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EDITORIAL

Can Acute Myocardial Infarction Sneak Out From Takotsubo?

Makoto Hirai, MD, PhD

he new clinical entity of takotsubo cardiomyopathy (TC) was first introduced by Sato et al in 1990,1 8 years ahead of the first report on the condition from the United States. Dote et al reported 5 cases of TC in 1991.2 Takotsubo is an authentic Japanese ceramic pod with a narrow mouth used to trap octopus and its shape resembles the systolic left ventriculogram of TC patients. Other names used for the condition are apical ballooning syndrome, broken heart syndrome, and stress cardiomyopathy.3 Clinical and scientific interest in TC has dramatically increased since (ie, 2 publications in 2000, 50 or less per year before 2006, and nearly 300/year from 2008 to 2010).4 Although exaggerated sympathetic stimulation is thought to be central to this syndrome, the precise pathophysiological mechanisms have not yet been fully elucidated.4,5 Because there have been many informative papers from all over the world, the clinical features of TC are well established.37 Symptoms such as chest pain and shortness of breath develop abruptly, typically in postmenopausal women, after emotionally or physically stressful events. Emotional precipitants have reportedly included death of a family member or a pet, public speaking, financial loss, automobile accidents, and natural disasters such as earthquakes. TC is an acute cardiac syndrome with ST-segment elevation on 12-lead ECG and wall motion abnormalities in the apical and mid-portions of the left ventricle, despite the lack of obstructive coronary artery disease. These abnormalities on ECG and in wall motion extend beyond a single epicardial coronary distribution. Proposed Mayo clinic criteria have been used for the clinical diagnosis of TC.3 Because the symptoms and ECG findings of TC mimic those in patients with anterior acute myocardial infarction (AMI), from the clinical viewpoint, it is remarkably important, especially in the acute and subacute phases, to differentiate TC from AMI in order to apply appropriate therapeutic strategies. However, the differential diagnosis of TC and anterior AMI is often difficult. Recently, several reports have challenged the electrocardiographic differentiation of TC from AMI shortly after the onset of symptoms, with careful investigation of 12-lead ECGs.813

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In this issue of the Journal, Kosuge et al add new electrocardiographic differences in the distribution of negative T waves to differentiate TC from reperfused anterior AMI.14 Previously, Kosuge et al examined the 12-lead ECGs on admission

of 33 patients with TC and 342 with a first anterior AMI who were admitted within 6 h of symptom onset.11 ST-segment deviation was considered present if the deviation 80 ms after the J point was >0.05 mV in the limb leads and >0.1 mV in the precordial leads. TC shows ST-segment elevation more frequently in leads III, aVF, II, aVR, and I, and less frequently in leads aVL and V14, as compared with anterior AMI. They concluded that the combination of the presence of ST-segment elevation in lead aVR (ST-segment depression in lead aVR) and the absence of ST-segment elevation in lead V1 identified TC with a sensitivity of 91%, a specificity of 96%, and a predictive accuracy of 95%. Tamaru et al investigated the electrocardiographic criterion for differentiating TC from anterior AMI with ST-segment elevation.12 They compared the magnitude of the ST-segment elevation at the J point between 62 patients with TC and 280 with anterior AMI. Patients with anterior AMI and ST-segment elevation were divided into 3 subgroups based on the site of culprit lesion of the left anterior descending coronary artery: 140 with the lesion proximal to the first diagonal branch, 120 with the lesion between the first and second diagonal branches, and 20 with the lesion distal to the second diagonal branch. ST-segment elevation 0.1 mV in 1 of leads V35 without ST-segment elevation 0.1 mV in lead V1 showed a sensitivity of 74.2% and a specificity of 80.6% for differentiating TC from anterior AMI with a specificity >80% in each subgroup. Kosuge et al and Tamaru et al unanimously showed that, in the acute phase, ST-segment elevation in patients with TC is significantly less frequent in lead V1 and more frequent in leads aVL, aVR, II and aVF, as compared with anterior AMI.11,12 Deep symmetrical T-wave inversions develop in TC patients within 24 to 48 h of symptom onset (subacute phase). It has been reported that the development of T-wave inversion in patients with TC mimics that in some patients with anterior AMI. However, there have been no reports concerning the electrocardiographic criteria for differentiation of TC from anterior MI in patients with newly developed T-wave inversion. In this issue of the Journal, Kosuge et al investigate ECGs with the greatest amplitude of negative T waves in 34 patients with TC and 237 with a first reperfused anterior AMI admitted within 6 h of symptom onset.14 They found that negative T waves were consistently observed in leads aVR and V46, whereas negative T waves were rare in lead V1 in patients with TC. They propose that negative T waves in lead aVR (positive T waves in lead aVR) and no negative T waves in lead V1 identifies TC with a sen-

The opinions expressed in this article are not necessarily those of the editors or of the Japanese Circulation Society. Received December 6, 2011; accepted December 7, 2011; released online December 23, 2011 Nagoya University School of Health Sciences, Nagoya, Japan Mailing address: Makoto Hirai, MD, PhD, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya 4618673, Japan. E-mail: hirai@met.nagoya-u.ac.jp ISSN-1346-9843 doi: 10.1253/circj.CJ-11-1428 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp
Circulation Journal Vol.76, February 2012

306 sitivity of 94%, a specificity of 95%, and the highest diagnostic accuracy. The criteria would greatly help differentiate TC from reperfused anterior AMI after development of T-wave inversion. Because Kosuge et al examined ECGs with the greatest amplitude of negative T waves14 and Kurisu et al reported biphasic T-wave changes with the first negative peak on approximately day 3 and the second one 23 weeks after onset in patients with TC,13 it would be useful to take these things into consideration in practical, clinical application. Furthermore, it is of clinical importance to recognize that the same leads of the 12-lead ECG such as V1 and aVR consistently show significant differences in ST-segment elevation or T-wave inversion in patients with TC as compared with anterior AMI. Because 12-lead ECGs can be recorded currently by battery-driven recorders or by amplifiers attachable to a portable personal computer, their clinical usefulness is preserved even when and where commercial electricity supply is not available, such as in a serious earthquake or tsunami that might cause TC in patients.15 Precise ECG analyses such as reports by Kosuge et al are of paramount importance in emergency medicine, because the 12-lead ECG is a globally distributed, and well-standardized, non-invasive diagnostic modality.
References
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HIRAI M
5. Bybee KA, Kara T, Prasad A, Lerman A, Barsness GW, Wright RS, et al. Transient left ventricular apical ballooning: A syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004; 141: 858 865. 6. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation 2008; 118: 397 409. 7. Maron BJ, Towbin JA, Thiene G, Antzelvich C, Corrado D, Arnett D, et al. American Heart Association contemporary definitions and classification of the cardiomyopathies: American Heart Association scientific statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113: 1807 1816. 8. Ogura R, Hiasa Y, Takahashi T, Yamaguchi K, Fujiwara K, Ohara Y, et al. Specific findings of the standard 12-lead ECG in patients with Takotsubo cardiomyopathy: Comparison with the findings of acute anterior myocardial infarction. Circ J 2003; 67: 687 690. 9. Inoue M, Shimizu M, Ino H, Yamaguchi M, Terai H, Fujino N, et al. Differentiation between patients with takotsubo cardiomyopathy and those with anterior acute myocardial infarction. Circ J 2005; 69: 89 94. 10. Mitsuma W, Kodama M, Ito M, Tanaka K, Yanagawa T, Ikarashi N, et al. Serial electrocardiographic findings in women with Takotsubo cardiomyopathy. Am J Cardiol 2007; 100: 106 109. 11. Kosuge M, Ebina T, Hibi K, Morita S, Okuda J, Iwahashi N, et al. Simple and accurate electrocardiographic criteria to differentiate takotsubo cardiomyopathy from anterior acute myocardial infarction. J Am Coll Cardiol 2010; 55: 2514 2516. 12. Tamura A, Watanabe T, Ishihara M, Ando S, Naono S, Zaizen H, et al. A new electrocardiographic criterion to differentiate between Takotsubo cardiomyopathy and anterior wall ST-segment elevation acute myocardial infarction. Am J Cardiol 2011; 108: 630 633. 13. Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nakamura S, et al. Time course of electrocardiographic changes in patients with tako-tsubo syndrome: Comparison with acute myocardial infarction with minimal enzymatic release. Circ J 2004; 68: 77 81. 14. Kosuge M, Ebina T, Hibi K, Iwahashi N, Tsukahara K, Endo M, et al. Differences in negative T waves between takotsubo cardiomyopathy and reperfused anterior acute myocardial infarction. Circ J 2012; 76: 462 468. 15. Watanabe H, Kodama M, Ookura Y, Aizawa Y, Tanabe N, Chinushi M, et al. Impact of earthquakes on Takotsubo cardiomyopahty. JAMA 2005; 294: 305 307.

Circulation Journal Vol.76, February 2012