The "tako-tsubo" phenomenon and myocardial infarction.

Over the past 10 years there has been increasing evidence that acute emotional stress can induce myocardial infarction (MI) in individuals without overt coronary artery disease. (1,2) The lay population has recognized this phenomenon for centuries, and phrases like "scared to death" and "died as a result of a broken heart" have made their way into everyday language. In contrast, the medical community has been skeptical of this association. Initially described in Japan, (3) "tako-tsubo" cardiomyopathy was used to describe a syndrome which predominantly affected middle-aged women, was brought on by acute emotional stress, was characterized by mild creatinine kinase and troponin I elevations, and by the left ventriculogram demonstrating hypo- or akinesis from the mid portion of the anterior wall to the apex and hyperkinesis of the basal area. Importantly, all wall motion abnormalities resolved usually within 30 days. The term "tako tsubo" was used as the appearance of the left ventriculogram looked like a tako tsubo, an instrument used to trap octopi in Japan (tako = octopus, tsubo = pot).

Up until recently, most case reports have originated in Japanese women. We, (4) and others, (5) were among the first to describe this syndrome in Caucasian females. In this edition of the Southern Medical Journal, Tibrewala et al (6) describe a case of tako-tsubo cardiomyopathy complicated by left ventricular thrombus. Consistent with previous reports, the patient's left ventricular function rapidly returned to normal with resolution of the left ventricular thrombus with conservative management. Recognition of this syndrome saved the patient from longer term anticoagulation with associated risks.

The etiology of this condition is unclear. Coronary artery spasm and acute plaque rupture have been investigated with conflicting results. Ibanez et al (7) suggest that a dominant left anterior descending artery supplying the apex with associated plaque rupture in the mid vessel with thrombus formation, followed by resolution could account for the abnormalities, as demonstrated by intravascular ultrasound. Sharkey et al however did not demonstrate fixed atherosclerotic plaque in this region when assessed by cardiac magnetic resonance imaging. (8) Multivessel spasm seems unlikely given the discrepancy in the literature, with some investigators finding no angiographic spasm, (1) and others demonstrating spasm induced at angiography in > 70%. (9) Elevated circulating catecholamines appear to be a common feature. Wittstein et al (1) demonstrated supraphysiologic levels of catecholamines and stress-related neuropeptides, however the exact mechanism by which these catecholamines produce this striking syndrome is unclear. Microvascular spasm (10) and direct myocyte injury induced by catecholamines has been suggested, but as yet there is no clear evidence to support a direct relationship. Myocarditis has also been postulated, however the lack of evidence on cardiac biopsy, (9) and atypical MRI (8) and ECG findings, make this unlikely.

The striking predilection for female sex is a key feature of this syndrome. Prior case reports have demonstrated that women are more vulnerable to myocardial stunning, as evidenced by transient left ventricular dysfunction post subarachnoid hemorrhage. (11) However, whether there is a sex hormone-related effect is unclear at this time given the complexities in the differences of sex-related catecholamine metabolism.

Importantly, prognosis appears good. Nearly all the patients described have survived, despite some patients requiring inotropic or mechanical support. Treatment at this stage is empirical; however, the association with catecholamine excess suggests mechanical support is preferred over inotropic support in those patients with hemodynamic compromise.

Is the tako-tsubo phenomenon an exotic event in women or does it shed light on the possible mechanism by which acute stress might trigger MI? A recent review of stress, behavior and heart disease accepted a proven relationship between acute extraordinary stress (earthquakes, missile attacks, and penalty shoot outs at the World Cup Soccer), and a possible relationship between more common stressors and acute myocardial infarction. (12) This review excluded data obtained retrospectively. More recently, the Interheart study. (13) a case-control study which retrospectively assessed psychosocial stressors in the year preceding myocardial infarction demonstrated that acute life events (financial stress, stressful life events, stress at home, stress at work) were associated with an increased risk of myocardial infarction [odds ratio of 1.48 (95% CI 1.33-1.64)]. This study demonstrated that the risk was increased in both men and women, as well as across ethnic groups. Could the tako-tsubo effect shed light upon the mechanism linking psychosocial stress and MI? We believe that further investigation is required to elucidate the nature of this intriguing condition. Prospective studies are needed to test the associations found in Interheart, along with a formal investigation into endothelial function, (14) the coagulation cascade (15) and markers of inflammation, (16) which have been implicated in the pathogenesis of stress-induced MI. This will then determine if this syndrome is an oddity, or if it is vitally important, in that it provides a link between emotional stress and myocardial infarction.

Acknowledgments

Dr. Kim Connelly is supported by a postgraduate research scholarship from the National Heart Foundation of Australia.

References

1. Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539-548.

2. Dec GW. Recognition of the apical ballooning syndrome in the United States. Circulation 2005;111:388-390.

3. Dote K, Sato H, Tateishi H, et al. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J Cardiol 1991;21:203-214.

4. Connelly KA, Maclsaac AI, Jelinek VM. Stress, myocardial infarction, and the "tako-tsubo" phenomenon. Heart. Sep 2004;90:e52.

5. Desmet WJ, Adriaenssens BF, Dens JA. Apical ballooning of the left ventricle: first series in white patients. Heart 2003;89:1027-1031.

6. Tibrewala AV, Moss B, Copper HA. A rare case of tako-tsubo cardiomyopathy complicated by a left ventricular thrombus, South Med J 2006;99:70-73.

7. Ibanez B, Navarro F, Cordoba M, P, et al. Tako-tsubo transient left ventricular apical ballooning: is intravascular ultrasound the key to resolve the enigma? Heart 2005;91:102-104.

8. Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 2005;111:472-479.

9. Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J. 2002;143:448-455.

10. Bybee KA, Prasad A, Barsness GW, et al. Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am J Cardiol 2004;94:343-346.

11. Mayer SA, Lin J, Homma S, et al. Myocardial injury and left ventricular performance after subarachnoid hemorrhage. Stroke 1999;30:780-786.

12. Bunker SJ, Colquhoun DM, Esler MD, et al. "Stress" and coronary heart disease: psychosocial risk factors. Med J Aust 2003;178:272-276.

13. Rosengren A, Hawken S, Ounpuu S, et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:953-962.

14. Kop WJ, Krantz DS, Howell RH, et al. Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses. J Am Coll Cardiol 2001;37:1359-1366.

15. von Kanel R, Mills PJ, Fainman C, et al. Effects of psychological stress and psychiatric disorders on blood coagulation and fibrinolysis: a biobehavioral pathway to coronary artery disease? Psychosom Med 2001;63:531-544.

16. Lewthwaite J, Owen N, Coates A, et al. Circulating human heat shock protein 60 in the plasma of British civil servants: relationship to physiological and psychosocial stress. Circulation 2002;106:196-201.</p> <pre> There's no bitterness that smolders, no chip on any shoulder That a random act of kindness couldn't cure. --Great Big Sea </pre> <p>Kim Connelly, MBBS, FRACP, Andrew MacIsaac, MD, FRACP, FCSANZ, and Michael V. Jelinek, MD, FRACP, FCSANZ

From the Department of Cardiology, St. Vincent's Hospital, Melbourne 3065, Australia.

Reprint requests to Dr. Kim Connelly, Cardiac Investigation Unit, St Vincent's Hospital, PO Box 2900, Fitzroy 3065, Victoria, Australia. Email: [e-mail]

Accepted October 25, 2005.