascular disease (CVD) and all-cause mortality in healthy men. We examined the association of HRR to CVD-related and all-cause mortality in men with diabetes. RESEARCH DESIGN AND METHODS—In this cohort study we examined 2,333 men with documented diabetes (mean age 49.4 years) that had baseline 5-min HRR measurement following maximal exercise (heart ratepeak − heart rate5 min of recovery) at The Cooper Clinic, Dallas, TX. We identified HRR quartiles as quartile 1 75 bpm. Hazard ratios (HRs) for cardiovascular and all-cause death were adjusted for age, cardiorespiratory fitness, resting heart rate, fasting blood glucose, BMI, smoking habit, alcohol consumption, total cholesterol, triglyceride, and history of CVD at baseline. RESULTS—During a median of 14.9 years follow-up, there were 142 deaths that were considered CVD related and 287 total deaths. Compared with men in the highest quartile of HRR, adjusted HRs in the first, second, and third quartiles were 2.0 (95% CI 1.1–3.8), 1.5 (0.8–2.7), and 1.5 (0.9–2.8), respectively, for cardiovascular death (P for trend < 0.001). Similarly, for all-cause death, adjusted HRs in the first, second, and third quartiles were 2.0 (1.3–3.2), 1.5 (1.0–2.3), and 1.5 (1.1–2.3) (P for trend < 0.001). CONCLUSIONS—Among men with diabetes, a decreased HRR, even measured as long as 5 min after recovery, was independently predictive of cardiovascular and all-cause death.

OBJECTIVES: To evaluate the prognostic value in older adults of two predictors of mortality: impaired functional capacity and an attenuated heart rate recovery. SETTING: Academic medical center. DESIGN: Prospective study with mean 3.7 years follow-up. PARTICIPANTS: Seven thousand three hundred fifty-four adults aged 65 and older consecutively referred for exercise testing between 1990 and 1999. Patients with heart failure, valvular disease, atrial fibrillation, and pacemakers were excluded. MEASUREMENTS: The primary endpoint was all-cause mortality. Impaired functional capacity was defined as the peak exercise workload in the lowest quintile of metabolic equivalents achieved according to prespecified strata of age and sex. Heart rate recovery was defined as the fall in heart rate during the first minute after exercise and was abnormal if 12 or fewer beats per minute, except for patients undergoing stress echocardiography, in which case 18 or fewer beats per minute was abnormal. RESULTS: There were 842 deaths. Patients with impaired functional capacity were at increased risk for death (23% vs 9%, hazard ratio (HR) = 2.7, 95% confidence interval (CI) = 2.2–3.1, P < .0001) as were patients with an abnormal heart rate recovery (17% vs 9%, HR = 2.0, 95% CI = 1.8–2.3, P < .0001). After adjusting for age, sex, coronary history, and other confounders, impaired functional capacity (adjusted HR = 2.1, 95% CI = 1.8–2.4) and an abnormal heart rate recovery (adjusted HR = 1.5, 95% CI = 1.3–1.7) independently predicted death. No interactions between these two variables with age were noted. CONCLUSIONS: In older patients, impaired functional capacity and heart rate recovery were independent predictors of death.

A 45-year-old man with a strong family history of premature heart disease has no symptoms of coronary disease and a normal electrocardiogram. His fasting level of total cholesterol is 225 mg per deciliter, the low-density lipoprotein cholesterol level is 160 mg per deciliter, and the high-density lipoprotein cholesterol level is 35 mg per deciliter. He has no history of hypertension and does not smoke cigarettes. Should he be advised to take aspirin to reduce his risk of myocardial infarction?

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.

Diabetes is associated with abnormal autonomic function and increased mortality. Abnormal heart rate recovery after exercise, a measure of autonomic dysfunction, is also associated with increased mortality. The objective of this study was to determine the association of fasting plasma glucose with abnormal heart rate recovery and its prognostic importance in healthy adults. We studied 5,190 healthy adults who did not have medically treated diabetes (mean age 45 years, 39% women), were enrolled in the Lipid Research Clinics’ Prevalence Study, and underwent exercise testing. Heart rate recovery was defined as the change from peak heart rate to that after 2 min of recovery; an abnormal value was ≤42 bpm. All-cause mortality was assessed over 12 years. A total of 504 participants (10%) had impaired fasting glucose, and 131 (3%) had untreated diabetes. An abnormal heart rate recovery was found in 1,699 (33%). Compared with participants who had normal fasting plasma glucose, abnormal heart rate recovery was more common among those with impaired fasting glucose (42 vs. 31%; relative risk, 1.34; 95% confidence interval [CI], 1.20–1.50; P < 0.0001) and those with diabetes (50 vs. 31%; relative risk, 1.61; 95% CI, 1.35–1.92; P < 0.0001). Fasting plasma glucose remained an independent predictor of abnormal heart rate recovery even after adjustment for age, sex, and other confounders (P = 0.0003). An abnormal heart rate recovery added to impaired fasting plasma glucose for the prediction of death. Fasting plasma glucose is strongly and independently associated with abnormal heart rate recovery, even at nondiabetic levels.

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.

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.

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.

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