Objectives This study evaluated effects of protease-activated receptor-1 antagonist vorapaxar (Merck, Whitehouse Station, New Jersey) versus placebo among the TRACER (Thrombin Receptor Antagonist for ...Clinical Event Reduction in Acute Coronary Syndrome) study patients with non–ST-segment elevation acute coronary syndromes undergoing coronary artery bypass grafting (CABG). Background Platelet activation may play a key role in graft occlusion, and antiplatelet therapies may reduce ischemic events, but perioperative bleeding risk remains a major concern. Although the TRACER study did not meet the primary quintuple composite outcome in the overall population with increased bleeding, an efficacy signal with vorapaxar was noted on major ischemic outcomes, and preliminary data suggest an acceptable surgical bleeding profile. We aimed to assess efficacy and safety of vorapaxar among CABG patients. Methods Associations between treatment and ischemic and bleeding outcomes were assessed using time-to-event analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox hazards model. Event rates were estimated using the Kaplan-Meier method. Results Among 12,944 patients, 1,312 (10.1%) underwent CABG during index hospitalization, with 78% on the study drug at the time of surgery. Compared with placebo CABG patients, vorapaxar-treated patients had a 45% lower rate of the primary endpoint (i.e., a composite of death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization during index hospitalization) (HR: 0.55; 95% CI: 0.36 to 0.83; p = 0.005), with a significant interaction (p = 0.012). The CABG-related Thrombolysis In Myocardial Infarction major bleeding was numerically higher with vorapaxar, but not significantly different between vorapaxar and placebo (9.7% vs. 7.3%; HR: 1.36; 95% CI: 0.92 to 2.02; p = 0.12), with no excess in fatal bleeding (0% vs. 0.3%) or need for reoperation (4.7% vs. 4.6%). Conclusions In non–ST-segment elevation acute coronary syndrome patients undergoing CABG, vorapaxar was associated with a significant reduction in ischemic events and no significant increase in major CABG-related bleeding. These data show promise for protease-activated receptor 1 antagonism in patients undergoing CABG and warrant confirmatory evidence in randomized trials. (Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome TRA·CER Study P04736AM3; NCT00527943 )
Echocardiography is a well-accepted tool for the diagnosis and quantification of pericardial effusion (PEff). Given the increasing use of computed tomographic (CT) scanning, more PEffs are being ...initially diagnosed by computed tomography. No study has compared quantification of PEff by computed tomography and echocardiography. The objective of this study was to assess the accuracy of quantification of PEff by 2-dimensional echocardiography and computed tomography compared to the amount of pericardial fluid drained at pericardiocentesis. We retrospectively reviewed an institutional database to identify patients who underwent chest computed tomography and echocardiography before percutaneous pericardiocentesis with documentation of the amount of fluid withdrawn. Digital 2-dimensional echocardiographic and CT images were retrieved and quantification of PEff volume was performed by applying the formula for the volume of a prolate ellipse, π × 4/3 × maximal long-axis dimension/2 × maximal transverse dimension/2 × maximal anteroposterior dimension/2, to the pericardial sac and to the heart. Nineteen patients meeting study qualifications were entered into the study. The amount of PEff drained was 200 to 1,700 ml (mean 674 ± 340). Echocardiographically calculated pericardial effusion volume correlated relatively well with PEff volume (r = 0.73, p <0.001, mean difference −41 ± 225 ml). There was only moderate correlation between CT volume quantification and actual volume drained (r = 0.4, p = 0.004, mean difference 158 ± 379 ml). In conclusion, echocardiography appears a more accurate imaging technique than computed tomography in quantitative assessment of nonloculated PEffs and should continue to be the primary imaging in these patients.
Abstract Background The association between lower estimated glomerular filtration rate (eGFR) and incident cardiovascular disease is less clear within the normal or mildly impaired range. Methods ...Using the Chronic Kidney Disease EPIdemiology collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) eGFR formulas, we analyzed outpatients ≥ 22 years old from 2004-2006 with 60 mL/min/1.73 m2 < eGFR < 130 mL/min/1.73 m2 , without prior cardiovascular disease, and with and without proteinuria. Results During a median follow-up of 96 months and > 10 million patient-years of follow-up, 103,506 and 104,315 cardiovascular events were recorded using CKD-EPI (n = 1,341,400, mean age 49.2 years, 42.6% male) and MDRD (n = 1,284,762, mean age 50.2 years, 43.4% male) formulas, respectively (incident event rates 4.4% and 4.6%, respectively). Adjusting for age, sex, and major cardiovascular risk factors, a 10-unit eGFR increase was independently associated with a mean decrease of 3.0% and 1.0% in incident cardiovascular events, using CKD-EPI and MDRD, respectively ( P < .001 for both), with a sharp decrease in events in the 100-mL/min/1.73 m2 < eGFR < 130 mL/min/1.73 m2 range in the CKD-EPI, but not the MDRD, cohort. Using net reclassification analysis, CKD-EPI was more accurate in predicting events than MDRD (Net Reclassification Improvement 0.39, P < .001 stratifying patients to eGFR deciles and 0.64, P < .001 as a continuous variable). Using both formulas, eGFR was predictive of incident cardiovascular disease for patients without proteinuria, but not for the 2.4% with proteinuria ( P < .001 for interaction). Conclusion Higher eGFR is associated with fewer cardiovascular events in adults without prior cardiovascular disease and without proteinuria, particularly in the 100-mL/min/1.73 m2 < eGFR < 130 mL/min/1.73 m2 range, indicating that eGFR, especially using the CKD-EPI formula, may be an independent risk marker for incident cardiovascular disease.
Spontaneous reperfusion (SR) of the infarct-related artery may occur in patients with ST-segment-elevation myocardial infarctions (STEMIs). Limited data are available on the angiographic ...characteristics of these patients. The objective of this study was to determine if there are differences in the distance of the culprit lesion from the coronary ostium in patients with STEMIs with and without SR. Patients who presented with acute STEMIs <12 hours after pain onset and who underwent coronary angiography were entered into the study. Measurement of the distance from the coronary ostium to the culprit lesion was performed. A total of 469 patients with STEMIs were included in the study, of whom 77 met criteria for SR (significant relief of chest pain associated with ≥50% resolution of ST-segment elevation on follow-up electrocardiography) and 392 did not. A highly significant difference was seen in ostial to culprit lesion distance, with the culprit lesions in the SR group being more distal than those in the non-SR group (45 ± 22 vs 39 ± 20 mm, p <0.009). In conclusion, the findings of this study demonstrate that the location of the culprit lesion in patients with STEMIs who undergo SR is more distal in the involved artery than in patients with STEMIs who do not undergo SR.
Individuals aged >85 years constitute the world's most rapidly growing age group. Despite the rapid growth of this population and its high incidence of cardiovascular morbidity, normative data ...concerning cardiac structure and function are limited. The objective of this study was to define cardiac structure and function in an age-homogenous, community-dwelling population of subjects born in 1920 and 1921. Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed using a portable echocardiograph at the subject's place of residence. Standard echocardiographic assessment of cardiac structure and function was performed. Four hundred fifty subjects (219 men, 231 women) were enrolled in the study. The cohort exhibited large left atrial volumes (64.6 ± 26 ml) and high left ventricular (LV) mass indexes (122 ± 36 g/m2 ) with normal LV volumes. Ejection fractions were preserved (55.3 ± 10.2%), but tissue Doppler s-wave velocities (lateral 7.8 ± 2.1 cm/s, septal 6.7 ± 1.9 cm/s) were reduced. Reduced tissue Doppler e waves (lateral 7.3 ± 2.2 cm/s, septal 6.2 ± 2 cm/s) and elevated E/e′ ratios (12.2 ± 4.9) indicated significantly impaired diastolic function. In conclusion, the findings of this study demonstrate a high prevalence of left atrial enlargement, elevated LV mass, evidence of LV systolic dysfunction with preserved ejection fractions, and significant LV diastolic dysfunction in a community-dwelling cohort of 85-year-olds. The finding of elevated E/e′ ratios in a subset free of known cardiovascular disease should be considered when clinical assessment of LV diastolic dysfunction in this age group is performed.
Although degenerative aortic valve disease is common with increasing age, limited data exist regarding prevalence and prognosis of aortic valve disease among the oldest old. Subjects were recruited ...from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed at home in 498 randomly selected subjects. Subjects were divided into 3 groups; normal subjects, subjects with valve calcium but without stenosis (AVC), and subjects with aortic stenosis (AS). Survival status at 5-year follow-up was assessed via the centralized population registry. AVC was noted in 55% of the study subjects and AS was seen in 8.2%. There were no significant differences between the 3 groups in any of the clinical parameters examined including risk factors for atherosclerotic heart disease. Of the 498 subjects, 107 (21%) had died at the time of 5-year follow-up. Five-year mortality was similar among the normal (17%) and AVC (20%) subjects but was significantly higher among the subjects with AS (46%; p <0.0001). AS was associated with a nearly fourfold increased likelihood of mortality (hazard ratio 3.7, 95% confidence interval 1.4 to 9.3). In conclusion, among subjects ≥85 years of age, the prevalence of AS is higher than previously reported and not associated with traditional vascular risk factors. AS but not AVC alone was independently predictive of 5-year mortality.
Abstract Background Frailty is a biological syndrome reflecting a state of decreased physiologic reserve of increasing importance in cardiovascular disease given the aging of the population. The ...relationship between frailty and indices of cardiac structure and function remain unclear, particularly in the "oldest old". The objective of this study was to examine the association between cardiac function and frailty in an age-homogenous, community-dwelling population of subjects aged 85-6 yearsSubjects were recruited at ages 85-6 from the Jerusalem Longitudinal Cohort Study that has followed an age homogenous cohort of Jerusalem residents. Subjects underwent echocardiography at their place of residence with standard assessment of cardiac structure and function. Frailty was defined according to the “phenotype of frailty” as including at least three of the following: weakness, slowness, low physical activity level, exhaustion and weight loss. 405 subjects (193 males, 212 females) were enrolled in the study. Subjects defined as frail had significantly lower ejection fraction as compared to the non-frail group (53.7 ± 0.09 % vs. 56.4 ± 0.09% ; p< 0.04). In addition, frail subjects had increased LV mass index (130.6 ± 36.2 g/m2 vs. 119.2 ± 31.1 g/m2; p < 0.03) and LA volume index (41.9 ± 14.7 cc/m2 vs. 36.7 ± 13.1 cc/m2; p< 0.001). Indices of diastolic function (E/e)' were not significantly different in the two groups (11.5 vs.11.8; p = NS). In this age-homogenous cohort of the oldest old, structural changes and indices of systolic but not diastolic function were associated with frailty.
Individuals aged >85 years are the world's most rapidly growing age group and have a high incidence of cardiovascular mortality. The objective of this study was to prospectively determine the ...prognosis of abnormal cardiac structure and function in an age-homogenous, community-dwelling population of subjects born in 1920 and 1921. Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed with a portable echocardiograph at the subjects' places of residence. Standard echocardiographic assessment of cardiac structure and function was performed. Five-year mortality was assessed through a centralized government database. Five hundred two subjects (235 men, 267 women) were enrolled in the study, of whom 107 (21%) had died at the time of 5-year follow-up. Subjects who died had significantly higher left atrial volume indexes (42.3 ± 16.5 vs 36.6 ± 12.5 ml/m2 , p <0.01) and left ventricular mass indexes (133.1 ± 47.6 vs 119.8 ± 30.6 g/m2 , p <0.05). Ejection fractions were significantly lower in subjects who died (52.5 ± 11.5% vs 56.4 ± 9.4%, p <0.003), but indexes of left ventricular diastolic function were not significantly different between the 2 groups (E/e′ ratio 13.0 ± 5.3 vs 12.2 ± 4.9, p = 0.18). In conclusion, elevated left atrial volume index and left ventricular mass index and decreased LV systolic function predicted 5-year mortality in a community-dwelling population of subjects aged 85 years, even after correction for possible confounders. Left ventricular diastolic dysfunction did not predict 5-year mortality in this cohort.
Objective Transesophageal echocardiography (TEE) during liver transplantation (LT) has been shown to be helpful in managing fluid therapy, monitoring myocardial function, and identifying ...intraoperative LT complications. The present study sought to investigate the current utilization of TEE by anesthesiologists during LT as well as issues of training and credentialing in this monitoring modality. Design A survey distributed by electronic mail. Setting LT centers in the United States in which more than 50 liver transplantation procedures were performed annually. Participants Survey respondents were contact persons in the LT divisions of the anesthesiology department of selected centers. Interventions Data collection only. Measurement and Main Results A total of 40 high-volume LT centers were identified, and survey responses were received from 30 of those. Among 217 anesthesiologists, 86% performed TEE in some or all LT cases. Most users performed a limited-scope examination, although some performed a comprehensive TEE examination during LT. Most users acquired their TEE skills informally. Only 12% of users were board certified to perform TEE, and only 1 center reported having a policy related to credentialing requirements for TEE. Conclusions There is high utilization of intraoperative TEE by anesthesiologists to perform limited-scope examinations during LT cases. Training to perform such examinations is mostly informal, and credentialing processes are lacking. An opportunity exists to establish guidelines, training programs, and standards for quality assurance in the use of this valuable monitoring modality.
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