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The objective is to assess the comparative effectiveness and safety of dual-antiplatelet therapy (DAPT) vs triple therapy (TT) with DAPT + oral anticoagulant (OAC) in patients with anterior ST-segment elevation myocardial infarction (STEMI) and with new-onset anterior/apical wall-motion abnormalities (WMAs) treated with primary percutaneous coronary intervention (PCI).Patients with STEMI and new-onset anterior/apical WMA may benefit from the addition of OAC to prevent left ventricular thrombus and cardioembolic events.A multicenter, retrospective cohort study was conducted. Patients with a concomitant indication for OAC were excluded. Patients discharged on TT were compared with patients discharged on DAPT using adjusted Cox proportional hazards analysis and inverse probability of treatment weighting. The primary endpoint was the net adverse clinical event (NACE) rate at 6 months (composite of all-cause mortality, non-fatal MI, stroke, or transient ischemic attack, systemic thromboembolism or type 3 or 5 Bleeding Academic Research Consortium [BARC] bleeding).A total of 1666 patients were included, among which 627 were treated with TT and 1039 were treated with DAPT. A NACE occurred in 55 patients (6.03 per 100 patient-years) in the TT group and in 74 patients (7.18 per 100 patient-years) in the DAPT group (adjusted hazard ratio, 0.86; 95% confidence interval, 0.55-1.32). Adjusted risk of the individual components of the primary endpoint, ischemic events, and bleeding events were similar between both groups (P.05 for all).The addition of OAC to DAPT in anterior STEMI patients with new-onset WMA treated with PCI was not associated with a significant reduction in NACE.

Evaluate a web-based tailored nursing intervention, TAVIE en m@rche, on increasing daily steps after an acute coronary syndrome.Parallel two-group multicentre randomized trial.An experimental group receiving TAVIE en m@rche, was compared to a control group receiving hyperlinks to public websites. Acute coronary syndrome patients who were insufficiently active were recruited from three coronary care units. Daily steps at 12 weeks were the primary outcome. Secondary outcomes included self-reported walking and moderate to vigorous physical activity (MVPA). Exploratory outcomes were angina frequency, emergency department visits, hospitalizations and secondary prevention programme attendance.Primary data were analysed for 39 participants. No significant effects were found. At 12 weeks 275.9 more daily steps and 1,464.3 more energy expenditure in MVPA were found in the experimental group relative to the control. No effects were found for angina frequency, emergency department visits, hospitalizations and secondary prevention programme attendance.The lack of effect on our primary result may be explained by the intervention goal that was mismatched to the needs of our mostly sufficiently active sample at randomization, resulting in no meaningful change in daily steps. Although the non-significantly greater increase in self-reported MVPA may represent gains in health among the participants that accessed TAVIE en m@rche, this result should be interpreted with caution.From 40%-60% of acute coronary syndrome patients self-report insufficient levels of physical activity. No effect was found on the primary outcome of daily steps. Although not significant, a greater increase in MVPA was found at 12 weeks. The primary outcome can be explained by most of the sample having attained the physical activity recommendation at randomization. Caution in interpreting the non-significant increase in MVPA is warranted due to attrition bias and statistical uncertainty. Future directions may consider the timing of randomization in relation to meeting the needs of insufficiently active acute coronary syndrome patients.目的: 评估基于网络的定制护理干预(TAVIE en m@rche)对于急性冠脉综合征后增加每日行走步数的作用。 设计: 平行的两组多中心随机研究 方法: 对比接受TAVIE en m @ rche的实验组与接收公共网站超链接的对照组。我们从三个冠心病重症监护病房招募了活动不足的急性冠状动脉综合征患者。研究主要结果是12周的每日步数。次要结果包括患者自己报告的行走和中等强度到高强度的身体活动(MVPA)。探索性结果为心绞痛发作频率、急诊就诊、住院和二级预防方案出现次数。 结果: 我们分析了39名参与者的原始数据,没有发现显著影响。在十二周中,相比于对照组,实验组的中等强度到高强度的身体活动中,每日步数增加了275.9步,并且增加了1464.3的能量消耗。心绞痛发作频率、急诊就诊、住院和二级预防方案出现次数没有受到影响。 结论: 没有对主要结果产生影响的原因可能是干预目标与随机分配的多数活动充分的样本需求不匹配,导致每日步数没有出现有意义的变化。尽管患者自己报告的中等强度到高强度的身体活动并没有显著地大幅增长,这可能意味着访问TAVIE en m@rche的参与者健康状况有所改善,但是对于这一结果,应当谨慎解释。 影响: 40%至60%的急性冠状动脉综合征患者自己报告的身体活动不足。每日步行没有对主要结果产生影响。尽管不显著,但在十二周中,每日中等强度到高强度的身体活动有所增长。出现这样的主要结果的原因是,大多数样本在随机分组时已经得到了活动身体的建议。由于损耗性偏差和统计不确定性,对这一非显著增长,应当谨慎解释。今后的研究方向可能会考虑随机化的时间,以满足缺少身体活动的急性冠状动脉综合征患者的需求。.

Background Training physicians to provide effective behavior change counseling using approaches such as motivational communication (MC) is an important aspect of noncommunicable chronic disease prevention and management. However, existing evaluation tools for MC skills are complex, invasive, time consuming, and impractical for use within the medical context. Objective The objective of this study is to develop and validate a short web-based tool for evaluating health care provider (HCP) skills in MC—the Motivational Communication Competency Assessment Test (MC-CAT). Methods Between 2016 and 2021, starting with a set of 11 previously identified core MC competencies and using a 5-step, mixed methods, integrated knowledge translation approach, the MC-CAT was created by developing a series of 4 base cases and a scoring scheme, validating the base cases and scoring scheme with international experts, creating 3 alternative versions of the 4 base cases (to create a bank of 16 cases, 4 of each type of base case) and translating the cases into French, integrating the cases into the web-based MC-CAT platform, and conducting initial internal validity assessments with university health students. Results The MC-CAT assesses MC competency in 20 minutes by presenting HCPs with 4 out of a possible 16 cases (randomly selected and ordered) addressing various behavioral targets (eg, smoking, physical activity, diet, and medication adherence). Individual and global competency scores were calculated automatically for the 11 competency items across the 4 cases, providing automatic scores out of 100. From the factorial analysis of variance for the difference in competency and ranking scores, no significant differences were identified between the different case versions across individual and global competency (P=.26 to P=.97) and ranking scores (P=.24 to P=.89). The initial tests of internal consistency for rank order among the 24 student participants were in the acceptable range (α=.78). Conclusions The results suggest that MC-CAT is an internally valid tool to facilitate the evaluation of MC competencies among HCPs and is ready to undergo comprehensive psychometric property analyses with a national sample of health care providers. Once psychometric property assessments have been completed, this tool is expected to facilitate the assessment of MC skills among HCPs, skills that will better support patients in adopting healthier lifestyles, which will significantly reduce the personal, social, and economic burdens of noncommunicable chronic diseases.

Poor health behaviors (e.g., smoking, poor diet, and physical inactivity) are major risk factors for noncommunicable chronic diseases (NCDs). Evidence supporting traditional advice-giving approaches to promote behavior change is weak or short lived. Training physicians to improve their behavior change counseling/communication skills is important, yet the evidence for the efficacy and acceptability of existing training programs is lacking and there is little consensus on the core competencies that physicians should master in the context of NCD management. The purpose of this study is to generate an acceptable, evidence-based, stakeholder-informed list of the core communication competencies that physicians should master in the context of NCD management. Using a modified Delphi process for consensus achievement, international behavior change experts, physicians, and allied health care professionals completed four phases of research, including eight rounds of online surveys and in-person meetings over 2 years (n = 13–17 participated in Phases I, III, and IV and n = 39–46 in Phase II). Eleven core communication competencies were identified: reflective listening, expressing empathy, demonstrating acceptance, tolerance, and respect, responding to resistance, (not) negatively judging or blaming, (not) expressing hostility or impatience, eliciting “change-talk”/evocation, (not) being argumentative or confrontational, setting goals, being collaborative, and providing information neutrally. These competencies were used to define a unified approach for conducting behavior change counseling in medical settings: Motivational Communication. The results may be used to inform and standardize physician training in behavior change counseling and communication skills to reduce morbidity and mortality related to poor health behaviors in the context of NCD prevention and management.

Out of hospital cardiac arrest (OHCA) is associated with a low rate of survival to hospital discharge and high rates of neurological morbidity among survivors. Programmatic efforts to institute and integrate OHCA best care practices from the bystander response through to the in-hospital phase have been associated with improved patient outcomes. This Canadian Cardiovascular Society position statement was developed to provide comprehensive yet practical recommendations to guide the in-hospital care of OHCA patients. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system recommendations have been generated. Recommendations on initial care delivery on the basis of presenting rhythm, appropriate use of targeted temperature management, postarrest angiography, and revascularization in the initial phase of care of the OHCA patient are detailed within this statement. In addition, further description of best practices on sedation, use of neuromuscular blockade, oxygenation targets, hemodynamic monitoring, and blood product transfusion triggers in the critical care environment are contained in this document. Last, discussion of optimal care systems for the OHCA patient is provided. These guidelines aim to serve as a practical guide to optimize the in-hospital care of survivors of cardiac arrest and encourage the adoption of "best practice" protocols and treatment pathways. Emphasis is placed on integrating these aspects of in-hospital care as part of a postarrest "care bundle." It is hoped that this position statement can assist all medical professionals who treat survivors of cardiac arrest.

Medical care in Canadian cardiac units has changed considerably over the past 3 decades in response to an increasingly complex and diverse patient population admitted with acute cardiac pathology. To maintain the highest level of care for these patients, there is a pressing need to evolve traditional coronary care units into contemporary cardiac intensive care units. In this article we aim to highlight the current variations in Canadian units, develop approaches to overcome logistical and infrastructural obstacles, and propose staffing and training recommendations that would allow for the establishment of contemporary cardiac intensive care units.

Graphical abstract, Highlights • A case of very severe transcatheter heart valve thrombosis is described. • The patient was treated with warfarin with success. • The first line of treatment of transcatheter heart valve thrombosis is anticoagulation. • A trial of 2-3 months of warfarin should be tried before considering alternatives.

Objective The American Heart Association has endorsed depression as a cardiac risk factor and recommends screening as part of routine practice. This has been met with controversy due to inconsistencies in the data linking depression treatment to better cardiovascular outcomes. Our objective was to prospectively assess the association between depression treatment (defined as being prescribed antidepressant medication) and major adverse cardiovascular events (MACE) in patients referred for exercise stress tests. Method Two thousand three hundred eighty-five consecutive patients presenting for myocardial perfusion exercise stress tests underwent a sociodemographic, medical, and psychiatric interview (Primary Care Evaluation of Mental Disorders [PRIME-MD]) and completed the Beck Depression Inventory (BDI). History of cardiovascular disease (CVD) and antidepressant use was self-reported and verified via chart review. Participants followed over an 8.8-year follow up, and information regarding MACE incidence (including cardiac mortality, nonfatal myocardial infarction, revascularization procedures, cerebrovascular events) was obtained from provincial administrative databases. Results 8% (n = 190) of the sample were taking antidepressants at baseline, 41% (n = 916) had a history of CVD, and 38.7% (n = 921) had depression according to the PRIME-MD or BDI. Antidepressant treatment was associated with a 30% reduced risk of MACE (Hazard ratio [HR] = 0.697; 95% confidence interval [CI] = [0.504, 0.964]; p = .029). A 46% reduction in risk was associated with antidepressant treatment among those without CVD (HR = 0.542; 95% CI [0.299, 0.981]; p = .043). In depressed patients, a 33% reduction in risk of MACE associated with antidepressant use was seen (adjusted HR = 0.674; 95% CI [0.440, 1.033]; p = .07). Conclusions Antidepressants may be cardio-protective among patients presenting for stress testing independent of risk factors including CVD and depression. Results support treating depression with antidepressants in this population to reduce risk of MACE. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence. The present update to the 2011 and 2013 Canadian Cardiovascular Society APT guidelines incorporates new evidence on how to optimize APT use, particularly in situations in which few to no data were previously available. The recommendations update focuses on the following primary topics: (1) the duration of dual APT (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome and non-acute coronary syndrome indications; (2) management of DAPT in patients who undergo noncardiac surgery; (3) management of DAPT in patients who undergo elective and semiurgent coronary artery bypass graft surgery; (4) when and how to switch between different oral antiplatelet therapies; and (5) management of antiplatelet and anticoagulant therapy in patients who undergo PCI. For PCI patients, we specifically analyze the particular considerations in patients with atrial fibrillation, mechanical or bioprosthetic valves (including transcatheter aortic valve replacement), venous thromboembolic disease, and established left ventricular thrombus or possible left ventricular thrombus with reduced ejection fraction after ST-segment elevation myocardial infarction. In addition to specific recommendations, we provide values and preferences and practical tips to aid the practicing clinician in the day to day use of these important agents.

Background: Despite the health benefits of increasing physical activity in the secondary prevention of acute coronary syndrome (ACS), up to 60% of ACS patients are insufficiently active. Evidence supporting the effect of Web-based interventions on increasing physical activity outcomes in ACS patients is growing. However, randomized controlled trials (RCTs) using Web-based technologies that measured objective physical activity outcomes are sparse. Objective: Our aim is to evaluate in insufficiently active ACS patients, the effect of a fully automated, Web-based tailored nursing intervention (TAVIE en m@rche) on increasing steps per day. Methods: A parallel two-group multicenter RCT (target N=148) is being conducted in four major teaching hospitals in Montreal, Canada. An experimental group receiving the 4-week TAVIE en m@rche intervention plus a brief “booster” at 8 weeks, is compared with the control group receiving hyperlinks to publicly available websites. TAVIE en m@rche is based on the Strengths-Based Nursing Care orientation to nursing practice and the Self-Determination Theory of human motivation. The intervention is centered on videos of a nurse who delivers the content tailored to baseline levels of self-reported autonomous motivation, perceived competence, and walking behavior. Participants are recruited in hospital and are eligible if they report access to a computer and report less than recommended physical activity levels 6 months before hospitalization. Most outcome data are collected online at baseline, and 5 and 12 weeks postrandomization. The primary outcome is change in accelerometer-measured steps per day between randomization and 12 weeks. The secondary outcomes include change in steps per day between randomization and 5 weeks, and change in self-reported energy expenditure for walking and moderate to vigorous physical activity between randomization, and 5 and 12 weeks. Theoretical outcomes are the mediating role of self-reported perceived autonomy support, autonomous and controlled motivations, perceived competence, and barrier self-efficacy on steps per day. Clinical outcomes are quality of life, smoking, medication adherence, secondary prevention program attendance, health care utilization, and angina frequency. The potential moderating role of sex will also be explored. Analysis of covariance models will be used with covariates such as sex, age, fatigue, and depression symptoms. Allocation sequence is concealed, and blinding will be implemented during data analysis. Results: Recruitment started March 30, 2016. Data analysis is planned for November 2017. Conclusions: Finding alternative interventions aimed at increasing the adoption of health behavior changes such as physical activity in the secondary prevention of ACS is clearly needed. Our RCT is expected to help support the potential efficacy of a fully automated, Web-based tailored nursing intervention on the objective outcome of steps per day in an ACS population. If this RCT is successful, and after its implementation as part of usual care, TAVIE en m@rche could help improve the health of ACS patients at large. Trial Registration: ClinicalTrials.gov NCT02617641; https://clinicaltrials.gov/ct2/show/NCT02617641 (Archived by WebCite at http://www.webcitation.org/6pNNGndRa) [JMIR Res Protoc 2017;6(4):e64]

Background— Women diagnosed with coronary artery disease (CAD) typically experience worse outcomes relative to men, possibly through diagnosis and treatment delays. Reasons for these delays may be influenced by mood and anxiety disorders, which are more prevalent in women and have symptoms (eg, palpitations and fatigue) that may be confounded with CAD. Our study examined sex differences in the association between mood and anxiety disorders and myocardial ischemia in patients with and without a CAD history presenting for exercise stress tests. Methods and Results— A total of 2342 patients (women n=760) completed a single photon emission computed tomographic exercise stress test (standard Bruce Protocol) and underwent a psychiatric interview (The Primary Care Evaluation of Mental Disorders) to assess mood and anxiety disorders. Ischemia was assessed using single photon emission computed tomography, with odds ratio used to calculate the effect of sex and mood/anxiety on the presence of ischemia during stress testing by CAD history in a stratified analyses, adjusted for relevant covariates. There was a sex by anxiety interaction with ischemia in those without a CAD history ( P =0.015): women with anxiety were more likely to exhibit ischemia during exercise than women without anxiety (odds ratio, 1.75; 95% confidence interval, 1.05–2.89). No significant effects were observed for men nor mood. Conclusions— Women with anxiety and no CAD history had higher rates of ischemia than women without anxiety. Results suggest that anxiety symptoms, many of which overlap with those of CAD, might mask CAD symptoms among women (but not men) and contribute to referral and diagnostic delays. Further research is needed to confirm this hypothesis.

Objectives The present study aims to document the problem of suicidality in emergency department (ED) patients with unexplained chest pain and to assess the strength and independence of the relationship between panic and suicidal ideation (SI) in this population. Method This cross-sectional study included 572 ED patients with unexplained chest pain. SI, history of suicide attempts, history of SI and the presence of thoughts about how to commit suicide were assessed. Logistic regression analyses were used to quantify the relationship between current SI and panic. Results Approximately 15% [95% confidence interval (CI), 12%–18%] of patients reported current SI, and 33% (95% CI, 29%–37%) reported history of SI. Nearly 19% (95% CI, 16%–22%) of patients had thought about a method to commit suicide, and 33% (95% CI, 29%–37%) had a history of a suicide attempt. Panic attacks were diagnosed in 42% (95% CI, 38%–46%) of patients, and 45% (95% CI, 39%–51%) of those had panic disorder. Panic increased the crude likelihood of current SI [odds ratio (OR)=2.53, 1.4–4.5]. This increase in SI risk remained significant after controlling for confounding factors (OR=1.70, 95% CI, 1.0–2.9). Conclusions Suicidality and SI were common and often severe in our sample of ED patients with unexplained chest pain.

Purpose This study aimed at (1) establishing the prevalence of paniclike anxiety in emergency department (ED) patients with unexplained chest pain (UCP); (2) describing and comparing the sociodemographic, medical, and psychiatric characteristics of UCP patients with and without paniclike anxiety; and (3) measuring the rate of identification of panic in this population. Basic Procedure A structured interview, the Anxiety Disorders Interview Schedule for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , was administered to identify paniclike anxiety and evaluate patients' psychiatric status. Anxious and depressive symptoms were evaluated with self-report questionnaires. Medical information was extracted from patients' medical records. Main Findings The prevalence of paniclike anxiety was 44% (95% CI, 40%-48%) in the sample (n = 771). Psychiatric disorders were more common in panic patients (63.4% vs 20.1%), as were suicidal thoughts (21.3% vs 11.3%). Emergency physician diagnosed only 7.4% of panic cases. Principal Conclusions Paniclike anxiety is common in ED patients with UCP, and this condition is rarely diagnosed in this population.

ACADEMIC EMERGENCY MEDICINE 2011; 18:322–325 © 2011 by the Society for Academic Emergency Medicine Abstract Objectives: The objective was to demonstrate the derivation and the preliminary validation of a brief screening score to improve recognition of panic-like anxiety in emergency department (ED) patients with unexplained chest pain. Methods: This cross-sectional study included 507 ED patients with unexplained chest pain randomly assigned to the derivation condition (n = 201) or the validation condition (n = 306). The Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) acted as the criterion standard for panic diagnosis. Receiver operating characteristic (ROC) curves were used to determine which of the sociodemographic, medical, and questionnaire response variables best predicted the presence of panic-like anxiety in the derivation condition. The selected predictors were entered in a logistic regression analysis to determine variables to be included in the screening score. The predictive validity of the resulting score was evaluated in both conditions. Results: The four-item Panic Screening Score (PSS) identified panic-like anxiety with a sensitivity of 63% (95% confidence interval [CI] = 52% to 73%) and a specificity of 84% (95% CI = 76% to 90%) in the derivation phase. The positive predictive value was 74% (95% CI = 62% to 93%) and the negative predictive value was 76% (95% CI = 68% to 89%). In the validation phase, the sensitivity and specificity were 53% (95% CI = 44% to 62%) and 85% (95% CI = 78% to 89%), respectively. The positive predictive value was 72% (95% CI = 62% to 80%) and the negative predictive value was 71% (95% CI = 65% to 77%). Conclusions: The PSS may be useful to identify patients with unexplained chest pain who could benefit from referral to mental health professionals or their primary care providers for evaluation of panic attack and panic disorder. Prospective studies to improve and validate the PSS, followed by impact analysis, are mandatory before clinical implementation. ACADEMIC EMERGENCY MEDICINE 2011; 18:1–4 © 2011 by the Society for Academic Emergency Medicine

Background: Several patient characteristics have been shown to increase the risk of inadequate platelet inhibition by aspirin, yet underlying mechanisms remain mostly unknown. We explored whether oxidative stress, via isoprostane formation, was associated with inadequate platelet response to aspirin. Additionally, we sought to investigate whether individual pre-selected demographic, hematological or biochemical parameters further increased the risk of inadequate platelet response to aspirin. Methods: Two hundred consecutive subjects suffering from stable coronary artery disease and under daily aspirin therapy were enrolled in our study. Inadequate platelet response to aspirin was defined as residual platelet aggregation ≥20% per arachidonic acid-induced light transmission aggregometry. Morning urinary samples were used to determine levels of isoprostanes (8-iso-PGF2α) using an enzyme immunoassay. Results: Eight subjects were deemed to present inadequate platelet response to aspirin. Wide intersubject variability was observed in urinary 8-iso-PGF2α levels. However, levels were similar between aspirin responders and non-responders. Patients with inadequate platelet response to aspirin had higher platelet counts and received the lowest daily aspirin dose when compared to responders, suggesting subtherapeutic aspirin therapy due to increased platelet production. Only platelet count remained independently predictive of inadequate platelet response to aspirin in a multiple logistic regression model. Conclusions: Urinary 8-iso-PGF2α levels, a reflection of systemic oxidative stress, did not appear to contribute to impaired platelet responsiveness to aspirin, while increased platelet production may partly explain this phenomenon. © 2009 Elsevier Ireland Ltd. All rights reserved.

Hyporesponsiveness to antiplatelet agents has been linked to an increased risk of major adverse cardiovascular events. However, light transmission aggregometry (LTA), the gold standard methodology for assessing platelet function, requires expertise and is labour-intensive, which render its use in clinical settings impractical. We assessed whether platelet count drop (PCD), a technique widely available in any haematology laboratory, could replace LTA in testing for inhibition of platelet aggregation induced by antiplatelet agents.One hundred and sixty-one coronary artery disease patients taking aspirin alone and 91 patients taking a combination of aspirin and clopidogrel were enrolled. Platelet aggregation was measured by LTA and PCD stimulated with 1.6 mM of arachidonic acid (AA) for aspirin and 5 and 20 microM of adenosine diphosphate (ADP) for clopidogrel.Correlation between AA-induced LTA and PCD was nonexistent (r=-0.043, p=0.587), while correlation between ADP-induced LTA and PCD was low (r=0.374, p0.0001 for ADP 5 microM and r=0.402, p0001 for ADP 20 microM ). PCD, whether stimulated with AA or ADP, overestimated platelet aggregation as assessed by LTA, by 13-18%. The wide 95% limits of agreement suggest that the assays can disagree significantly in individual patients.Although the PCD method is widely available in non-specialized laboratories, our results demonstrate that there is poor correlation with the current gold standard, i.e. LTA. Thus, PCD should not be used in replacement of LTA to assess antiplatelet responsiveness.

Background: Adequate platelet inhibition before percutaneous coronary intervention (PCI) reduces periprocedural and long-term ischemic complications. Reduced response to clopidogrel has been associated with subsequent major adverse cardiovascular events. Strategies to optimize platelet inhibition pre-PCI are under investigation. This study evaluated the effect on platelet aggregation of four different dosing regimens of clopidogrel given before elective PCI in a randomized, prospective, double-blind, and placebo-controlled design. Methods: One hundred twenty participants were randomized to one of four groups of clopidogrel: (a) 300 mg on the day prior to angiography; (b) 600 mg on the day prior to angiography; (c) 300 mg followed by 75 mg daily started 1 week prior to angiography; and (d) 300 mg followed by 150 mg daily started 1 week prior to angiography. Platelet aggregation was assessed by light transmission aggregometry (LTA) after stimulation with adenosine diphosphate 20 μM at baseline and at the time of diagnostic coronary angiography. The absolute change in platelet aggregation between these two time points was considered the main outcome measure. Results: At the time of diagnostic coronary angiography, the 300-mg/150-mg daily regimen achieved the greatest decrease in platelet aggregation (37 ± 19%), while the 300 mg regimen provided the smallest (20 ± 22%), an absolute difference between the two groups of 17.2 ± 5.1% (P = 0.005). Conclusions: A 300-mg loading dose of clopidogrel followed by 150 mg daily for 1 week prior to coronary angiography provides more effective platelet inhibition, as defined by LTA, compared to the standard 300-mg loading dose regimen at the time of coronary intervention.

Variable biological effect of aspirin is suggested to be related to pharmacological resistance. The incidence of this so-called "resistant" state varies with the study population and the assay used. We determined performance features of five assays used to assess aspirin effects in non-smoking healthy volunteers not taking any drug known to interfere with platelet function. Blood and urine samples were obtained immediately before and after 8-10 days of aspirin 80 mg intake. Forty-five participants 19-59 years old were enrolled. The sensitivity (SE), specificity (SP), and optimal cut-off (CO) value to detect the effect of aspirin were: light transmission aggregometry (LTA) with 1.6 mM arachidonic acid (AA) - SE 100%, SP 95.9%, CO 20%; LTA with adenosine diphosphate (ADP) 10 microM - SE 84.4%, SP 77.8%, CO 70%; VerifyNow Aspirin - SE 100%, SP 95.6%, CO 550 ARU; platelet count drop - SE 82.2%, SP 86,7%, CO 55%; TEG((R)) - SE 82,9%, SP 75,8%, CO 90%; and urinary 11-dehydrothromboxane B(2) levels (11-dHTB(2)) - SE 62.2%, SP 82.2%, CO 60 pg/ml. AA-induced LTA and the VerifyNow assay reliably detected aspirin intake in all subjects; there was wide overlap in pre- and post- aspirin results with ADP-induced LTA, platelet count drop, TEG((R)) and urinary 11-dHTB(2) assays. These results suggest that some of the variability in the reported incidence of "aspirin resistance" is unrelated to aspirin intake but related to inherent limitations of some assays to detect aspirin mediated effects or to underlying platelet reactivity variability independent of aspirin-mediated cyclooxygenase-1 inhibition.

The emergence of point-of-care assays enabling bedside testing such as the VerifyNow P2Y12 system might prove useful in clinical settings. The aim of this study was to evaluate the ability of the VerifyNow P2Y12 assay to estimate the inhibition of platelet aggregation provided by clopidogrel in the absence of baseline off-drug aggregation data. Sixty-eight patients with coronary artery disease scheduled to initiate clopidogrel therapy underwent platelet aggregation testing by VerifyNow P2Y12 at baseline and after clopidogrel administration. The inhibition reported by the VerifyNow assay (relative to thrombin receptor activating peptide-induced platelet aggregation, serving as baseline) was compared with that calculated with the actual adenosine diphosphate-induced baseline obtained with the same methodology. The postclopidogrel thrombin receptor activating peptide-induced aggregation showed a great discordance with that induced by adenosine diphosphate before clopidogrel with a bias of 24 units (95% limits of agreement from -142 to 190 units). Moreover, the inhibition reported by the assay overestimated the standard before-and-after testing data by an average of 8% (95% limits of agreement from -49% to 65%), making its use without a true baseline comparator unsatisfactory. The VerifyNow P2Y12 assay fails to accurately quantify platelet inhibition achieved by clopidogrel compared with before-and-after testing. Further studies are required to establish the clinical usefulness of the VerifyNow P2Y12 assay to accurately predict the occurrence of major adverse cardiovascular events in patients with reduced clopidogrel efficacy before it can be implemented in clinical practice. At present, the use of this assay in clinical care cannot be recommended for monitoring clopidogrel therapy.

Aims We sought to compare the results obtained from six major platelet function tests in the assessment of the prevalence of aspirin resistance in patients with stable coronary artery disease. Methods and results 201 patients with stable coronary artery disease receiving daily aspirin therapy (≥80 mg) were recruited. Platelet aggregation was measured by: (i) light transmission aggregometry (LTA) after stimulation with 1.6 mM of arachidonic acid (AA), (ii) LTA after adenosine diphosphate (ADP) (5, 10, and 20 µM) stimulation, (iii) whole blood aggregometry, (iv) PFA-100®, (v) VerifyNow Aspirin®; urinary 11-dehydro-thromboxane B2 concentrations were also measured. Eight patients (4%, 95% CI 0.01–0.07) were deemed resistant to aspirin by LTA and AA. The prevalence of aspirin resistance varied according to the assay used: 10.3–51.7% for LTA using ADP as the agonist, 18.0% for whole blood aggregometry, 59.5% for PFA-100®, 6.7% for VerifyNow Aspirin®, and finally, 22.9% by measuring urinary 11-dehydro-thromboxane B2 concentrations. Results from these tests showed poor correlation and agreement between themselves. Conclusion Platelet function tests are not equally effective in measuring aspirin's antiplatelet effect and correlate poorly amongst themselves. The clinical usefulness of the different assays to classify correctly patients as aspirin resistant remains undetermined.

Acetylsalicylic acid, or aspirin (ASA), is widely used in patients with cardiovascular disease to prevent acute ischemic events. However, platelet response to ASA is not equal in all individuals, and a high variability in the prevalence of ASA resistance is reported in the literature (0.4-83%). Actually, ASA resistance is poorly understood; this stems from the fact that its definition is unclear, its presence can be evaluated by a number of assays that are not equivalent, and its prevalence may vary widely based on the population studied. This article (1) exposes the difficulties in defining ASA resistance; (2) discusses the mechanisms by which ASA resistance may occur; (3) presents the characteristics that may put patients at greater risk of exhibiting ASA resistance; and (4) discusses the clinical impact of ASA resistance in patients requiring chronic therapy.

ST-segment depression is commonly seen in patients with acute coronary syndromes. Most authors have attributed it to transient reductions in coronary blood flow due to nonocclusive thrombus formation on a disrupted atherosclerotic plaque and dynamic focal vasospasm at the site of coronary artery stenosis. However, ST-segment depression was never reproduced in classic animal models of coronary stenosis without the presence of tachycardia. We hypothesized that ST-segment depression occurring during acute coronary syndromes is not entirely explained by changes in epicardial coronary artery resistance and thus evaluated the effect of a slow, progressive epicardial coronary artery occlusion on the ECG and regional myocardial blood flow in anesthetized pigs. Slow, progressive occlusion over 72 min (SD 27) of the left anterior descending coronary artery in 20 anesthetized pigs led to a 90% decrease in coronary blood flow and the development of ST-segment elevation associated with homogeneous and transmural myocardial blood flow reductions, confirmed by microspheres and myocardial contrast echocardiography. ST-segment depression was not observed in any ECG lead before the development of ST-segment elevation. At normal heart rates, progressive epicardial stenosis of a coronary artery results in myocardial ischemia associated with homogeneous, transmural reduction in regional myocardial blood flow and ST-segment elevation, without preceding ST-segment depression. Thus, in coronary syndromes with ST-segment depression and predominant subendocardial ischemia, factors other than mere increases in epicardial coronary resistance must be invoked to explain the heterogeneous parietal distribution of flow and associated ECG changes.

We sought to evaluate the impact of a continuous intravenous infusion of perflutren on systemic pulmonary artery pressures at clinically relevant doses for myocardial perfusion imaging in pigs.Five anesthetized, ventilated, open-chest pigs were administered perflutren intravenously at a rate of 0.0364 mL/kg/min over approximately 5 minutes.Optimal, sustained myocardial opacification was achieved in all animals. Perflutren produced transient, reversible increases in pulmonary artery pressures versus baseline: 10.6% (3.0 +/- 1.4 mm Hg; 95% confidence interval 1.7-4.2; P.01) for systolic, 15.2% (2.5 +/- 1.4 mm Hg; 95% confidence interval 1.3-3.7; P.05) for diastolic, and 11.6% (2.6 +/- 1.1 mm Hg; 95% confidence interval 1.68-3.65; P.01) for mean pressures. Heart rate and systemic arterial pressures displayed nonsignificant increases during perflutren infusion compared with baseline.A continuous intravenous infusion of perflutren at a rate achieving optimal, sustained myocardial perfusion imaging in pigs induces a mild, transient, not clinically significant increase in pulmonary artery pressures without affecting heart rate or systemic arterial pressures.

Objectives This study evaluates the impacts of seasonal and lunar cycles on anxiety and mood disorders, panic and suicidal ideation in patients consulting the emergency department (ED) with a complaint of unexplained chest pain (UCP). Methods Patients with UCP were recruited from two EDs. Psychiatric diagnoses were evaluated with the Anxiety Disorders Interview Schedule for DSM-IV. Results Significant seasonal effects were observed on panic and anxiety disorders, with panic more frequently encountered during spring [odds ratio (OR)=1.378, 95% confidence interval (CI)=1.002–1.896] and anxiety disorders during summer (OR=1.586, 95% CI=1.037–2.425). Except for one significant finding, no significant effects of lunar cycles were observed. These findings encourage ED professionals and physicians to abandon their beliefs about the influence of lunar cycles on the mental health of their patients. Such unfounded beliefs are likely to be maintained by self-fulfilling prophecies.

Study Objective. To evaluate the effect of tirofiban (a glycoprotein IIb-IIIa inhibitor) in preventing streptokinase-induced, antibody-mediated platelet aggregation after administration of streptokinase or development of a streptococcal infection. Design. Prospective analysis. Setting. Research center of a Canadian hospital. Participants. Forty-five healthy volunteers, 45 patients who had received streptokinase within the past 3 years, and 13 patients who had a severe streptococcal infection also within the past 3 years. Intervention. Blood samples were drawn to measure the extent of inhibition of streptokinase-induced, antibody-mediated platelet activation and aggregation by tirofiban. Measurements and Main Results. Platelet aggregation was measured by using a turbidimetric method. The extent of inhibition by tirofiban was measured by incubating tirofiban for 2 minutes before adding streptokinase 5000 U/ml. Also, tirofiban was added 2 minutes before adding adenosine 5′-diphosphate (ADP) 2 μM/L into the last tube as a comparison. Streptokinase-induced, antibody-mediated platelet aggregation was observed in 10 (22%) of the 45 patients treated with streptokinase, in 3 (23%) of the 13 patients with streptococcal infection, and in none of the 45 healthy volunteers. Tirofiban inhibited streptokinase-induced, antibody-mediated platelet aggregation by 89 ± 14% (p

Streptokinase use, in acute myocardial infarction, is hindered by failure to reperfuse (60%) and early reocclusion (16%). This phenomenon may, among other causes, be due to systemic inactivation of streptokinase, as well as streptokinase-induced platelet aggregation and clot propagation from antibodies to streptokinase produced after streptokinase administration or streptococcal infections. The purpose of this study was to determine the incidence of streptokinase-induced, antibody-mediated, platelet activation and aggregation after administration of SK or development of a streptococcal infection.We included 45 normal volunteers (Control group), as well as 45 patients who had received streptokinase (Streptokinase group) and 13 who had suffered a severe streptococcal infection (Streptococcal infection group) within the past 3 years. Extent of streptokinase-induced, antibody-mediated, platelet activation and aggregation, as well as anti-streptokinase antibody and streptokinase resistance titers (lowest streptokinase concentration to cause clot lysis within 10 min) were measured.Whereas streptokinase-induced, antibody-mediated, platelet activation was observed in 49% of streptokinase patients and in only 17% and 15% of streptococcal infection patients and normal volunteers (p0.05 Streptokinase vs. Control and Streptokinase vs. Streptococcal infection), streptokinase-induced platelet aggregation was observed in 23% of streptokinase patients and streptococcal infection patients, and in none of the control patients (p0.05).Streptokinase-induced, antibody-mediated, platelet activation and aggregation occur in patients with high titers of anti-streptokinase antibody and may play a role in failure of streptokinase therapy. Streptococcal infection patients behave like streptokinase patients in terms of the reactivity of their platelets to subsequent streptokinase dose in vitro.

Epidemiological studies have linked clopidogrel discontinuation with an increased incidence of ischemic events. This has led to the hypothesis that clopidogrel discontinuation may result in a pharmacological rebound. We evaluated the impact of clopidogrel discontinuation on platelet function. Platelet aggregation was measured by light transmission aggregometry (LTA) in response to adenosine diphosphate (ADP) 0.5, 1, 1.5, 2.5, 5 and 10 µM and by VerifyNow® P2Y12, in 37 clinically stable coronary artery disease (CAD) patients scheduled to discontinue clopidogrel treatment, and 37 clinically stable CAD patients not taking clopidogrel. Platelet function was assessed the day before clopidogrel cessation and 1, 3, 7, 14, 21 and 28 days after. Clopidogrel had been initiated a median of 555 days (ranging from 200 to 2280 days) before the treating cardiologist recommended its discontinuation. All participants were taking aspirin, most commonly 80 mg daily although a minority was prescribed 325 mg daily. Following clopidogrel discontinuation, VerifyNow® P2Y12 did not detect any rebound platelet activity, but ADP-induced LTA showed platelet sensitization to ADP, particularly at low ADP levels. Increased platelet activity was detectable seven days after clopidogrel cessation and remained higher than in controls 28 days after discontinuation. No clinical event occurred in any of the participants during the 28 days following clopidogrel cessation. In conclusion, platelet sensitization to ADP as a consequence of chronic clopidogrel administration may partially explain the recrudescence of ischemic events following clopidogrel discontinuation in otherwise stable coronary artery patients.

Objective To document the prevalence and characteristics of nonfearful panic attacks (NFPA) and their consequences on panic identification and access to mental health services in patients with noncardiac chest pain. Method This cross-sectional sample included 339 patients with noncardiac chest pain and panic attacks. A structured interview was used to collect data on panic attacks, psychiatric morbidity, sociodemographic variables, and previous consultations with a psychiatrist or psychologist. Medical files were reviewed to assess the rate of NFPA identification in the emergency department. Results In our sample of patients with noncardiac chest pain, 39% of those with panic attacks reported NFPA. Psychiatric morbidity was lower in patients with NFPA than in patients with typical panic attacks (49.6% vs 71.1%), as was the mean number of panic symptoms (6 vs 7.8). The rate of panic attack identification was similar in both the groups, but patients with NFPA were less likely to have consulted a psychiatrist or psychologist during their lifetime (34% vs 46%). Conclusions NFPA were highly prevalent in our sample of emergency department patients with noncardiac chest pain. NFPA is associated with significant psychiatric morbidity but these patients were less likely to follow through with referral to a psychiatrist or psychologist than patients with typical panic attacks were.

Background: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. Materials and methods: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 μg/kg/min i.v.) for 48–108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) ( n =26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) ( n =27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. Results: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7±59.8 and 187.5±81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients ( P =NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 μM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P =0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. ≥30 min for tirofiban and unfractionated heparin ( P =NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P =0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. Interpretation: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.

Objectives. We hypothesized that l-arginine would improve abnormal coronary vasodilation in response to physiologic stress in patients with atherosclerosis and its risk factors by reversing coronary endothelial dysfunction.Background. Studies have demonstrated that physiologic coronary vasodilation correlates with endothelial function and that l-arginine, the substrate for nitric oxide synthesis, improves the response to acetylcholine (Ach).Methods. Changes in coronary blood flow and epicardial diameter response to Ach, adenosine and cardiac pacing were measured in 32 patients with coronary atherosclerosis or its risk factors and in 7 patients without risk factors and normal coronary angiograms.Results. Intracoronary l-arginine did not alter baseline coronary vascular tone, but the epicardial and microvascular responses to Ach were enhanced (both p < 0.001). The improvement after l-arginine was greater in epicardial segments that initially constricted with Ach; similarly, l-arginine abolished microvascular constriction produced by higher doses of Ach. Thus, there was a negative correlation between the initial epicardial and vascular resistance responses to Ach and the magnitude of improvement with l-arginine (r = −0.55 and r = −0.50, respectively, p < 0.001). d-Arginine did not affect the responses to Ach, and adenosine responses were unchanged with l-arginine. Cardiac pacing-induced epicardial constriction was abolished by l-arginine, but microvascular dilation remained unaffected.Conclusions. Thus, l-arginine improved endothelium-dependent coronary epicardial and microvascular function in patients with endothelial dysfunction. Prevention of epicardial constriction during physiologic stress by l-arginine in patients with endothelial dysfunction may be of therapeutic value in the treatment of myocardial ischemia.

Objectives The current study was designed (1) to assess insomnia symptoms and sleep-related beliefs in a population of patients presenting in emergency department with unexplained chest pain (UCP) and (2) to examine the associations between insomnia and pain. Methods This is a report of secondary data from a cross-sectional study performed in the emergency department of 2 academic hospitals. Patients with UCP seen in an emergency department were assessed using sleep questionnaires and the Anxiety Disorders Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, fourth edition . Results Nearly every second patient with UCP (44%) seen in an emergency department suffered from clinically significant insomnia symptoms. Most patients with an anxiety or a mood disorder had insomnia, but a minority of patients with insomnia had an anxiety or a mood disorder. Insomniacs with an anxiety disorder were similar to insomniacs without comorbid anxiety for sleep-related beliefs and depressive symptoms, and both groups of insomniacs reported more depressive symptoms and faulty beliefs than both groups of good sleepers, i.e., either with or without an anxiety disorder. Results from regression analyses revealed that insomnia was associated with pain on univariate regression analysis and accounted for 1.3% of the variance in both pain intensity and interference. However, this association was rendered nonsignificant when additional variables were added to the model. Conclusions Insomnia symptoms are an important, but often disregarded, feature present in a significant proportion of patients with UCP. As insomnia showed stronger associations with pain than anxiety or depression, it may represent an important factor contributing to the development and recurrence of UCP.

SummaryHigh on-treatment platelet reactivity (HPR) has been identified as an independent risk factor for ischaemic events. The randomised, doubleblind, TRIPLET trial included a pre-defined comparison of HPR in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) following a placebo/600-mg clopidogrel loading dose (LD) immediately before a subsequent prasugrel 60-mg or 30-mg LD. Platelet reactivity was assessed using the VerifyNow® P2Y12 assay (P2Y12 Reaction Units, PRU) within 24 hours (h) following the placebo/clopidogrel LD (immediately prior to prasugrel LD), and at 2, 6, 24, 72 h following prasugrel LDs. The impact of CYP2C19 predicted metaboliser phenotype (extensive metaboliser [EM] and reduced metabolisers [RM]) on HPR status was also assessed. HPR (PRU ≥240) following the clopidogrel LD (prior to the prasugrel LD) was 58.5% in the combined clopidogrel LD groups. No significant difference was noted when stratified by time between the clopidogrel and prasugrel LDs (≤6 hs vs >6 h). At 6 h following the 2nd loading dose in the combined prasugrel LD groups, HPR was 7.1%, with 0% HPR by 72 h. There was no significant effect of CYP2C19 genotype on pharmacodynamic (PD) response following either prasugrel LD treatments at any time point, regardless of whether it was preceded by a clopidogrel 600-mg LD. In conclusion, in this study, patients with ACS intended for PCI showed a high prevalence of HPR after clopidogrel 600-mg LD regardless of metaboliser status. When prasugrel LD was added, HPR decreased substantially by 6 h, and was not seen by 72 h.

Limited data exist regarding the management of patients with acute coronary syndrome (ACS) in high-income countries compared with low/middle-income countries. We aimed to compare in-hospital trends of revascularization and prescription of medications at discharge in patients with ACS from high-income (Canada and United States) and low/middle-income (India, Iran, Pakistan, and Tunisia) countries. Data from a double-blind, placebo-controlled, randomized trial investigating the effect of bupropion on smoking cessation in patients after an enzyme-positive ACS was used for our study. A total of 392 patients, 265 and 127 from high-income and from low/middle-income countries, respectively, were enrolled. Patients from high-income countries were older, and were more likely to have diagnosed hypertension and dyslipidemia. During the index hospitalization, patients from high-income countries were more likely to be treated by percutaneous coronary intervention (odds ratio [OR] 19.7, 95% confidence interval [CI] 10.5 to 37.0). Patients with ST elevation myocardial infarction from high-income countries were more often treated by primary percutaneous coronary intervention (OR 16.3, 95% CI 6.3 to 42.3) in contrast with thrombolytic therapy (OR 0.24, 95% CI 0.14 to 0.41). Patients from high-income countries were also more likely to receive evidence-based medications at discharge (OR 2.32, 95% CI 1.19 to 4.52, a composite of aspirin, clopidogrel, and statin). In conclusion, patients with ACS in low/middle-income countries were less likely to be revascularized and to receive evidence-based medications at discharge. Further studies are needed to understand the underutilization of procedures and evidence-based medications in low/middle-income countries.

BACKGROUND Left ventricular (LV) diastolic function declines with the normal aging process. Because these changes are related to impaired active LV relaxation as well as to structural alterations, we hypothesized that verapamil might improve LV filling in elderly normal subjects compared with young normal subjects. METHODS AND RESULTS We studied 27 normal volunteers (between 20 and 71 years old), with normal exercise tests and echocardiograms, by radionuclide angiography before and after 3 to 4 days of oral verapamil therapy. Indexes of global LV function were derived from analysis of background-corrected time-activity curves. Subjects were recruited from three age groups: young (26 +/- 4 years, n = 10), middle-aged (46 +/- 5 years, n = 9), and elderly (66 +/- 3 years, n = 8). Baseline resting heart rate, blood pressure, peak systolic wall stress, and LV ejection fraction did not differ among groups. Baseline peak LV filling rate (expressed in fractional stroke volume per second) was reduced in the middle-aged group (5.8 +/- 1.2, P < .01) and the elderly group (4.3 +/- 1.0, P < .01) compared with the young group (7.8 +/- 1.2). With verapamil, resting heart rate, peak systolic wall stress, LV ejection fraction, and peak ejection rate did not change in any group. Peak filling rate increased in the middle-aged group (to 6.8 +/- 1.5 SV/s, P < .01) and the elderly group (to 5.7 +/- 1.0 SV/s, P < .01) but did not change in the young group (8.0 +/- 1.4 SV/s). Also, time to peak filling rate decreased with verapamil in the elderly group (from 185 +/- 31 to 147 +/- 15 milliseconds, P < .01). The magnitude of change in filling rate was correlated positively with age (r = .55, P < .005). CONCLUSION Verapamil selectively enhances LV diastolic filling in middle-aged and elderly subjects, compared with young adults, without affecting systolic function. This observation supports the hypothesis that the impairment of LV filling accompanying the normal aging process is, at least in part, a reversible phenomenon.

To elucidate the role of physical activity in the pathogenesis of acute ischemic syndromes in patients with coronary artery disease (CAD), we hypothesized that platelet activation occurs when coronary blood flow velocity and shear stress increase across an atherosclerotic vascular bed. We measured platelet aggregation by using angiologic catheterization to obtain simultaneous samples of whole blood from the coronary sinus and the aorta while at rest, 2 minutes after the onset of rapid atrial pacing, and 10 minutes after termination of pacing. Of 82 consecutive patients included in our study, 36 had stenosis of the left coronary artery, 12 had stenosis of the right coronary artery only, and 34 had no evidence of CAD. Samples taken at rest revealed no arteriovenous difference in platelet aggregation between patients with CAD and those without CAD. In patients with significant stenosis (> or = 50%) of the left coronary artery, atrial pacing caused platelet aggregation to increase in samples from the coronary sinus (64 +/- 9% increase; p < 0.01) but not in blood from the aorta (2 +/- 8% decrease; difference not significant). This increase was transient, with aggregation returning almost to resting values 10 minutes after pacing ended. Atrial pacing elicited no change in platelet aggregation in samples from either the coronary sinus or aorta of patients with nonsignificant stenosis (< 50%) of the left coronary artery, patients with significant stenosis of the right coronary artery only, and patients free of CAD. Thus, under resting conditions, no evidence of platelet activation across the coronary bed was seen regardless of CAD status.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND 99mTc-sestamibi and thallium imaging have similar accuracy when used for diagnostic purposes, but whether sestamibi provides accurate information regarding myocardial viability in patients with chronic coronary artery disease has not been established. Since there is minimal redistribution of sestamibi over time, it may overestimate nonviable myocardium in patients with left ventricular dysfunction, in whom blood flow may be reduced at rest. METHODS AND RESULTS We studied 54 patients with chronic coronary artery disease with a mean ejection fraction of 34 +/- 14%. Patients underwent stress/redistribution/reinjection thallium tomography and, within a mean of 5 days, same-day rest/stress sestamibi imaging using the same exercise protocol and with patients achieving the same exercise duration. Of the 111 reversible thallium defects on either the redistribution or reinjection study, 40 (36%) were determined to be irreversible on the rest/stress sestamibi study, whereas only 3 of 63 irreversible thallium defects despite reinjection (5%) were classified to be reversible by sestamibi imaging. The concordance regarding reversibility of myocardial defects between thallium stress/redistribution/reinjection and same day rest/stress sestamibi studies was 75%. A subgroup of 25 patients also underwent positron emission tomography (PET) studies with 15O-labeled water and [18F]fluorodeoxyglucose (FDG) at rest after an oral glucose load. As in the overall group of 54 patients, there was concordance between thallium and sestamibi imaging regarding defect reversibility in 51 of 73 regions (70%). In the remaining 22 discordant regions (30%), 18 (82%) appeared irreversible by sestamibi imaging but were reversible by thallium imaging. Myocardial viability was confirmed in 17 of 18 regions, as evidenced by normal FDG uptake (10 regions) or FDG/blood flow mismatch (7 regions) on PET. These regions were present in 16 of the 25 patients studied (64%). We then explored methods to improve the sestamibi results. First, when the 18 discordant regions with irreversible sestamibi defects were further analyzed according to the severity of defects, 14 (78%) demonstrated only mild-to-moderate reduction in sestamibi activity (51% to 85% of normal activity), suggestive of predominantly viable myocardium, and the overall concordance between thallium and sestamibi studies increased to 93%. Second, when an additional 4-hour redistribution image was acquired in 18 patients after the injection of sestamibi at rest, 6 of 16 discordant irreversible regions (38%) on the rest/stress sestamibi study became reversible, thereby increasing the concordance between thallium and sestamibi studies to 82%. CONCLUSIONS These data indicate that same-day rest/stress sestamibi imaging will incorrectly identify 36% of myocardial regions as being irreversibly impaired and nonviable compared with both thallium redistribution/reinjection and PET. However, the identification of reversible and viable myocardium can be greatly enhanced with sestamibi if an additional redistribution image is acquired after the rest sestamibi injection or if the severity of reduction in sestamibi activity within irreversible defects is considered.

The objective was to demonstrate the derivation and the preliminary validation of a brief screening score to improve recognition of panic-like anxiety in emergency department (ED) patients with unexplained chest pain.This cross-sectional study included 507 ED patients with unexplained chest pain randomly assigned to the derivation condition (n = 201) or the validation condition (n = 306). The Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) acted as the criterion standard for panic diagnosis. Receiver operating characteristic (ROC) curves were used to determine which of the sociodemographic, medical, and questionnaire response variables best predicted the presence of panic-like anxiety in the derivation condition. The selected predictors were entered in a logistic regression analysis to determine variables to be included in the screening score. The predictive validity of the resulting score was evaluated in both conditions.The four-item Panic Screening Score (PSS) identified panic-like anxiety with a sensitivity of 63% (95% confidence interval [CI] = 52% to 73%) and a specificity of 84% (95% CI = 76% to 90%) in the derivation phase. The positive predictive value was 74% (95% CI = 62% to 93%) and the negative predictive value was 76% (95% CI = 68% to 89%). In the validation phase, the sensitivity and specificity were 53% (95% CI = 44% to 62%) and 85% (95% CI = 78% to 89%), respectively. The positive predictive value was 72% (95% CI = 62% to 80%) and the negative predictive value was 71% (95% CI = 65% to 77%).The PSS may be useful to identify patients with unexplained chest pain who could benefit from referral to mental health professionals or their primary care providers for evaluation of panic attack and panic disorder. Prospective studies to improve and validate the PSS, followed by impact analysis, are mandatory before clinical implementation.

The aim of our study was to compare the electrocardiographic recordings in an experimental open-chest swine model before and after left-sided thoracotomy to detect any surgery-induced fluctuations that might interfere with subsequent experimental interventions. We obtained electrocardiograms from 8 deeply anesthetized domestic swine and compared the respective ST-segment potentials obtained after vascular surgery and after left-sided thoracotomy and dissection of the left anterior descending coronary artery. Compared with baseline recordings, no significant ST-segment deviation on any of the electrocardiographic leads occurred after vascular surgery. However, statistically significant ST-segment depression was observed after thoracotomy. Invasive surgical procedures in open-chest swine models may lead to morphologic changes in the ST segment. The physiologic mechanism of these changes is not fully understood.

Objectives . The purpose of this study was to determine the incidence and prognostic importance of myocardial ischemia detected by ambulatory monitoring in low risk, medically managed patients with coronary artery disease. Background . Previous studies have demonstrated that certain high risk subsets of patients with coronary artery disease have improved survival with revascularization. The remaining low risk medically managed patients may still have episodes of silent ischemia during daily living, but the frequency and prognostic implications of such episodes in this group are unknown. Methods . We prospectively studied the incidence and prognostic significance of ST segment changes recorded during daily activities in 116 asymptomatic or mildly symptomatic low risk patients with native coronary artery disease who were followed up for 29 ± 13 months. Low risk patients were selected after excluding patients with 1) left main disease; 2) three-vessel coronary artery disease and left ventricular dysfunction at rest; 3) three-vessel disease and inducible ischemia during exercise; and 4) two-vessel disease, left ventricular dysfunction and inducible ischemia. Results . Forty-five patients (39%) had transient episodes of ST segment depression during 48-h electrocardiographie (ECG) monitoring (total 217 episodes, lasting 7,223 min, 82% of episodes silent). There were eight acute cardiac events (seven myocardial infarctions, one episode of unstable angina) and nine patients underwent elective revascularization. Seven of the eight acute events occurred in patients without silent ischemia during monitoring. Kaplan-Meier survival analysis revealed no significant differences in event-free survival from either acute or total events in subgroups with or without silent ischemia during ambulatory ECG monitoring. None of the clinical, treadmill exercise, radionuclide ventriculographic or cardiac catheterization variables were predictive of outcome by Cox mullivariate proportional hazard function analysis. Analysis of coronary arteriograms before and after acute cardiac events revealed that in five of the six patients studied, acute occlusion occurred in a coronary artery different from the artery with the severest stenosis on initial angiography. Conclusions . In patients categorized as at low risk on the basis of the results of cardiac catheterization and stress testing, silent myocardial ischemia during daily life was not uncommon, and its presence failed to predict future coronary events.

SummaryNitric oxide (NO) inhibits platelet aggregation. Accordingly, we hypothesized that complexes of diethylamine and spermine with NO (DEA/NO and SPER/NO, respectively), two vasodilators previously shown to release NO spontaneously in aqueous solution, may also be useful antiplatelet agents. Platelet aggregation was measured in whole blood or platelet-rich plasma by impedance aggregometry after addition of collagen. In whole blood, the dose response curve for DEA/NO added 1 min before collagen was similar to that for aspirin (60% inhibition at 10-4 M), while SPER/NO and sodium nitroprusside were less potent by an order of magnitude. In platelet-rich plasma, 10-6 M DEA/NO caused 60% inhibition, while SPER/NO and sodium nitroprusside were as active only at 10-5 M; aspirin’s potency was unchanged from that in whole blood. In vivo, DEA/NO and sodium nitroprusside produced significant platelet inhibition 1 min after intravenous injection in the rabbit at 50 nmol/kg. Similar in vivo platelet inhibition was observed with SPER/NO and aspirin, but only at higher dose. The effects of DEA/NO and sodium nitroprusside were transient, lasting less than 30 min after treatment, while the activity of SPER/NO and aspirin was sustained throughout the 30 min experiment. The magnitude and duration of the antiplatelet effects of DEA/NO and SPER/NO correlate with the rates at which they release nitric oxide spontaneously in aqueous solution. Thus, NO/nucleophile complexes merit further exploration both as research tools and as potential antiplatelet agents.

Introduction Intersubject variability in platelet response to aspirin could be related to genetic factors that regulate platelet enzymes or receptors. This study evaluates the impact of the selected polymorphisms in the COX-1 gene, the CYP5A1 gene, the P2RY1 receptor gene, and the GPIIbIIIa receptor gene on platelet response to aspirin and risk of suffering from major adverse cardiovascular and cerebrovascular events (MACCE). Materials and methods 192 Caucasian patients with stable coronary artery disease treated with daily aspirin were recruited and followed for 3 years. Platelet aggregation was measured by light transmission aggregometry with arachidonic acid (1.6 mM) and adenosine diphosphate (5, 10 or 20 μM) used as agonists. Genotyping was performed by standard PCR methods. Results Arachidonic acid-induced platelet aggregation was unaffected by the COX-1 22C/T and by the PlA1/A2 polymorphisms. However, carriers of the 1622 G/G genotype of the P2RY1 gene had significantly higher levels of arachidonic acid-induced platelet aggregation compared with non-carriers (AA 2.0%, AG 2.0% vs. GG 9.0%, p = 0.047). Carrying the 1622 G/G genotype increased the risk of inadequate platelet response to aspirin, defined as arachidonic acid-induced aggregation ≥ 20%, by a factor of 8.5 (1.4 – 53.3, p = 0.022) and the risk of 3-year MACCE by a factor of 7 (1.4 – 34.7, p = 0.017). Conclusion The 1622A/G mutation of the P2RY1 gene could contribute to inadequate platelet response to aspirin and is associated with an increased risk of suffering from MACCE.

BACKGROUND A subgroup of patients with chest pain and angiographically normal epicardial coronary arteries have reduced dilator response to metabolic or pharmacological stimuli, but the mechanisms responsible for this reduced dilator response are unknown. In this study, we have investigated whether microvascular endothelial dysfunction is a cause of the observed reduced vasodilator reserve. METHODS AND RESULTS The functional response of the microvasculature was studied with rapid atrial pacing at 150 beats per minute. Fifty-one patients, 20 hypertensive and 31 normotensive, with chest pain and normal epicardial coronary arteries (< 10% stenosis) were studied. Endothelial function was tested with incremental infusions of acetylcholine to achieve estimated intracoronary concentrations ranging from 10(-7) M to 10(-5) M. Endothelium-independent smooth muscle vasomotion was measured using intracoronary sodium nitroprusside. Endothelial dysfunction of epicardial coronary arteries, demonstrated as severe (> 50%) constriction with < 10(-5) M acetylcholine concentration, was evident in five patients (10%). In the remaining 46 patients, coronary blood flow increased with acetylcholine (mean, 78 +/- 43%) and atrial pacing (mean, 51 +/- 37%), and coronary vascular resistance decreased by 35 +/- 16% and 29 +/- 14%, respectively, but the responses were heterogeneous. There was a correlation between the coronary resistance change with acetylcholine and the change with atrial pacing: r = 0.68, p < 0.001 in these 46 patients. Thus, patients with depressed dilation with atrial pacing had reduced endothelium-dependent dilation with acetylcholine, and vice versa. However, the microvascular dilation caused by sodium nitroprusside was not significantly different between patients with and those without reduced dilation with atrial pacing, indicating that the vasodilator defect was not caused by smooth muscle dysfunction. There were no differences in the vasodilator responses with atrial pacing, acetylcholine, or nitroprusside between normotensive and hypertensive patients. Multivariate regression analysis was performed to determine whether age, sex, serum cholesterol level, hypertension, presence of mild epicardial vessel atherosclerosis, resting left ventricular function, change in left ventricular ejection fraction with exercise, vasodilation with acetylcholine, and vasodilation with sodium nitroprusside were independently related to the vasodilator response to atrial pacing. Only the change in coronary vascular resistance with acetylcholine was independently correlated with the change in resistance with atrial pacing: R2 = 0.46, p < 0.0001. CONCLUSIONS Patients with chest pain, normal epicardial coronary arteries, and reduced vasodilation in response to atrial pacing appear to have associated endothelial dysfunction of the coronary microvasculature. Thus, microvascular endothelial dysfunction may contribute to the reduced vasodilator reserve with atrial pacing and anginal chest pain in these patients.

BACKGROUND Platelet aggregation is believed to contribute to the precipitation of acute ischemic syndromes. Because physical activity has been proposed as one possible trigger in converting a patient with chronic coronary artery disease to one with an acute ischemic syndrome, we examined the hypothesis that platelets become activated when coronary blood flow velocities (and thereby shear stress) increase across an atherosclerotic bed. METHODS AND RESULTS During catheterization, 82 patients (36 with left coronary artery disease, 12 with only right coronary artery disease, and 34 with normal coronary arteries) had measurement of whole blood platelet aggregation performed on blood samples obtained simultaneously from the coronary sinus and aorta at rest, 2 minutes after onset of rapid atrial pacing, and 10 minutes after pacing was terminated. There was no arteriovenous difference in platelet aggregation under resting conditions in patients with versus those without coronary artery disease. Atrial pacing in patients with left coronary artery disease (greater than or equal to 50% stenosis in a major epicardial vessel) caused an increase in platelet aggregation in the coronary sinus blood (+64 +/- 9%, p less than 0.01) but not in arterial blood (2 +/- 8% decrease, p = NS). This increase was transient and returned nearly to baseline 10 minutes after termination of pacing. Patients with nonsignificant left coronary artery disease, those with normal coronary arteries, and patients with significant disease only in the right coronary artery (venous drainage not into the coronary sinus) did not show any changes in either the coronary sinus or arterial blood with atrial pacing. CONCLUSIONS There is no evidence of platelet activation across a normal or an atherosclerotic coronary bed at rest. When coronary blood flow increases in the presence of significant (greater than or equal to 50%) narrowing of epicardial coronary arteries, however, platelets are activated and aggregate more easily. This mechanism may play a role in the precipitation of acute ischemic syndromes in patients with coronary artery disease.

BACKGROUND There is a circadian pattern in the occurrence of cardiac events in patients with coronary artery disease. Whether changes in coronary vascular tone contribute to these phenomena is unknown. We measured the ischemic threshold, defined as either the heart rate or rate-pressure product at 1-mm ST segment depression during treadmill exercise and used it as an index of the lowest coronary vascular resistance; the premise was that when ischemic threshold became lower, coronary vascular resistance was higher, and vice versa. METHODS AND RESULTS Fifteen patients (group A) with stable coronary artery disease underwent four identical treadmill exercise tests in 24 hours, and ischemic threshold was measured as the heart rate at the onset of 1-mm ST depression. Before each treadmill test, postischemic forearm vascular resistance was measured after 5 minutes of forearm occlusion, using strain-gauge plethysmography. Sixteen additional patients (group B) underwent two treadmill tests at 8 AM and 1 PM, and ischemic threshold was measured as the heart rate-blood pressure product at 1-mm ST depression. A circadian variation was noted: In group A, the heart rate-derived ischemic threshold was lower at 8 AM and 9 PM compared with noon and 5 PM (p less than 0.03). Also, in group B, the rate-pressure product-derived ischemic threshold was 8 +/- 2% lower at 8 AM compared with 1 PM (p = 0.008). A circadian variation parallel to the observed variation in ischemic threshold was also noted in the postischemic forearm blood flow, which was lower in the morning and at night (p less than 0.004). There was a strong correlation between postischemic forearm blood flow and ischemic threshold (p less than 0.0001), such that ischemic threshold was lower at the time of day when postischemic forearm blood flow was lower, and vice versa. CONCLUSIONS A lower ischemic threshold in the morning suggests that the ischemia-induced coronary vascular resistance is increased at this time, a finding supported by a similar variation in postischemic forearm vascular resistance. Parallel changes in forearm and coronary resistance suggest that generalized (neural or humoral factors) rather than local factors are responsible for the observed circadian changes. Increased coronary tone in the mornings may not only contribute to the higher incidence of transient ischemia but may help trigger acute cardiac events at this time.

To determine predictors of exercise benefit in patients with hypertrophic cardiomyopathy after operative relief of left ventricular (LV) outflow tract obstruction, 30 patients underwent catheterization and exercise testing before and 6 months after operation, and hemodynamic measurements were obtained. The increase in maximal oxygen consumption (VO2max) during treadmill exercise testing was chosen as an index of exercise benefit. Univariate analysis showed a significant positive correlation of operative change in VO2max with preoperative LV end-diastolic and pulmonary arterial wedge pressures, operative change in exercise duration, and operative reductions in LV end-diastolic and pulmonary arterial wedge pressures and resting LV outflow tract gradient, and a significant negative correlation with preoperative VO2max and percent predicted VO2max. Multivariate analysis by stepwise linear regression of only significant univariate variables selected only preoperative percent predicted VO2max, and operative reduction in LV end-diastolic pressure and resting LV outflow tract gradient as significant predictors of postoperative change in VO2max. Stepwise regression analysis, applied only to preoperative exercise and catheterization hemodynamic variables, selected only preoperative percent predicted VO2max and preoperative LV end-diastolic pressure as predictors of improvement in exercise capacity. Thus, patients with obstructive hypertrophic cardiomyopathy, after failing medical therapy, are most likely to demonstrate improvement in exercise capacity if preoperative exercise testing demonstrates limited exercise capacity and if surgery achieves reduction in elevated resting LV outflow tract gradients and LV filling pressures.