Can Myocardial Infarction Be Rapidly Identified in Emergency Department Patients Who Have Left Bundle-Branch Block?

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1 ORIGINAL CONTRIBUTION Can Myocardial Infarction Be Rapidly Identified in Emergency Department Patients Who Have Left Bundle-Branch Block? From the Department of Internal Medicine, Division of Cardiology, * Department of Emergency Medicine, and Department of Radiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA. Received for publication March 6, Revision received October 30, Accepted for publication December 1, Presented in part at the American College of Cardiology annual meeting, Atlanta, GA, March 1998, and New Orleans, LA, March Reprints not available from the authors. Address for correspondence: Michael C. Kontos, MD, 12th and Marshall Streets, PO Box , Richmond, VA ; , fax Copyright 2001 by the American College of Emergency Physicians /2001/$ /1/ doi: /mem Michael C. Kontos, MD * Robert H. McQueen, MD * Robert L. Jesse, MD, PhD * James L. Tatum, MD Joseph P. Ornato, MD See editorial, p Study objectives: Fibrinolytic therapy is recommended for patients who have chest pain and left bundle-branch block (LBBB). However, the presence of baseline ECG abnormalities makes early accurate identification of acute myocardial infarction (AMI) difficult. The predictive ability of clinical and ECG variables for identifying patients with LBBB and AMI has not been well studied. We sought to determine the prevalence and predictors of myocardial infarction among patients presenting to the emergency department with LBBB on the initial ECG who were evaluated for myocardial infarction. Methods: All patients presenting to the ED were prospectively risk stratified on the basis of clinical and historical variables. ECGs from patients with LBBB were compared retrospectively with previously published criteria for identification of AMI. The ability of a new LBBB to predict AMI was also determined. Results: Twenty-four (13%) of the 182 patients with LBBB had AMI. Clinical and historical variables were similar in patients with and without AMI. A new LBBB had a sensitivity of 42% and a specificity of 65%. The presence of concordant ST-segment elevation or depression had specificities and positive predictive values of 100%; however, sensitivities were only 8% and 17%, respectively. The best diagnostic criterion was the presence of concordant ST-segment elevation or depression on the ECG or an initially elevated creatine kinase MB (sensitivity, 63%; specificity, 99%). Conclusion: ECG criteria for identifying patients with AMI and LBBB identify only a small minority of patients with AMI. Treating all patients with LBBB and chest pain with fibrinolytics would result in treatment of a significant number of patients without AMI. [Kontos MC, McQueen RH, Jesse RL, Tatum JL, Ornato JP. Can myocardial infarction be rapidly identified in emergency department patients who have left bundle-branch block? Ann Emerg Med. May 2001;37: ] MAY :5 ANNALS OF EMERGENCY MEDICINE 431

2 INTRODUCTION Patients with left bundle-branch block (LBBB) represent an important minority of patients with acute myocardial infarction (AMI) who have a mortality often significantly higher than that of other patients with AMI. 1 Despite published guidelines for treatment of AMI, 2 only a minority of patients presenting with LBBB on the initial ECG receive early reperfusion therapy. 3,4 Reasons for the lack of treatment include the presence of baseline ECG abnormalities, which makes accurate identification of AMI difficult; the frequent presence of nonchest pain or atypical presentations 3 ; and the substantial variation in prevalence of myocardial infarction (MI) in reported series (Table 1) Because fibrinolytic therapy is beneficial only in patients with AMI, therapy should be limited to patients having a high likelihood for AMI. The purpose of this study is to determine the prevalence, as well as the ability, of clinical, ECG, and biochemical markers of necrosis to rapidly detect AMI among an unselected population presenting to the emergency department with LBBB undergoing an evaluation for possible myocardial ischemia. MATERIALS AND METHODS The chest pain protocol used at our institution has been described in detail previously. 11 All patients who present to the Medical College of Virginia Hospital s ED with chest pain or other symptoms suggestive of myocardial ischemia undergo prompt clinical evaluation by ED house staff and attending physicians. After the initial evaluation, patients who have ST-segment elevation (level 1) or who have Table 1. Previous studies including patients with LBBB. No. of No. of Patients Total Patients With LBBB No. of With LBBB and AMI Study Patients (%) (%) Rude et al, MILIS 8 3, (4.8) 82 (46) Fesmire et al (5) 3 (13) Otto and Aufderheide (4.2) 5 (28) Sgarbossa et al, GUSTO-I 7 26, (0.6) 131 (90) Cannon et al, TIMI III Registry 9 1, (8.9) 40 (32) Kudenchek et al, MITI 10 3, (2) 22 (37) * Our study 7, (2.4) 24 (13) * Included MI and ischemia as end points. ischemic ECG changes or typical symptoms with known coronary disease (level 2) are admitted directly to the coronary care unit (CCU). Patients considered at low risk for AMI undergo further risk stratification by using early rest myocardial perfusion imaging. 11 Patients considered at low risk for AMI and moderate risk for unstable angina are admitted (level 3), whereas patients considered at low risk for both AMI and unstable angina undergo perfusion imaging in the ED (level 4). Patients who have images that are negative or unchanged from previous studies are discharged and scheduled for outpatient stress testing, whereas those with positive imaging results are admitted. For the purposes of this analysis, patients with LBBB on the initial ECG were retrospectively classified into 1 of 3 risk levels on the basis of the initial evaluation and treatment initiation: 1. High risk (level 1). These patients were considered to have AMI and received fibrinolytic therapy or underwent immediate coronary angiography for assessment of need for urgent revascularization. 2. Moderate risk (level 2). These patients were considered to have a high risk for myocardial ischemia on the basis of presenting symptoms, prior history, or both; were admitted to the CCU; and were treated with standard anti-ischemia therapy without fibrinolytic agents (intravenous heparin, nitroglycerin, and β-blockers when not contraindicated). 3. Low risk (levels 3 and 4 combined). These patients were considered to be at low risk for AMI on the basis of presenting symptoms and history and underwent further risk stratification with early rest myocardial perfusion imaging. All patients admitted to the CCU underwent serial sampling of total creatine kinase (CK; Vitros, Johnson and Johnson, New Brunswick, NJ) and CK-MB levels by means of mass assay and myoglobin measurement (Opus Magnum, Behring Diagnostics, Auckland, New Zealand). For myoglobin measurement, the manufacturer s suggested upper reference limit of 92 µg/l was used. For CK-MB measurement, an upper reference limit of 8.0 ng/ml was used. 12 A CK relative index (RI) was calculated with the following formula: CK-MB 100/Total CK. Diagnosis of AMI was confirmed by an elevation of CK- MB to 8.0 ng/ml with an RI of 4.0 in association with a characteristic increase and decrease in markers. After June 1996, an elevation in troponin I was also required for the diagnosis of AMI (to exclude patients in whom CK-MB elevations were caused by skeletal muscle damage rather than MI). Patients who had troponin I eleva- 432 ANNALS OF EMERGENCY MEDICINE 37:5 MAY 2001

3 tions without CK-MB and RI criteria for MI were not considered to have AMI. Only the initial visit was used for patients presenting more than once during the study period. Patient data were collected prospectively as part of an ongoing quality assurance process by using a standardized data collection form with retrospective analysis of patient s records to supply mission information. Data analysis was performed after removing all patient identifiers. This study was reviewed and approved by the Exempt Committee on the Conduct on Human Research. LBBB was defined by the presence of a QRS duration of 120 ms; a QS or rs complex in lead V1; absence of Q waves in leads I, V 5, and V 6 ; and an R wave peak time of at least 60 ms in leads I, V 5, or V 6. ECGs were also analyzed for the presence of 1 of 3 previously defined criteria for AMI 7 : ST-segment elevation of 1 mm concordant with the QRS complex; ST-segment depression of 1 mm in leads V 1, V 2, or V 3 ; and ST-segment elevation of 5 mm discordant with the QRS complex. All ECGs were read independently by 2 cardiologists unaware of the clinical variables and patient outcome. Disagreements were resolved by a third cardiologist. The chronicity of the LBBB was determined by comparing the presenting ECG with the most recent previous ECG available in our hospital s computerized ECG records, which are retrieved routinely in the ED. If no prior ECG was available for comparison, the age were considered indeterminate. Comparisons were made with the Student t test or χ 2 analysis for categoric and proportional variables, respectively. Statistical analysis was performed with a standard statistical software package (SAS 6.11, SAS, Cary, NC). A P value of.05 was considered statistically significant. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated in the standard fashion, with 95% CIs calculated as previ- Table 2. Distribution of the patients on the basis of the initial triage risk group and incidence of AMI. No. No. With AMI Risk Group (%) (%) High risk 9 (5) 6 (67) Moderate risk 98 (54) 14 (14) Low risk 75 (41) 4 (5.3) Total 182 (100) 24 (13) ously described. 13 Agreement between the 2 sets of ECG interpretations was assessed with the κ coefficient. 14 RESULTS From June 1994 through February 2000, 7,725 patients underwent further evaluation for myocardial ischemia after the initial ED assessment; 182 (2.4%) had LBBB present on the initial ECG. The mean age of the patients was 66±14 years (median, 68 years). The distribution of patients on the basis of the initial risk assessment and the incidence of AMI in each group are shown in Table 2. The only significant difference in clinical variables was that patients with AMI were significantly older (Table 3). Eleven patients with LBBB were discharged from the ED after perfusion imaging (8 with negative results and 3 unchanged from previous studies). MI was diagnosed in 24 (13%) of the 182 patients. The mean peak CK level in these patients was 970±1,870 U/L (median, 340 U/L; range, 104 to 8,334 U/L). An additional 5 patients had elevated troponin I values without meeting CK-MB and RI criteria for AMI. The distribution of patients with and without AMI according to whether the LBBB was new, persistent, or of indeterminate age is shown in the Figure. In patients with new LBBB, the mean time elapsed from the most recent ECG was 1.7±2.2 years (median, 8 months; range, 3 days- 8.6 years). AMI occurred in 2 (8%) of the 26 patients in whom the most recent non-lbbb ECG was within 6 months Table 3. Comparison of demographic and clinical variables in patients with LBBB with and without AMI. With AMI Without AMI Clinical Variable (n=24) (n=158) Age (y) 73±11 65±14 * Age >65 y 17 (71) 82 (52) Male sex 7 (29) 48 (30) Hypertension 20 (83) 107 (68) Diabetes 9 (38) 45 (28) Tobacco use 4 (17) 49 (31) Family history coronary disease 2 (8) 27 (17) Previous MI 8 (33) 40 (25) Prior revascularization 4 (17) 38 (24) Typical symptoms 7 (35) 61 (45) Shortness of breath 13 (65) 93 (69) Numbers in parentheses indicate percentages. * P<.01. Based on 23 patients with and 147 patients without AMI who had data available. MAY :5 ANNALS OF EMERGENCY MEDICINE 433

4 of the ED visit and in 5 (14%) of the 36 patients in whom the most recent non-lbbb ECG was within 1 year of the ED visit. The incidence of AMI was higher in patients with new (18%, P<.05) and indeterminate-age LBBB (27%, P<.004) compared with patients with old LBBB (6%). Although the presence of a new or indeterminate LBBB had a high sensitivity, specificity and PPV were low (Table 4). Specific ECG criteria for the diagnosis of AMI in the setting of LBBB 7 were identified in 22 patients (Table 4), 11 of whom had AMI. The presence of any one of these 3 criteria had a sensitivity of 46%, a specificity of 93%, and PPVs and NPVs of 50% and 92%, respectively. Diagnostic accuracy was not significantly changed after excluding lowrisk patients and only analyzing the intermediate- and high-risk patients. Interobserver agreement for the presence or absence of AMI by these ECG criteria was 90%, with a κ coefficient of Although not significant, mean peak CK (2,750±3,330 U/L versus 370±240 U/L) and CK-MB (212±250 ng/ml versus 32±31 ng/ml) levels tended to be higher in the 6 patients who had concordant ST-segment depression or elevation compared with the 18 patients with AMI without the ECG findings. The highest peak CK level in patients without concordant ST-segment elevation or depression was 872 U/L, with 61% of the 18 patients having peak CK levels of less than 300 U/L. The predictive value of biochemical markers at the time of presentation was also evaluated. Myoglobin data were available in 149 patients (82% of admitted patients). Figure. Number of patients with (open bars) and without (shaded bars) AMI on the basis of whether the LBBB was new, old, or of indeterminate age No. of patients 56 New Indeterminate New + Indeterminate 65 Old 4 Elevations were present in 12 (67%) of the 18 patients with AMI and in 20 (15%) of the 131 patients without AMI. Elevations in the initial CK-MB level and RI were present in 10 (42%) of the 24 patients with AMI and in 2 (1.4%) of the 140 admitted patients without AMI. By using the combination of either an initial positive CK-MB level and RI or an ECG that demonstrated ST-segment elevation or depression concordant with the QRS complex resulted in the highest diagnostic accuracy. Sensitivity was significantly improved when compared with the ECG alone (63% versus 25%, P<.01), with nonsignificant changes in specificity, PPVs, and NPVs (Table 4). Addition of myoglobin to the combination of concordant ST-segment depression or elevation on the ECG or an elevated CK-MB level and RI significantly reduced specificity (99% to 85%, P<.01) and PPV (88% to 43%, P<.01) without improving sensitivity or NPV. Limiting analysis to only the high- and intermediate-risk patients (levels 1 and 2) resulted in no significant change in any of the predictive indices. Myocardial perfusion imaging was performed in 75 patients in whom the initial risk for AMI was thought to be low; 49 (65%) patients had positive study results, of whom 3 had AMI. Mean ejection fraction, which was assessed in 102 patients without AMI within 3 months of the ED visit, was 39%±18% (median, 39%), with 51% having ejection fractions of 40% and 36% having ejection fractions of 30%. DISCUSSION Our study showed a low prevalence of AMI in patients with LBBB who underwent ED evaluation for myocardial ischemia. Proposed ECG criteria for identifying patients with AMI in the setting of LBBB occurred either too infrequently or had a predictive value too low to identify most of the patients with AMI. Clinical and historical criteria were not useful for identifying patients who had AMI. The highest accuracy for diagnosing AMI at the time of ED presentation was either the presence of concordant STsegment elevation or depression on the ECG or a positive CK-MB level and RI. Administration of fibrinolytic therapy to patients with AMI and ST-segment elevation has conclusively been shown to decrease mortality. 1 In the Fibrinolytic Collaborative Group, 1 patients with bundle-branch block and presumed AMI who were treated with fibrinolytic therapy had a 25% reduction in mortality. These findings are the basis for the current treatment recommendations. 2 However, 2 important considerations limit the applicability of this finding to patients with LBBB. First, in several of these 434 ANNALS OF EMERGENCY MEDICINE 37:5 MAY 2001

5 studies, MI was not confirmed; mortality was the only end point. Second, most studies did not specifically differentiate between patients with right bundle-branch block and LBBB. If a large proportion of the patients had right bundle-branch block, which does not obscure ischemic ECG changes, the beneficial effects in patients with LBBB would be overestimated. The reported prevalence of AMI among patients who have LBBB undergoing an evaluation for myocardial ischemia has varied considerably (Table 1). Differences among the various studies can be attributed to variations in patient selection and entry criteria. For example, in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) I study, 7 all patients were treated with fibrinolytic therapy; therefore, the smaller proportion of patients with LBBB included likely reflected physician willingness to give fibrinolytic therapy only when clinical suspicion for AMI was high. In contrast, in the Thrombolysis in Myocardial Ischemia III Registry of patients with presumed AMI and unstable angina, only 32% of the 127 patients with LBBB were diagnosed with AMI. 9 Studies that included all patients undergoing an evaluation of possible myocardial ischemia have found even lower rates, with only a minority of patients with LBBB having AMI. A wide variety of different ECG criteria for identifying AMI in patients with LBBB have been proposed. 15 However, most of these criteria were evaluated in small studies, were not validated prospectively, and did not differentiate between acute and previous infarction. Sgarbossa et al 7 proposed criteria based on the GUSTO I experience, which demonstrated a high sensitivity and specificity for identifying patients with AMI. In our study, only 11 of the 24 patients with AMI met 1 of these 3 ECG criteria. Similar to prior studies, 7,16 the presence of either ST-segment depression or elevation of 1 mm concordant with the QRS complex had a high specificity for identifying patients with AMI, indicating that these 2 criteria can be used to select patients for fibrinolytic therapy. In contrast, ST-segment elevation of 5 mm discordant with the QRS complex was not as useful because only 26% of the patients had AMI. Similar results were reported by Shlipak et al, 16 as well as in the validation cohort of Sgarbossa et al. 7 The presence of a new LBBB has been thought to identify patients who have AMI. 2,7 To our knowledge, no previous study has specifically addressed this issue. We found that 20 of the 24 patients who had AMI had either a new LBBB or an LBBB of indeterminate age. Although useful for identifying patients who have a higher likelihood of AMI, the predictive value was low because less than one quarter of patients with a new or indeterminate-aged LBBB had AMI. In contrast, only 4 of the 69 patients with an old LBBB had AMI, indicating that this group of patients appears at lower risk for AMI. We found that clinical and historical variables were not useful for differentiating between patients with and without AMI. In addition, overall accuracy for predicting AMI by physicians was relatively low because only 29% of all patients with AMI were initially considered at high risk. Others have found that physicians using clinical criteria Table 4. Predictive accuracy of various ECG and clinical variables for identifying patients with LBBB and AMI. AMI No AMI Relative Criteria No. (n) (n) Sensitivity Specificity PPV NPV Risk ST-segment elevation, concordant, 1 mm (2 26) 100 (98 100) 100 (33 100) 88 (82 92) 29 ( ) ST-segment depression, 1 mm in leads V 1, V 2, or V (7 36) 100 (98 100) 100 (50 100) 89 (83 93) 63 (1.1 1,240) ST-segment elevation, discordant, 5 mm (9 41) 93 (88 96) 31 (14 56) 89 (83 93) 3.5 (1.0 11) Any ECG changes (28 65) 93 (88 96) 50 (30 70) 92 (86 95) 11 (3.6 31) New LBBB (24 62) 65 (57 72) 15 (8 26) 88 (81 93) 1.3 ( ) New or indeterminate-age LBBB (64 93) 41 (34 49) 18 (12 26) 94 (86 98) 3.5 (1.2 11) Clinical impression (high-risk only) (12 45) 98 (94 99) 67 (35 88) 90 (84 93) 17 (2.7 75) Initial CK-MB/RI * (24 62) 99 (95 100) 83 (55 95) 91 (85 94) 49 ( ) Initial myoglobin (43 84) 85 (77 90) 38 (23 55) 95 (89 98) 11 (3.5 33) Initial CK-MB/RI * or + ECG (42 79) 99 (95 100) 88 (65 97) 94 (89 97) 115 (14 580) Initial myoglobin, CK-MB/RI or + ECG (60 94) 85 (77 90) 43 (28 59) 97 (92 99) 28 ( ) CK-MB/RI, CK-MB of 8 ng/ml and RI of 4; + ECG, concordant ST-segment elevation or depression. * Based on the 164 patients who were admitted. Based on 18 patients with AMI and 131 patients without AMI who had an initial myoglobin measurement available. MAY :5 ANNALS OF EMERGENCY MEDICINE 435

6 alone have difficulty accurately identifying patients with and without AMI. 17 The sensitivity for diagnosing AMI was significantly improved by considering the results of the initial CK-MB measurements, without significantly affecting specificity. Point of care biochemical markers of myocardial necrosis have the potential to aid in early and rapid detection of AMI. 18 However, using early marker sampling to select patients for fibrinolytic therapy has several limitations. CK-MB levels are often not elevated until several hours after the onset of myocardial necrosis, which is associated with a decrease in the beneficial effects of fibrinolytic therapy. Myoglobin is released earliest after onset of necrosis but lacks myocardial specificity. 19 Moreover, elevations in myocardial markers do not necessarily identify patients who will benefit from fibrinolytic therapy. Treatment with fibrinolytic therapy in non ST-segment elevation coronary syndromes is associated with a higher rate of adverse outcomes and is not currently recommended. Rather than identifying patients for fibrinolytic therapy, those who have early marker elevations may be candidates for early diagnostic coronary angiography or, alternatively, treatment with glycoprotein IIb/IIIa antagonists. 23 The high mortality associated with patients who have LBBB and AMI 4 points to the need for additional diagnostic tools. Unfortunately, all currently available techniques have important limitations. Imaging techniques, such as echocardiography and myocardial perfusion imaging, cannot reliably differentiate among ischemia, new MI, and old MI. Segmental wall motion abnormalities and perfusion defects are frequently seen in patients with prior MI and are not uncommon in patients with nonischemic cardiomyopathies The significant number of patients who had prior MI, reduced ejection fractions, and perfusion defects without AMI in the current study indicates that in this population, these techniques would be associated with a high false-positive rate. The limitations of biochemical markers and the ECG have been discussed above. Although early coronary angiography may be useful in certain high-risk patients, many patients with LBBB do not have significant coronary disease. 9 In addition, only a minority of hospitals have catheterization facilities, limiting this option. Potential tools include use of serial ST-segment monitoring 27 and body-surface potential maps, which may have increased diagnostic utility in patients with LBBB. 28,29 The results of the current study, as well as those of other studies, 5,9,10 indicate that the majority of patients with LBBB who undergo an ED evaluation for possible AMI will have the diagnosis excluded; therefore, administration of fibrinolytic therapy to all patients with LBBB and possible AMI would result in the treatment of many patients who do not have AMI. A recent study performing decision analysis found that routine administration of fibrinolytic therapy to all patients with LBBB and possible AMI would result in a small but significant mortality reduction. 16 However, the risks of fibrinolytic therapy may be magnified in patients with LBBB. The risk of intracranial hemorrhage is increased in the elderly and in patients with hypertension, an important consideration given the high incidence of these variables in patients with LBBB. 4,33 In addition, recent studies have suggested decreased effectiveness of fibrinolytic agents in patients over the age of 75 years. 34 Finally, the benefit provided by fibrinolytic treatment is lower in patients with smaller infarctions. 31 In the current study, 61% of the patients without concordant ST-segment elevation or depression had a peak CK level under 300 U/L, which is consistent with a smallsized MI. It may be argued that in patients with prior MI (27% of the patients in our study), a small-sized infarct area may represent a significant proportion of the remaining viable myocardium, and therefore, early reperfusion therapy would offer greater benefit. However, a significantly greater mortality reduction in patients with prior MI has not been shown. 1 Given the small size of the MIs (based on peak CK values) in patients without concordant ST-segment elevation or depression, initiation of glycoprotein IIb/IIIa inhibitors may be an alternative treatment option in these patients. Glycoprotein IIb/IIIa antagonists have a lower risk of bleeding complications and significantly reduce ischemic events in patients with non ST-segment elevation MI and are a currently recommended treatment for patients with non ST-segment elevation acute coronary syndromes. 23 In summary, the number of patients with LBBB included in the current study was not large; however, it was more than that found in previous studies We did not attempt to locate previous ECGs obtained at other institutions or by the patient s physician in those patients without an ECG available from our computerized ECG records. This should not have significantly affected the results of this study because the majority of patients receive their care at the Medical College of Virginia Hospitals. In addition, the logistical difficulties of retrieval from outside sources at night or weekends would limit the ability to aid in ED rapid decisionmaking. We did not analyze the predictive ability of other proposed ECG criteria for identifying patients with LBBB and AMI. Prior studies have not found 436 ANNALS OF EMERGENCY MEDICINE 37:5 MAY 2001

7 criteria other than those used in the current study to be useful. 7,16 We did not consider patients with troponin elevations without elevated CK-MB levels to have AMI. Although previous studies have shown that patients with troponin elevations are at increased risk for adverse cardiac events, 38 the lack of a significant increase in CK-MB levels indicates that the amount of myocardial damage is small or that it occurs late after onset of infarction, and therefore, fibrinolytic therapy is unlikely to be of significant benefit. 31 The prevalence of AMI among patients with LBBB on the initial ECG undergoing an evaluation for myocardial ischemia is low. Current recommendations would result in administering fibrinolytic therapy to many patients who will not have AMI. Better methods are needed for identifying patients who have LBBB and AMI who will benefit from fibrinolytic therapy. REFERENCES 1. Fibrinolytic Therapy Trialists (FTT) Collaborative Group. 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