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Background: Impaired systolic function and congestive heart failure (CHF) are powerful predictors of adverse outcomes in patients with myocardial infarction (MI). However, there are little data in which both of these variables were assessed in heterogenous patients admitted from the emergency department for exclusion of ischemia., Methods: Consecutive patients admitted for MI exclusion who had ejection fraction (EF) measured were included. Systolic dysfunction was defined as EF <40%. Congestive heart failure was diagnosed based on clinical or x-ray evidence in the first 24 hours. Multivariate analysis was used to determine predictors of 30-day and 1-year mortality., Results: Of the 4,343 consecutive patients admitted, 3,682 (85%) had EF assessed (including 97% of the troponin I [TnI]-positive patients) and were included. One-year unadjusted mortality was 9.5%, but in the presence of systolic dysfunction or CHF, it increased to 22% and 26%, respectively. The most important multivariate predictors of 30-day and 1-year mortality were similar and included CHF (OR for 1-year mortality 2.5, 95% CI 1.9-3.4), TnI elevations (OR 2.0, 95% CI 1.5-2.6), and severe renal failure (OR 5.2, 95% CI 3.7-7.2). Systolic dysfunction was predictive of 1 year (OR 1.9, 95% CI 1.4-2.5) but not 30-day mortality. Results were similar in the 3,018 patients who were troponin-negative., Conclusions: Congestive heart failure is an independent predictor of both short- and long-term mortality in patients admitted for MI exclusion. In contrast, systolic dysfunction predicts long-term but not short-term mortality. One cannot be used as a surrogate for the other.

Background: Little is known about the association between clopidogrel use and long-term outcomes after stent implantation for acute coronary syndromes (ACS) in clinical practice., Methods: This retrospective cohort study included patients with ACS receiving drug-eluting stent (DES) or bare-metal stent (BMS) and discharged from all Veterans Health Administration hospitals from 2003 to 2004. Clopidogrel use was assessed by pharmacy dispensing data. Multivariable Cox regression assessed the association between clopidogrel discontinuation and outcomes with clopidogrel use as a time-varying covariate and adjusting for demographics, comorbidities, hospital presentation, and treatment variables. Median follow-up was 538 days., Results: Of 1455 patients with ACS, 65.8% received BMS and 34.2% received DES. The median number of days of clopidogrel use was 299. In multivariable analysis, clopidogrel discontinuation was associated with higher all-cause mortality (hazard ratio [HR] 2.40, 95% confidence interval [CI] 1.61-3.58). The findings were consistent for patients receiving BMS (HR 2.65, 95% CI 1.59-4.42) or DES (HR 2.00, 95% CI 1.06-3.75) and for the outcomes of acute myocardial infarction (AMI) and AMI or mortality. When follow-up was divided into 6-month intervals, the association between clopidogrel discontinuation and higher mortality remained consistent up to 18 months after hospital discharge. In secondary analysis of patients who were event-free at 6 months, clopidogrel discontinuation was associated with higher risk for AMI among patients receiving DES (HR 3.57, 95% CI 1.13-11.3) compared with BMS (HR 1.26, 95% CI 0.58-2.74)., Conclusion: Clopidogrel discontinuation after extended use was still associated with increased mortality risk. Clinical trials are urgently needed to define the optimal duration of clopidogrel therapy after stent implantation for ACS.

Background: Because of possible adverse outcomes, many of the >6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medical errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification., Methods: By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA., Results: Eight studies of >1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively., Conclusions: A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED.

Background: Ejection fraction (EF) and renal failure (RF) are powerful predictors of mortality in patients with myocardial infarction (MI). There are limited data assessing the predictive value of EF and RF compared with clinical variables in patients without ST elevation using troponin as the diagnostic MI criteria., Methods: Consecutive patients admitted from the emergency department underwent serial assessment of cardiac markers, including troponin I. Abnormal EF was defined as < 50%; RF, as creatinine clearance (CrCl) < 60 mL/min. Multivariate analysis was used to compare clinical variables, CrCl, and EF for predicting short- and long-term outcomes., Results: A total of 3074 patients had EF assessed. Mild to moderately reduced EF and CrCl were present in 639 (21%) and 582 (19%) patients, with 403 (13%) and 233 (7.6%) having severe systolic dysfunction and severe RF, respectively. Abnormal EF and RF were both present in 13% of patients (1-year mortality 26%), whereas 52% had both normal EF and CrCl (1-year mortality 3.2%). The presence of either systolic dysfunction or RF increased mortality 3- to 4-fold compared with patients without either. The most important multivariate predictors of 1-year mortality were EF (OR 2.6 [95% CI 1.7-3.8, P < .0001]) and CrCl (OR 2.8 [95% CI 1.8-4.2, P < .0001])., Conclusions: Both RF and EF are strong predictors of cardiac mortality in patients admitted for exclusion of MI. Prediction models that do not include these 2 variables will underestimate risk.

Background: The significance of troponin I (TnI) elevations in patients with renal failure (RF) admitted for possible myocardial ischemia is unclear. We therefore compared outcomes in patients with and without TnI elevations based on renal function., Methods: Consecutive patients without ST elevation admitted for exclusion of ischemia underwent serial assessment of cardiac markers including TnI. Coronary angiography, significant disease, and revascularization were determined, and 1-year cardiac mortality and all-cause mortality were assessed. Mortality was assessed based on TnI elevations in patients with no (creatinine clearance [CrCl] > or = 60 mL/min), moderate (CrCl 30-59 mL/min), and severe (CrCl < 30 mL/min) RF., Results: Troponin I elevations were present in 17% of the 3774 consecutive patients and were significantly more frequent in patients with RF (CrCl < 30 mL/min: 26%; CrCl 30-59 mL/min: 19%; CrCl > 60 mL/min: 13%, all P < or = .01). Coronary angiography was performed significantly less frequently in patients with RF, whether TnI elevations were present. One-year all-cause mortality increased with both RF and TnI positivity (TnI [+] vs TnI [-], CrCl < 30 mL/min: 52% vs 26%; CrCl 30-59 mL/min: 21% vs 14%; CrCl > 60 mL/min: 8.9% vs 4.9%, all P < .001) . Troponin I was the most important independent predictor of mortality in the 3 RF groups (odds ratio 3.3 for CrCl < 30 mL/min, 2.2 for CrCl 30-59 mL/min, and 3.3 for CrCl > 60 mL/min)., Conclusions: Troponin I elevations identified a high-risk cohort, and its prognostic value was not diminished in patients with RF.

Background: Recent recommendations are that troponin should replace creatine kinase (CK)-MB as the diagnostic standard for myocardial infarction (MI). The impact of this change has not been well described. Our objective was to determine the impact of a troponin standard on the prevalence of acute non-ST-elevation MI., Methods: The current study was a retrospective analysis of consecutive patients without ST-segment elevation admitted for exclusion of myocardial ischemia to an inner city urban tertiary care center. All patients underwent serial marker sampling (CK, CK-MB, and cardiac troponin I [cTnI]). Patients with ST elevation consistent with acute MI (n = 130) or who did not have an 8 hour cTnI (n = 124) were excluded. The impact of 3 different cTnI diagnostic values were examined in 2181 patients: the lower limit of detectability (LLD); an optimal diagnostic value (OPT), chosen using receiver operator characteristic curve analysis; and the manufacturer's suggested upper reference level (URL), when compared to a gold standard CK-MB MI definition. In addition, MI prevalence was assessed using different CK-MB MI definitions and evaluated in patients with ischemic changes only., Results: The prevalence CK-MB MI was 7.8%. Using the various cTnI diagnostic values, the incidence of MI increased the prevalence by 28% to 195%. Using the optimal diagnostic value for cTnI, patients with cTnI elevations not meeting CK-MB MI criteria had an intermediate 30-day mortality (5.4%) compared to those with CK-MB MI (7.1%). Grouping the cTnI positive, CK-MB MI negative patients with the CK-MB MI patients rather than the non-CK-MB MI patients reduced mortality for both the MI (to 5.9%) and non-MI groups (from 1.9% to 1.6%)., Conclusions: Changing to a troponin standard will have a substantial impact on the number of patients diagnosed with MI. The revised definition for MI will have important clinical and health care implications.

Background: Both 2-dimensional echocardiography and myocardial perfusion imaging (MPI) with technetium-99m based agents have been used to identify patients in the emergency department with myocardial infarction (MI). However, the inclusion of small numbers of patients in prior studies limits the accurate assessment of sensitivity of the 2 techniques., Methods: Gated MPI was used as part of the initial triage process in patients initially considered at low to moderate risk for acute coronary syndromes (no ST elevation or depression). Patients diagnosed with MI also underwent echocardiography. MPI results were considered positive if there was a perfusion defect associated with abnormal wall motion or thickening, and echocardiographic results were considered positive if there were segmental wall motion abnormalities or ejection fraction of less than 40%., Results: Both tests were performed on 141 patients. The sensitivities for MI for echocardiography (91%; 95% CI, 86%-95%) and MPI (89%; 95% CI, 83%-94%) were similar. Patients who had either negative echocardiographic results (peak creatine kinase level [CK], 325 +/- 206 vs 582 +/- 614 U/L; P =.003) or negative MPI results (peak CK, 313 +/- 227 vs 590 +/- 620 U/L; P =.001) had smaller MIs as estimated with peak CK values. Ejection fraction was highly correlated between the 2 techniques (r = 0.82; P <.001)., Conclusion: Both echocardiography and MPI have a high sensitivity for identifying patients in the emergency department who have MI. False negative studies with either technique were associated with small MIs.

Objective: Recent studies have demonstrated that glycoprotein (GP) IIb/IIIa inhibitors can reduce cardiac events in patients with acute coronary syndromes (ACS). However, little is known about how many patients are actually eligible for treatment. Our purpose was to determine how many patients admitted for possible myocardial infarction (MI) meet GP IIb/IIIa inhibitor treatment criteria., Methods: Patients admitted for possible MI who underwent a standard protocol that included serial sampling of total creatine kinase (CK), CK-MB, and troponin I (TnI) were retrospectively assigned to different treatment algorithms on the basis of criteria from GP IIb/IIIa inhibitor trials: an electrocardiogram (ECG) consistent with acute MI or ischemia, and myocardial marker elevations. Elevated CK-MB was considered diagnostic of MI. High-risk ACS was defined as ischemic ECG changes or troponin elevations without CK-MB elevations., Results: A total of 2179 patients were admitted for MI exclusion. MI was identified in 304 patients (14.0%) (123 ST-elevation, 49 ischemic ECG, 132 nonischemic ECG). Another 273 patients (12.5%) without CK-MB criteria for MI met high-risk ACS criteria (172 ischemic ECG, 120 TnI elevations). Ischemic ECGs or elevated myocardial markers identified 454 (21%) patients as eligible for treatment. Inclusion of patients with ST elevation increased eligibility to 26.5%. Of the 454 non-ST-elevation ACS patients, 340 (74%) were identified early by the ECG or the initial markers., Conclusions: A large proportion of patients admitted for possible MI met criteria for treatment with GP IIb/IIIa inhibitors. The non-ST-elevation ACS group was >3 times larger than the ST-elevation MI group. These findings have important implications for treatment of patients with ACS.

Background: A nonischemic electrocardiogram (ECG) in association with myocardial infarction (MI) indicates a small MI in some but not all cases. Myocardial perfusion imaging using technetium-99m sestamibi offers the ability to better characterize these "electrically silent" infarctions., Methods: Patients considered low risk for myocardial infarction with a normal or nonischemic ECG (no significant ST elevation, ST depression, ischemic T-wave inversion, or left bundle branch block) underwent early emergency department perfusion imaging, followed by serial myocardial marker sampling. Risk area (defect size) was quantitated by use of a 50% threshold from multiple short-axis slices., Results: A total of 87 patients with nonischemic ECGs had myocardial infarction (mean peak creatine kinase [CK] 710 +/- 720 U/L, range 111-3196 U/L). Peak CKs were lower in the 7 patients with negative perfusion imaging (420 +/- 290 U/L vs 730 +/- 740 U/L, P =.06). Mean risk area was 18% +/- 11% of the left ventricle (range 0%-62%) and was not significantly different among the different infarct-related arteries. Patients with normal ECGs had a similar risk area compared with other patients (16% +/- 12% vs 19 +/- 12%, P =.25). Coronary angiography was performed in 81 patients, with significant stenoses in 74 (91%) (37 one-vessel, 19 two-vessel, 18 three-vessel), with the infarct related artery most commonly the left circumflex (n = 32 [38%])., Conclusions: The ischemic risk area in patients with a nonischemic ECG was comparable to patients with inferior ST-elevation myocardial infarction found in previous studies. A nonischemic ECG does not predict a small ischemic risk area.

Background: Accurate identification of patients at high risk for acute coronary syndromes among those seen in the emergency department (ED) with possible myocardial ischemia and nonischemic electrocardiograms is problematic. Both 2-dimensional echocardiography and myocardial perfusion imaging with technetium-99m sestamibi can identify patients at low and high risk; however, comparative studies are lacking., Methods and Results: Patients initially considered at low or moderate risk for myocardial ischemia on the basis of the presenting history, physical examination, and electrocardiogram underwent both echocardiography and myocardial perfusion imaging within 4 hours of ED presentation. Positive echocardiography was defined as the presence of segmental wall motion abnormalities or moderate to severe global systolic dysfunction; positive perfusion imaging was defined as a perfusion defect in association with abnormal wall motion, thickening, or both. End points included MI, percutaneous transluminal coronary angioplasty, and positive stress perfusion imaging. Both imaging procedures were performed in the ED on 185 patients. Six patients had MI, and an additional 4 patients underwent percutaneous transluminal coronary angioplasty. Echocardiography and perfusion imaging were positive in all 10. Overall agreement between the 2 techniques was high (concordance 89%, kappa coefficient 0.74) in the 27 patients who had MI or underwent coronary angiography. For all patients, concordance was 89%, with a kappa coefficient of 0.66., Conclusions: Agreement between echocardiography and perfusion imaging with technetium-99m sestamibi is high when used in patients in the ED with possible myocardial ischemia. Both techniques identified patients at high risk who required admission and those who could be safely discharged directly from the ED.