Peter A. Smars

A CLINICAL TRIAL OF A CHEST-PAIN OBSERVATION UNIT FOR PATIENTS WITH UNSTABLE ANGINA

BACKGROUND Nearly half of patients hospitalized with unstable angina eventually receive a non-cardiac-related diagnosis, yet 5 percent of patients with myocardial infarction are inappropriately discharged from the emergency department. We evaluated the safety, efficacy, and cost of admission to a chest-pain observation unit (CPU) located in the emergency department for such patients. METHODS We performed a community-based, prospective, randomized trial of the safety, efficacy, and cost of admission to a CPU as compared with those of regular hospital admission for patients with unstable angina who were considered to be at intermediate risk for cardiovascular events in the short term. A total of 424 eligible patients were randomly assigned to routine hospital admission (a monitored bed under the care of the cardiology service) or admission to the CPU (where patients were cared for according to a strict protocol including aspirin, heparin, continuous ST-segment monitoring, determination of creatine kinase isoenzyme levels, six hours of observation, and a study of cardiac function). The CPU was managed by the emergency department staff. Patients whose test results were negative were discharged, and the others were hospitalized. Primary outcomes (nonfatal myocardial infarction, death, acute congestive heart failure, stroke, or out-of-hospital cardiac arrest) and use of resources were compared between the two groups. RESULTS The 212 patients in the hospital-admission group had 15 primary events (13 myocardial infarctions and 2 cases of congestive heart failure), and the 212 patients in the CPU group had 7 events (5 myocardial infarctions, 1 death from cardiovascular causes, and 1 case of congestive heart failure). There was no significant difference in the rate of cardiac events between the two groups (odds ratio for the CPU group as compared with the hospital-admission group, 0.50; 95 percent confidence interval, 0.20 to 1.24). No primary events occurred among the 97 patients who were assigned to the CPU and discharged. Resource use during the first six months was greater among patients assigned to hospital admission than among those assigned to the CPU (P<0.01 by the rank-sum test). CONCLUSIONS A CPU located in the emergency department can be a safe, effective, and cost-saving means of ensuring that patients with unstable angina who are considered to be at intermediate risk of cardiovascular events receive appropriate care.

Syncope Evaluation in the Emergency Department Study (SEEDS) A Multidisciplinary Approach to Syncope Management

Background—The primary aim and central hypothesis of the study are that a designated syncope unit in the emergency department improves diagnostic yield and reduces hospital admission for patients with syncope who are at intermediate risk for an adverse cardiovascular outcome. Methods and Results—In this prospective, randomized, single-center study, patients were randomly allocated to 2 treatment arms: syncope unit evaluation and standard care. The 2 groups were compared with &khgr;2 test for independence of categorical variables. Wilcoxon rank sum test was used for continuous variables. Survival was estimated with the Kaplan-Meier method. One hundred three consecutive patients (53 women; mean age 64±17 years) entered the study. Fifty-one patients were randomized to the syncope unit. For the syncope unit and standard care patients, the presumptive diagnosis was established in 34 (67%) and 5 (10%) patients (P<0.001), respectively, hospital admission was required for 22 (43%) and 51 (98%) patients (P<0.001), and total patient-hospital days were reduced from 140 to 64. Actuarial survival was 97% and 90% (P=0.30), and survival free from recurrent syncope was 88% and 89% (P=0.72) at 2 years for the syncope unit and standard care groups, respectively. Conclusions—The novel syncope unit designed for this study significantly improved diagnostic yield in the emergency department and reduced hospital admission and total length of hospital stay without affecting recurrent syncope and all-cause mortality among intermediate-risk patients. Observations from the present study provide benchmark data for improving patient care and effectively utilizing healthcare resources.

Incremental Value of the Leukocyte Differential and the Rapid Creatine Kinase-MB Isoenzyme for the Early Diagnosis of Myocardial Infarction

Acute electrocardiographic ST-segment elevation is highly predictive of myocardial infarction in patients who present with prolonged chest pain [1, 2].However, although most patients with infarction do not have ST elevation [2, 3], they do have a substantial in-hospital mortality [4]. These patients cannot currently be distinguished in the emergency department from patients with unstable angina and other acute chest-pain syndromes [5]. As a result, patients with infarction but no ST elevation and patients with unstable angina have been grouped together in clinical trials [6]. The identification of patients who will have an infarction but who do not have ST-segment elevation may permit more appropriate triage and therapy for these patients. Markers reported for the early identification of acute myocardial infarction include initial clinical variables [7], rapid creatine kinase-MB measurements [8], creatine kinase-MB isoforms [9], myoglobin [10], troponin T [11], and cortisol [12]. The value of the total leukocyte count for the diagnosis of myocardial infarction has long been recognized [13]. Elevation of the total leukocyte count is probably caused by the increase in cortisol levels during an acute stress reaction [14]. The potential value of the leukocyte differential has probably been obscured by the great variation in the traditional manual leukocyte differential, which has a coefficient of variation of 20% to 30% [15]. Widely available, fast, and accurate automated hematology analyzers have greatly decreased the analytical variation for leukocyte differentials [16]. Although the leukocyte differential is influenced by corticosteroid use and other stressful illnesses, an initial study of patients presenting with chest pain to the emergency department suggested that many of these other causes could be identified by simple clinical assessment. In our initial study, we also found that myocardial infarction, but not unstable angina, often altered the leukocyte differential by elevating the neutrophil count and decreasing the lymphocyte count. These changes thereby caused relative lymphocytopenia and granulocytosis, frequently without an elevation of the total leukocyte count (unpublished observations). Because the automated leukocyte differential is widely available, fast, and inexpensive, it offers an attractive combination of incremental value for the diagnosis of infarction with little incremental cost. We therefore conducted a prospective, blinded study to assess the potential incremental value of the leukocyte differential as an early diagnostic tool. We examined whether relative lymphocytopenia, abnormal total creatine kinase levels, or abnormal rapid creatine kinase-MB measurements were useful for the early diagnosis of acute myocardial infarction in patients presenting to the emergency department with chest pain. Methods Patients The study group of 384 patients was selected from 511 consecutive patients aged 20 years or older who presented to the emergency department with anterior or left lateral chest pain between 8 March and 31 August 1992 and from whom initial blood samples were obtained (Figure 1). Eleven patients who presented twice and three patients who presented three times during this period were included separately for each visit. Exclusion criteria were the following: infection in the previous week detected by history or initial clinical evaluation (34 patients); exogenous glucocorticoid use within the previous month (25 patients); documentation of malignancy in the previous 5 years (20 patients); transfer from other hospitals after diagnosis (17 patients); major trauma, major gastrointestinal bleeding, surgery, dialysis, or resuscitation in the previous week (8 patients); and insufficient data to exclude myocardial infarction (17 of 20 patients dismissed from the emergency department who did not return after 24 hours for blood tests as part of the protocol and 6 patients who were admitted but had only one determination of the creatine kinase level because of low clinical suspicion). Of the 127 patients who were excluded, 4 patients had evidence of infarction (see below). Figure 1. Flow diagram showing patient selection and the prevalence of ST-segment elevation and positive serum markers (defined as both a relative lymphocytopenia and an elevated rapid creatine kinase-MB level) in patients with and patients without myocardial infarction. The study protocol was approved by the Mayo Clinic institutional review board. In the protocol, the leukocyte differential was identified only as test X. Only five of the investigators and one representative of the institutional review board knew the identity of test X. Patients who were not admitted were asked to return the next day as part of the protocol for the measurement of creatine kinase levels and leukocyte counts, but only 3 of 20 such patients returned. To determine the value of blood samples and electrocardiograms for the early diagnosis of acute myocardial infarction, we used only the initial measurements. Definition of Myocardial Infarction A final diagnosis of myocardial infarction was made if one of the following two criteria was met: 1) standard creatine kinase-MB isoenzyme level greater than 9.6 ng/mL within 48 hours [73 patients] or 2) sudden unexplained death within 72 hours of presentation (1 patient). The absence of myocardial infarction was defined by the absence of these criteria. In five patients, the final clinical (discharge) diagnosis differed from that defined above. Clinical records for these patients were reviewed by two experienced cardiologists blinded to the results of test X. One patient had a previously defined myopathy. In the other four patients, creatine kinase-MB levels were mildly elevated, and no further evidence of infarction was observed. These patients were considered by the panel to not have infarction and were categorized as such for the analysis. Initial electrocardiograms were reviewed independently by one cardiologist (who was blinded to the patients history, clinical diagnosis, and blood test results) for the presence of diagnostic ST-segment elevation, defined as an elevation of more than 0.1 mV in two electrically contiguous leads. Electrocardiograms showing ST-segment elevation that was not seen on previous electrocardiograms from our institution or ST elevation in patients for whom previous electrocardiograms were not available were considered positive. Electrocardiograms showing no ST-segment elevation or an elevation that was unchanged from previous electrocardiograms were considered negative. Laboratory Measurements Peripheral blood leukocyte counts were estimated with a widely available automated hematology analyzer, Coulter STK-R (Hialeah, Florida) [16]. This instrument uses approximately 10 000 cells per differential to produce, within minutes, a precise three-part leukocyte differential consisting of granulocytes, lymphocytes, and monocytes. The normal ranges for leukocyte concentrations were defined as the central 95th percentile for 150 healthy adults and have been used since 1984 [16]: 45.8% to 73.7% for granulocytes and 20.3% to 46.7% for lymphocytes. The total creatine kinase activity was determined on the Kodak Ektachem E700XR (Eastman Kodak Company, Rochester, New York) [17]. The upper limits of normal were determined to be 176 U/L for women and 336 U/L for men on the basis of values from 160 healthy adults. Creatine kinase-MB levels were measured on the Magic Lite system (CIBA Corning Diagnostics, Medfield, Massachusetts) using a two-site chemiluminescent immunoassay method; the cut-off value for the detection of myocardial infarction was 9.7 ng/mL [18]. After this initial clinical testing, serum specimens were frozen at 70C until they were thawed for measurements of cortisol and rapid creatine kinase-MB levels. Rapid creatine kinaseMB measurements were done on the Stratus II system (Baxter Diagnostics, Inc., Miami, Florida) using a two-site fluorometric immunoassay [19]. The upper limit of normal was chosen to be 4.7 ng/mL, which is three standard deviations greater than the mean value for 73 patients with cardiac disorders but no current myocardial infarction [20]. Cortisol levels were tested by RIA (Diagnostics Products Corporation, Los Angeles, California). The upper limit of normal was 690 nmol/L (25 g/dL) at 0800 h [20]. The amount of the sample was insufficient for the determination of the total creatine kinase level in one patient without an infarction, for the determination of rapid creatine kinaseMB levels in 9 patients (1 with infarction and 8 without infarction), and for the measurement of cortisol levels in 8 patients without infarction. Laboratory variables were measured without knowledge of clinical or other laboratory results. Statistical Analysis We used the Wilcoxon rank-sum test to assess whether patients with and patients without infarction differed significantly for individual variables. We determined the sensitivity and specificity for individual variables using the abnormal thresholds of greater than 10.4 109/L (in women) or 10.9 109/L (in men) for total leukocyte counts and of greater than 689.75 nmol/L (25 g/dL) for serum cortisol levels, as well as the cut-off values described above for total creatine kinase levels, rapid creatine kinase-MB levels, granulocytosis, and lymphocytopenia. Because exogenous estrogen replacement therapy increases cortisol levels, cortisol values from 29 women (4 with infarctions) who were receiving estrogens were excluded from the analysis of cortisol results. Sex, age, abnormal total creatine kinase levels, abnormal rapid creatine kinase-MB levels, and relative lymphocytopenia were entered into a multivariate logistic regression analysis to predict the presence of infarction in the 345 patients without electrocardiographic ST-segment elevation and for whom complete blood test data were available (10 patients with incomplete data were

Outcome of patients with a final diagnosis of chest pain of undetermined origin admitted under the suspicion of acute coronary syndrome: A report from the Rochester Epidemiology Project☆

STUDY OBJECTIVES Patients presenting to the emergency department (ED) with chest pain after a recent negative inpatient evaluation for cardiac pathology represent a dilemma for the emergency physician. The purposes of this study were to assess the outcome of patients discharged with a diagnosis of chest pain of undetermined origin and to identify predisposing factors for further cardiac events. METHODS The resources of the Rochester Epidemiology Project were used to identify all admitted ED patients with chest pain with suspected acute coronary syndrome who received a discharge diagnosis of chest pain of undetermined origin from 1985 through 1992. Patient records were reviewed for the occurrence of adverse cardiac events and subsequent ED visits for recurrent chest pain within 12 months of discharge. Associations between patient characteristics and an adverse cardiac event were evaluated univariately and summarized by using odds ratios (ORs). Long-term mortality was also determined. RESULTS Among 1,973 admitted ED patients with chest pain, 230 were given a diagnosis of chest pain of undetermined origin. Ten (4.4%) of 230 patients experienced an adverse cardiac event. Factors significantly associated with an adverse cardiac event included an abnormal ECG on admission (OR 9.5; 95% confidence interval [CI] 2.0 to 45.8), preexisting diabetes mellitus (OR 7.1; 95% CI 1.8 to 27.2), and preexisting coronary artery disease (OR 28.4; 95% CI 3.5 to 229.0). Thirty-three (14%) patients returned to the ED within 12 months of discharge; 5 patients were given a diagnosis of a cardiac condition, and 5 were given a diagnosis of a gastrointestinal condition. In long-term follow-up, 46 patients died, with a mean time from hospital discharge to death of any cause of 6.1 years and an estimated 5-year survival of 91.4%. CONCLUSION Among patients discharged from the hospital with a diagnosis of chest pain of undetermined origin, those with an initial abnormal ECG, preexisting diabetes, or preexisting coronary artery disease are at higher risk of a subsequent adverse cardiac event. In the absence of such factors, cardiac outcome is excellent.

Non-invasive resting magnetocardiographic imaging for the rapid detection of ischemia in subjects presenting with chest pain

Background: Early diagnosis of ischemia is complicated by the poor sensitivity of standard tests and contraindication for stress testing in unstable angina patients. Magnetocardiography (MCG) imaging can be used for the rapid, non-invasive detection of ischemia at rest. Methods: We studied 125 patients with presumed ischemic chest pain. All were chest pain free at the time of scanning. A 6-minute resting MCG scan (CardioMag Imaging, Inc., New York, 9-channel system) was performed. Following the MCG scan, automated software data analysis was performed, and quantitative scores were automatically calculated for each subject. The presence of ischemia was determined after testing with serial troponins, stress testing, and/or coronary angiography. Results: The mean age was 59.4 ± 13.6 years. Most patients (86.4%) had non-ischemic 12-lead ECG and normal troponin (86.2%). Fifty-five patients (44.0%) were determined to be ischemic. The MCG sensitivity, specificity, positive and negative predictive value was 76.4, 74.3, 70.0 and 80.0%, respectively, for the detection of ischemia (p < 0.0001). Conclusions: MCG is a new rapid, non-invasive imaging tool able to detect repolarization abnormalities at rest consistent with ischemia in patients presenting with chest pain syndrome and normal or non-specific 12-lead ECG and normal troponin.

Effect of Exercise Treadmill Testing and Stress Imaging on the Triage of Patients With Chest Pain: CHEER Substudy

OBJECTIVE To determine whether stress imaging for patients who are unsuitable for exercise treadmill testing (ETT) as part of a chest pain unit (CPU) triage strategy resulted in incremental benefit in clinical outcomes and relative costs compared with patients randomized to routine hospital admission. PATIENTS AND METHODS Clinical outcomes and medical resource utilization were examined at the Mayo Clinic in Rochester, Minn, for 212 intermediate-risk patients with unstable angina randomized to a CPU and compared with 212 patients randomized to routine admission from November 21, 1995, to March 18, 1997. Patients in stable condition in the CPU underwent ETT; if patients were unsuitable for ETT, stress imaging was performed. Costs for CPU evaluation and outcomes were assessed during a 6-month follow-up. RESULTS During the observation period, 60 patients (28%) were admitted to the hospital. Of the 152 remaining patients, 125 (82%) underwent ETT (91 had normal results), and 27 (18%) underwent stress imaging (3 had normal results). Patients with normal ETT or stress imaging results had no primary events at 6-month follow-up. Patients admitted to the hospital who underwent stress imaging had an insignificantly higher 6-month event rate compared with patients who underwent ETT (16.7% vs 8.1%; P=.38). The standardized resource-based relative-value units (RBRVUs) for patients who underwent ETT and stress imaging during follow-up were 19.4 and 56.4 RBRVUs, respectively, compared with 51.4 (ETT) and 52.1 (stress imaging) RBRVUs for similar numbers of patients randomized to routine admission. CONCLUSIONS Exercise treadmill testing safely stratified most intermediate-risk patients with unstable angina and was less costly than routine admission. Patients not suitable for ETT are likely to have abnormal stress imaging results. They represent a higher-risk cohort that could be routinely admitted to the hospital without reducing the effectiveness of the CPU strategy.

Clinical risk stratification in the emergency department predicts long-term cardiovascular outcomes in a population-based cohort presenting with acute chest pain: primary results of the Olmsted county chest pain study.

The long-term cardiovascular outcomes of a population-based cohort presenting to the emergency department (ED) with chest pain and classified with a clinical risk stratification algorithm are not well documented. The Olmsted County Chest Pain Study is a community-based study that included all consecutive patients presenting with chest pain consistent with unstable angina presenting to all EDs in Olmsted County, Minnesota. Patients were classified according to the Agency for Health Care Policy and Research (AHCPR) criteria. Patients with ST elevation myocardial infarction and chest pain of noncardiac origin were excluded. Main outcome measures were major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days and at a median follow-up of 7.3 years, and mortality through a median of 16.6 years. The 2271 patients were classified as follows: 436 (19.2%) as high risk, 1557 (68.6%) as intermediate risk, and 278 (12.2%) as low risk. Thirty-day MACCE occurred in 11.5% in the high-risk group, 6.2% in the intermediate-risk group, and 2.5% in the low-risk group (p < 0.001). At 7.3 years, significantly more MACCE were recorded in the intermediate-risk (hazard ratio [HR], 1.91; 95% confidence intervals [CI], 1.33-2.75) and high-risk groups (HR, 2.45; 95% CI, 1.67-3.58). Intermediate- and high-risk patients demonstrated a 1.38-fold (95% CI, 0.95-2.01; p = 0.09) and a 1.68-fold (95% CI, 1.13-2.50; p = 0.011) higher mortality, respectively, compared to low-risk patients at 16.6 years. At 7.3 and at 16.6 years of follow-up, biomarkers were not incrementally predictive of cardiovascular risk. In conclusion, a widely applicable rapid clinical algorithm using AHCPR criteria can reliably predict long-term mortality and cardiovascular outcomes. This algorithm, when applied in the ED, affords an excellent opportunity to identify patients who might benefit from a more aggressive cardiovascular risk factor management strategy. Abbreviations: ACC = American College of Cardiology, AHA = American Heart Association, AHCPR = Agency for Health Care Policy and Research, CI = confidence intervals, ECG = electrocardiogram, ED = emergency department, GRACE = Global Registry of Acute Coronary Events, HR = hazard ratio, MACCE = major adverse cardiovascular and cerebrovascular events, STEMI = ST elevation myocardial infarction, TIMI = Thrombolysis in Myocardial Infarction, TRS = derivation of the TIMI risk score, UA/NSTEMI = unstable angina/non-ST-segment elevation myocardial infarction.

Outcomes in patients with chest pain evaluated in a chest pain unit: The Chest Pain Evaluation in the Emergency Room study cohort

BACKGROUND Limited data exist on the long-term outcomes of patients who undergo evaluation in a chest pain unit (CPU). METHODS Our study included patients with chest pain at intermediate risk for acute cardiovascular events enrolled in the CHEER study. The primary outcome included a composite of death, myocardial infarction, acute heart failure, stroke, and out-of-hospital cardiac arrest. The secondary outcome included a composite of cardiovascular death, myocardial infarction, acute heart failure, stroke, revascularization, and unstable angina. Data were obtained through a medical record review. We compared outcomes between groups randomized to the CPU versus admission, those admitted from the CPU versus dismissed home, and those who were admitted versus dismissed home after a cardiac stress test in the emergency department. RESULTS The final analysis included 407 patients. Median surveillance length was 5.5 years. No differences in the primary outcome or secondary outcome existed between patients randomized to the CPU versus admitted to hospital (21.6% vs 20.2% and 29.9% vs 33.0%, respectively, P > .05 for all comparisons). Patients admitted from the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.26) than patients dismissed from the CPU. Patients admitted after a cardiac stress test in the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.42) than patients dismissed from the CPU. CONCLUSIONS A CPU does not increase long-term adverse outcomes in patients with chest pain at intermediate risk for an acute event.

Syncope evaluation in the emergency department.

Purpose of review In the absence of an established critical pathway to evaluate patients with syncope presenting to the emergency department, this review is timely because of new clinical evidences supporting a specialized syncope management unit in the emergency department, and it is relevant because of the potential impact on a very large and heterogeneous population. Recent findings Three observational syncope studies from Italy showed a high degree of variability in practice patterns, diagnostic yields, and lengths of hospital stay. An appropriate and efficacious syncope management pathway in the emergency department remains far from established. In a randomized trial from a tertiary care hospital in the US, the SEEDS study demonstrated that a designated ‘syncope unit’ in the emergency department, with a multidisciplinary effort and appropriate resources, significantly improved diagnostic yield, reduced hospital admission and total length of hospital stay in intermediate-risk patients. Long-term follow-up showed that reduced hospital stay did not negatively affect survival and recurrent syncope. Summary Limited randomized trial data suggest a designated syncope unit in the emergency department holds promise to provide specialized and efficient care for patients with syncope. Additional data are needed to assess the general applicability of this critical pathway in community-based hospitals.

Long-Term Cardiovascular Outcomes In Patients With Angina Pectoris Presenting With Bundle Branch Block

Long-term outcomes of unselected patients with angina pectoris and bundle branch block (BBB) on initial electrocardiogram are not well established. The Olmsted County Chest Pain Study is a community-based cohort of 2,271 consecutive patients presenting to 3 Olmsted County emergency departments with angina from 1985 through 1992. Patients were followed for major adverse cardiovascular events (MACEs) including death, myocardial infarction, stroke, and revascularization at 30 days and over a median follow-up period of 7.3 years and for mortality only through a median of 16.6 years. Cox models were used to estimate associations between BBB and cardiovascular outcomes. Mean age of the cohort on presentation was 63 years, and 58% were men. MACEs at 30 days occurred in 11% with right BBB (RBBB), 8.8% with left BBB (LBBB), and 6.4% in patients without BBB (p = 0.17). Over a median follow-up of 7.3 years, patients with BBB were at higher risk for MACEs (RBBB, hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.44 to 2.38, p <0.001; LBBB, HR 2.04, 95% CI 1.62 to 2.56, p <0.001) compared to those without BBB. Over a median of 16.6 years, the 2 BBB groups had lower survival rates than patients without BBB (RBBB, HR 2.19, 95% CI 1.73 to 2.78, p <0.001; LBBB, HR 3.32, 95% CI 2.67 to 4.13, p ≤0.001), but after adjustment for multiple risk factors an increased risk of mortality for LBBB remained significant. In conclusion, appearance of LBBB or RBBB in patients presenting with angina predicts adverse long-term cardiovascular outcomes compared to patients without BBB.