Point-of-care platelet function testing predicts bleeding in patients exposed to clopidogrel undergoing coronary artery bypass grafting: Verify pre-op TIMI 45--a pilot study.

BACKGROUND: Guidelines recommend delaying coronary artery bypass grafting (CABG) for 5 days after discontinuing clopidogrel. However, platelet function may recover quicker in certain individuals. HYPOTHESIS: We hypothesized that perioperative measurement of platelet function with a point-of-care P2Y12 inhibitor assay could predict bleeding during CABG in patients exposed to clopidogrel. METHODS: Verify Pre-Op TIMI 45 was a prospective pilot study of 39 patients on clopidogrel who subsequently underwent CABG. Preoperative on-treatment platelet reactivity was assessed with VerifyNow P2Y12 Reaction Units (PRU), with higher PRU indicating more reactive platelets. Outcomes were stratified by PRU quartiles, as well as prespecified cutpoints for the lowest quartile (PRU 173), a cutpoint for major bleeding determined by the Youden index using receiver operator curve analysis (PRU 207), and clopidogrel resistance (PRU 230). RESULTS: Patients in higher PRU quartiles experienced smaller decreases in hemoglobin and hematocrit (P < 0.05 for all comparisons), less major bleeding (P = 0.021), and less major or minor bleeding (P = 0.003). Patients above the PRU 207 and 230 cutpoints had less chest-tube output (P = 0.041 and P = 0.012, respectively), less major bleeding (P = 0.005 and P = 0.036, respectively), and less major or minor bleeding (P = 0.013 and P < 0.001, respectively). By receiver operator curve analysis, preoperative PRU ≤ 207 discriminated between patients with and without major bleeding during surgery (area under the curve: 0.76, 95% confidence interval: 0.59-0.94, P = 0.018). CONCLUSIONS: In this pilot study, we found that point-of-care platelet function assessment could predict bleeding in patients recently exposed to clopidogrel undergoing CABG.

Epicardial adipose tissue volume and coronary artery calcium to predict myocardial ischemia on positron emission tomography-computed tomography studies.

BACKGROUND: There appears to be an association of epicardial adipose tissue (EAT) with coronary artery disease (CAD) and its risk factors. EAT is assumed to influence CAD development by altering vasomotor tone and via toxic paracrine effects. The relationship of EAT to myocardial perfusion has not been studied. METHODS: Quantification of EAT and CAC was performed on positron emission tomography/computed tomography (PET/CT) studies in 45 subjects (77% intermediate pre-test probability of CAD) with mild-moderate myocardial ischemia (5-14% perfusion defect, n = 23), severe ischemia (≥15% defect, n = 22) and a control group with no ischemia matched for CAD risk factors (n = 52). RESULTS: EAT volume showed a better correlation with myocardial ischemia than total CAC (r = .47 vs r = .28, P < .01). EAT volume increased significantly from the control group to subjects with mild-moderate and severe ischemia (96.9, 124.5, and 143.9 cm(3), P < .01 for both ischemia groups vs controls). Total mean CAC was significantly higher in the severe ischemia group (676.3) than in control group (229.4) (P < .01). Multivariable logistic regression analyses showed that EAT volume was, but CAC was not, a significant predictor of ischemia after adjustment for age, sex, body mass index, and each other. EAT volume was a better predictor of ischemia than total CAC [area under the curve (AUC): .764 vs .6291, P = .04]. The combination of EAT + CAC (AUC = .7694) did not improve over EAT volume alone (P = .57). CONCLUSIONS: In this study, EAT volume assessed by CT was an independent predictor of ischemia on PET, and outperformed CAC score in a CAD naïve population at intermediate pre-test probability of disease.

Adenosine stress magnetic resonance imaging in women with low risk chest pain: the Emory University experience.

OBJECTIVES: The purpose of this study was to evaluate the accuracy of adenosine stress magnetic resonance imaging (ASMRI) for the evaluation of women with low-risk chest pain (CP). BACKGROUND: Coronary artery disease (CAD) can present differently among women than among men. There is increased interest in the use of ASMRI for lower risk patients in the emergency department to rule out CAD, and it would be valuable to assess its performance specifically in women. METHODS: This study included 82 women with low-risk CP who presented to the emergency department during a 2-year period at our institution and were evaluated by ASMRI. Clinical events were followed by review of medical records. RESULTS: The specificity of ASMRI for ischemia detection in this small cohort of patients was 100%. Sensitivity was 94.9%, negative predictive value 100%, and positive predictive value 42.9%. CONCLUSIONS: ASMRI may be used as the initial imaging modality for ruling out CAD in women with low-risk CP because of its very high sensitivity, specificity, and negative predictive value for the detection of ischemia. Further randomized controlled trials comparing ASMRI with established noninvasive nuclear and echocardiographic stress modalities are needed.

A right atrial mass, patent foramen ovale, and indwelling central venous catheter in a patient with a malignancy: a diagnostic and therapeutic dilemma.

A 33-year-old woman with a history of gestational trophoblastic disease presented for investigation of a right atrial mass. She had been receiving chemotherapy administered via a Port-a-Cath system for 2 months prior to presentation. On transesophageal echocardiography and magnetic resonance imaging, she was found to have a mass attached to the right atrial free wall, with a segment projecting across a patent foramen ovale. Because of the risk for an embolic event, the mass was surgically removed and the patent foramen ovale repaired. Pathology showed an organized thrombus. This case emphasizes the need for high suspicion for thrombus when a right atrial mass is found in a patient with a hypercoagulable state due to underlying malignancy who has a central venous catheter.

Epicardial adipose tissue and coronary artery plaque characteristics.

OBJECTIVE: Epicardial adipose tissue (EAT) has been implicated in the pathogenesis of coronary atherosclerosis. The association of EAT volume with type of coronary artery plaque on computed tomography angiography (CTA) is not known. METHODS: Coronary artery calcium (CAC) scoring and EAT volume measurement were performed on 214 consecutive patients (mean age 54+/-14 years) referred for coronary CTA. CAC was performed on non-contrast images, while EAT volume, the severity of luminal stenoses, and plaque characterization were assessed using contrast-enhanced CTA images. EAT volume was also indexed to body surface area (EAT-i). RESULTS: EAT volume correlated with age, height, body mass index (BMI), and CAC score. EAT volume increased significantly with the severity of luminal stenosis (p<0.001), and in patients with no plaques, calcified, mixed, and non-calcified plaques (62+/-33mL, 63+/-22mL, 98+/-47mL, and 99+/-36mL, respectively, p<0.001). The EAT volume was significantly larger in patients with mixed or non-calcified plaques compared to patients with calcified plaques or no plaques (all p<0.01 or smaller). The trend remained significant after adjustment for traditional risk factors for coronary artery disease. In adjusted models EAT was an independent predictor of CAC [exp(B)=3.916, p<0.05], atherosclerotic plaques of any type [exp(B)=4.532, p<0.01], non-calcified plaques [exp(B)=3.849, p<0.01], and obstructive CAD [exp(B)=3.824, p<0.05]. The above results were unchanged after replacing EAT with EAT-i. CONCLUSION: EAT volume was larger in the presence of obstructive CAD and non-calcified plaques. These data suggest that EAT is associated with the development of coronary atherosclerosis and potentially the most dangerous types of plaques.

Contrast-induced acute kidney injury in patients with renal dysfunction undergoing a coronary procedure and receiving non-ionic low-osmolar versus iso-osmolar contrast media.

BACKGROUND: Although the superiority of low-osmolar over high-osmolar contrast agents in prevention of contrast-induced acute kidney injury (CI-AKI) is generally accepted, the relative nephrotoxicity of iso-osmolar over low-osmolar agents has not yet clearly defined. We examined the incidence of CI-AKI according to the type of contrast agent used in a randomized study of ascorbic acid for CI-AKI prevention. METHODS: A total of 222 patients with baseline serum creatinine >or=1.2 mg/dL who were undergoing a coronary procedure and who were randomized to receive ascorbic acid or placebo were evaluated. The iso-osmolar agent iodixanol was used in 144 patients, whereas low-osmolar non-ionic agents were used in 78 patients (iomeprol, n = 40; iobitridol, n = 30; iopentol, n = 8). CI-AKI was defined by an absolute serum creatinine increase of >or=0.5 mg/dL or a relative increase of >or=25% measured 2 to 5 days after the procedure. RESULTS: The groups of patients who received iso-osmolar and low-osmolar non-ionic agents were well balanced in terms of demographic, clinical, and procedural characteristics. The overall CI-AKI incidence was 14.6% for the iso-osmolar iodixanol versus 14.1% for the combined low-osmolar non-ionic agents (iomeprol, 10%; iobitridol, 10%; iopentol, 50%). For iodixanol, the incidence of CI-AKI was 7.4% for patients randomized to receive ascorbic acid and 21.6% for placebo (P = 0.02). The corresponding incidences for the low-osmolar non-ionic agents were 9.1% and 20.6%, respectively (P = 0.19). CONCLUSION: No differences in CI-AKI incidence were apparent among patients receiving non-ionic iso-osmolar iodixanol and non-ionic low-osmolar contrast agents. The preventative effect of ascorbic acid was also similar.

Prognostic value of adenosine stress cardiovascular magnetic resonance in patients with low-risk chest pain.

BACKGROUND: Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients. METHODS: We studied 103 patients, mean 56.7 + or - 12.3 years of age, with chest pain and no electrocardiographic evidence of ischemia and negative cardiac biomarkers of necrosis, who were admitted to the Cardiac Decision Unit of our institution. All patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the following: regional wall motion abnormalities at rest; perfusion defects during stress (adenosine) and rest; and myocardial scar on late gadolinium enhancement images. The patients were followed for a mean of 277 (range 161-462) days. The primary end point was defined as the combination of cardiac death, nonfatal acute myocardial infarction, re-hospitalization for chest pain, obstructive coronary artery disease (>50% coronary stenosis on invasive angiography) and coronary revascularization. RESULTS: In 14 patients (13.6%), AS-CMR was positive. The remaining 89 patients (86.4%), who had negative AS-CMR, were discharged. No patient with negative AS-CMR reached the primary end-point during follow-up. The negative predictive value of AS-CMR was 100%. CONCLUSION: AS-CMR holds promise as a useful tool to rule out significant coronary artery disease in patients with low-risk chest pain. Patients with negative AS-CMR have an excellent short and mid-term prognosis.

Role of echocardiography in the assessment of myocardial viability.

In the assessment of chronic myocardial infarction, echocardiography plays a vital role through the recognition of hibernating yet potentially viable myocardium that could benefit from revascularization. Echocardiography provides information through basic evaluation of cardiac structure and through evaluation of the functional response to dobutamine stress. In addition, a number of newer modalities such as myocardial contrast echocardiography, tissue Doppler imaging, and strain imaging provide further diagnostic capability. This review assesses the role of echocardiography in the identification of patients with chronic myocardial infarction who could benefit from revascularization.

Effect of statin dose on incidence of atrial fibrillation: data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials.

BACKGROUND: Inflammation has been suggested as a factor in the initiation and maintenance of atrial fibrillation (AF). Several observational studies have suggested that statins, presumably through their anti-inflammatory properties, decrease the risk of AF. METHODS: We analyzed 2 large, randomized trials, PROVE IT-TIMI 22 and phase Z of the A to Z trial, which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up. We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy. From each trial, patients experiencing the onset of AF during follow-up were identified from the adverse event reports. RESULTS: Neither study showed a decreased AF risk with higher-dose statin. In PROVE IT-TIMI 22, 2.9% versus 3.3% in the high- versus standard-dose statin therapy, respectively, experienced the onset of AF over 2 years (OR 0.86, 95% CI 0.61-1.23, P = .41). In A to Z, rates were 1.6% versus 0.99%, respectively (OR 1.58, 95% CI 0.92-2.70, P = .096). In both trials, C-reactive protein levels (plasma or serum) tended to be higher among patients experiencing the onset of AF. CONCLUSION: Our randomized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with standard dose statin treatment.

Benefits and risks of clopidogrel pretreatment before coronary artery bypass grafting in patients with ST-elevation myocardial infarction treated with fibrinolytics in CLARITY-TIMI 28.

The Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial was a randomized, double-blind, placebo-controlled study of clopidogrel in 3,491 patients receiving fibrinolytic therapy for ST-segment elevation myocardial infarction. Patients were randomized to clopidogrel or placebo begun at the time of fibrinolysis. This analysis reports the outcomes among the 136 patients in the trial population who underwent coronary artery bypass grafting (CABG) during the index hospitalization. There was no difference in the rates of TIMI major or minor bleeding between the clopidogrel and placebo groups from randomization to the end of follow-up (13.6% vs. 14.3%, P = 1.0) or from the time of CABG to the end of follow-up (9.1% vs. 11.4%, P = 0.78). When any day for study medication discontinuation < or = 5 days prior to CABG was chosen as a cut point to evaluate bleeding risk for clopidogrel vs. placebo, there was no excess bleeding in the clopidogrel group. Among patients undergoing CABG, there was a trend toward reduction in the risk of cardiovascular death, recurrent MI, or recurrent ischemia requiring urgent revascularization at 30 days for those taking clopidogrel (OR 0.66, 95% CI 0.27-1.5; P = 0.37), consistent with the benefit seen in the overall trial population (OR 0.80, CI 0.65-0.97; P = 0.03). In conclusion, early clopidogrel treatment among CLARITY-TIMI 28 patients undergoing CABG was not associated with an increase in the rate of peri-operative bleeding and showed a trend toward reduction in 30-day ischemic events.

Critical pathways using platelet testing to potentially optimize the use of oral antiplatelet therapy.

Although monitoring anticoagulation is standard practice, monitoring antiplatelet therapy has not yet widely been adopted as a means of assessing antithrombotic response. However, bedside devices have recently become available that facilitate more rapid assessment of antithrombotic response, allowing this information to be developed into a critical pathway. Three major opportunities exist for oral antiplatelet therapy: (1) optimizing the dose of aspirin for long-term therapy; (2) optimizing the dose of clopidogrel, especially in percutaneous coronary intervention, acutely and during long-term therapy; and (3) evaluating the level of platelet inhibition before coronary artery bypass grafting or other major surgery. Several critical pathways are proposed that may assist clinicians in trying to ensure adequate platelet inhibition in these important clinical situations.

The clinical potential of a point-of-care assay to assess interindividual variability in platelet aggregation among patients taking clopidogrel.

Clopidogrel is an important component of medical therapy for patients with acute coronary syndromes and those receiving coronary artery stents. Despite use of clopidogrel, a significant number of patients experience recurrent adverse ischemic events. Interindividual variability of platelet aggregation in response to clopidogrel may be an explanation for some of these recurrent events, and small trials have linked "clopidogrel resistance" as measured by platelet function tests to adverse events. Additionally, the degree of clopidogrel-induced platelet inhibition appears to be a factor determining bleeding risk at coronary artery bypass grafting. A point-of-care device that could accurately and rapidly measure the degree of platelet inhibition among patients taking clopidogrel could be clinically valuable. Such a device would have the potential to allow therapeutic decision-making based on the degree of platelet inhibition, especially for patients undergoing percutaneous coronary intervention or coronary artery bypass grafting.

A point-of-care assay to measure platelet aggregation in patients taking clopidogrel.

Clopidogrel is an important component of medical therapy for patients with acute coronary syndromes and those receiving coronary stents. Despite the use of clopidogrel, a significant number of patients experience recurrent adverse ischemic events. Inter-individual variability of platelet aggregation in response to clopidogrel may provide an explanation for some of these recurrent events, and small trials have linked clopidogrel resistance, as measured by platelet function tests, to adverse events. The VerifyNow P2Y12 assay (Accumetrics, Inc., CA, USA) is a point-of-care device that can accurately and rapidly measure the degree of platelet inhibition in patients taking clopidogrel. This assay can identify patients with a poor response to clopidogrel, and could potentially lead to change in therapy.