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ST-segment depression in lead aVR predicts predischarge left ventricular dysfunction in patients with reperfused anterior acute myocardial infarction with anterolateral ST-segment elevation
ST-segment depression in lead aVR predicts predischarge left ventricular dysfunction in patients with reperfused anterior acute myocardial infarction with anterolateral ST-segment elevation Masami Kosuge, MD, Kazuo Kimura, MD, Toshiyuki Ishikawa, MD, Tsutomu Endo, MD, Yoichiro Hongo, MD, Tomohiko Shigemasa, MD, Yuji Iwasawa, MD, Osamu Tochikubo, MD, and Satoshi Umemura, MD Yokohama, Japan
Background Patients with an anterolateral acute myocardial infarction (AMI) have a worse prognosis, and those with additional inferolateral wall involvement might be higher risk because of more extensive area at risk. Lead –aVR obtained by inversion of images in lead aVR has been reported to provide useful information for inferolateral lesion.
Methods We examined the relation between ST-segment deviation in lead aVR on admission electrocardiogram (ECG) and left ventricular function in 105 patients with an anterolateral AMI undergoing successful reperfusion ≤6 hours after onset. Patients were classified according to ST-segment deviation in lead aVR on admission ECG: group A, 23 patients with ST elevation of ≥0.5 mm; group B, 47 patients without ST deviation; and group C, 35 patients with ST depression of ≥0.5 mm.
Results There were no differences among the 3 groups in age, sex, or site of the culprit lesion. In groups A, B, and C, the peak creatine kinase level was 3661 ± 1428, 4440 ± 1889, and 6959 ± 2712 mU/mL, and the left ventricular ejection fraction (LVEF) measured by predischarge left ventriculography was 54% ± 9%, 48% ± 7%, and 37% ± 9%, respectively (P < .01). During hospitalization, congestive heart failure occurred more frequently in group C than in groups A or B (P < .05). ST-segment depression in lead aVR had a higher predictive accuracy than other ECG findings in identifying patients with predischarge LVEF ≤35%.
Conclusions We conclude that in patients with an anterolateral AMI, ST-segment depression in lead aVR on admission ECG is useful for predicting larger infarct and left ventricular dysfunction despite successful reperfusion. (Am Heart J 2001; 142:51-7.)
Anterior acute myocardial infarction (AMI) has been reported to be high risk,1 and especially those with ST-segment elevation in leads I and aVL are associated with a larger infarction size and a poorer short-term outcome, probably because of extensive area at risk with anterolateral wall involvement.2,3 We postulated that patients with an anterolateral AMI with additional inferolateral wall involvement, which is a part of territory supplied by large left anterior descending coronary artery (LAD), might be higher risk because of more extensive area at risk. However, it is difficult to assess the extent of area at risk to inferolateral wall in anterior AMI on a conventional 12-lead electrocardio-
gram (ECG). Recently, Menown and Adgey4 reported that lead –aVR (30 degrees) obtained by inversion of images in lead aVR (–150) provided useful information for inferolateral lesion unavailable by conventional 12lead ECG.4 Therefore the use of lead aVR might permit a more accurate estimation of the extent of area at risk in AMI. The aim of the current study was to investigate whether ST-segment deviation in lead aVR identifies a higher-risk group of patients with an anterolateral AMI.
From the Department of Cardiology, Yokohama City University Medical Center, Yokohama, Japan. Submitted December 7, 2000; accepted March 28, 2001. Reprint requests: Kazuo Kimura, MD, Department of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/116073 doi:10.1067/mhj.2001.116073
Between December 1990 and May 1999, 105 patients (91 men and 14 women, mean age 58 years, range 29 to 81 years) with AMI who fulfilled the following criteria were admitted to our coronary care unit within 6 hours from symptom onset: (1) typical chest pain lasting for at least 30 minutes, (2) STsegment elevation of ≥2.0 mm in >2 contiguous precordial leads as well as ST-segment elevation of ≥1.0 mm in leads I, aVL, or both, (3) a subsequent increase in serum creatine kinase levels to more than twice the upper limit of normal, (4)
Methods Patients
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no history or electrocardiographic evidence of a previous myocardial infarction, (5) no electrocardiographic evidence of left ventricular hypertrophy or bundle branch block, (6) no findings of primary valvular or myocardial disease, (7) successful reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade5 3 flow) of the LAD lesion as confirmed by coronary angiography within 6 hours from symptom onset, and (8) a patent LAD as confirmed by coronary angiography at discharge.
Coronary angiography Coronary angiography was performed with the use of the Judkins technique immediately after admission and a mean of 14 days after AMI. The culprit lesion in the LAD was defined as the site with total occlusion or most severe stenosis or an eccentric lesion with a narrow neck or irregular border. The grade of collateral filling in the LAD was classified according to the criteria of Rentrop et al.6 Good collateral filling was defined as grade 2 or 3. Reperfusion was defined as TIMI grade 3 flow and was established spontaneously in 5 patients, by thrombolysis in 35 patients, and by primary or rescue coronary angioplasty in 65 patients. The allocation of reperfusion therapy was left to the physician’s discretion. Stenosis was considered significant if the lumen diameter was narrowed by ≥75% in any projection.
Electrocardiographic analysis On admission, a 12-lead ECG was recorded at a paper speed of 25 mm per second and an amplification of 10 mm/mV. The isoelectric line was defined as the level of the preceding TP segment. The degree of ST-segment deviation was measured to the nearest 0.5 mm, 20 milliseconds after the end of the QRS complex from each of the 12 standard leads. Measurements of 3 contiguous beats obtained by 2 independent observers blinded to all clinical and angiographic data were averaged for each lead. ST-segment deviation was considered clinically significant if it was ≥0.5 mm above the isoelectric line.
Left ventriculography Left ventricular function was evaluated on right anterior oblique views of left ventriculograms obtained a mean of 14 days after AMI. Left ventricular end-diastolic volume index, end-systolic volume index, and left ventricular ejection fraction (LVEF) were determined by the area length method described by Sandler and Dodge.7 Regional wall motion in the territory of the LAD was assessed by the centerline method8 and expressed as SD/chord.
Cardiac enzyme study Blood samples were obtained on admission and at 3-hour intervals during the first 24 hours, at 6-hour intervals for the next 2 days, and then daily until discharge. Serum creatine kinase activity was measured by the method of Rosalki.9
Statistical analysis Mean values ± SD were calculated for continuous variables, and absolute and relative frequencies were measured for discrete variables. Comparisons among the 3 groups were performed by nonparametric analysis of variance (Mann-Whitney
U test) for continuous variables and by the χ2 test for discrete variables. When the study group was limited to patients with totally occluded culprit lesions at initial coronary angiography, a multivariate logistic regression analysis that included left ventricular dysfunction (LVEF ≤35% at discharge) as the dependent variable and age, sex, method of reperfusion therapy, site of the culprit lesion, time from symptom onset to reperfusion, previous angina, collateral circulation, systolic blood pressure, heart rate on admission, and ST-segment depression in lead aVR as independent variables was performed. Odds ratios and 95% confidence intervals were calculated. A probability value of less than .05 was considered to indicate statistical significance.
Results Patient characteristics Patients were divided into 3 groups according to STsegment deviation in lead aVR on admission ECG: 23 patients with ST-segment elevation of ≥0.5 mm in lead aVR (group A, Figure 1, A), 47 without ST-segment deviation (group B, Figure 1, B), and 35 with ST-segment depression of ≥0.5 mm (group C, Figure 1, C). The baseline characteristics of the patients in the 3 groups are presented in Table I. Previous angina was less frequent in group C than in group A. No other factors significantly differed among the 3 groups.
Angiographic findings on admission (Table II) On initial coronary angiography, TIMI grade 0 or 1 flow in the LAD was more frequently demonstrated in groups B and C than in group A. The proximity of the culprit lesion to the first major septal perforator or to the first major diagonal branch was similar in the 3 groups. Good collateral circulation was slightly less frequent in group C than in group A, but the difference was not statistically significant. There were no significant differences among the 3 groups in the incidence of multivessel disease.
Electrocardiographic findings on admission (Table III) ST-segment deviation in limb leads. The sum of STsegment elevation in lateral leads was significantly higher in group C than in group A. There were no significant differences among the 3 groups in the sum of ST-segment depression in inferior leads. ST-segment deviation in precordial leads. The sum of ST-segment elevation in precordial leads was highest in group C, and the differences with groups A and B were particularly prominent in leads V5 and V6. Number of leads with ST-segment elevation. The number of leads with ST-segment elevation indicating the extent of area at risk was greater in groups B and C than in group A.
Infarct size and predischarge left ventricular function (Table IV) Infarct size as estimated on the basis of peak creatine kinase level was largest in group C, followed by group
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Figure 1
A
B Representative ECGs of the 3 groups. A, Group A, culprit lesion, Seg 6. Time from symptom onset to reperfusion, 3.3 hours. LVEF, 49% at discharge. B, Group B, culprit lesion, Seg 6. Time from symptom onset to reperfusion, 4.6 hours. LVEF, 44% at discharge.
B, and was smallest in group A. Predischarge LVEF and regional wall motion were lowest in group C, followed by group B, and were highest in group A. Predischarge left ventricular end-systolic and end-diastolic volumes were largest in group C and smallest in group A. When the study group was limited to patients with totally occluded culprit lesions at initial coronary angiography, in groups A, B, and C the peak creatine kinase level was
3965 ± 1785, 4515 ± 1996, and 7093 ± 2637 mU/mL (P < .05) and LVEF was 53% ± 10%, 48% ± 8%, and 37% ± 9% (P < .01), respectively.
In-hospital clinical course During hospitalization, congestive heart failure occurred in 1 patient (4%) in group A, 1 (2%) in group B, and 6 (17%) in group C (P < .05). Intra-aortic balloon
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Figure 1. Continued
Table I. Baseline characteristics Group A (n = 23) Age (y) Men (%) Previous angina Systolic blood pressure on admission (mm Hg) Heart rate on admission (beats/min) Time to recording ECG (h) Method of reperfusion Spontaneous reperfusion Thrombolysis Angioplasty Time to reperfusion (h)† Risk factors Smoking Hypercholesterolemia Diabetes mellitus Hypertension Family history of coronary artery disease Medication use before AMI Nitrates β-Blockers Calcium antagonists Angiotensin-converting enzyme inhibitors
Group B (n = 47)
Group C (n = 35)
55 ± 10 59 ± 10 59 ± 12 21 (91%) 43 (91%) 27 (77%) 19 (83%) 28 (60%) 13 (37%)* 153 ± 31 144 ± 26 140 ± 26 90 ± 16
83 ± 17
87 ± 16
2.0 ± 1.1
2.2 ± 1.4
2.7 ± 1.9
3 (14%) 10 (43%) 10 (43%) 3.5 ± 1.5
1 (2%) 1 (3%) 17 (36%) 8 (23%) 29 (62%) 26 (74%) 3.6 ± 1.5 4.1 ± 1.7
12 (52%) 6 (26%) 3 (13%) 14 (61%)
34 (72%) 26 (74%) 13 (28%) 7 (20%) 14 (30%) 11 (31%) 21 (45%) 20 (57%)
7 (30%)
13 (28%) 11 (35%)
1 (4%) 1 (4%) 2 (9%)
2 (4%) 4 (9%) 4 (9%)
1 (3%) 1 (3%) 4 (11%)
2 (9%)
2 (4%)
1 (3%)
Data presented are mean value ± SD or number of patients in group. Group A, Patients with ST-segment elevation in lead aVR; group B, patients without ST-segment deviation in lead aVR; group C, patients with ST-segment depression in lead aVR. *P < .05 versus groups A and B. †Patients were limited to those with totally occluded culprit lesions.
Table II. Angiographic and clinical characteristics Group A (n = 23)
C C, Group C, culprit lesion, Seg 6. Time from symptom onset to reperfusion, 3.5 hours. LVEF, 35% at discharge.
pumping was needed to maintain hemodynamic stability in 2 patients (9%) in group A, 4 (9%) in group B, and 8 (23%) in group C.
Group B (n = 47)
Group C (n = 35)
TIMI flow grade in LAD at initial angiography 0 or 1 18 (78%) 45 (96%)* 34 (97%)* 2 or 3 5 (22%) 2 (4%)* 1 (3%)* Culprit lesion Proximal to S1 18 (78%) 29 (62%) 24 (69%) Proximal to D1 14 (61%) 27 (57%) 25 (71%) Collateral grade ≥2† 10/18 (41%) 17/45 (37%) 8/34 (23%) Multivessel disease 5 (22%) 8 (17%) 6 (17%) Intra-aortic balloon 2 (9%) 4 (9%) 8 (23%) pump during hospitalization Congestive heart failure 1 (4%) 1 (2%) 6 (17%)‡ during hospitalization
Left ventricular dysfunction at discharge
Data presented are mean values ± SD or number of patients per group. S1, First major septal perforator; D1, first major diagonal branch. *P < .05 versus group A. †Rentrop classification. ‡P < .05 versus group B.
Regarding ST-segment deviation in the 3 groups, the differences were particularly prominent in leads V5 and V6. Therefore criteria for predicting predischarge left ventricular dysfunction (LVEF ≤35%) on the basis of the degree
of ST-segment deviation in leads V5 and V6 were calculated; the sensitivity, specificity, and positive and negative predictive values obtained with these criteria are shown
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Table III. Electrocardiographic findings
ST deviation in limb leads (mm) Sum of ST-segment elevation in lateral leads (I, aVL) Sum of ST-segment depression in inferior leads (II, III, AVF) ST deviation in precordial leads (mm) Sum of ST-segment elevation in leads V1-4 Sum of ST-segment elevation in leads V5, 6 No. leads with ST-segment elevation
Group A (n = 23)
Group B (n = 47)
Group C (n = 35)
1.5 ± 0.8 –3.5 ± 2.9 2.0 ± 1.2 11.7 ± 10.9 –0.7 ± 2.2 5.0 ± 2.1
1.7 ± 1.4 –3.1 ± 2.6 1.6 ± 1.1 15.6 ± 9.2 1.6 ± 2.9† 6.9 ± 1.0†
2.8 ± 1.9* –2.2 ± 4.7 1.5 ± 1.5 20.8 ± 9.2†‡ 4.6 ± 3.8†§ 7.1 ± 1.5†
Group A (n = 23)
Group B (n = 47)
Group C (n = 35)
Data presented are mean values ± SD. *P < .05 versus group A. †P < .01 versus group A. ‡P < .01 versus group B. §P < .05 versus group B.
Table IV. Infarct size and predischarge left ventricular function
Peak creatine kinase (mU/mL) Time from peak onset to peak creatine kinase (h) Left ventriculographic findings at discharge LVEF (%) SD/chords LVESVI (mL/m2) LVEDVI (mL/m2)
3661 ± 1428 12 ± 4
4440 ± 1889* 10 ± 4
6959 ± 2712*† 9±3
54 ± 9 –1.6 ± 0.9 31 ± 12 69 ± 17
48 ± 7* –2.4 ± 0.8* 41 ± 13* 80 ± 19*
37 ± 9*† –2.9 ± 0.7*† 57 ± 17*† 90 ± 23*†
Data presented are mean values ± SD. SD/chords, Regional wall motion of the anterior wall quantified by the centerline method; LVESVI, left ventricular end-systolic volume index; LVEDVI, left ventricular end-diastolic volume index. *P < .01 versus group A. †P < .01 versus group B.
Table V. Sensitivity, specificity, and accuracy of the electrocardiographic findings for prediction of predischarge left ventricular dysfunction Sensitivity (%)
Specificity (%)
Positive predictive value (%)
60* 60* 60* 90
75 69 69 80
35 32 33 51
Sum of ST-segment elevation in leads V5 and V6 of ≥3.5 mm ST-segment elevation in lead V5 of ≥2.5 mm ST-segment elevation in lead V6 of ≥1.0 mm ST-segment depression in lead aVR of ≥0.5 mm
Negative predictive value (%) 88* 88* 88* 97
Predictive accuracy (%) 71 68* 70* 82
*P < .05 versus ST-segment depression in lead aVR.
in Table V. ST-segment depression in lead aVR more accurately identified left ventricular dysfunction compared with ST-segment elevation in lead V5, lead V6, or both. When the study group was limited to patients with totally occluded culprit lesions at initial coronary angiography, a multivariate analysis found ST-segment depression in lead aVR and previous angina to be independently associated with left ventricular dysfunction (LVEF ≤35%) (Table VI).
Discussion In patients with anterior AMI, high ST-segment elevation in precordial and lateral leads or high inferior
ST-segment depression on admission ECG has been shown to be correlated with a large infarct size and high hospital mortality.10,11 Because these studies have examined the relationship between ST-segment deviation excluding lead aVR and infarct size in patients with anterior AMI, whether ST-segment deviation in lead aVR is related to infarct size remains unknown. Our study demonstrated that in patients with anterior AMI who had anterolateral ST-segment elevation, ST-segment depression in lead aVR was associated with an even larger infarction size despite successful reperfusion.
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Table VI. Factors associated with predischarge left ventricular dysfunction in multivariate analysis
Variable Age Sex Method of reperfusion Culprit lesion Time to reperfusion Previous angina Collateral circulation Systolic blood pressure on admission Heart rate on admission ST-segment depression in lead aVR
Odds ratio (95% confidence P interval) value 1.11 (0.95-1.29) 0.07 (0.01-27.8) 1.53 (0.11-21.4) 1.64 (0.04-73.2) 2.88 (0.76-10.9) 0.11 (1.04-4.67) 0.05 (0.10-2.17) 0.95 (0.90-1.01) 1.02 (0.92-1.14) 11.2 (0.99-127.3)
.182 .379 .753 .798 .118 .049 .119 .074 .703 .048
Previous reports on ST-segment deviation in lead aVR ST-segment elevation in lead aVR in addition to STsegment depression in the precordial leads is an important finding in acute subendocardial infarction.12,13 STsegment elevation in lead aVR during episodes of angina often indicates 3-vessel disease or left main stem coronary artery disease.14 Thus previous studies of STsegment deviation in lead aVR during acute myocardial ischemia have focused mainly on ST-segment elevation. To our knowledge, the clinical implications of STsegment depression in lead aVR during AMI have been assessed previously in only one study of patients with inferior or lateral, but not anterior, AMI.4
Mechanisms of ST-segment depression in lead aVR Engelen et al15 recently demonstrated that ST-segment elevation in lead aVR during anterior AMI strongly predicted LAD occlusion proximal to the first septal branch with a high specificity (95%) and a low sensitivity (43%). In our study, ST-segment elevation in lead aVR was present in only 18 (25%) of 71 patients with LAD occlusion proximal to the first major septal branch. These results show that LAD occlusion proximal to the first septal branch does not always cause ST-segment elevation in lead aVR. Our findings rather demonstrate that focusing on only ST-segment elevation in lead aVR as a sign of LAD occlusion proximal to the first septal perforator can not lead to identification of a subgroup at higher risk as suggested by ST-segment depression in lead aVR. Although the pathophysiologic features of ST-segment deviation in lead aVR during anterior AMI remains unclear, ST-segment elevation in lead aVR might be caused by injury current produced by transmural ischemia of the basal septum in proximal LAD occlusion; this current is directed toward the right shoulder.15 However, we can assume that ST-segment deviation in lead aVR is caused not only by the septal injury current but also by the injury current resulting from ischemia in the apical and inferolateral walls, which has
an opposite vector.4 Perhaps ST depression in lead aVR results when the force of the injury current produced by transmural ischemia in the inferolateral wall exceeds that produced by transmural ischemia in the basal septum. Because the location of the culprit lesion in relation to the first major septal perforator and the first major diagonal branch did not differ significantly among the 3 groups, in our study the direction of the injury current produced by transmural ischemia in the basal septum was considered similar in these 3 groups. Moreover, patients with ST-segment depression in lead aVR had higher ST-segment elevation in the precordial leads, particularly leads V5 and V6, suggesting more severe and extensive myocardial injury. Because these precordial leads face the posterolateral wall adjacent to the apex of the left ventricle,16 ST-segment depression in lead aVR might also be associated with posterolateral wall involvement in patients with anterior AMI. Furthermore, we speculate that the opposite vector of lead aVR (–150 degrees) is directed left and downward (+30 degreees), inferior to leads V5 to V6.4 Therefore ST-segment depression in lead aVR closely reflects more extensive and severe myocardial ischemia of the apical and inferolateral wall in the territory of the LAD, which cannot be identified in other leads of the conventional ECG.
Study limitations In the current study, patients with ST-segment depression in lead aVR were more likely to have TIMI grade 0 or 1 flow of the LAD, and this might have been associated with larger infarct size. However, when data from patients with totally occluded culprit lesions on initial coronary angiography were independently analyzed, variables of infarct size and predischarge left ventricular function were found to be similar to those of all patients in this study and a multivariate analysis found STsegment depression in lead aVR to be independently associated with left ventricular dysfunction. Therefore we believe that ST-segment depression in lead aVR reflects severe myocardial damage in a more extensive area at risk. Future studies should assess the clinical implications of ST-segment depression in lead aVR in a larger cohort of consecutive patients with anterior AMI because this study was a retrospective study of a small number of patients.
Conclusions We conclude that in patients who have anterior AMI with anterolateral ST-segment elevation, ST-segment depression in lead aVR on admission ECG is a simple and useful sign for predicting large infarct and left ventricular dysfunction at discharge.
References 1. Le KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Circulation 1995;91:1659-68.
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2. Yoshino H, Kachi E, Shimizu H, et al. Severity of residual stenosis of infarct-related lesion and left ventricular function after single-vessel anterior wall myocardial infarction: implication of ST-segment elevation in lead aVL of the admission electrocardiograms. Clin Cardiol 2000;23:175-80. 3. Udagawa H, Yoshino H, Kachi E, et al. ST-segment elevation in leads I and aVL predicts short-term prognosis in acute anterior wall myocardial infarction. Am J Cardiol 2000;85:101-4. 4. Menown IBA, Adgey AAJ. Improving the ECG classification of inferior and lateral myocardial infarction by inversion of lead aVR. Heart 2000;83:657-60. 5. TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial: phase I findings. N Engl J Med 1985;312:932-6. 6. Rentrop KP, Cohen M, Blanke H, et al. Change in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985;5:587-92. 7. Sandler H, Dodge HT. The use of single plane angiocardiograms for the calculation of left ventricular volume in man. Am Heart J 1968;75:325-34. 8. Sheehan FH, Bolson EL, Dodge HT, et al. Advantages and applications of the centerline method for characterizing regional ventricular function. Circulation 1986;74:293-305.
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9. Rosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705. 10. Willems JL, Willems RJ, Willems GM, et al. Significant of initial ST segment elevation and depression for the management of thrombolytic therapy in acute myocardial infarction. Circulation 1990;82:1147-58. 11. Haraphongse M, Tanomsup S, Jugdutt BI. Inferior ST segment depression during acute anterior myocardial infarction: clinical and angiographic correlations. J Am Coll Cardiol 1984;4:467-76. 12. Levine HD, Ford RV. Subendocardial infarction: report of six cases and survey of the literature. Circulation 1950;1:246-63. 13. Cook RW, Edwards JE, Prutt RD. Electrocardiographic changes in acute subendocardial infarction, 1: large subendocardial and large nontransmural infarcts. Circulation 1958;18:603-12. 14. Gorgels APM, Vos MA, Mulleneers R, et al. Value of the electrocardiogram in diagnosing the number of severely narrowed coronary arteries in rest angina pectoris. Am J Cardiol 1993;72:999-1003. 15. Engelen DJ, Gorgels AP, Cheriex EC, et al. Value of the electrocardiogram in localizing the occlusion site in the left anterior descending coronary artery in acute anterior myocardial infarction. J Am Coll Cardiol 1999;34:389-95. 16. Cooksey JD, Dunn M, Masseri E. Inferoposterior myocardial infarction: clinical vectocardiography and electrocardiography, 2. Chicago: Year Book Medical; 1977.
Background Patients with an anterolateral acute myocardial infarction (AMI) have a worse prognosis, and those with additional inferolateral wall involvement might be higher risk because of more extensive area at risk. Lead –aVR obtained by inversion of images in lead aVR has been reported to provide useful information for inferolateral lesion.
Methods We examined the relation between ST-segment deviation in lead aVR on admission electrocardiogram (ECG) and left ventricular function in 105 patients with an anterolateral AMI undergoing successful reperfusion ≤6 hours after onset. Patients were classified according to ST-segment deviation in lead aVR on admission ECG: group A, 23 patients with ST elevation of ≥0.5 mm; group B, 47 patients without ST deviation; and group C, 35 patients with ST depression of ≥0.5 mm.
Results There were no differences among the 3 groups in age, sex, or site of the culprit lesion. In groups A, B, and C, the peak creatine kinase level was 3661 ± 1428, 4440 ± 1889, and 6959 ± 2712 mU/mL, and the left ventricular ejection fraction (LVEF) measured by predischarge left ventriculography was 54% ± 9%, 48% ± 7%, and 37% ± 9%, respectively (P < .01). During hospitalization, congestive heart failure occurred more frequently in group C than in groups A or B (P < .05). ST-segment depression in lead aVR had a higher predictive accuracy than other ECG findings in identifying patients with predischarge LVEF ≤35%.
Conclusions We conclude that in patients with an anterolateral AMI, ST-segment depression in lead aVR on admission ECG is useful for predicting larger infarct and left ventricular dysfunction despite successful reperfusion. (Am Heart J 2001; 142:51-7.)
Anterior acute myocardial infarction (AMI) has been reported to be high risk,1 and especially those with ST-segment elevation in leads I and aVL are associated with a larger infarction size and a poorer short-term outcome, probably because of extensive area at risk with anterolateral wall involvement.2,3 We postulated that patients with an anterolateral AMI with additional inferolateral wall involvement, which is a part of territory supplied by large left anterior descending coronary artery (LAD), might be higher risk because of more extensive area at risk. However, it is difficult to assess the extent of area at risk to inferolateral wall in anterior AMI on a conventional 12-lead electrocardio-
gram (ECG). Recently, Menown and Adgey4 reported that lead –aVR (30 degrees) obtained by inversion of images in lead aVR (–150) provided useful information for inferolateral lesion unavailable by conventional 12lead ECG.4 Therefore the use of lead aVR might permit a more accurate estimation of the extent of area at risk in AMI. The aim of the current study was to investigate whether ST-segment deviation in lead aVR identifies a higher-risk group of patients with an anterolateral AMI.
From the Department of Cardiology, Yokohama City University Medical Center, Yokohama, Japan. Submitted December 7, 2000; accepted March 28, 2001. Reprint requests: Kazuo Kimura, MD, Department of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/116073 doi:10.1067/mhj.2001.116073
Between December 1990 and May 1999, 105 patients (91 men and 14 women, mean age 58 years, range 29 to 81 years) with AMI who fulfilled the following criteria were admitted to our coronary care unit within 6 hours from symptom onset: (1) typical chest pain lasting for at least 30 minutes, (2) STsegment elevation of ≥2.0 mm in >2 contiguous precordial leads as well as ST-segment elevation of ≥1.0 mm in leads I, aVL, or both, (3) a subsequent increase in serum creatine kinase levels to more than twice the upper limit of normal, (4)
Methods Patients
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no history or electrocardiographic evidence of a previous myocardial infarction, (5) no electrocardiographic evidence of left ventricular hypertrophy or bundle branch block, (6) no findings of primary valvular or myocardial disease, (7) successful reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade5 3 flow) of the LAD lesion as confirmed by coronary angiography within 6 hours from symptom onset, and (8) a patent LAD as confirmed by coronary angiography at discharge.
Coronary angiography Coronary angiography was performed with the use of the Judkins technique immediately after admission and a mean of 14 days after AMI. The culprit lesion in the LAD was defined as the site with total occlusion or most severe stenosis or an eccentric lesion with a narrow neck or irregular border. The grade of collateral filling in the LAD was classified according to the criteria of Rentrop et al.6 Good collateral filling was defined as grade 2 or 3. Reperfusion was defined as TIMI grade 3 flow and was established spontaneously in 5 patients, by thrombolysis in 35 patients, and by primary or rescue coronary angioplasty in 65 patients. The allocation of reperfusion therapy was left to the physician’s discretion. Stenosis was considered significant if the lumen diameter was narrowed by ≥75% in any projection.
Electrocardiographic analysis On admission, a 12-lead ECG was recorded at a paper speed of 25 mm per second and an amplification of 10 mm/mV. The isoelectric line was defined as the level of the preceding TP segment. The degree of ST-segment deviation was measured to the nearest 0.5 mm, 20 milliseconds after the end of the QRS complex from each of the 12 standard leads. Measurements of 3 contiguous beats obtained by 2 independent observers blinded to all clinical and angiographic data were averaged for each lead. ST-segment deviation was considered clinically significant if it was ≥0.5 mm above the isoelectric line.
Left ventriculography Left ventricular function was evaluated on right anterior oblique views of left ventriculograms obtained a mean of 14 days after AMI. Left ventricular end-diastolic volume index, end-systolic volume index, and left ventricular ejection fraction (LVEF) were determined by the area length method described by Sandler and Dodge.7 Regional wall motion in the territory of the LAD was assessed by the centerline method8 and expressed as SD/chord.
Cardiac enzyme study Blood samples were obtained on admission and at 3-hour intervals during the first 24 hours, at 6-hour intervals for the next 2 days, and then daily until discharge. Serum creatine kinase activity was measured by the method of Rosalki.9
Statistical analysis Mean values ± SD were calculated for continuous variables, and absolute and relative frequencies were measured for discrete variables. Comparisons among the 3 groups were performed by nonparametric analysis of variance (Mann-Whitney
U test) for continuous variables and by the χ2 test for discrete variables. When the study group was limited to patients with totally occluded culprit lesions at initial coronary angiography, a multivariate logistic regression analysis that included left ventricular dysfunction (LVEF ≤35% at discharge) as the dependent variable and age, sex, method of reperfusion therapy, site of the culprit lesion, time from symptom onset to reperfusion, previous angina, collateral circulation, systolic blood pressure, heart rate on admission, and ST-segment depression in lead aVR as independent variables was performed. Odds ratios and 95% confidence intervals were calculated. A probability value of less than .05 was considered to indicate statistical significance.
Results Patient characteristics Patients were divided into 3 groups according to STsegment deviation in lead aVR on admission ECG: 23 patients with ST-segment elevation of ≥0.5 mm in lead aVR (group A, Figure 1, A), 47 without ST-segment deviation (group B, Figure 1, B), and 35 with ST-segment depression of ≥0.5 mm (group C, Figure 1, C). The baseline characteristics of the patients in the 3 groups are presented in Table I. Previous angina was less frequent in group C than in group A. No other factors significantly differed among the 3 groups.
Angiographic findings on admission (Table II) On initial coronary angiography, TIMI grade 0 or 1 flow in the LAD was more frequently demonstrated in groups B and C than in group A. The proximity of the culprit lesion to the first major septal perforator or to the first major diagonal branch was similar in the 3 groups. Good collateral circulation was slightly less frequent in group C than in group A, but the difference was not statistically significant. There were no significant differences among the 3 groups in the incidence of multivessel disease.
Electrocardiographic findings on admission (Table III) ST-segment deviation in limb leads. The sum of STsegment elevation in lateral leads was significantly higher in group C than in group A. There were no significant differences among the 3 groups in the sum of ST-segment depression in inferior leads. ST-segment deviation in precordial leads. The sum of ST-segment elevation in precordial leads was highest in group C, and the differences with groups A and B were particularly prominent in leads V5 and V6. Number of leads with ST-segment elevation. The number of leads with ST-segment elevation indicating the extent of area at risk was greater in groups B and C than in group A.
Infarct size and predischarge left ventricular function (Table IV) Infarct size as estimated on the basis of peak creatine kinase level was largest in group C, followed by group
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Figure 1
A
B Representative ECGs of the 3 groups. A, Group A, culprit lesion, Seg 6. Time from symptom onset to reperfusion, 3.3 hours. LVEF, 49% at discharge. B, Group B, culprit lesion, Seg 6. Time from symptom onset to reperfusion, 4.6 hours. LVEF, 44% at discharge.
B, and was smallest in group A. Predischarge LVEF and regional wall motion were lowest in group C, followed by group B, and were highest in group A. Predischarge left ventricular end-systolic and end-diastolic volumes were largest in group C and smallest in group A. When the study group was limited to patients with totally occluded culprit lesions at initial coronary angiography, in groups A, B, and C the peak creatine kinase level was
3965 ± 1785, 4515 ± 1996, and 7093 ± 2637 mU/mL (P < .05) and LVEF was 53% ± 10%, 48% ± 8%, and 37% ± 9% (P < .01), respectively.
In-hospital clinical course During hospitalization, congestive heart failure occurred in 1 patient (4%) in group A, 1 (2%) in group B, and 6 (17%) in group C (P < .05). Intra-aortic balloon
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Figure 1. Continued
Table I. Baseline characteristics Group A (n = 23) Age (y) Men (%) Previous angina Systolic blood pressure on admission (mm Hg) Heart rate on admission (beats/min) Time to recording ECG (h) Method of reperfusion Spontaneous reperfusion Thrombolysis Angioplasty Time to reperfusion (h)† Risk factors Smoking Hypercholesterolemia Diabetes mellitus Hypertension Family history of coronary artery disease Medication use before AMI Nitrates β-Blockers Calcium antagonists Angiotensin-converting enzyme inhibitors
Group B (n = 47)
Group C (n = 35)
55 ± 10 59 ± 10 59 ± 12 21 (91%) 43 (91%) 27 (77%) 19 (83%) 28 (60%) 13 (37%)* 153 ± 31 144 ± 26 140 ± 26 90 ± 16
83 ± 17
87 ± 16
2.0 ± 1.1
2.2 ± 1.4
2.7 ± 1.9
3 (14%) 10 (43%) 10 (43%) 3.5 ± 1.5
1 (2%) 1 (3%) 17 (36%) 8 (23%) 29 (62%) 26 (74%) 3.6 ± 1.5 4.1 ± 1.7
12 (52%) 6 (26%) 3 (13%) 14 (61%)
34 (72%) 26 (74%) 13 (28%) 7 (20%) 14 (30%) 11 (31%) 21 (45%) 20 (57%)
7 (30%)
13 (28%) 11 (35%)
1 (4%) 1 (4%) 2 (9%)
2 (4%) 4 (9%) 4 (9%)
1 (3%) 1 (3%) 4 (11%)
2 (9%)
2 (4%)
1 (3%)
Data presented are mean value ± SD or number of patients in group. Group A, Patients with ST-segment elevation in lead aVR; group B, patients without ST-segment deviation in lead aVR; group C, patients with ST-segment depression in lead aVR. *P < .05 versus groups A and B. †Patients were limited to those with totally occluded culprit lesions.
Table II. Angiographic and clinical characteristics Group A (n = 23)
C C, Group C, culprit lesion, Seg 6. Time from symptom onset to reperfusion, 3.5 hours. LVEF, 35% at discharge.
pumping was needed to maintain hemodynamic stability in 2 patients (9%) in group A, 4 (9%) in group B, and 8 (23%) in group C.
Group B (n = 47)
Group C (n = 35)
TIMI flow grade in LAD at initial angiography 0 or 1 18 (78%) 45 (96%)* 34 (97%)* 2 or 3 5 (22%) 2 (4%)* 1 (3%)* Culprit lesion Proximal to S1 18 (78%) 29 (62%) 24 (69%) Proximal to D1 14 (61%) 27 (57%) 25 (71%) Collateral grade ≥2† 10/18 (41%) 17/45 (37%) 8/34 (23%) Multivessel disease 5 (22%) 8 (17%) 6 (17%) Intra-aortic balloon 2 (9%) 4 (9%) 8 (23%) pump during hospitalization Congestive heart failure 1 (4%) 1 (2%) 6 (17%)‡ during hospitalization
Left ventricular dysfunction at discharge
Data presented are mean values ± SD or number of patients per group. S1, First major septal perforator; D1, first major diagonal branch. *P < .05 versus group A. †Rentrop classification. ‡P < .05 versus group B.
Regarding ST-segment deviation in the 3 groups, the differences were particularly prominent in leads V5 and V6. Therefore criteria for predicting predischarge left ventricular dysfunction (LVEF ≤35%) on the basis of the degree
of ST-segment deviation in leads V5 and V6 were calculated; the sensitivity, specificity, and positive and negative predictive values obtained with these criteria are shown
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Table III. Electrocardiographic findings
ST deviation in limb leads (mm) Sum of ST-segment elevation in lateral leads (I, aVL) Sum of ST-segment depression in inferior leads (II, III, AVF) ST deviation in precordial leads (mm) Sum of ST-segment elevation in leads V1-4 Sum of ST-segment elevation in leads V5, 6 No. leads with ST-segment elevation
Group A (n = 23)
Group B (n = 47)
Group C (n = 35)
1.5 ± 0.8 –3.5 ± 2.9 2.0 ± 1.2 11.7 ± 10.9 –0.7 ± 2.2 5.0 ± 2.1
1.7 ± 1.4 –3.1 ± 2.6 1.6 ± 1.1 15.6 ± 9.2 1.6 ± 2.9† 6.9 ± 1.0†
2.8 ± 1.9* –2.2 ± 4.7 1.5 ± 1.5 20.8 ± 9.2†‡ 4.6 ± 3.8†§ 7.1 ± 1.5†
Group A (n = 23)
Group B (n = 47)
Group C (n = 35)
Data presented are mean values ± SD. *P < .05 versus group A. †P < .01 versus group A. ‡P < .01 versus group B. §P < .05 versus group B.
Table IV. Infarct size and predischarge left ventricular function
Peak creatine kinase (mU/mL) Time from peak onset to peak creatine kinase (h) Left ventriculographic findings at discharge LVEF (%) SD/chords LVESVI (mL/m2) LVEDVI (mL/m2)
3661 ± 1428 12 ± 4
4440 ± 1889* 10 ± 4
6959 ± 2712*† 9±3
54 ± 9 –1.6 ± 0.9 31 ± 12 69 ± 17
48 ± 7* –2.4 ± 0.8* 41 ± 13* 80 ± 19*
37 ± 9*† –2.9 ± 0.7*† 57 ± 17*† 90 ± 23*†
Data presented are mean values ± SD. SD/chords, Regional wall motion of the anterior wall quantified by the centerline method; LVESVI, left ventricular end-systolic volume index; LVEDVI, left ventricular end-diastolic volume index. *P < .01 versus group A. †P < .01 versus group B.
Table V. Sensitivity, specificity, and accuracy of the electrocardiographic findings for prediction of predischarge left ventricular dysfunction Sensitivity (%)
Specificity (%)
Positive predictive value (%)
60* 60* 60* 90
75 69 69 80
35 32 33 51
Sum of ST-segment elevation in leads V5 and V6 of ≥3.5 mm ST-segment elevation in lead V5 of ≥2.5 mm ST-segment elevation in lead V6 of ≥1.0 mm ST-segment depression in lead aVR of ≥0.5 mm
Negative predictive value (%) 88* 88* 88* 97
Predictive accuracy (%) 71 68* 70* 82
*P < .05 versus ST-segment depression in lead aVR.
in Table V. ST-segment depression in lead aVR more accurately identified left ventricular dysfunction compared with ST-segment elevation in lead V5, lead V6, or both. When the study group was limited to patients with totally occluded culprit lesions at initial coronary angiography, a multivariate analysis found ST-segment depression in lead aVR and previous angina to be independently associated with left ventricular dysfunction (LVEF ≤35%) (Table VI).
Discussion In patients with anterior AMI, high ST-segment elevation in precordial and lateral leads or high inferior
ST-segment depression on admission ECG has been shown to be correlated with a large infarct size and high hospital mortality.10,11 Because these studies have examined the relationship between ST-segment deviation excluding lead aVR and infarct size in patients with anterior AMI, whether ST-segment deviation in lead aVR is related to infarct size remains unknown. Our study demonstrated that in patients with anterior AMI who had anterolateral ST-segment elevation, ST-segment depression in lead aVR was associated with an even larger infarction size despite successful reperfusion.
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Table VI. Factors associated with predischarge left ventricular dysfunction in multivariate analysis
Variable Age Sex Method of reperfusion Culprit lesion Time to reperfusion Previous angina Collateral circulation Systolic blood pressure on admission Heart rate on admission ST-segment depression in lead aVR
Odds ratio (95% confidence P interval) value 1.11 (0.95-1.29) 0.07 (0.01-27.8) 1.53 (0.11-21.4) 1.64 (0.04-73.2) 2.88 (0.76-10.9) 0.11 (1.04-4.67) 0.05 (0.10-2.17) 0.95 (0.90-1.01) 1.02 (0.92-1.14) 11.2 (0.99-127.3)
.182 .379 .753 .798 .118 .049 .119 .074 .703 .048
Previous reports on ST-segment deviation in lead aVR ST-segment elevation in lead aVR in addition to STsegment depression in the precordial leads is an important finding in acute subendocardial infarction.12,13 STsegment elevation in lead aVR during episodes of angina often indicates 3-vessel disease or left main stem coronary artery disease.14 Thus previous studies of STsegment deviation in lead aVR during acute myocardial ischemia have focused mainly on ST-segment elevation. To our knowledge, the clinical implications of STsegment depression in lead aVR during AMI have been assessed previously in only one study of patients with inferior or lateral, but not anterior, AMI.4
Mechanisms of ST-segment depression in lead aVR Engelen et al15 recently demonstrated that ST-segment elevation in lead aVR during anterior AMI strongly predicted LAD occlusion proximal to the first septal branch with a high specificity (95%) and a low sensitivity (43%). In our study, ST-segment elevation in lead aVR was present in only 18 (25%) of 71 patients with LAD occlusion proximal to the first major septal branch. These results show that LAD occlusion proximal to the first septal branch does not always cause ST-segment elevation in lead aVR. Our findings rather demonstrate that focusing on only ST-segment elevation in lead aVR as a sign of LAD occlusion proximal to the first septal perforator can not lead to identification of a subgroup at higher risk as suggested by ST-segment depression in lead aVR. Although the pathophysiologic features of ST-segment deviation in lead aVR during anterior AMI remains unclear, ST-segment elevation in lead aVR might be caused by injury current produced by transmural ischemia of the basal septum in proximal LAD occlusion; this current is directed toward the right shoulder.15 However, we can assume that ST-segment deviation in lead aVR is caused not only by the septal injury current but also by the injury current resulting from ischemia in the apical and inferolateral walls, which has
an opposite vector.4 Perhaps ST depression in lead aVR results when the force of the injury current produced by transmural ischemia in the inferolateral wall exceeds that produced by transmural ischemia in the basal septum. Because the location of the culprit lesion in relation to the first major septal perforator and the first major diagonal branch did not differ significantly among the 3 groups, in our study the direction of the injury current produced by transmural ischemia in the basal septum was considered similar in these 3 groups. Moreover, patients with ST-segment depression in lead aVR had higher ST-segment elevation in the precordial leads, particularly leads V5 and V6, suggesting more severe and extensive myocardial injury. Because these precordial leads face the posterolateral wall adjacent to the apex of the left ventricle,16 ST-segment depression in lead aVR might also be associated with posterolateral wall involvement in patients with anterior AMI. Furthermore, we speculate that the opposite vector of lead aVR (–150 degrees) is directed left and downward (+30 degreees), inferior to leads V5 to V6.4 Therefore ST-segment depression in lead aVR closely reflects more extensive and severe myocardial ischemia of the apical and inferolateral wall in the territory of the LAD, which cannot be identified in other leads of the conventional ECG.
Study limitations In the current study, patients with ST-segment depression in lead aVR were more likely to have TIMI grade 0 or 1 flow of the LAD, and this might have been associated with larger infarct size. However, when data from patients with totally occluded culprit lesions on initial coronary angiography were independently analyzed, variables of infarct size and predischarge left ventricular function were found to be similar to those of all patients in this study and a multivariate analysis found STsegment depression in lead aVR to be independently associated with left ventricular dysfunction. Therefore we believe that ST-segment depression in lead aVR reflects severe myocardial damage in a more extensive area at risk. Future studies should assess the clinical implications of ST-segment depression in lead aVR in a larger cohort of consecutive patients with anterior AMI because this study was a retrospective study of a small number of patients.
Conclusions We conclude that in patients who have anterior AMI with anterolateral ST-segment elevation, ST-segment depression in lead aVR on admission ECG is a simple and useful sign for predicting large infarct and left ventricular dysfunction at discharge.
References 1. Le KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Circulation 1995;91:1659-68.
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2. Yoshino H, Kachi E, Shimizu H, et al. Severity of residual stenosis of infarct-related lesion and left ventricular function after single-vessel anterior wall myocardial infarction: implication of ST-segment elevation in lead aVL of the admission electrocardiograms. Clin Cardiol 2000;23:175-80. 3. Udagawa H, Yoshino H, Kachi E, et al. ST-segment elevation in leads I and aVL predicts short-term prognosis in acute anterior wall myocardial infarction. Am J Cardiol 2000;85:101-4. 4. Menown IBA, Adgey AAJ. Improving the ECG classification of inferior and lateral myocardial infarction by inversion of lead aVR. Heart 2000;83:657-60. 5. TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial: phase I findings. N Engl J Med 1985;312:932-6. 6. Rentrop KP, Cohen M, Blanke H, et al. Change in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985;5:587-92. 7. Sandler H, Dodge HT. The use of single plane angiocardiograms for the calculation of left ventricular volume in man. Am Heart J 1968;75:325-34. 8. Sheehan FH, Bolson EL, Dodge HT, et al. Advantages and applications of the centerline method for characterizing regional ventricular function. Circulation 1986;74:293-305.
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9. Rosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705. 10. Willems JL, Willems RJ, Willems GM, et al. Significant of initial ST segment elevation and depression for the management of thrombolytic therapy in acute myocardial infarction. Circulation 1990;82:1147-58. 11. Haraphongse M, Tanomsup S, Jugdutt BI. Inferior ST segment depression during acute anterior myocardial infarction: clinical and angiographic correlations. J Am Coll Cardiol 1984;4:467-76. 12. Levine HD, Ford RV. Subendocardial infarction: report of six cases and survey of the literature. Circulation 1950;1:246-63. 13. Cook RW, Edwards JE, Prutt RD. Electrocardiographic changes in acute subendocardial infarction, 1: large subendocardial and large nontransmural infarcts. Circulation 1958;18:603-12. 14. Gorgels APM, Vos MA, Mulleneers R, et al. Value of the electrocardiogram in diagnosing the number of severely narrowed coronary arteries in rest angina pectoris. Am J Cardiol 1993;72:999-1003. 15. Engelen DJ, Gorgels AP, Cheriex EC, et al. Value of the electrocardiogram in localizing the occlusion site in the left anterior descending coronary artery in acute anterior myocardial infarction. J Am Coll Cardiol 1999;34:389-95. 16. Cooksey JD, Dunn M, Masseri E. Inferoposterior myocardial infarction: clinical vectocardiography and electrocardiography, 2. Chicago: Year Book Medical; 1977.