Search

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.

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

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

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

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

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.

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.

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.

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.

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.

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

The scientific priorities of the National Heart, Lung, and Blood Institute (NHBLI) are delineated in the NHLBI Strategic Plan, which was released in March 2007 ([1][1]). The plan lays out a broad agenda for government-funded biomedical research and training in cardiovascular disease, lung and blood

OBJECTIVES The aim of this study was to evaluate whether preoperative clinical and test data could be used to predict the effects of myocardial revascularization on functional status and quality of life in patients with heart failure and ischemic LV dysfunction. BACKGROUND Revascularization of viable myocardial segments has been shown to improve regional and global LV function. The effects of revascularization on exercise capacity and quality of life (QOL) are not well defined. METHODS Sixty three patients (51 men, age 66 ± 9 years) with moderate or worse LV dysfunction (LVEF 0.28 ± 0.07) and symptomatic heart failure were studied before and after coronary artery bypass surgery. All patients underwent preoperative positron emission tomography (PET) using FDG and Rb-82 before and after dipyridamole stress; the extent of viable myocardium by PET was defined by the number of segments with metabolism-perfusion mismatch or ischemia. Dobutamine echocardiography (DbE) was performed in 47 patients; viability was defined by augmentation at low dose or the development of new or worsening wall motion abnormalities. Functional class, exercise testing and a QOL score (Nottingham Health Profile) were obtained at baseline and follow-up. RESULTS Patients had wall motion abnormalities in 83 ± 18% of LV segments. A mismatch pattern was identified in 12 ± 15% of LV segments, and PET evidence of viability was detected in 30 ± 21% of the LV. Viability was reported in 43 ± 18% of the LV by DbE. The difference between pre- and postoperative exercise capacity ranged from a reduction of 2.8 to an augmentation of 5.2 METS. The degree of improvement of exercise capacity correlated with the extent of viability by PET (r = 0.54, p = 0.0001) but not the extent of viable myocardium by DbE (r = 0.02, p = 0.92). The area under the ROC curve for PET (0.76) exceeded that for DbE (0.66). In a multiple linear regression, the extent of viability by PET and nitrate use were the only independent predictors of improvement of exercise capacity (model r = 0.63, p = 0.0001). Change in Functional Class correlated weakly with the change in exercise capacity (r = 0.25), extent of viable myocardium by PET (r = 0.23) and extent of viability by DbE (r = 0.31). Four components of the quality of life score (energy, pain, emotion and mobility status) significantly improved over follow-up, but no correlations could be identified between quality of life scores and the results of preoperative testing or changes in exercise capacity. CONCLUSIONS In patients with LV dysfunction, improvement of exercise capacity correlates with the extent of viable myocardium. Quality of life improves in most patients undergoing revascularization. However, its measurement by this index does not correlate with changes in other parameters nor is it readily predictable.

OBJECTIVESThe study aim was to determine observational differences in costs of care by the coronary disease diagnostic test modality.BACKGROUNDA number of diagnostic strategies are available with few data to compare the cost implications of the initial test choice.METHODSWe prospectively enrolled 11,372 consecutive stable angina patients who were referred for stress myocardial perfusion tomography or cardiac catheterization. Stress imaging patients were matched by their pretest clinical risk of coronary disease to a series of patients referred to cardiac catheterization. Composite 3-year costs of care were compared for two patients management strategies: 1) direct cardiac catheterization (aggressive) and 2) initial stress myocardial perfusion tomography and selective catheterization of high risk patients (conservative). Analysis of variance techniques were used to compare costs, adjusting for treatment propensity and pretest risk.RESULTSObservational comparisons of aggressive as compared with conservative testing strategies reveal that costs of care were higher for direct cardiac catheterization in all clinical risk subsets (range: $2,878 to $4,579), as compared with stress myocardial perfusion imaging plus selective catheterization (range: $2,387 to $3,010, p < 0.0001). Coronary revascularization rates were higher for low, intermediate and high risk direct catheterization patients as compared with the initial stress perfusion imaging cohort (13% to 50%, p < 0.0001); cardiac death or myocardial infarction rates were similar (p > 0.20).CONCLUSIONSObservational assessments reveal that stable chest pain patients who undergo a more aggressive diagnostic strategy have higher diagnostic costs and greater rates of intervention and follow-up costs. Cost differences may reflect a diminished necessity for resource consumption for patients with normal test results.

Objectives. This study sought to examine the prognostic importance of chronotropic incompetence among patients referred for stress echocardiography. Background. Although chronotropic incompetence has been shown to be predictive of an adverse prognosis, it is not clear if this association is independent of exercise-induced myocardial ischemia. Methods. Consecutive patients (146 men and 85 women; mean age 57 years) who were not taking beta-adrenergic blocking agents and were referred for symptom-limited exercise echocardiography were followed for a mean of 41 months. Chronotropic incompetence was assessed in two ways: (1) failure to achieve 85% of the age-predicted maximum heart rate and (2) a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate and physical fitness. Results. The primary end point, a composite of death, nonfatal myocardial infarction, unstable angina and late (>3 months after the exercise test) myocardial revascularization, occurred in 41 patients. Failure to achieve 85% of the age-predicted maximum heart rate was predictive of events (relative risk [RR] 2.47, 95% confidence interval [CI] 1.28 to 4.79, p = 0.007); similarly, a low chronotropic index was predictive (RR 2.44, 95% CI 1.31 to 4.55, p = 0.005). Even after adjusting for myocardial ischemia and other possible confounders, failure to achieve 85% of age-predicted maximum heart rate was predictive (adjusted RR 2.20, 95% CI 1.11 to 4.37, p = 0.02). A low chronotropic index also remained predictive (adjusted RR 1.85, 95% CI 0.98 to 3.47, p = 0.06). Conclusions. Chronotropic incompetence is predictive of an adverse cardiovascular prognosis even after adjusting for echocardiographic myocardial ischemia.

Objectives. This study sought to determine whether the duration of pretreatment with the adenosine diphosphate receptor antagonist ticlopidine prior to intracoronary stenting is associated with the incidence of procedure-related non–Q-wave myocardial infarctions (MIs).Background. Dual antiplatelet therapy with ticlopidine and aspirin is routinely used with stenting, although ticlopidine is commonly not begun until the day of the procedure. Periprocedural MIs are at least partially platelet-dependent events. As the maximal platelet inhibitory effects of this drug take 2 to 3 days to be realized, we hypothesized that longer treatment prior to stenting would be associated with lower rates of procedure-related MIs.Methods. We reviewed outcomes in 175 consecutive patients treated with ticlopidine prior to stenting at the Cleveland Clinic Foundation. Those patients with an elevation in creatine kinase above our laboratory normal (>210 IU/L) with ≥4% MB fraction on routine evaluation were defined as having a non–Q-wave MI.Results. There were 28 patients (16%) who had a non–Q-wave MI. Longer duration of ticlopidine pretreatment was strongly associated with a lower incidence of procedure-related non–Q-wave MIs (duration of pretreatment

We sought to determine the relative influence of estimated functional capacity and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) findings on prediction of short-term all-cause and cardiac-related mortality.Decreased functional capacity and abnormal Tl-201 SPECT findings are predictive of increased cardiovascular risk and mortality. However, the relative importance of these variables as predictors of all-cause mortality is not well established.Analyses were based on 3,400 consecutive adults undergoing symptom-limited exercise Tl-201 SPECT testing at the Cleveland Clinic Foundation between September 1990 and December 1993; none had previous invasive procedures, heart failure or valve disease. Estimated functional capacity, classified by age and gender, and thallium perfusion defects, expressed as a stress extent thallium score on a 12-segment scale, were analyzed to determine their relative prognostic importance during 2 years of follow-up.Of 3,400 patients, 108 (3.2%) died during follow-up; 32 deaths were identified as cardiac related. On univariable analysis, estimated functional capacity was a strong predictor of death, with 62 (57%) deaths occurring in patients achieving6 metabolic equivalents (METs) (log-rank chi-square 86, p0.0001). On multivariable analysis, the strongest independent predictors of all-cause mortality were fair or poor functional capacity (adjusted relative risk [RR] 3.96, 95% confidence interval [CI] 2.36 to 6.64, chi-square 27, p0.0001) and age (adjusted RR for 10 years 2.25, 95% CI 1.80 to 2.80, chi-square 27, p0.0001). The presence of SPECT thallium perfusion defects was a less powerful predictor of death (for each two additional segments with defects, adjusted RR 1.21, 95% CI 1.03 to 1.43, chi-square 5, p = 0.02). Cardiac mortality was predicted by both fair or poor functional capacity (adjusted RR 4.37, 95% CI 1.59 to 12.00, chi-square 8, p = 0.004) and by stress extent thallium score (adjusted RR 1.62, 95% CI 1.25 to 2.11, chi-square 13, p = 0.0003).In this clinically low risk group, estimated functional capacity was a strong and overwhelmingly important independent predictor of all-cause mortality among patients undergoing exercise Tl-201 SPECT testing. The extent of myocardial perfusion defects was of comparable importance for the prediction of cardiac mortality.

Objectives. This study prospectively compared the incremental prognostic benefit of exercise echocardiography with that of exercise testing in a large cohort.Background. Exercise echocardiography is widely accepted as a diagnostic tool, but the prognostic information provided by this test, incremental to clinical and stress testing evaluation, is ill- defined.Methods. Clinical, exercise and echocardiographic variables were studied in a consecutive group of 500 patients undergoing exercise echocardiography. After exclusion of patients who underwent revascularization within 3 months of the stress test (n = 16, 3%) and those lost to follow-up (n = 21, 4%), the remaining 463 patients (mean [±SD] age 57 ± 12 years, 302 men) were followed-up for 44 ± 11 months. Outcome was related to the exercise and echocardiographic findings, and the incremental prognostic benefit of exercise echocardiography was compared with that of standard exercise testing.Results. Cardiac events occurred in 81 patients (17%), including 33 (7%) with spontaneous events (cardiac death, myocardial infarction and unstable angina) and 48 with late revascularizations due to progressive symptoms. In a multivariate Cox proportional hazards model, the likelihood of any cardiac eventwas increased in the presence of ischemia (relative risk [RR] 5.06, 95% confidence interval [CI] 3.09 to 8.29, p < 0.001) and lessened by more maximal stress, measured as percent age-predicted maximal heart rate (RR per 5% increment 0.84, 95% CI 0.77 to 0.92, p < 0.001). Spontaneous eventswere more strongly predicted by ischemia (RR 8.20, 95% CI 3.41 to 19.71, p < 0.001) and percent age-predicted maximal heart rate (RR per 5% increment 0.78, 95% CI 0.67 to 0.91, p < 0.001). An interactive logistic regression model showed that the addition of echocardiographic to exercise and clinical data offered incremental predictive value.Conclusions. The presence of ischemia on the exercise echocardiogram can predict whether patients will experience an event. This relation is independent of, and incremental to, clinical and exercise data.(J Am Coll Cardiol 1997;30:83–90)

Objectives. The purpose of this investigation was to derive population-based reference values for M-mode echocardiographic dimensions that can be applied in epidemiologic studies, clinical trials and clinical practice and to determine optimal methods for adjusting these dimensions for body size. Background. M-mode echocardiography remains an important modality for studying cardiovascular disease; this is especially true with regard to detecting target organ damage in systemic hypertension. Most previously published reference values were derived from hospital-based series or relatively small samples and were not gender specific. Methods. Using a sample of 288 men and 524 women who were between 20 and 45 years of age and who were free of cardiovascular disease, reference values were derived for end-diastolic and end-systolic left ventricular internal dimensions, left ventricular wall thickness and left atrial dimension. The relations between these dimensions and height, a measure of body size relatively independent of obesity, were investigated using various regression models. Results. Nomograms for mean and 95th percentile values in men and women were constructed on the basis of linear regression models relating echocardiographic dimensions to height. Adjustment for body surface area greatly attenuated associations between obesity and cardiac dimensions in a separate healthy but less restricted sample of 411 men and 503 women. Conclusions. Gender-specific M-mode reference values and nomograms, with mean and 95th percentile values for echocardiographic dimensions as a function of height, are reported. The use of body surface area as means of body size adjustment is called into question.

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.

One of the most important tasks clinical cardiologists perform is assessment of risk [(1)][1]. Recent work has focused on the ability of a number of measures to predict the likelihood of death or major cardiac event for the purpose of optimally targeting treatment at patients who are most likely to

Increased left ventricular mass has been shown to be a significant independent predictor of cardiovascular risk. The purpose of this study was to assess the separate and combined relations of obesity and hypertension with left ventricular mass and geometry. Echocardiographic findings in subjects in the Framingham Heart Study who were free of cardiopulmonary disease and were not taking cardiovascular medications were examined. M-mode studies that were adequate for estimating left ventricular mass were available in 624 men and 1,209 women. Height and weight measured at the time of echocardiography were used to calculate body mass index (in kg/m2), a measure of obesity. Casual sitting blood pressure measurements were obtained to detect rest hypertension. In subgroup analyses of lean normotensive, obese normotensive, lean hypertensive and obese hypertensive subjects, hypertension and obesity each had significant independent associations with left ventricular mass and wall thickness (all p less than 0.001 in men and women). Obesity was also associated with left ventricular internal diameter (p less than 0.001 in men and women). There were no synergistic influences of hypertension and obesity on any echocardiographic left ventricular variables. It is concluded that obesity and hypertension each have distinct associations with left ventricular mass and geometry. These strengths of association are additive but not synergistic.

Because coronary heart disease is the leading cause of death in the industrialized world [(1)][1], many clinical investigations of purported cardiac risk factors and new treatments focus on death as a primary end point. It is intuitively appealing to attempt to better understand the association

“Let me tell you how I like to \_\_\_|\\_\_\_|\\_\_\_|\\_\__|.” Cardiovascular medicine trainees hear their faculty utter this phrase often. Let me tell you how I decide when, how, or whether to prescribe statins, or to order some type of noninvasive test, or to send a patient to the

Importance Electrocardiography is the most commonly used diagnostic test in cardiology. Properly interpreted, it contributes significantly to the diagnosis and management of patients with cardiac disorders. Importantly, it is essential to the diagnosis of cardiac arrhythmias and the acute

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.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.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.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]).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.

ObjectivesThe study was done to determine the prognostic importance of frequent ventricular ectopy in recovery after exercise among patients with systolic heart failure (HF).BackgroundAlthough ventricular ectopy during recovery after exercise predicts death in patients without HF, its prognostic importance in patients with significant ventricular dysfunction is unknown.MethodsSystematic electrocardiographic data during rest, exercise, and recovery were gathered on 2,123 consecutive patients with left ventricular systolic ejection fraction ≤35% who were referred for symptom-limited metabolic treadmill exercise testing. Severe ventricular ectopy was defined as the presence of ventricular triplets, sustained or nonsustained ventricular tachycardia, ventricular flutter, polymorphic ventricular tachycardia, or ventricular fibrillation. The primary end point was all-cause mortality, with censoring for interval cardiac transplantation.ResultsOf 2,123 patients, 140 (7%) had severe ventricular ectopy during recovery. There were 530 deaths (median follow-up among survivors 2.9 years). Severe ventricular ectopy during recovery was associated with an increased risk of death (three-year death rates 37% vs. 22%, hazard ratio [HR] 1.76; 95% confidence interval [CI] 1.32 to 2.34, p < 0.0001). After adjustment for ventricular ectopy at rest and during exercise, peak oxygen uptake, and other potential confounders, severe ventricular ectopy during recovery remained predictive of death (adjusted HR 1.48; 95% CI 1.10 to 1.97; p = 0.0089), whereas ventricular ectopy during exercise was not predictive of death in this cohort.ConclusionsSevere ventricular ectopy during recovery after exercise is predictive of increased mortality in patients with severe HF and can be used as a prognostic indicator of adverse outcomes in HF cohorts.

OBJECTIVES We sought to determine the association of etiology of constrictive pericarditis (CP), pericardial calcification (CA), and other clinical variables with long-term survival after pericardiectomy. BACKGROUND Constrictive pericarditis is the result of a spectrum of primary cardiac and noncardiac conditions. Few data exist on the cause-specific survival after pericardiectomy. The impact of CA on survival is unclear. METHODS A total of 163 patients who underwent pericardiectomy for CP over a 24-year period at a single surgical center were studied. Constrictive pericarditis was confirmed by the surgical report. Vital status was obtained from the Social Security Death Index. RESULTS Etiology of CP was idiopathic in 75 patients (46%), prior cardiac surgery in 60 patients (37%), radiation treatment in 15 patients (9%), and miscellaneous in 13 patients (8%). Median follow-up among survivors was 6.9 years (range 0.8 to 24.5 years), during which time there were 61 deaths. Perioperative mortality was 6%. Idiopathic CP had the best prognosis (7-year Kaplan-Meier survival: 88%, 95% confidence interval [CI] 76% to 94%) followed by postsurgical (66%, 95% CI 52% to 78%) and postradiation CP (27%, 95% CI 9% to 58%). In bootstrap-validated proportional hazards analyses, predictors of poor overall survival were prior radiation, worse renal function, higher pulmonary artery systolic pressure (PAP), abnormal left ventricular (LV) systolic function, lower serum sodium level, and older age. Pericardial calcification had no impact on survival. CONCLUSIONS Long-term survival after pericardiectomy for CP is related to underlying etiology, LV systolic function, renal function, serum sodium, and PAP. The relatively good survival with idiopathic CP emphasizes the safety of pericardiectomy in this subgroup.

Background:Although myocardial revascularization is often performed to alleviate dwumented myocardial ischemia, the impact of this practice on survival has not been demonstrated in randomized trials. Standard obsewatlonal analyses suffer from severe confounding and selection biases. Methods:We used propensity analysis to determine whether revascularization following stress echocardiography (STE) improved survival among 7957 patients in 3 different institutions. During the first 3 months after STE, 317 (4%) underwent revascularization. We generated a propensity score using logistic modeling involving 13 demographic, clinical, and echocardiographic variables. Results: Patients who underwent revascularization were older (64 vs. 61 years) and more likely to have ischemia (63% vs. 20%). We propensity matched these 317 patients with 317 patients who did not undergo revascularization with resulting similarities of age (64 vs 64 years) and equivalent rates of ischemia (63% vs 62%). During 5 years of follow- up, 75 patients (25%) who did not undergo revascularization died, whereas only 50 patients (16%) who did undergo revascularization died (propensity and covariate adjusted hazard ratio after 3 months 0.51, 95% Cl 0.31-0.83, P=O.O073). Absolute benefits were primarily noted in patients with ischemia in 12 vascular territories (Figure). Conclusion: Early myocardial revascularization is likely to lead to a survival benefit, especially among patients with inducible multivessel ischemia.