Prognosis is worse with elevated cardiac troponin in nonacute coronary syndrome compared with acute coronary syndrome.

BACKGROUND: Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations. METHODS: We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain. Patients were grouped as ACS, non-ACS cardiovascular disease, noncardiac chest pain and chest pain not otherwise specified (NOS). We examined the prognostic ability of cTnI for the clinical endpoints of mortality and major adverse cardiovascular event (MACE; a composite of acute myocardial infarction, unstable angina, revascularization, reinfarction, and congestive heart failure and stroke) at 180-day follow-up. RESULTS: Among 1982 patients analyzed, 14% had ACS, 21% had non-ACS cardiovascular disease, 31% had a noncardiac diagnosis and 34% had chest pain NOS. cTnI elevation above the 99th percentile was observed in 52, 18, 6 and 7% in these groups, respectively. cTnI elevation was associated with mortality and MACE, and their relationships were more prominent in noncardiac diagnosis and chest pain NOS than in ACS and non-ACS cardiovascular diagnoses for mortality, and in non-ACS patients than in ACS patients for MACE (hazard ratio for doubling of cTnI 1.85, 2.05, 8.26 and 4.14, respectively; P for interaction 0.011 for mortality; 1.04, 1.23, 1.54 and 1.42, respectively; P for interaction <0.001 for MACE). CONCLUSION: In patients presenting to the ED with chest pain, cTnI elevation was associated with a worse prognosis in non-ACS patients than in ACS patients.

Finding acute coronary syndrome with serial troponin testing for rapid assessment of cardiac ischemic symptoms (FAST-TRAC): a study protocol.

OBJECTIVE: To determine the utility of a highly sensitive troponin assay when utilized in the emergency department. METHODS: The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician's clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00880802.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

BACKGROUND: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. METHODS: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. RESULTS: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. CONCLUSIONS: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

Accuracy of a novel stress echocardiography pattern for myocardial bridging in patients with angina and no obstructive coronary artery disease - A retrospective and prospective cohort study.

BACKGROUND: Myocardial bridge (MB) may cause angina in patients with no obstructive coronary artery disease (CAD). We previously reported a novel stress echocardiography (SE) pattern of focal septal buckling with apical sparing in the end-systolic to early-diastolic phase that is associated with the presence of an MB. We evaluated the diagnostic accuracy of this pattern, and prospectively validated our results. METHODS: The retrospective cohort included 158 patients with angina who underwent both SE and coronary CT angiography (CCTA). The validation cohort included 37 patients who underwent CCTA in the emergency department for angina, and prospectively underwent SE. CCTA was used as a reference standard for the presence/absence of an MB, and also confirmed no obstructive CAD. RESULTS: In the retrospective cohort, an MB was present in 107 (67.7%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91.6%, 70.6%, 86.7% and 80%, respectively. On logistic regression, focal septal buckling and Duke treadmill score were associated with an MB. In the validation cohort, an MB was present in 31 (84%). The sensitivity, specificity PPV and NPV were 90.3%, 83.3%, 96.5% and 62.5%, respectively. On logistic regression, focal septal buckling was associated with an MB. CONCLUSION: Presence of focal septal buckling with apical sparing on SE is an accurate predictor of an MB in patients with angina and no obstructive CAD. This pattern can reliably be used to screen patients who may benefit from advanced non-invasive/invasive testing for an MB as a cause of their angina.

Copeptin to rule out myocardial infarction in Blacks versus Caucasians.

BACKGROUND: Copeptin in combination with troponin has been shown to have incremental value for the early rule-out of myocardial infarction, but its performance in Black patients specifically has never been examined. In light of a potential for wider use, data on copeptin in different relevant cohorts are needed. This is the first study to determine whether copeptin is equally effective at ruling out myocardial infarction in Black and Caucasian races. METHODS: This analysis of the CHOPIN trial included 792 Black and 1075 Caucasian patients who presented to the emergency department with chest pain and had troponin-I and copeptin levels drawn. RESULTS: One hundred and forty-nine patients were diagnosed with myocardial infarction (54 Black and 95 Caucasian). The negative predictive value of copeptin at a cut-off of 14 pmol/l (as in the CHOPIN study) for myocardial infarction was higher in Blacks (98.0%, 95% confidence interval (CI) 96.2-99.1%) than Caucasians (94.1%, 95% CI 92.1-95.7%). The sensitivity at 14 pmol/l was higher in Blacks (83.3%, 95% CI 70.7-92.1%) than Caucasians (53.7%, 95% CI 43.2-64.0%). After controlling for age, hypertension, heart failure, chronic kidney disease and body mass index in a logistic regression model, the interaction term had a P value of 0.03. A cut-off of 6 pmol/l showed similar sensitivity in Caucasians as 14 pmol/l in Blacks. CONCLUSIONS: This is the first study to identify a difference in the performance of copeptin to rule out myocardial infarction between Blacks and Caucasians, with increased negative predictive value and sensitivity in the Black population at a cut-off of 14 pmol/l. This also holds true for non-ST-segment elevation myocardial infarction and, although numbers were small, similar trends exist in the normal troponin population. This may have significant implications for early rule-out strategies using copeptin.

Necessity of hospitalization and stress testing in low risk chest pain patients.

BACKGROUND: Copeptin is a marker of endogenous stress including early myocardial infarction(MI) and has value in early rule out of MI when used with cardiac troponin I(cTnI). OBJECTIVES: The goal of this study was to demonstrate that patients with a normal electrocardiogram and cTnI<0.040µg/l and copeptin<14pmol/l at presentation and after 2 h may be candidates for early discharge with outpatient follow-up potentially including stress testing. METHODS: This study uses data from the CHOPIN trial which enrolled 2071 patients with acute chest pain. Of those, 475 patients with normal electrocardiogram and normal cTnI(<0.040µg/l) and copeptin<14pmol/l at presentation and after 2 h were considered "low risk" and selected for further analysis. RESULTS: None of the 475 "low risk" patients were diagnosed with MI during the 180day follow-up period (including presentation). The negative predictive value of this strategy was 100% (95% confidence interval(CI):99.2%-100.0%). Furthermore no one died during follow up. 287 (60.4%) patients in the low risk group were hospitalized. In the "low risk" group, the only difference in outcomes (MI, death, revascularization, cardiac rehospitalization) was those hospitalized underwent revascularization more often (6.3%[95%CI:3.8%-9.7%] versus 0.5%[95%CI:0.0%-2.9%], p=.002). The hospitalized patients were tested significantly more via stress testing or angiogram (68.6%[95%CI:62.9%-74.0%] vs 22.9%[95%CI:17.1%-29.6%], p<.001). Those tested had less cardiac rehospitalizations during follow-up (1.7% vs 5.1%, p=.040). CONCLUSIONS: In conclusion, patients with a normal electrocardiogram, troponin and copeptin at presentation and after 2 h are at low risk for MI and death over 180days. These low risk patients may be candidates for early outpatient testing and cardiology follow-up thereby reducing hospitalization.

Serial sampling of copeptin levels improves diagnosis and risk stratification in patients presenting with chest pain: results from the CHOPIN trial.

BACKGROUND: Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combination with a negative troponin. However, management of patients with chest pain with a positive copeptin in the setting of a negative troponin is unclear. METHODS: The multicentre CHOPIN trial enrolled 2071 patients with acute chest pain. Of these, 476 subjects with an initial negative troponin but an elevated copeptin (>14 pmol/L) were included in this study. Copeptin and troponin levels were rechecked at 2 h and the final diagnosis of AMI was made by two independent, blinded cardiologists. Follow-up at 30 days was obtained for major adverse cardiac events (MACEs), including death, AMI and urgent revascularisation. RESULTS: Of the 476 patients analysed, 365 (76.7%) had a persistently elevated copeptin at 2 h and 111 patients (23.3%) had a copeptin that fell below the cut-off of 14 pmol/L. When the second copeptin was elevated there were 18 AMIs (4.9%) compared with 0 (0%) when the second copeptin was negative (p=0.017), yielding a negative predictive value of 100% (95% CI 96.7% to 100%). On 30-day follow-up there were 36 MACEs (9.9%) in the positive second copeptin group and 2 (1.8%) MACEs in the negative second copeptin group (p=0.006). CONCLUSIONS: Patients with chest pain with an initial negative troponin but positive copeptin are common and carry an intermediate risk of AMI. A second copeptin drawn 2 h after presentation may help risk stratify and potentially rule out AMI in this cohort.

Midregional proadrenomedullin predicts mortality and major adverse cardiac events in patients presenting with chest pain: results from the CHOPIN trial.

OBJECTIVES: Chest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE). METHODS: This was a subanalysis of the CHOPIN study, a 16-center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6-month all-cause mortality and the secondary endpoint was 30-day and 6-month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure. RESULTS: MR-proADM performed similarly to troponin (cTnI; c-statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR-proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6-month mortality risk versus 0.9% risk for those in the bottom nine deciles (p < 0.0001). MR-proADM, history of coronary artery disease (CAD), and hypertension were predictors of short-term MACE, while history of CAD, hypertension, cTnI, and MR-proADM were predictors of long-term MACE. CONCLUSIONS: In patients with chest pain, MR-proADM predicts mortality and MACE in all-comers with chest pain and has similar prediction in those with a noncardiac diagnosis. This exploratory analysis is primarily hypotheses-generating and future prospective studies to identify its utility in risk stratification should be considered.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: a collaborative meta-analysis.

BACKGROUND: Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. METHODS: MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. RESULTS: From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative. CONCLUSION: High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

Ambulatory cardiac monitoring for discharged emergency department patients with possible cardiac arrhythmias.

INTRODUCTION: Many emergency department (ED) patients have symptoms that may be attributed to arrhythmias, necessitating outpatient ambulatory cardiac monitoring. Consensus is lacking on the optimal duration of monitoring. We describe the use of a novel device applied at ED discharge that provides continuous prolonged cardiac monitoring. METHODS: We enrolled discharged adult ED patients with symptoms of possible cardiac arrhythmia. A novel, single use continuous recording patch (Zio®Patch) was applied at ED discharge. Patients wore the device for up to 14 days or until they had symptoms to trigger an event. They then returned the device by mail for interpretation. Significant arrhythmias are defined as: ventricular tachycardia (VT) ≥4 beats, supraventricular tachycardia (SVT) ≥4 beats, atrial fibrillation, ≥3 second pause, 2nd degree Mobitz II, 3rd degree AV Block, or symptomatic bradycardia. RESULTS: There were 174 patients were enrolled and all mailed back their devices. The average age was 52.2 (± 21.0) years, and 55% were female. The most common indications for device placement were palpitations 44.8%, syncope 24.1% and dizziness 6.3%. Eighty-three patients (47.7%) had ≥1 arrhythmias and 17 (9.8%) were symptomatic at the time of their arrhythmia. Median time to first arrhythmia was 1.0 days (IQR 0.2-2.8) and median time to first symptomatic arrhythmia was 1.5 days (IQR 0.4-6.7). 93 (53.4%) of symptomatic patients did not have any arrhythmia during their triggered events. The overall diagnostic yield was 63.2% CONCLUSION: The Zio®Patch cardiac monitoring device can efficiently characterize symptomatic patients without significant arrhythmia and has a higher diagnostic yield for arrhythmias than traditional 24-48 hour Holter monitoring. It allows for longer term monitoring up to 14 days.

Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism.

RATIONALE: Not all patients with acute pulmonary embolism (PE) have a high risk of an adverse short-term outcome. OBJECTIVES: This prospective cohort study aimed to develop a multimarker prognostic model that accurately classifies normotensive patients with PE into low and high categories of risk of adverse medical outcomes. METHODS: The study enrolled 848 outpatients from the PROTECT (PROgnosTic valuE of Computed Tomography) study (derivation cohort) and 529 patients from the Prognostic Factors for Pulmonary Embolism (PREP) study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, hemodynamic collapse, and/or adjudicated recurrent PE. MEASUREMENTS AND MAIN RESULTS: A complicated course occurred in 63 (7.4%) of the 848 normotensive patients with acute symptomatic PE in the derivation cohort and in 24 patients (4.5%) in the validation cohort. The final model included the simplified Pulmonary Embolism Severity Index, cardiac troponin I, brain natriuretic peptide, and lower limb ultrasound testing. The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the simplified Pulmonary Embolism Severity Index and brain natriuretic peptide testing showed a negative predictive value for a complicated course of 99.1 and 100% in the derivation and validation cohorts, respectively. The combination of all modalities had a positive predictive value for the prediction of a complicated course of 25.8% in the derivation cohort and 21.2% in the validation cohort. CONCLUSIONS: For normotensive patients who have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, hemodynamic collapse, and/or recurrent PE within the following 30 days.

Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction).

OBJECTIVES: The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED). BACKGROUND: Copeptin is secreted from the pituitary early in the course of AMI. METHODS: This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99 th percentile 40 ng/l; 10% coefficient of variation 0.03 µg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results. RESULTS: AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001). CONCLUSIONS: Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws.

Short-term (90 min) diagnostic performance for acute non-ST segment elevation myocardial infarction and 30-day prognostic evaluation of a novel third-generation high sensitivity troponin I assay.

OBJECTIVES: We evaluated a third-generation high sensitivity "guidelines acceptable" troponin I assay (hs-cTnI) against a contemporary "clinically usable" troponin assay (cTnI). DESIGN AND METHODS: Remnant samples of undifferentiated emergency department (ED) patients with suspected acute coronary syndrome were enrolled. Baseline and 90-minute samples were analyzed for cTnI and hs-cTnI. Sensitivity, specificity, positive and negative predictive values for AMI and 30-day adverse cardiac events (ACE) were compared. RESULTS: Of 486 ED patients, there were 465 patients who had blood remaining at the presentation for the hs-cTnI assays, with 12 AMIs. At presentation, the clinical sensitivity and specificity for AMI was 75% and 97% for cTnI and 83.3 and 82.1% for hs-cTnI. There were 407 patients who had paired baseline and 90-minute blood samples for cTnI and hs-cTnI including 9 of the 12 AMI patients. The sensitivity and specificity was 77.7% and 96.5% for cTnI and 100% and 81.9% for hs-cTnI at 90 min. A Δ change of 30% increase from baseline to 90 min improved the specificity to 94.5% (95% CI 92%-96%) without lowering the sensitivity. When AMI was defined as a Δ30% change of hs-cTnI at t=0 and 90 min and one hs-cTnI result >99th percentile cutoff, more than 3 times as many patients met the diagnostic criteria for AMI compared to results from the normal sensitive troponin assay; 28 (6.9%) for hs-cTnI vs. 9 (2.2%) with cTnI. There were 37 in-hospital or 30-day events, producing an OR of 3.03, 95% CI: 0.86-9.59 for cTnI, and 2.54, 95% CI: 1.27-5.10 for hs-cTnI, which detected 11 more cases. CONCLUSIONS: The hs-cTnI assay achieved a 90-minute rule out for AMI and detected more 3 times as many AMI cases. The specificity increased with the Δ30% criteria. The hs-cTnI assay also detected more cases of patient at risk for adverse cardiac events at 30 days.

Therapy and outcomes in massive pulmonary embolism from the Emergency Medicine Pulmonary Embolism in the Real World Registry.

STUDY AIM: Clinical guidelines recommend fibrinolysis or embolectomy for acute massive pulmonary embolism (PE) (MPE). However, actual therapy and outcomes of emergency department (ED) patients with MPE have not previously been reported. We characterize the current management of ED patients with MPE in a US registry. METHODS: A prospective, observational, multicenter registry of ED patients with confirmed PE was conducted from 2006 to 2008. Massive PE was defined as PE with an initial systolic blood pressure less than 90 mm Hg. We compared inpatient and 30-day mortality, bleeding complications, and recurrent venous thromboembolism. RESULTS: Of 1875 patients enrolled, 58 (3.1%) had MPE. There was no difference in frequency of parenteral anticoagulation (98.3% [95% confidence interval {CI}, 90.5-101.6] vs 98.5% [95% CI, 97.9-99.1], P = .902) between patients with and without MPE. Fibrinolytic therapy and embolectomy were infrequently used but were used more in patients with MPE than in patients without MPE (12.1% [95% CI, 3.7-20.5] vs 2.4% [95% CI, 1.7-3.1], P < .001, and 3.4% [95% CI, 0.0-8.1] vs 0.7% [95% CI, 0.3-1.1], P = .022, respectively). Comparison of outcomes revealed higher all-cause inpatient mortality (13.8% [95% CI, 4.9-22.7] vs 3.0% [95% CI, 2.2-3.8], P < .001), higher risk of inpatient bleeding complications (10.3% [95% CI, 2.5-18.1] vs 3.5% [95% CI, 2.7-4.3], P = .007), and a higher 30-day mortality (14.0% [95% CI, 4.4-23.6] vs 1.8% [95% CI, 1.2-2.4], P < .001) for patients with MPE. CONCLUSIONS: In a contemporary registry of ED patients, MPE mortality was 4-fold higher than patients without MPE, yet only 12% of the MPE cohort received fibrinolytic therapy. Variability exists between the treatment of MPE and current recommendations.

Predictors of 30-day cardiovascular events in patients with prior percutaneous coronary intervention or coronary artery bypass grafting.

OBJECTIVES: Risk stratification of patients with potential acute coronary syndrome (ACS) is difficult. Patients with prior revascularization are considered higher risk, but they can also have symptoms from noncardiac causes. This study evaluated whether the presenting clinical characteristics were predictive of an increased risk of 30-day cardiovascular events in patients with prior revascularization presenting to the emergency department (ED) with symptoms of potential ACS. METHODS: This was a secondary analysis of the DISPO-ACS study, a 2000-patient, four-site, randomized controlled trial of patients presenting with potential ACS. Process outcomes were evaluated using point-of-care cardiac markers compared to standard laboratory-based markers. Data included demographics, history, presenting symptoms, laboratory and electrocardiogram (ECG) results, hospital course, and 30-day cardiovascular events (death, acute myocardial infarction [AMI], revascularization). The association between presenting characteristics and 30-day cardiovascular events was assessed using univariable analysis and logistic regression; odds ratios (ORs) with 95% confidence intervals (CIs) are given. RESULTS: Of 2,000 patients enrolled, 611 had prior revascularization (538 percutaneous coronary intervention [PCI], 232 coronary artery bypass graft [CABG], 159 both). The mean (±SD) age was 66 (±14) years, 44% were female, and 22% were black. By 30 days, 101 patients (17%) had cardiovascular events (81 during the index visit, 20 during follow-up). There were four deaths, 28 AMIs, and 67 revascularizations within 30 days; 20 patients had multiple endpoints. Being male (OR = 1.67, 95% CI = 1.07 to 2.62) or nonblack (OR = 1.95, 95% CI = 1.07 to 3.56) or having a family history of coronary artery disease (CAD; OR = 2.09, 95% CI = 1.32 to 3.3), elevated lipids (OR = 1.71, 95% CI = 1.04 to 2.82), prior AMI (OR = 1.79, 95% CI = 1.16 to 2.76), abnormal ECG on arrival (OR = 2.1, 95% CI = 1.33 to 3.34), and a positive initial troponin (OR = 14.7, 95% CI = 6.8 to 32.2) were predictive of cardiovascular events. The multivariable model found family history of CAD (OR = 2.06, 95% CI = 1.26 to 3.36), abnormal initial ECG (OR = 1.89, 95% CI = 1.16 to 3.09), and positive initial troponin (OR = 13.3, 95% CI = 5.9 to 29.6) remained predictive of 30-day cardiovascular events. CONCLUSIONS: In patients with prior revascularization, the initial ECG and early cardiac marker elevations, but not clinical presentation, predict odds of 30-day death, AMI, or revascularization.

Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry).

OBJECTIVES: In a large U.S. sample, this study measured the presentation features, testing, treatment strategies, and outcomes of patients diagnosed with pulmonary embolism (PE) in the emergency department (ED). BACKGROUND: No data have quantified the demographics, clinical features, management, and outcomes of outpatients diagnosed with PE in the ED in a large, multicenter U.S. study. METHODS: Patients of any hemodynamic status were enrolled from the ED after confirmed acute PE or with a high clinical suspicion prompting anticoagulation before imaging for PE. Exclusions were inability to provide informed consent (where required) or unavailability for follow-up. RESULTS: A total of 1,880 patients with confirmed acute PE were enrolled from 22 U.S. EDs. Diagnosis of PE was based upon positive results of computerized tomographic pulmonary angiogram in most cases (n = 1,654 [88%]). Patients represented both sexes equally, and racial and ethnic composition paralleled the overall U.S. ED population. Most (79%) patients with PE were employed, and one-third were older than age 65 years. The mortality rate directly attributed to PE was 20 in 1,880 (1%; 95% confidence interval [CI]: 0% to 1.6%). Mortality from hemorrhage was 0.2%, and the all-cause 30-day mortality rate was 5.4% (95% CI: 4.4% to 6.6%). Only 3 of 20 patients with major PE that ultimately proved fatal had systemic anticoagulation initiated before diagnostic confirmation, and another 3 of these 20 received a fibrinolytic agent. CONCLUSIONS: Patients diagnosed with acute PE in U.S. EDs have high functional status, and their mortality rate is low. These registry data suggest that appropriate initial medical management of ED patients with severe PE with anticoagulation is poorly standardized and indicate a need for research to determine the appropriate threshold for empiric treatment when PE is suspected before diagnostic confirmation.

A multicenter randomized controlled trial comparing central laboratory and point-of-care cardiac marker testing strategies: the Disposition Impacted by Serial Point of Care Markers in Acute Coronary Syndromes (DISPO-ACS) trial.

STUDY OBJECTIVE: Point-of-care testing reduces time to cardiac marker results in patients evaluated for acute coronary syndromes, yet evidence this translates to a decreased length of stay is lacking. We hypothesized that point-of-care testing decreases length of stay in patients being evaluated for acute coronary syndromes in the emergency department (ED). METHODS: Patients being evaluated for possible acute coronary syndromes at 4 EDs in the United States were randomized to having point-of-care markers as well as central laboratory markers, or central laboratory markers only (laboratory arm). Point-of-care markers were obtained using early serial testing at presentation and at 90, 180, and 360 minutes as required by the treating physician. Evaluation, treatment, and disposition decisions were at the treating physician's discretion. Length of stay was from presentation to the time of departure from the ED, either to an inpatient setting or to home. RESULTS: There were 1,000 patients in each study arm. There were 520 patients discharged home from the ED. Median (interquartile range) time to discharge home was 4.6 hours (3.5 to 6.1 hours) in laboratory patients and 4.5 hours (3.5 to 6.1 hours) in point-of-care patients. Median (interquartile range) time to transfer to an inpatient setting for admitted patients was 5.5 hours (4.2 to 7.5 hours) in laboratory patients, and 5.4 hours (4.1 to 7.3 hours) in point-of-care patients. At one site, time to transfer to the floor was reduced in the point-of-care arm compared with the laboratory arm (difference in medians 0.45 hours; 95% confidence interval [CI] -0.14 to 1.04 hours). At one site, time to ED departure for discharged patients was higher in the point-of-care arm than the laboratory arm (difference in medians 1.25 hours; 95% CI 0.13 to 2.36 hours). CONCLUSION: The effect of point-of-care testing on length of stay in the ED varies between settings. At one site, point-of-care testing decreased time to admission, whereas at another, point-of-care testing increased time to discharge. Potential effects of point-of-care testing on patient throughput should be considered in the full context of ED operations.

Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Our purpose was to evaluate the impact of nesiritide on renal function in patients with acute decompensated heart failure and baseline renal dysfunction. BACKGROUND: Although nesiritide is approved for the treatment of acute decompensated heart failure, retrospective analyses have raised concerns that it may cause worsened renal function. To date, no randomized clinical trials have prospectively evaluated this issue. METHODS: Consecutive patients with acute decompensated heart failure and baseline renal dysfunction were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive nesiritide (0.01 microg/kg/min with or without a 2-microg/kg bolus) or placebo (5% dextrose in water) for 48 h in addition to their usual care. Predefined primary end points of the trial were a rise in serum creatinine by > or =20% and change in serum creatinine. RESULTS: Seventy-five patients were enrolled (39 nesiritide, 36 placebo). The groups had similar baseline age (74.9 vs. 75.5 years, respectively), blood pressure (123/64 vs. 125/64 mm Hg) and serum creatinine (1.82 vs. 1.86 mg/dl). There were no significant differences in the incidence of a 20% creatinine rise (23% vs. 25%) or in the change in serum creatinine (-0.05 vs. +0.05 mg/dl). There were no significant differences in the secondary end points of change in weight (-2.19 vs. -1.58 kg), intravenous furosemide (125 vs. 107 mg), discontinuation of the infusion due to hypotension (13% vs. 6%), or 30-day death/hospital readmission (33% vs. 25%). CONCLUSIONS: In this randomized, double-blind, placebo-controlled clinical trial, nesiritide had no impact on renal function in patients with acute decompensated heart failure. (BNP-CARDS trial; http://www.clinicaltrials.gov/ct/show/NCT00186329?order=1; NCT00186329).

Statin-induced rhabdomyolysis.

Simvastatin and other HMG-CoA reductase inhibitors (statins) are one of the most frequently prescribed class of medications in the United States, with over 15 million Americans taking these drugs. Relatively rare adverse effects related to the known toxic effects of these drugs are more common than generally realized. Clinically significant statin-induced rhabdomyolysis is an uncommon but life-threatening adverse effect. We describe a case of simvastatin-induced rhabdomyolysis. Current knowledge of the pharmacology of the HMG-CoA reductase inhibitors and the drug interactions that potentiate these adverse effects are discussed. The clinical features of rhabdomyolysis and current treatment recommendations are presented.