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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

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

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

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

The minimal depth of a maximal subtree is a dimensionless order statistic measuring the predictiveness of a variable in a survival tree. We derive the distribution of the minimal depth and use it f...

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.

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

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 increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed. Genet Med 2009:11(8):559-567.

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...

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

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 A 1.5‐day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's ( AHA's ) near‐term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. Methods and Results A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference. Presentation topics included updates on data as viewed from conventional medical and nonmedical sources, building and using Big Data repositories, articulation of the goals of data sharing, and principles of responsible data sharing. Facilitated breakout sessions were conducted to examine what each of the 7 stakeholder domains wants from Big Data under ideal circumstances and the possible roles that the AHA might play in meeting their needs. Important areas that are high priorities for further study regarding Big Data include a description of the methodology of how to acquire and analyze findings, validation of the veracity of discoveries from such research, and integration into investigative and clinical care aspects of future cardiovascular and stroke medicine. Potential roles that the AHA might consider include facilitating a standards discussion (eg, tools, methodology, and appropriate data use), providing education (eg, healthcare providers, patients, investigators), and helping build an interoperable digital ecosystem in cardiovascular and stroke science. Conclusion There was a consensus across stakeholder domains that Big Data holds great promise for revolutionizing the way cardiovascular and stroke research is conducted and clinical care is delivered; however, there is a clear need for the creation of a vision of how to use it to achieve the desired goals. Potential roles for the AHA center around facilitating a discussion of standards, providing education, and helping establish a cardiovascular digital ecosystem. This ecosystem should be interoperable and needs to interface with the rapidly growing digital object environment of the modern‐day healthcare system.

To describe and elucidate the time trends of the academic productivity of NHLBI's obesity-related research funding via bibliometric analysis of 30 years of NHLBI-supported obesity-related publications.In total, 3,545 NHLBI-funded obesity-related publications were identified in the Thomson Reuters InCites™ database. Shared references in a community detection algorithm were used to identify publication topics. Characteristics of publications and topical communities were analyzed based on citation count and percentile rank. A percentile rank90 was considered "highly cited."Obesity-related publications increased more than 10-fold over 30 years, whereas NHLBI-funded publications only increased twofold NHLBI-funded obesity publications were cited a median of 23 times (IQR 8-55, range 0-2,047, mean 52). Thirty percent of these publications were highly cited compared to the expected ten percent. Six topical communities were present in 1983 compared to 16 in 2013. The most highly cited topical areas were sleep (n = 199 publications, 38% highly cited), cardiovascular morbidity and mortality (n = 277, 36%), obesity correlates and consequences (n = 588, 35%), and asthma and inflammation (n = 283, 35%).NHLBI-funded obesity publications have contributed substantially to the obesity literature, with many highly cited. Publications grew in number and topical diversity over 30 years and grew at a faster rate than total NHLBI publications.

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.

There are conflicting data about the ability of peer review percentile rankings to predict grant productivity, as measured through publications and citations. To understand the nature of these apparent conflicting findings, we analyzed bibliometric outcomes of 6873 de novo cardiovascular R01 grants funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1980 and 2011. Our outcomes focus on top-10% articles, meaning articles that were cited more often than 90% of other articles on the same topic, of the same type (eg, article, editorial), and published in the same year. The 6873 grants yielded 62 468 articles, of which 13 507 (or 22%) were top-10% articles. There was a modest association between better grant percentile ranking and number of top-10% articles. However, discrimination was poor (area under receiver operating characteristic curve [ROC], 0.52; 95% confidence interval, 0.51–0.53). Furthermore, better percentile ranking was also associated with higher annual and total inflation-adjusted grant budgets. There was no association between grant percentile ranking and grant outcome as assessed by number of top-10% articles per $million spent. Hence, the seemingly conflicting findings on peer review percentile ranking of grants and subsequent productivity largely reflect differing questions and outcomes. Taken together, these findings raise questions about how best National Institutes of Health (NIH) should use peer review assessments to make complex funding decisions.

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.

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

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

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

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 …

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.

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.

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

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

OBJECTIVE—Insulin resistance is associated with autonomic dysfunction. An attenuated decrease in heart rate after exercise (or heart rate recovery [HRR]) predicts all-cause mortality and is believed to reflect decreased parasympathetic activity. Utilizing triglyceride/HDL cholesterol concentration as a marker of insulin resistance, we sought to assess the association between insulin resistance and HRR. RESEARCH DESIGN AND METHODS—Our study population included 4,963 healthy adults who participated in the Lipid Research Clinics Prevalence Study and underwent exercise testing. HRR was considered abnormal if it did not drop ≥42 bpm 2 min after completion of exercise. Fasting blood specimens were drawn. RESULTS—Individuals in the highest quartile of triglyceride/HDL cholesterol had a significantly higher prevalence of abnormal HRR (40 vs. 30%, multivariable-adjusted prevalence ratio 1.18, 95% CI 1.01–1.39; P = 0.04). As a continuous variable, an increase in 1 SD of triglyceride–to–HDL cholesterol ratio was associated with a greater likelihood of an abnormal HRR, even after adjusting for >20 covariates (adjusted OR 1.16, 95% CI 1.07–1.25; P < 0.001). During 12 years of follow-up, there were 284 deaths. In age- and sex-adjusted analysis, participants with an abnormal HRR and high triglyceride–to–HDL cholesterol ratio had significantly higher mortality than those with a normal HRR and high triglyceride–to–HDL cholesterol ratio (hazard ratio = 1.49, 95% CI 1.08–2.04; P = 0.015). CONCLUSIONS—HRR is associated with triglyceride–to–HDL cholesterol ratio and identifies patients with insulin resistance who are at increased risk of death.

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.