Body surface mapping vs 12-lead electrocardiography to detect ST-elevation myocardial infarction
Original Contribution
Body surface mapping vs 12-lead electrocardiography to detect ST-elevation myocardial infarction
Joseph P. Ornato MD a,?, Ian B.A. Menown MD b, Mary Ann Peberdy MD a,
Michael C. Kontos MD, PhD a, John W. Riddell MD c, George L. Higgins III MD d,e,
Suzanne J. Maynard MD f, Jennifer Adgey MD c
aInternal Medicine Virginia Commonwealth University Health System, PO Box 980401, Richmond, VA 23298-0401, USA
bCraigavon Cardiac Centre, Craigavon, Northern Ireland BT63 5XD, UK
cRegional Medical Cardiology Centre, Royal Victoria Hospital Belfast, Northern Ireland BT12 6BA, UK
dUniversity of Vermont College of Medicine, Burlington, VT 05401, USA
eMaine Medical Center, Portland, ME 04102, USA
fMater Hospital Belfast, Northern Ireland BT14 6AB, UK
Received 13 March 2008; revised 13 June 2008; accepted 16 June 2008
Abstract A prospective, multicenter trial was conducted in patients with nontraumatic chest pain in 4 hospitals to determine whether an 80-lead body surface map electrocardiogram system (80-lead BSM ECG) improves detection of ST-segment elevation in acute myocardial infarction (STEMI) compared with a standard 12-lead electrocardiogram in an emergency department (ED) setting. A trained ED or cardiology staff member (technician or nurse) recorded a 12-lead ECG and 80-lead BSM ECG from each subject at initial presentation. Serial biomarkers (total creatine kinase [CK], CK-MB, and/or troponin) were obtained according to individual hospital practice. Of the 647 patients evaluated, 589 had available biomarkers results. Eighty-lead BSM ECG improved detection of biomarker-confirmed STEMI compared with the 12-lead ECG for CK-MB-defined STEMI (100% vs 72.7%, P = .031; n = 364) or troponin-defined STEMI (92.9% vs 60.7%, P = .022; n = 225). Specificity for STEMI was high (range, 94.9%-97.1%) with no significant difference between 80-lead BSM ECG and 12-lead ECG. right ventricular involvement complicating inferior STEMI was detected by 80-lead BSM ECG in 2 (22%) of 9 patients with CK-MB-defined MI and in 2 (22%) of 9 patients with troponin-defined MI. The infarct location missed most commonly on 12-lead ECG but detected by 80-lead BSM ECG was inferoposterior MI. We conclude that BSM using 80-lead BSM ECG is more sensitive for detection of STEMI than 12-lead ECG, while retaining similar specificity.
(C) 2009
Introduction
Despite advances in the treatment of acute myocardial infarction (AMI), coronary heart disease remains the
* Corresponding author. Tel.: +1 804 828 5250; fax: +1 804 828 8597.
E-mail address: [email protected] (J.P. Ornato).
leading cause of death in the United States [1-3]. Approximately 200 000 cases of AMI each year prove fatal [4]. In an estimated 2% of cases, AMI is not recognized on initial presentation, and patients are discharged inappropri- ately from the emergency department (ED) [5,6]. Missed AMIs result in larger malpractice payments than any other condition commonly seen in the ED [7,8]. Improving the
0735-6757/$ - see front matter (C) 2009 doi:10.1016/j.ajem.2008.06.010
speed and accuracy of diagnosis in patients who present with chest pain may help prevent inappropriate discharge and permit earlier intervention, which can limit myocardial damage and reduce morbidity and mortality [9,10].
biochemical markers of Myocardial necrosis (total creatine kinase [CK], CK-MB, and troponin) are now considered the gold standard for diagnosis of AMI [11]. Elevated levels of CK-MB and Cardiac troponin T or troponin I have high specificity for AMI but take 4 to 6 hours to increase and do not reliably exclude AMI until 12 hours after symptom onset [11].
The standard 12-lead electrocardiogram (ECG) has been the principal method used to diagnose ST-segment elevation in acute MI (STEMI) in real time at the bedside. It remains a central tool for diagnosis, guiding appropriate therapy, and predicting prognosis [12]. However, as demonstrated in a study of 1041 patients presenting with chest pain, the sensitivity of the initial 12-lead ECG for diagnosing AMI is relatively poor [13]. The use of additional right precordial and posterior leads has been shown to increase ECG sensitivity for AMI [14,15]. Thus, a more sensitive, real- time diagnostic tool that allows early detection of more STEMI cases than the standard 12-lead ECG might permit early intervention in more patients.
The primary objective of this study was to determine whether the 80-lead body surface map electrocardiogram system (80-lead BSM ECG) could detect STEMI more frequently than a standard 12-lead ECG when used to evaluate patients in the ED when an acute coronary syndrome was suspected.
Methods
This prospective multicenter trial was conducted in patients suspected of having acute coronary syndrome who presented to the ED of the Medical College of Virginia Hospital at Virginia Commonwealth University Health System in Richmond, Va; the Maine Medical Center in Portland, Me; Manchester Royal Infirmary in Manchester, England; or the Royal Victoria Hospital in Belfast, Northern Ireland. Inclusion criteria were age of more than 18 years, ability to give informed consent, and presentation to the ED within 12 hours of onset of symptoms consistent with or suggestive of AMI or unstable angina. Exclusion criteria were presentation to the ED more than 12 hours after onset of symptoms, having undergone cardiopulmonary resuscitation or electrical defibrillation before ED admission, or having received medication before ED admission that would invalidate written informed consent.
Materials
As soon after ED admission as possible (usually within 10 minutes), a trained ED or cardiology staff member (technician or nurse) performed a 12-lead ECG, which was
followed within 30 minutes by 80-lead BSM ECG (Meridian Medical Technologies, Inc [Columbia, Md], which is now Heartscape Technologies, Inc [Columbia, Md]), a system that has been described previously [13,14,16,17]. Briefly, the system consisted of flexible plastic anterior and posterior electrode vests and a recording unit. The anterior vest contained 64 electrodes (including 3 proximal limb leads) and the posterior vest, 16 electrodes (Fig. 1). It allowed the clinician to record 80 uni-electrode ECG signals with respect to the Wilson central terminal. Self-adhesive hydrogel pads were placed at each electrode site with the “leads” screen printed onto the plastic surface. The electrodes were arranged in vertical strips to facilitate placement at referenced anatomical
Fig. 1 Eighty-lead BSM ECG (A) and 12-lead ECG (B) from a study subject. The 80-lead BSM ECG map shows an area of ST (J point) elevation (maximum = +0.68 mm) over the lower right posterior chest wall and an area of ST depression (minimum =
-1.49 mm) over the left anterolateral chest wall, in keeping with acute posterior MI. Underlying ECG traces from the posterior electrodes with ST elevation are displayed. The accompanying 12-lead ECG shows no significant ST elevation and only minor nonspecific ST depression in leads V3, V4, and V5.
landmarks (anterior: right midaxillary, right midclavicular, right parasternal, left parasternal, left medial clavicular, left midclavicular, left anterior-axillary, and left midaxillary lines; posterior: left posterior-axillary, left paraspinal, right posterior-axillary, and right midaxillary lines). Vest appli- cation took 3 to 4 minutes. Maps were recorded over 5 to 10 seconds at a sampling rate of 1 kHz and a bandwidth of
0.05 to 100 Hz and transferred in digital format for core Laboratory analysis.
12-Lead ECG and 80-lead BSM ECG analysis
The 12-lead ECG and 80-lead BSM ECG recordings were presented separately and in random order to an expert panel of 3 cardiologists at the Royal Victoria Hospital. The panelists were blinded to biomarker results and clinical data other than age, sex, and race. Each panel member had at least 2 years of clinical experience with 12-lead ECG and BSM recording and interpretation in a busy cardiac ED.
All 12-lead ECGs were evaluated according to American College of Cardiology ECG guidelines [12]. A 12-lead ECG diagnosis of STEMI required an ST-segment elevation of at least 1 mm at the J point in 1 or more leads excluding Lead aVR and ST-segment morphology in keeping with STEMI rather than differential diagnoses, such as early repolariza- tion or pericarditis.
Although automatic processing is possible, an indepen- dent technician manually processed all 80-lead BSM ECGs. Lead quality was rechecked, and those of unacceptable quality were substituted using a linear grid interpolation; if more than 6 leads were of poor quality, the map was disregarded. QRS onset, QRS offset, and T-wave offset “beat markers” were placed to facilitate the calculation of BSM variables. Printouts were obtained from the processed map of the 12-lead ECG (obtained from the BSM recording), an 80-lead ECG, and 4 color-contour maps displaying (i) the area under the QRS complex, (ii) the area under the ST-T segment (from J point to end of T wave),
(iii) the amount (isopotential) of ST elevation/depression at the J point, and (iv) the amount (isopotential) of ST elevation/depression at the J point + 60 milliseconds. Body surface map interpretation was in keeping with our previously published method [17]. For diagnosis of STEMI, of the 4 color maps, the map displaying the amount of ST elevation/depression at the J point is typically the most useful. A BSM-based diagnosis of STEMI required (a) an ST J-point elevation of at least 1 mm in 1 or more anterior electrodes or at least 0.5 mm in 1 or more posterior electrodes (a threshold of 0.5 mm for posterior electrodes has been previously validated [18] and (b) ST morphology (on the map based 12-lead or 80-lead ECG) suggestive of acute STEMI. Fig. 1 from a patient with acute chest pain shows only nonspecific 12-lead ECG changes but a corresponding color map of the ST elevation/depression at the J point with significant posterior ST elevation (with STEMI confirmed by biomarkers).
The standard 12-lead ECG data were presented to each individual panel member in random order and separate to the BSM-based data (12-lead from map, 80-lead ECG, and color maps) to enable blinded assessments of one method independent of the other. The diagnosis of STEMI on 12- lead ECG or BSM was reached by panel consensus.
Biomarker assessment
The decision to measure a single or multiple biomarkers, and the number and timing of those measurements, was made by the treating physicians. CK-MB and/or troponin were thus selected based on physician preference and usual standards of care at each of the participating hospitals. Upper reference ranges for CK-MB and troponin were set according to local hospital laboratory ranges. The study population consisted of patients who had CK-MB and/or troponin measured. Patients who had neither measured were excluded from analysis.
Statistical methods
Diagnoses obtained from BSMs and 12-lead ECGs were compared using the McNemar test for matched pairs with biomarker-confirmed STEMI as the gold standard. Results for STEMI-defined by elevated CK-MB, elevated tropo- nin, or the composite of elevated CK-MB or troponin- were calculated separately. Similar analyses were per- formed for any biomarker-confirmed AMI (STEMI or non- STEMI). Categorical demographic parameters, such as ethnicity and sex, were compared relative to the perfor- mance of the standard 12-lead ECG and BSM using the Fisher exact test. Continuous parameters were summarized using the arithmetic mean and SD. All reported probability values were 2-sided. Probability of less than .05 was considered significant.
The study protocol was reviewed and approved by the institutional review board of each participating hospital. Other than the BSM recording, the course of treatment was not altered in any substantive way for any patient.
Results
Six hundred forty-seven patients met the inclusion criteria and consented to participate. Table 1 contains a summary of patient demographics at the time of study enrollment.
Of the 647 patients, 58 were excluded from analysis because their clinicians chose not to send cardiac biomarkers. Because of changes in the American College of Cardiology definition of MI, which now includes acknowledgement of troponin as a key cardiac marker [19], results were analyzed and reported for MI diagnosed by CK-MB or troponin. The study population consisted of 589 patients who had CK-MB (n = 364) or troponin (n = 225) analyses obtained.
The 80-lead BSM ECG had significantly higher sensitiv- ity than standard 12-lead ECG in the detection of STEMI whether it was defined by elevated CK-MB (100% vs 72.7%, P = .031; n = 364) or troponin (92.9% vs 60.7%, P = .022;
n = 225) while retaining similar specificity (Table 2). The STEMIs detected by 80-lead BSM ECG but missed by the 12-lead ECG were most commonly posterior or inferopos- terior (4 of 6 CK-MB-defined MI, 8 of 11 troponin-defined MI). Right ventricular involvement complicating inferior STEMI was detected by the 80-lead BSM ECG in 2 (22%) of 9 patients with CK-MB-defined MI and in 2 (22%) of 9 patients with troponin-defined MI. An additional CK-MB- defined anterior STEMI, 2 troponin-defined anterior STE- MIs, 1 CKMB-defined inferior STEMI, and 1 troponin- defined inferior STEMI were detected by the 80-lead BSM ECG compared with the 12-lead ECG.
Because patients presenting with chest pain and ST- segment depression in V1 and V2 may have posterior STEMI or posterior extension of a concomitant inferior/lateral STEMI, we reanalyzed our study data to quantify the effect of adding ST-segment depression in V1 and V2 as part of the diagnostic 12-lead ECG strategy. On the 12-lead ECG, 4 patients had ST-segment depression of 1 mm or more in leads V1 and V2. Of these 4, only 2 had biomarker elevation (the others being false positives). Of the 2 with biomarker- positive ST-segment depression, only 1 had posterior ST- segment elevation on the associated map. On the body map,
16 patients had posterior ST-segment elevation. Of these, 13 had biomarker elevation (and 3 were false positive). Only 1 of the 13 patients with biomarker-positive posterior ST- segment elevation had ST-segment depression of 1 mm or more in leads V1 and V2 (a patient with inferolateral MI and posterior extension). Thus, use of ST-segment depression in V1 and V2 on the 12-lead ECG had suboptimal sensitivity for MI with posterior ST-segment elevation, whereas posterior ST-segment elevation on the map had improved positive predictive value for MI.
Subgroup analysis
Given the differing incidence of early repolarization and other normal variants that may occur between ethnic subgroups, analysis was performed with respect to ethnic origin. In all subgroups, trends were observed for improved sensitivity with the 80-lead BSM ECG compared with the 12-lead ECG for diagnosis of STEMI, while retaining similar specificity.
Discussion
The primary finding of this study is that the 80-lead BSM can improve the rate of detection of STEMI over the standard
Table 2 Sensitivity and specificity of 80-lead BSM ECG vs standard 12-lead ECG for detection of STEMI as defined by (a) elevated CK-MB, (b) elevated troponin, and (c) composite of elevated CK-MB or elevated troponin
(a) CK-MB (n = 364, STEMI = 22) (b) Troponin (n = 225, STEMI =28)
12-Lead ECG
80-Lead BSM ECG
P a
STEMI correctly detected (% sensitivity)
16 (72.7)
22 (100.0)
0.031
STEMI correctly excluded STEMI correctly detected STEMI correctly excluded (% sensitivity) (% sensitivity) (% sensitivity)
332 (97.1) 17 (60.7) 190 (96.4)
330 (96.5) 26 (92.9) 187 (94.9)
ns 0.022 ns
a Two-tailed exact significance (P) calculated using McNemar test.
12-lead ECG significantly. The 80-lead BSM ECG appears particularly useful in detecting STEMI in the inferoposterior region. The 80-lead BSM ECG sensitivity was consistently higher than that of 12-lead ECG in the detection of STEMI, regardless of the biomarker used to confirm the diagnosis, while retaining consistently high specificity (N90%)- equivalent to that of 12-lead ECG. Our results further confirm the inability of ST-segment depression in the standard Right precordial leads to allow accurate differentia- tion of STEMI involving the posterior wall from other causes of anterior ST-segment depression. In addition to the expected increased rate of detection of right ventricular and posterior involvement (as previously reported [17]), there was also an increased rate of detection of anterior STEMI. This may be attributable to a greater density of regional sampling resulting in increased accuracy in the interpretation of ST morphology.
The use of additional leads in an ECG is not a new idea. In 1978, Melendez and colleagues [15] reported that using 3 additional leads (V7-V9) improved the rate of detection of myocardial injury in patients with AMI and provided the only ECG evidence of MI in about 7% of cases. As noted, Zalenski and colleagues [20] showed that the addition of posterior (V7-V9) and right ventricular (V4R-V6R) leads improved sensitivity for AMI by 8.4% over 12-lead ECG but concluded that the additional leads only modestly improved overall accuracy of diagnosis. However, Menown and colleagues demonstrated that, even compared with an “extended” 12-lead ECG with additional right ventricular (V2R, V4R) and posterior chest leads (V7, V9), the 80-lead BSM significantly improved detection of acute ST-segment elevation in patients with inferior wall AMI and RV or posterior wall involvement [17]. The 80-lead BSM has been shown to improve AMI detection in patients presenting with chest pain with ST depression only on the 12-lead ECG [21], and in a study of 103 patients with non-STEMI (22), an 80-lead BSM ECG diagnostic algorithm significantly improved sensitivity, detecting 64% of non-STEMI com- pared with a 12-lead ECG diagnostic algorithm (32%) or the admitting physician‘s 12-lead ECG interpretation (42%).
In this study, the 80-lead BSM ECG specificity for detecting STEMI was not significantly different from that of 12-lead ECG, and thus, use of 80-lead BSM ECG should not result in a significant increase of false-positive diagnoses. These specificity results stand in contrast to the results reported by Zalenski et al [20], in which the reported 8.4% (P = .03) increase in sensitivity was offset by a 7.0% decrease in specificity (P = .06).
This study focused on patients with STEMI, primarily because the ST-elevation MIs are the most critical to diagnose early. Further research is required to determine the benefit from immediate management strategies such as antithrombotic/fibrinolytic therapies or percutaneous coron- ary intervention. Clearly, patients with complete occlusion of for example a large right or dominant left circumflex posterolateral branch would be expected to derive benefit
from a timely Reperfusion strategy, although demonstrating a mortality advantage, particularly in Contemporary practice, would likely require a study size of more than 20 000.
Diagnostic criteria for AMI without ST elevation on 12- lead ECG or BSM are less specific but are the subject of ongoing research. The largest difference between the 12-lead ECG and the 80-lead BSM ECG groups was seen in patients whose diagnosis was based on troponin. Because these infarcts tend to be smaller, this suggests that the 80-lead BSM ECG may be particularly useful, compared with the 12-lead ECG, for identifying patients with smaller but nevertheless prognostically significant infarctions.
The high percentage of enrollment of African American patients, a group often underrepresented in clinical studies, was of importance. Indeed, the potential value of the 80-lead BSM ECG in this subgroup, whose 12-lead ECG assessment is often complicated by coincidental early repolarization, merits additional study.
The 80-lead BSM ECG has also been shown to be a practical technology that can be performed rapidly by trainED technicians in the ED. In a study from Maine Medical Center, 24 consecutive ED patients underwent 12- lead ECG and 80-lead BSM ECG recordings performed by trained technicians [22]. Acquisition time was defined as the elapsed time from the beginning of patient preparation through obtaining a completed and saved 12- or 80-lead recording. The mean 12-lead ECG acquisition time was
3.1 minutes (95% confidence interval; range, 2.6-3.5 min)
vs 6.6 minutes (95% confidence interval; range, 6.1- 7.2 min) for BSM acquisition; 87% of BSMs were obtained in less than 8 minutes. The mean time to obtain a 12-lead plus a Right-sided ECG was 3.9 minutes (95% confidence interval; range, 3.6-4.3 min); 12-lead plus right-sided readings were performed by a research nurse with awareness of the investigational objective.
Limitations
All 12-lead ECG tracings were interpreted without BSM information. In contrast, as the 80-lead BSM ECG includes 3 limb leads, it enables assessment of a standard 12-lead ECG in addition to ECG tracings outside the conventional precordial leads. Thus, the 80-lead BSM ECG not only builds upon but also increases the diagnostic capabilities of the standard 12-lead ECG. This gives physicians the ability to view the additional information of the 80-lead data in light of the 12-lead results.
Although it would have been logical to compare the body map findings with the 12-lead ECG measured from the identical beat as part of the PRIME recording, the Food and Drug Administration procedures for evaluation of a new technology require comparison of the body map with an independent standard 12-lead ECG. Although the protocol required recording of the body map within 30 minutes of the 12-lead ECG, in most cases, the body map was obtained by the research technician or nurse immediately after the 12-
lead ECG. The data collectors were research personnel rather than caregivers, so they were not distracted by having to provide patient care between the 2 recordings. Fibrinolytic therapy, if indicated based on the standard 12 lead ECG, was encouraged as soon as possible. Typically the drug was initiated during or slightly before the PRIME recording. Thus, if ST-segment resolution occurred in some patients, this would have minimized the diagnostic ST-segment elevation features on the subsequent map.
Summary
The 80-lead BSM ECG has greater sensitivity for detecting STEMI than the 12-lead ECG, while retaining equivalent specificity. Inferoposterior MIs were the most common events missed by the 12-lead ECG but detected by the 80-lead BSM ECG.
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