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EASI-Derived vs standard 12-lead electrocardiogram for Selvester QRS score estimations of chronic myocardial infarct size, using cardiac magnetic resonance imaging as gold standard
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Journal of Electrocardiology 42 (2009) 145 – 151 www.jecgonline.com
EASI-Derived vs standard 12-lead electrocardiogram for Selvester QRS score estimations of chronic myocardial infarct size, using cardiac magnetic resonance imaging as gold standard☆ Annika E. Welinder, MD,a,⁎ Galen S. Wagner, MD, b B. Milan Horáček, PhD, c Thomas N. Martin, MD, d Charles Maynard, PhD, e Olle Pahlm, MD, PhD a a
Department of Clinical Physiology, University Hospital, Lund, Sweden b Duke University Medical Center, Durham, NC c Faculty of Medicine of Dalhousie University, Halifax, Nova Scotia, Canada d Department of Cardiology, Western Infirmary, Glasgow, Scotland, UK e Department of Health Services, University of Washington, Seattle, WA Received 4 September 2008
Abstract
Background: The size of myocardial infarction (MI) is of significance for the prognosis. Selvester scores might be valuable for this estimation. Objective: To compare the differences in Selvester scores for chronic MI provided from standard and EASI-derived 12-lead electrocardiograms (ECGs) and to compare these scores to the MI size measured by delayed-enhancement magnetic resonance imaging (DE-MRI). Methods: Thirty-seven patients were studied. In connection with their DE-MRI scan follow-up after chest pain, body surface potential mapping was performed. Standard and EASI 12-lead ECGs were constructed from the maps. Two investigators manually performed the measurements required for scoring with the Selvester system using a quad-plot format of the ECGs. One of the investigators repeated this once for the standard leads. Results: The differences between the 2 ECG estimations of MRI-measured MI size were not statistically significant. Neither the association nor the agreement between MRI and EASI-lead measurements or between MRI and standard-lead measurements were very strong. Conclusions: The differences between ECG and MRI measurements of MI size indicate that both methods may need improvement. © 2009 Elsevier Inc. All rights reserved.
Introduction In the Western world, coronary artery disease is a major cause of morbidity and mortality. The standard 12-lead electrocardiogram (ECG) remains an important diagnostic tool, although several different modalities in cardiology have been developed over the years. The immediate treatment of patients with chest pain on arrival to hospital depends to a large extent on the appearance of the ECG. To facilitate quantitative ECG measurements, a “quad-plot printing format,” which is a fourfold enlargement of the ECG,1 can ☆ This study was supported in part by the Region of Scania, Kristianstad, Sweden. ⁎ Corresponding author. Department of Clinical Physiology, Lund University Hospital, SE-221 85 Lund, Sweden. Tel.: +46 46 17 33 07; fax: +46 46 15 17 69. E-mail address: [email protected]
0022-0736/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2008.10.010
be constructed which allows the waveforms to be viewed more clearly and measured more precisely. When recording the 12-lead ECG, time is required to correctly position the 6 chest electrodes on the patient, and therefore electrodes are easily misplaced. The chest electrodes may interfere with other clinical procedures, and in many clinical situations it would therefore be very valuable to use an ECG-recording system with fewer electrodes on easily located places on the torso. This would make the ECG recording more rapid, and the risk of electrode misplacement as well as interference with other clinical procedures would be reduced. The 12-lead ECG derived from Dower's EASI orthogonal 3-lead system2 has been evaluated in adults and has been shown to have a high correlation with the standard 12-lead ECG, for example, for classification of arrhythmias,3-6 for detection of myocardial ischemia,3,4,7,8 and other cardiac
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abnormalities. It has also been shown that the EASI lead system is less susceptible to myoelectrical noise and at least as insensitive to baseline wander as the standard MasonLikar lead system during ECG monitoring.9 The Selvester QRS scoring system10 is a system for identifying and estimating myocardial infarct size from the standard 12-lead ECG, and it has been shown to correlate significantly with anatomically measured sizes of single MI in the anterior,11 inferior,12 and posterolateral13 thirds of the left ventricle. The estimations of infarct size in the Selvester scoring system are based on quantitative QRS changes in the standard 12-lead ECG. However, the scoring system correlates to a lesser degree with sizes of multiple MI of the left ventricle.14 The primary purpose of the present study was to compare the differences in Selvester scores for chronic myocardial infarction (MI) provided from EASI-derived vs standard 12-lead ECGs in patients who are in the chronic phase after their first episode of chest pain suggestive of acute coronary syndrome. The quad-plot display was used to facilitate the required quantitative measurements.1 The second purpose was to systematically compare the Selvester scores from the 12-lead systems to the cardiac magnetic resonance imaging (MRI)–measured MI size to determine their relative accuracies in estimating chronic MI size. Materials and methods Study population Forty patients enrolled in the Magnetic Resonance in Acute Coronary Syndromes study at the Glasgow Western Infirmary15 were eligible for inclusion in this substudy. The study complies with the Declaration of Helsinki. The Ethics Committee of the North Glasgow University Hospitals NHS Trust approved the protocol for the study, and all participants gave their written informed consent. The patients had been admitted to the Glasgow Western Infirmary with their first episode of chest pain suggestive of acute coronary syndrome and were returning for their 6- or 12-month MRI scan follow-up. In connection with this visit, body surface potential mapping (BSPM)16 was performed and this procedure provided the recording sites required for both the standard and EASI methods. The 37 patients meeting the following inclusion criteria formed the study group: 1. Admitted to the hospital with his/her first episode of chest pain, and returning for a 6- or 12-month followup. 2. No ECG confounding factors (bundle branch block, fascicular block, ventricular hypertrophy, or previous MI). 3. No exclusion criteria for MRI. Electrocardiogram acquisition method and presentation formats For each patient, BSPM was made with 120 electrodes placed in a standardized way on the front and back of the torso. 16 Details regarding data acquisition and signal
Fig. 1. Sites for the E, A, S, and I electrodes of the EASI lead system. A fifth ground electrode can be placed anywhere.
processing have been described elsewhere.17 The averaged PQRST waveforms from the standard 12-lead ECG leads and the EASI ECG leads were extracted from the BSPM data. Thus the standard 12-lead and the EASI ECGs were simultaneously acquired. The 4 electrode positions of the EASI lead system are shown in Fig. 1. Positions A, E, and I are those of the Frank vectorcardiographic system. E is placed on the lower extreme of the sternum. A and I are placed on the left and right midaxillary lines in the same transverse plane as E. S is placed on the sternal manubrium. Three bipolar, quasiorthogonal leads of the EASI lead system were generated by pairwise subtraction of signals recorded at the E, A, S, and I sites. Lead AI views the electrical activity of the heart in a left-to-right direction. Lead AS views the electrical activity of the heart both in left-toright and in caudal-cranial directions, but also contains a small anterior-posterior component. Lead ES views the electrical activity of the heart in a caudal-cranial direction and also contains a considerable anterior-posterior component. Optimal algebraic transfer coefficients have been determined for generating a derived 12-lead ECG from the ECG recorded at the EASI positions.18 Each lead of the derived 12-lead ECG was constructed by linear combination of AI, ES, and AS, for example, derived V2 = a ⁎ AI + b ⁎ ES + c ⁎ AS. The optimum transfer coefficients (a, b, c) have been calculated for each lead to minimize the aggregated root-mean-square (RMS)f difference between the standard and the EASI-derived 12lead ECGs. Root-mean-square differences were computed starting at the onset of the QRS complex and ending at the end of the T wave. The resulting RMS difference expressed the “goodness-of-fit”, that is, the similarity of the 2 sets of waveforms. The standard and the EASI-derived 12-lead ECGs were printed in a quad-plot format. 1 The quad-plot format magnifies the ECG waveforms fourfold (100 mm/s and
f
RMS denotes square root of the mean value of the squared differences.
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40 mm/mV compared to the conventional scale; 25 mm/s and 10 mm/mV), allowing the waveforms to be seen more clearly and thereby facilitating the quantitative measurements of the PQRST waveform durations and the amplitudes needed for QRS scoring. Fig. 2 shows an example of the quad-plot format in comparison to the conventional format for aVL, for both standard and EASI-derived 12-lead ECGs. The quad-plot format was used for all the ECG analysis.
each other and blinded to the MRI results. About 2 weeks later, one of the investigators performed the QRS scoring once again for the quad plots of all the standard 12-lead ECGs. This was done without having access to the first sets of scores. Differences in points between the 2 observers were assessed in conference for comparison with the MRI results.
The Selvester QRS scoring system, and the identification and quantification of myocardial infarct
The differences in Selvester scores provided from EASIderived vs standard 12-lead ECGs were compared to the intrareader variation in Selvester scores for the standard 12-lead ECGs. We also investigated whether differences in Selvester scores between the 12-lead systems particularly occurred in certain leads. Finally, the results from the 2 lead systems were systematically compared to the cardiac MRI results. Both the association and the agreement between the 2 lead systems and between the 2 lead systems and cardiac MRI were compared.
The Selvester QRS scoring system uses 50 criteria, generating a total of 31 points.14 The Q- and R-wave durations; the Q-, R-, and S-wave amplitudes; and the R/Qand R/S-amplitude ratios for 10 of the ECG leads (I, II, aVL, aVF, and V1-V6) were measured and checked against established thresholds. Each point has been designed to represent approximately 3% MI of the left ventricle. Two investigators manually performed the measurements of the QRS waveforms required for the QRS scoring with the Selvester system using the quad plots of the EASI-derived and the standard 12-lead ECGs for each patient. The observers performed the QRS scoring independently of
Comparison of standard and EASI-derived 12-lead ECGs
Cardiac MRI Cardiac MRI examination was carried out using a 1.5-T whole-body scanner (Siemens Sonata) using a phased-array chest coil as the receiver during breath-hold and gated to the ECG. For the measurement of left ventricular dimensions, a steady-state free-precession (SSFP) sequence was used to acquire a short-axis cinematographic (CINE) stack of the left ventricle (field of view, 340 mm; slice thickness, 8 mm; interslice gap, 2 mm; repetition time, 47.5 ms; echo time, 1.58 ms; flip angle, 60°). Immediately after this, delayed-enhancement magnetic resonance imaging (DE-MRI) was performed using the standard segmented gradient-echo inversion-recovery sequence as described elsewhere19,20 for the determination of location and size of MI. Briefly, gadolinium-DTPA-BMA (GE Healthcare, Waukesha, WI, USA), 0.2 mmol/kg, was administered intravenously, and delayed enhancement short axis images were acquired 10 to 20 minutes later (field of view, 340 mm; slice thickness, 8 mm; interslice gap, 2 mm; echo time, 4.3 ms; flip angle, 30°; optimum inversion time adjusted to null normal myocardium [range, 200-300 ms]). Identical short-axis slice positions were used for the CINE and the DE-MRI investigations. Measurement of the left ventricle mass was evaluated using manual planimetry on commercially available Argus software (Siemens, Erlangen, Germany) by an observer blinded to all other clinical data. The DE-MRI data were analyzed using CMR Tools (Imperial College, London, UK). Regions of MI by DE-MRI were defined as those with hyperenhancement involving at least the subendocardium. The signal intensities of gadolinium-enhanced myocardium and normal myocardium were measured with computer-assisted planimetry and delineated manually. Statistical methods
Fig. 2. Example of the quad-plot format in comparison with the conventional format for the standard 12-lead ECG and for the EASI-derived 12-lead ECG, respectively. The small complex illustrates the conventional format, 25 mm/s and 10 mm/mV, and the large complex illustrates the quad-plot format, 100 mm/s and 40 mm/mV.
The associations between MI size derived from the standard and EASI leads, from EASI leads and MRI, as well as from MRI and standard leads were assessed by calculating Spearman rank correlations, and the comparison of the
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Table 1 Difference in Selvester scores for EASI leads vs standard leads, and the intrareader variation in Selvester scores for standard leads, among the total number of patients Difference in Selvester scores
Number of patients
EASI leads vs standard leads Intrareader variation for standard leads
0
1
2
3
4
18 32
9 4
5 1
4 0
1 0
differences in MI size estimates by the 2 lead sets and each set separately in comparison with MRI-MI was evaluated using the Bland-Altman method.21 Within-individual differences between the various methods were compared with the Wilcoxon signed ranks test. Results Location of and differences in Selvester scores As shown in Table 1, the difference in Selvester scores between EASI leads and standard leads was larger than the intrareader variation in Selvester scores for standard leads. For 18 of the 37 patients, the Selvester scores from the EASI leads and the standard leads were equal; for 13, the score from the EASI leads was higher than from the standard leads; and for the remaining 6 patients, the score from the EASI leads was lower than from the standard leads. Fig. 3 illustrates that differences between the 12-lead systems occurred more frequently in the precordial than in the limb leads. Association and agreement between standard and EASI-derived 12-lead ECGs Fig. 4 illustrates a good (Spearman rank correlation coefficient, 0.82) association between measurements made
Fig. 3. Differences between scores in the 12-lead systems occurred more frequently in the precordial leads than in the limb leads.
Fig. 4. Good association (Spearman rank correlation coefficient, 0.82) regarding % MI between standard leads and EASI leads. The line is the identity line.
on recordings from the 2 lead systems, but also indicates that the EASI leads often gave higher Selvester scores and thereby estimated the MI size to a larger % of the left ventricle than the standard leads. We found that the mean absolute difference in % infarcted left ventricle between the standard leads and the EASI leads was 2.8 ± 3.5. However, the EASI leads may estimate a difference of 12 % more or 9 % less infarcted left ventricle compared to the standard leads, as illustrated in Fig. 5. Thus the agreement between the 2 lead systems may at times be less than satisfactory.
Fig. 5. Bland-Altman plot for standard leads vs EASI leads. The x axis represents the average % MI of the standard leads and the EASI leads. The broken line just below the x axis represents the mean difference in % MI between standard leads and EASI leads for all the patients, and the 2 outer broken lines represent 2 SDs from the mean difference. The y axis represents the difference in % MI between the standard leads and the EASI leads.
A.E. Welinder et al. / Journal of Electrocardiology 42 (2009) 145–151
Comparison of differences The difference between the intrareader variation in Selvester scores for the standard leads, and the difference between the EASI leads and the standard leads was not statistically significant (P .26). Association and agreement between MRI and the 2 lead systems Fig. 6A illustrates that the association between the EASI leads and MRI (Spearman rank correlation coefficient, 0.58) was moderate as was also the association between the standard leads and MRI (Spearman rank correlation coefficient, 0.60), which is illustrated in Fig. 6B. Fig. 6
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also shows that both the EASI-derived and the standard 12-lead ECGs often underestimated the % infarcted left ventricle in comparison to the cardiac MRI, and, furthermore, that the 2 lead systems in several cases both missed to detect MI and made false MI calls in comparison to the cardiac MRI. We found that the mean absolute difference in % infarcted left ventricle between MRI and the EASI leads was 6.3 ± 7.6, and that the EASI leads may estimate a difference of 27% more or 22% less infarcted left ventricle compared to MRI. The mean absolute difference in % infarcted left ventricle between MRI and the standard leads was 6.2 ± 7.3, and the standard leads might also estimate a large difference, 18% more or 28% less infarcted left ventricle, compared to MRI. Thus, the agreement between MRI and the EASI leads, and the agreement between MRI and the standard leads may differ significantly in individual cases. Comparison of differences The difference between the differences between MRI and EASI-derived 12-lead ECGs and the differences between MRI and standard 12-lead ECGs was not statistically significant (P .08).
Discussion
Fig. 6. A, Moderate (Spearman rank correlation coefficient, 0.58) association regarding % MI between MRI and EASI leads. The line is the identity line. B, Moderate (Spearman rank correlation coefficient, 0.60) association regarding % MI between MRI and standard leads. The line is the identity line.
The results of this study reveal that neither the association nor the agreement between MI size estimates by Selvester scores from either of the 2 lead systems and by MRI was very strong. The MRI is used in the clinic as gold standard for deciding whether myocardium is viable or not. However, today there is no consensus for how different parameters ought to be set for accurate MI visualization and sizing by cardiac MRI, with the consequence that differences in MI size between laboratories can be significant. This could perhaps, at least partly, be an explanation to the weak association and agreement between MI size estimates by Selvester scores from either of the 2 lead systems and by MRI. Furthermore, the results also indicate that there is room for improvement, as regards the Selvester QRS scoring system. The standard 12-lead ECG is the international standard in adults in resting situations, and is an important diagnostic tool in the acute situation, for the immediate treatment of patients with acute MI, but also for the selection of postinfarction therapy. In both situations, it is of great value to further improve the diagnostic capability of the ECG. The Selvester QRS scoring system which, in previous studies, has been shown to correlate significantly with anatomically measured sizes of single MI in the anterior,11 inferior,12 and posterolateral13 thirds of the left ventricle is one such aid that could be used for patients admitted with their first episode of chest pain suggestive for acute coronary syndrome. However, to make the Selvester QRS scoring system useful in the clinical practice it would be necessary to automate the system as it takes a lot of time to do the scoring manually. Another previous study has shown that when
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comparing the Selvester QRS scores measured manually from both standard format and quad-plot format of standard 12-lead ECGs, higher scores were often measured from the quad-plot format, thus indicating that a systematic underestimation of infarct size may occur when the Selvester QRS score is measured manually from a standard format.1 The design of this study gives a perspective of the differences in Selvester QRS scores between the quad-plot format of EASI-derived and standard 12-lead ECGs by relating the differences between the 2 lead systems to the intrareader variation in Selvester scores for standard 12-lead ECGs, and by relating the results from the 12-lead systems to the results from the cardiac MRI. The present study shows that the differences in Selvester scores between the EASI leads and the standard leads were larger than the intrareader variation in Selvester scores for the standard leads. This difference was, however, not statistically significant, which could be a consequence of the small size of the study population. Limitations When doing the Selvester scoring, the investigators had only access to the average complexes of the ECGs. Therefore, when there was a lot of noise in the ECGs, it was sometimes difficult to be sure of the location of the beginning of the QRS complex and to decide whether there was a Q wave or not. If the complete ECG signal had been available, it might have been simpler to make these decisions. The small size of the study population could be the reason why the difference between the intrareader variation in Selvester scores for standard 12-lead ECGs, and the differences between EASI-derived and standard 12-lead ECGs was not statistically significant. For 8 of the 37 patients, there was a time lag between the BSPM and the cardiac MRI scanning. For all those patients, the BSPM was made after the MRI scans. The reasons were either that the patient already had had the 12-month MRI scan before the collection of BSPM had started, or that the patient had had the 6-month MRI scan and did not want to go through another MRI scan but agreed to BSPM. Such patients could have experienced a new incident, which then perhaps will show on the ECGs but not on the MRI scan, or if the patient had a smaller MI it might not show on the ECGs but on the MRI scan. Only 1 of these patients had a smaller MI shown on the ECGs but not on the MRI scan. The time difference between the ECGs and the MRI scan for this patient was 39 days. For 1 of the patients, there was no discrepancy in the result between the ECGs and the MRI scan, and for the remaining 6 patients the ECGs showed smaller or no MI compared to the MRI scan. Several parameters, for example, contrast dose, time between injection of the contrast agent and image acquisition, the relative contrast and brightness used in the image display, and how the delineation of the region of hyperenhancement is done, etc, are of great importance for accurate MI visualization and sizing. Today, however, there is no international consensus for how these parameters ought
to be set,22 and, consequently, there could be large variations in MI size between different laboratories and clinics.
Conclusions The difference between the intrareader variation in Selvester scores for standard 12-lead ECGs and the differences between EASI-derived and standard 12-lead ECGs was not statistically significant, which indicates that the Selvester QRS scoring system could be of value for improving the diagnostic performance also from the EASIderived 12-lead ECG. Neither the association nor the agreement between MRI and EASI-derived or between MRI and standard 12-lead ECGs was very strong which suggests that the Selvester QRS scoring system needs to be further improved. References 1. Wagner GS, Greenfield Jr JC, Rembert JC, et al. Comparison of the Selvester QRS scoring system applied on standard versus highresolution electrocardiographic recordings. J Electrocardiol 2007;40: 288 [electronic publication 2007 Feb 5]. 2. Dower GE, Yakush A, Nazzal SB, Jutzy RV, Ruiz CE. Deriving the 12lead electrocardiogram from four (EASI) electrodes. J Electrocardiol 1988;21:S182. 3. Drew BJ, Pelter MM, Wung SF, Adams MG, Taylor C, Evans Jr T. Accuracy of the EASI 12-lead electrocardiogram compared to the standard 12-lead cardiogram for diagnosing multiple cardiac abnormalities. J Electrocardiol 1999;32(Suppl):1. 4. Klein MD, Key-Brothers I, Feldman CL. Can the vectorcardiographically derived EASI ECG be a suitable surrogate for the standard ECG in selected circumstances. Comput Cardiol 1997;24:721. 5. Denes P. The importance of derived 12-lead electrocardiography in the interpretation of arrhythmias detected by Holter monitoring. Am Heart J 1992;124:905. 6. Drew BJ, Scheinman MM, Evans Jr T. Comparison of a vectorcardiographically derived 12-lead electrocardiogram with the standard electrocardiogram during wide complex tachycardia and its potential application for continuous bedside monitoring. Am J Cardiol 1992;69: 612. 7. Drew BJ, Adams MG, Pelter MM, Wung SF, Caldwell MA. Comparison of standard and derived 12-lead electrocardiograms for diagnosis of coronary angioplasty-induced myocardial ischemia. Am J Cardiol 1997;78:639. 8. Feldman CL, MacCallum G, Hartley LH. Comparison of the standard ECG with the EASI cardiogram for ischemia detection during exercise monitoring. Comput Cardiol 1997;24:343. 9. Welinder A, Sörnmo L, Feild DQ, et al. Comparison of signal quality between EASI and Mason-Likar 12-lead electrocardiograms during physical activity. Am J Crit Care 2004;13:228. 10. Selvester RH, Wagner GS, Hindman NB. The Selvester QRS scoring system for estimating myocardial infarct size. The development and application of the system. Arch Intern Med 1985;145:1877. 11. Ideker RE, Wagner GS, Ruth WK, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size: II. Correlation with quantitative anatomic findings for anterior infarcts. Am J Cardiol 1982; 49:1604. 12. Roark SF, Ideker RE, Wagner GS, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size: III. Correlation with quantitative anatomic findings for inferior infarcts. Am J Cardiol 1983; 51:382. 13. Ward RM, White RD, Ideker RE, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size: IV. Correlation with quantitative anatomic findings for posterolateral infarcts. Am J Cardiol 1984;53:706.
A.E. Welinder et al. / Journal of Electrocardiology 42 (2009) 145–151 14. Sevilla DC, Wagner NB, Pegues R, et al. Correlation of the complete version of the Selvester QRS scoring system with quantitative anatomic findings for multiple left ventricular myocardial infarcts. Am J Cardiol 1992;69:465. 15. Martin TN, Groenning BA, Murray HM, et al. ST-Segment deviation analysis of the admission 12-lead electrocardiogram as an aid to early diagnosis of acute myocardial infarction with a cardiac magnetic resonance imaging gold standard. J Am Coll Cardiol 2007;50:1021. 16. Horáček BM, Warren JW, Penney CJ, et al. Optimal electrocardiographic leads for detecting acute myocardial ischemia. J Electrocardiol 2001;34(Suppl):97. 17. Horáček BM, Warren JW, Albano A, et al. Development of an automated Selvester Scoring System for estimating the size of myocardial infarction from the electrocardiogram. J Electrocardiol 2006;39:162.
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18. Feild DQ, Feldman CL, Horáček BM. Improved EASI coefficients: their derivation, values, and performance. J Electrocardiol 2002;35 (Suppl):23. 19. Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000;343:1445. 20. Simonetti OP, Kim RJ, Fieno DS, et al. An improved MR imaging technique for the visualization of myocardial infarction. Radiology 2001;218:215. 21. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307. 22. Engblom H, Arheden H, Foster JE, Martin TN. Myocardial infarct quantification: Is magnetic resonance imaging ready to serve as gold standard for electrocardiology? J Electrocardiol 2007;40:243 [review].
Journal of Electrocardiology 42 (2009) 145 – 151 www.jecgonline.com
EASI-Derived vs standard 12-lead electrocardiogram for Selvester QRS score estimations of chronic myocardial infarct size, using cardiac magnetic resonance imaging as gold standard☆ Annika E. Welinder, MD,a,⁎ Galen S. Wagner, MD, b B. Milan Horáček, PhD, c Thomas N. Martin, MD, d Charles Maynard, PhD, e Olle Pahlm, MD, PhD a a
Department of Clinical Physiology, University Hospital, Lund, Sweden b Duke University Medical Center, Durham, NC c Faculty of Medicine of Dalhousie University, Halifax, Nova Scotia, Canada d Department of Cardiology, Western Infirmary, Glasgow, Scotland, UK e Department of Health Services, University of Washington, Seattle, WA Received 4 September 2008
Abstract
Background: The size of myocardial infarction (MI) is of significance for the prognosis. Selvester scores might be valuable for this estimation. Objective: To compare the differences in Selvester scores for chronic MI provided from standard and EASI-derived 12-lead electrocardiograms (ECGs) and to compare these scores to the MI size measured by delayed-enhancement magnetic resonance imaging (DE-MRI). Methods: Thirty-seven patients were studied. In connection with their DE-MRI scan follow-up after chest pain, body surface potential mapping was performed. Standard and EASI 12-lead ECGs were constructed from the maps. Two investigators manually performed the measurements required for scoring with the Selvester system using a quad-plot format of the ECGs. One of the investigators repeated this once for the standard leads. Results: The differences between the 2 ECG estimations of MRI-measured MI size were not statistically significant. Neither the association nor the agreement between MRI and EASI-lead measurements or between MRI and standard-lead measurements were very strong. Conclusions: The differences between ECG and MRI measurements of MI size indicate that both methods may need improvement. © 2009 Elsevier Inc. All rights reserved.
Introduction In the Western world, coronary artery disease is a major cause of morbidity and mortality. The standard 12-lead electrocardiogram (ECG) remains an important diagnostic tool, although several different modalities in cardiology have been developed over the years. The immediate treatment of patients with chest pain on arrival to hospital depends to a large extent on the appearance of the ECG. To facilitate quantitative ECG measurements, a “quad-plot printing format,” which is a fourfold enlargement of the ECG,1 can ☆ This study was supported in part by the Region of Scania, Kristianstad, Sweden. ⁎ Corresponding author. Department of Clinical Physiology, Lund University Hospital, SE-221 85 Lund, Sweden. Tel.: +46 46 17 33 07; fax: +46 46 15 17 69. E-mail address: [email protected]
0022-0736/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2008.10.010
be constructed which allows the waveforms to be viewed more clearly and measured more precisely. When recording the 12-lead ECG, time is required to correctly position the 6 chest electrodes on the patient, and therefore electrodes are easily misplaced. The chest electrodes may interfere with other clinical procedures, and in many clinical situations it would therefore be very valuable to use an ECG-recording system with fewer electrodes on easily located places on the torso. This would make the ECG recording more rapid, and the risk of electrode misplacement as well as interference with other clinical procedures would be reduced. The 12-lead ECG derived from Dower's EASI orthogonal 3-lead system2 has been evaluated in adults and has been shown to have a high correlation with the standard 12-lead ECG, for example, for classification of arrhythmias,3-6 for detection of myocardial ischemia,3,4,7,8 and other cardiac
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A.E. Welinder et al. / Journal of Electrocardiology 42 (2009) 145–151 3
abnormalities. It has also been shown that the EASI lead system is less susceptible to myoelectrical noise and at least as insensitive to baseline wander as the standard MasonLikar lead system during ECG monitoring.9 The Selvester QRS scoring system10 is a system for identifying and estimating myocardial infarct size from the standard 12-lead ECG, and it has been shown to correlate significantly with anatomically measured sizes of single MI in the anterior,11 inferior,12 and posterolateral13 thirds of the left ventricle. The estimations of infarct size in the Selvester scoring system are based on quantitative QRS changes in the standard 12-lead ECG. However, the scoring system correlates to a lesser degree with sizes of multiple MI of the left ventricle.14 The primary purpose of the present study was to compare the differences in Selvester scores for chronic myocardial infarction (MI) provided from EASI-derived vs standard 12-lead ECGs in patients who are in the chronic phase after their first episode of chest pain suggestive of acute coronary syndrome. The quad-plot display was used to facilitate the required quantitative measurements.1 The second purpose was to systematically compare the Selvester scores from the 12-lead systems to the cardiac magnetic resonance imaging (MRI)–measured MI size to determine their relative accuracies in estimating chronic MI size. Materials and methods Study population Forty patients enrolled in the Magnetic Resonance in Acute Coronary Syndromes study at the Glasgow Western Infirmary15 were eligible for inclusion in this substudy. The study complies with the Declaration of Helsinki. The Ethics Committee of the North Glasgow University Hospitals NHS Trust approved the protocol for the study, and all participants gave their written informed consent. The patients had been admitted to the Glasgow Western Infirmary with their first episode of chest pain suggestive of acute coronary syndrome and were returning for their 6- or 12-month MRI scan follow-up. In connection with this visit, body surface potential mapping (BSPM)16 was performed and this procedure provided the recording sites required for both the standard and EASI methods. The 37 patients meeting the following inclusion criteria formed the study group: 1. Admitted to the hospital with his/her first episode of chest pain, and returning for a 6- or 12-month followup. 2. No ECG confounding factors (bundle branch block, fascicular block, ventricular hypertrophy, or previous MI). 3. No exclusion criteria for MRI. Electrocardiogram acquisition method and presentation formats For each patient, BSPM was made with 120 electrodes placed in a standardized way on the front and back of the torso. 16 Details regarding data acquisition and signal
Fig. 1. Sites for the E, A, S, and I electrodes of the EASI lead system. A fifth ground electrode can be placed anywhere.
processing have been described elsewhere.17 The averaged PQRST waveforms from the standard 12-lead ECG leads and the EASI ECG leads were extracted from the BSPM data. Thus the standard 12-lead and the EASI ECGs were simultaneously acquired. The 4 electrode positions of the EASI lead system are shown in Fig. 1. Positions A, E, and I are those of the Frank vectorcardiographic system. E is placed on the lower extreme of the sternum. A and I are placed on the left and right midaxillary lines in the same transverse plane as E. S is placed on the sternal manubrium. Three bipolar, quasiorthogonal leads of the EASI lead system were generated by pairwise subtraction of signals recorded at the E, A, S, and I sites. Lead AI views the electrical activity of the heart in a left-to-right direction. Lead AS views the electrical activity of the heart both in left-toright and in caudal-cranial directions, but also contains a small anterior-posterior component. Lead ES views the electrical activity of the heart in a caudal-cranial direction and also contains a considerable anterior-posterior component. Optimal algebraic transfer coefficients have been determined for generating a derived 12-lead ECG from the ECG recorded at the EASI positions.18 Each lead of the derived 12-lead ECG was constructed by linear combination of AI, ES, and AS, for example, derived V2 = a ⁎ AI + b ⁎ ES + c ⁎ AS. The optimum transfer coefficients (a, b, c) have been calculated for each lead to minimize the aggregated root-mean-square (RMS)f difference between the standard and the EASI-derived 12lead ECGs. Root-mean-square differences were computed starting at the onset of the QRS complex and ending at the end of the T wave. The resulting RMS difference expressed the “goodness-of-fit”, that is, the similarity of the 2 sets of waveforms. The standard and the EASI-derived 12-lead ECGs were printed in a quad-plot format. 1 The quad-plot format magnifies the ECG waveforms fourfold (100 mm/s and
f
RMS denotes square root of the mean value of the squared differences.
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40 mm/mV compared to the conventional scale; 25 mm/s and 10 mm/mV), allowing the waveforms to be seen more clearly and thereby facilitating the quantitative measurements of the PQRST waveform durations and the amplitudes needed for QRS scoring. Fig. 2 shows an example of the quad-plot format in comparison to the conventional format for aVL, for both standard and EASI-derived 12-lead ECGs. The quad-plot format was used for all the ECG analysis.
each other and blinded to the MRI results. About 2 weeks later, one of the investigators performed the QRS scoring once again for the quad plots of all the standard 12-lead ECGs. This was done without having access to the first sets of scores. Differences in points between the 2 observers were assessed in conference for comparison with the MRI results.
The Selvester QRS scoring system, and the identification and quantification of myocardial infarct
The differences in Selvester scores provided from EASIderived vs standard 12-lead ECGs were compared to the intrareader variation in Selvester scores for the standard 12-lead ECGs. We also investigated whether differences in Selvester scores between the 12-lead systems particularly occurred in certain leads. Finally, the results from the 2 lead systems were systematically compared to the cardiac MRI results. Both the association and the agreement between the 2 lead systems and between the 2 lead systems and cardiac MRI were compared.
The Selvester QRS scoring system uses 50 criteria, generating a total of 31 points.14 The Q- and R-wave durations; the Q-, R-, and S-wave amplitudes; and the R/Qand R/S-amplitude ratios for 10 of the ECG leads (I, II, aVL, aVF, and V1-V6) were measured and checked against established thresholds. Each point has been designed to represent approximately 3% MI of the left ventricle. Two investigators manually performed the measurements of the QRS waveforms required for the QRS scoring with the Selvester system using the quad plots of the EASI-derived and the standard 12-lead ECGs for each patient. The observers performed the QRS scoring independently of
Comparison of standard and EASI-derived 12-lead ECGs
Cardiac MRI Cardiac MRI examination was carried out using a 1.5-T whole-body scanner (Siemens Sonata) using a phased-array chest coil as the receiver during breath-hold and gated to the ECG. For the measurement of left ventricular dimensions, a steady-state free-precession (SSFP) sequence was used to acquire a short-axis cinematographic (CINE) stack of the left ventricle (field of view, 340 mm; slice thickness, 8 mm; interslice gap, 2 mm; repetition time, 47.5 ms; echo time, 1.58 ms; flip angle, 60°). Immediately after this, delayed-enhancement magnetic resonance imaging (DE-MRI) was performed using the standard segmented gradient-echo inversion-recovery sequence as described elsewhere19,20 for the determination of location and size of MI. Briefly, gadolinium-DTPA-BMA (GE Healthcare, Waukesha, WI, USA), 0.2 mmol/kg, was administered intravenously, and delayed enhancement short axis images were acquired 10 to 20 minutes later (field of view, 340 mm; slice thickness, 8 mm; interslice gap, 2 mm; echo time, 4.3 ms; flip angle, 30°; optimum inversion time adjusted to null normal myocardium [range, 200-300 ms]). Identical short-axis slice positions were used for the CINE and the DE-MRI investigations. Measurement of the left ventricle mass was evaluated using manual planimetry on commercially available Argus software (Siemens, Erlangen, Germany) by an observer blinded to all other clinical data. The DE-MRI data were analyzed using CMR Tools (Imperial College, London, UK). Regions of MI by DE-MRI were defined as those with hyperenhancement involving at least the subendocardium. The signal intensities of gadolinium-enhanced myocardium and normal myocardium were measured with computer-assisted planimetry and delineated manually. Statistical methods
Fig. 2. Example of the quad-plot format in comparison with the conventional format for the standard 12-lead ECG and for the EASI-derived 12-lead ECG, respectively. The small complex illustrates the conventional format, 25 mm/s and 10 mm/mV, and the large complex illustrates the quad-plot format, 100 mm/s and 40 mm/mV.
The associations between MI size derived from the standard and EASI leads, from EASI leads and MRI, as well as from MRI and standard leads were assessed by calculating Spearman rank correlations, and the comparison of the
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Table 1 Difference in Selvester scores for EASI leads vs standard leads, and the intrareader variation in Selvester scores for standard leads, among the total number of patients Difference in Selvester scores
Number of patients
EASI leads vs standard leads Intrareader variation for standard leads
0
1
2
3
4
18 32
9 4
5 1
4 0
1 0
differences in MI size estimates by the 2 lead sets and each set separately in comparison with MRI-MI was evaluated using the Bland-Altman method.21 Within-individual differences between the various methods were compared with the Wilcoxon signed ranks test. Results Location of and differences in Selvester scores As shown in Table 1, the difference in Selvester scores between EASI leads and standard leads was larger than the intrareader variation in Selvester scores for standard leads. For 18 of the 37 patients, the Selvester scores from the EASI leads and the standard leads were equal; for 13, the score from the EASI leads was higher than from the standard leads; and for the remaining 6 patients, the score from the EASI leads was lower than from the standard leads. Fig. 3 illustrates that differences between the 12-lead systems occurred more frequently in the precordial than in the limb leads. Association and agreement between standard and EASI-derived 12-lead ECGs Fig. 4 illustrates a good (Spearman rank correlation coefficient, 0.82) association between measurements made
Fig. 3. Differences between scores in the 12-lead systems occurred more frequently in the precordial leads than in the limb leads.
Fig. 4. Good association (Spearman rank correlation coefficient, 0.82) regarding % MI between standard leads and EASI leads. The line is the identity line.
on recordings from the 2 lead systems, but also indicates that the EASI leads often gave higher Selvester scores and thereby estimated the MI size to a larger % of the left ventricle than the standard leads. We found that the mean absolute difference in % infarcted left ventricle between the standard leads and the EASI leads was 2.8 ± 3.5. However, the EASI leads may estimate a difference of 12 % more or 9 % less infarcted left ventricle compared to the standard leads, as illustrated in Fig. 5. Thus the agreement between the 2 lead systems may at times be less than satisfactory.
Fig. 5. Bland-Altman plot for standard leads vs EASI leads. The x axis represents the average % MI of the standard leads and the EASI leads. The broken line just below the x axis represents the mean difference in % MI between standard leads and EASI leads for all the patients, and the 2 outer broken lines represent 2 SDs from the mean difference. The y axis represents the difference in % MI between the standard leads and the EASI leads.
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Comparison of differences The difference between the intrareader variation in Selvester scores for the standard leads, and the difference between the EASI leads and the standard leads was not statistically significant (P .26). Association and agreement between MRI and the 2 lead systems Fig. 6A illustrates that the association between the EASI leads and MRI (Spearman rank correlation coefficient, 0.58) was moderate as was also the association between the standard leads and MRI (Spearman rank correlation coefficient, 0.60), which is illustrated in Fig. 6B. Fig. 6
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also shows that both the EASI-derived and the standard 12-lead ECGs often underestimated the % infarcted left ventricle in comparison to the cardiac MRI, and, furthermore, that the 2 lead systems in several cases both missed to detect MI and made false MI calls in comparison to the cardiac MRI. We found that the mean absolute difference in % infarcted left ventricle between MRI and the EASI leads was 6.3 ± 7.6, and that the EASI leads may estimate a difference of 27% more or 22% less infarcted left ventricle compared to MRI. The mean absolute difference in % infarcted left ventricle between MRI and the standard leads was 6.2 ± 7.3, and the standard leads might also estimate a large difference, 18% more or 28% less infarcted left ventricle, compared to MRI. Thus, the agreement between MRI and the EASI leads, and the agreement between MRI and the standard leads may differ significantly in individual cases. Comparison of differences The difference between the differences between MRI and EASI-derived 12-lead ECGs and the differences between MRI and standard 12-lead ECGs was not statistically significant (P .08).
Discussion
Fig. 6. A, Moderate (Spearman rank correlation coefficient, 0.58) association regarding % MI between MRI and EASI leads. The line is the identity line. B, Moderate (Spearman rank correlation coefficient, 0.60) association regarding % MI between MRI and standard leads. The line is the identity line.
The results of this study reveal that neither the association nor the agreement between MI size estimates by Selvester scores from either of the 2 lead systems and by MRI was very strong. The MRI is used in the clinic as gold standard for deciding whether myocardium is viable or not. However, today there is no consensus for how different parameters ought to be set for accurate MI visualization and sizing by cardiac MRI, with the consequence that differences in MI size between laboratories can be significant. This could perhaps, at least partly, be an explanation to the weak association and agreement between MI size estimates by Selvester scores from either of the 2 lead systems and by MRI. Furthermore, the results also indicate that there is room for improvement, as regards the Selvester QRS scoring system. The standard 12-lead ECG is the international standard in adults in resting situations, and is an important diagnostic tool in the acute situation, for the immediate treatment of patients with acute MI, but also for the selection of postinfarction therapy. In both situations, it is of great value to further improve the diagnostic capability of the ECG. The Selvester QRS scoring system which, in previous studies, has been shown to correlate significantly with anatomically measured sizes of single MI in the anterior,11 inferior,12 and posterolateral13 thirds of the left ventricle is one such aid that could be used for patients admitted with their first episode of chest pain suggestive for acute coronary syndrome. However, to make the Selvester QRS scoring system useful in the clinical practice it would be necessary to automate the system as it takes a lot of time to do the scoring manually. Another previous study has shown that when
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comparing the Selvester QRS scores measured manually from both standard format and quad-plot format of standard 12-lead ECGs, higher scores were often measured from the quad-plot format, thus indicating that a systematic underestimation of infarct size may occur when the Selvester QRS score is measured manually from a standard format.1 The design of this study gives a perspective of the differences in Selvester QRS scores between the quad-plot format of EASI-derived and standard 12-lead ECGs by relating the differences between the 2 lead systems to the intrareader variation in Selvester scores for standard 12-lead ECGs, and by relating the results from the 12-lead systems to the results from the cardiac MRI. The present study shows that the differences in Selvester scores between the EASI leads and the standard leads were larger than the intrareader variation in Selvester scores for the standard leads. This difference was, however, not statistically significant, which could be a consequence of the small size of the study population. Limitations When doing the Selvester scoring, the investigators had only access to the average complexes of the ECGs. Therefore, when there was a lot of noise in the ECGs, it was sometimes difficult to be sure of the location of the beginning of the QRS complex and to decide whether there was a Q wave or not. If the complete ECG signal had been available, it might have been simpler to make these decisions. The small size of the study population could be the reason why the difference between the intrareader variation in Selvester scores for standard 12-lead ECGs, and the differences between EASI-derived and standard 12-lead ECGs was not statistically significant. For 8 of the 37 patients, there was a time lag between the BSPM and the cardiac MRI scanning. For all those patients, the BSPM was made after the MRI scans. The reasons were either that the patient already had had the 12-month MRI scan before the collection of BSPM had started, or that the patient had had the 6-month MRI scan and did not want to go through another MRI scan but agreed to BSPM. Such patients could have experienced a new incident, which then perhaps will show on the ECGs but not on the MRI scan, or if the patient had a smaller MI it might not show on the ECGs but on the MRI scan. Only 1 of these patients had a smaller MI shown on the ECGs but not on the MRI scan. The time difference between the ECGs and the MRI scan for this patient was 39 days. For 1 of the patients, there was no discrepancy in the result between the ECGs and the MRI scan, and for the remaining 6 patients the ECGs showed smaller or no MI compared to the MRI scan. Several parameters, for example, contrast dose, time between injection of the contrast agent and image acquisition, the relative contrast and brightness used in the image display, and how the delineation of the region of hyperenhancement is done, etc, are of great importance for accurate MI visualization and sizing. Today, however, there is no international consensus for how these parameters ought
to be set,22 and, consequently, there could be large variations in MI size between different laboratories and clinics.
Conclusions The difference between the intrareader variation in Selvester scores for standard 12-lead ECGs and the differences between EASI-derived and standard 12-lead ECGs was not statistically significant, which indicates that the Selvester QRS scoring system could be of value for improving the diagnostic performance also from the EASIderived 12-lead ECG. Neither the association nor the agreement between MRI and EASI-derived or between MRI and standard 12-lead ECGs was very strong which suggests that the Selvester QRS scoring system needs to be further improved. References 1. Wagner GS, Greenfield Jr JC, Rembert JC, et al. Comparison of the Selvester QRS scoring system applied on standard versus highresolution electrocardiographic recordings. J Electrocardiol 2007;40: 288 [electronic publication 2007 Feb 5]. 2. Dower GE, Yakush A, Nazzal SB, Jutzy RV, Ruiz CE. Deriving the 12lead electrocardiogram from four (EASI) electrodes. J Electrocardiol 1988;21:S182. 3. Drew BJ, Pelter MM, Wung SF, Adams MG, Taylor C, Evans Jr T. Accuracy of the EASI 12-lead electrocardiogram compared to the standard 12-lead cardiogram for diagnosing multiple cardiac abnormalities. J Electrocardiol 1999;32(Suppl):1. 4. Klein MD, Key-Brothers I, Feldman CL. Can the vectorcardiographically derived EASI ECG be a suitable surrogate for the standard ECG in selected circumstances. Comput Cardiol 1997;24:721. 5. Denes P. The importance of derived 12-lead electrocardiography in the interpretation of arrhythmias detected by Holter monitoring. Am Heart J 1992;124:905. 6. Drew BJ, Scheinman MM, Evans Jr T. Comparison of a vectorcardiographically derived 12-lead electrocardiogram with the standard electrocardiogram during wide complex tachycardia and its potential application for continuous bedside monitoring. Am J Cardiol 1992;69: 612. 7. Drew BJ, Adams MG, Pelter MM, Wung SF, Caldwell MA. Comparison of standard and derived 12-lead electrocardiograms for diagnosis of coronary angioplasty-induced myocardial ischemia. Am J Cardiol 1997;78:639. 8. Feldman CL, MacCallum G, Hartley LH. Comparison of the standard ECG with the EASI cardiogram for ischemia detection during exercise monitoring. Comput Cardiol 1997;24:343. 9. Welinder A, Sörnmo L, Feild DQ, et al. Comparison of signal quality between EASI and Mason-Likar 12-lead electrocardiograms during physical activity. Am J Crit Care 2004;13:228. 10. Selvester RH, Wagner GS, Hindman NB. The Selvester QRS scoring system for estimating myocardial infarct size. The development and application of the system. Arch Intern Med 1985;145:1877. 11. Ideker RE, Wagner GS, Ruth WK, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size: II. Correlation with quantitative anatomic findings for anterior infarcts. Am J Cardiol 1982; 49:1604. 12. Roark SF, Ideker RE, Wagner GS, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size: III. Correlation with quantitative anatomic findings for inferior infarcts. Am J Cardiol 1983; 51:382. 13. Ward RM, White RD, Ideker RE, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size: IV. Correlation with quantitative anatomic findings for posterolateral infarcts. Am J Cardiol 1984;53:706.
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