Donald Schreiber

Bedside Multimarker Testing for Risk Stratification in Chest Pain Units

Background—Earlier, rapid evaluation in chest pain units may make patient care more efficient. A multimarker strategy (MMS) testing for several markers of myocardial necrosis with different time-to...BackgroundEarlier, rapid evaluation in chest pain units may make patient care more efficient. A multimarker strategy (MMS) testing for several markers of myocardial necrosis with different time-to-positivity profiles also may offer clinical advantages. Methods and ResultsWe prospectively compared bedside quantitative multimarker testing versus local laboratory results (LL) in 1005 patients in 6 chest pain units. Myoglobin, creatine kinase-MB, and troponin I were measured at 0, 3, 6, 9 to 12, and 16 to 24 hours after admission. Two MMS were defined: MMS-1 (all 3 markers) and MMS-2 (creatine kinase-MB and troponin I only). The primary assessment was to relate marker status with 30-day death or infarction. More patients were positive by 24 hours with MMS than with LL (MMS-1, 23.9%; MMS-2, 18.8%; LL, 8.8%;P =0.001, all comparisons), and they became positive sooner with MMS-1 (2.5 hours, P =0.023 versus LL) versus MMS-2 (2.8 hours, P =0.026 versus LL) or LL (3.4 hours). The relation between baseline MMS status and 30-day death or infarction was stronger (MMS-1: positive, 18.8% event rate versus negative, 3.0%, P =0.001; MMS-2: 21.9% versus 3.2%, P =0.001) than that for LL (13.6% versus 5.5%, P =0.038). MMS-1 discriminated 30-day death better (positive, 2.0% versus negative, 0.0%, P =0.007) than MMS-2 (positive, 1.8% versus negative, 0.2%;P =0.055) or LL (positive, 0.0% versus negative, 0.5%;P =1.000). ConclusionsRapid multimarker analysis identifies positive patients earlier and provides better risk stratification for mortality than a local laboratory-based, single-marker approach.

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.

Adjunctive Platelet Glycoprotein IIb/IIIa Receptor Inhibition With Tirofiban Before Primary Angioplasty Improves Angiographic Outcomes

Background—Previous work has suggested that platelet glycoprotein IIb/IIIa receptor blockade may confer benefit in the treatment of acute myocardial infarction. The TIGER-PA pilot trial was a single-center randomized study to evaluate the safety, feasibility, and utility of early tirofiban administration before planned primary angioplasty in patients presenting with acute myocardial infarction. Methods and Results—A total of 100 patients presenting with acute myocardial infarction were randomized to either early administration of tirofiban in the emergency room or later administration in the catheterization laboratory. The primary outcome measures were initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion (“blush”). Thirty-day major adverse cardiac events were also assessed. Angiographic outcomes demonstrate a significant improvement in initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion when patients are given tirofiban in the emergency room before primary angioplasty. The rate of 30-day major adverse cardiac events suggests that early administration may be beneficial. Conclusions—This pilot study suggests that early administration of tirofiban improves angiographic outcomes and is safe and feasible in patients undergoing primary angioplasty for acute myocardial infarction.

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.

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.

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 physicians 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.

Drug-Related Emergency Department Visits in an Elderly Veteran Population

BACKGROUND Given that adverse drug events result in extensive costs and healthcare resource utilization, the goal is to better understand drug-related emergency department (ED) visits so that programs can be implemented to improve the quality of health care. OBJECTIVE To (1) determine the incidence of drug-related ED visits at a large, tertiary care, Veterans Affairs hospital; (2) identify causes of these drug-related ED visits; (3) determine patient outcomes, healthcare resource utilization, and costs associated with these visits; and (4) determine the proportion of adverse drug reaction (ADR)–related ED visits that were spontaneously reported to the hospitals ADR reporting program. METHODS We conducted a retrospective electronic chart review of all patients who visited the ED during the second week of each month in 2003. Causes for drug-related visits were identified. ADRs in this study included side effects, drug allergies, and drug–drug interactions (DDIs) and were assessed using the Naranjo probability scale. RESULTS A total of 2169 patients were included in the study. Drug-related visits accounted for 12.6% of all ED visits. The main causes of drug-related visits were ADRs and nonadherence, which accounted for 33% and 19% of drug-related visits, respectively. Only 11% of these ADRs were spontaneously reported to the hospitals ADR reporting program. Thirty-five percent of drug-related visits led to hospitalizations, which resulted in an average length of stay of 9.3 days. The institutions total cost of drug-related visits was approximately

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

1.5 million over 12 weeks. CONCLUSIONS Many ED visits are drug related and often result in hospitalization and increased healthcare resource utilization. Only a minimal number of the ADRs resulting in ED visits are spontaneously reported to hospital ADR reporting programs.

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

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

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.