Tako-Tsubo Cardiomyopathy

Author: Alessandro Matteo Fili
Date: 27/02/2011



Takotsubo cardiomyopathy, also known as transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, broken-heart-syndrome, Gebrochenes-Herz-Syndrom, and simply stress cardiomyopathy, is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the myocardium . Because this weakening can be triggered by emotional stress, such as the death of a loved one, a break-up, or constant rejection, the condition is also known as broken heart syndrome. Stress cardiomyopathy is a well-recognized cause of acute heart failure, lethal ventricular arrhythmias, and ventricular rupture.

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Takotsubo cardiomiopathy is a quite rare event: Incidence in general population is 1:36.000. In a subset of 100 patients with toracic pain ongoing coronarographic studies only 1 o 2 are recognized as TTS. Usuallly patients are post-menopausal women. Male/Female ratio is about 1:3.


The typical presentation of someone with takotsubo cardiomyopathy is ECG changes suggestive of an anterior wall myocardial infraction, frequently presenting as a global T-wave inversion.

During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging out of the apex of the heart with preserved function of the base that earned the syndrome its name "tako tsubo", or octopus trap in Japan, where it was first described.

The cause appears to involve high circulating levels of catecholamines (mainly adrenaline/epinephrine). Evaluation of individuals with takotsubo cardiomyopathy typically includes a coronary angiogram, which will not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within 2 months. Takotsubo cardiomyopathy is more commonly seen in post-menopausal women. Often there is a history of a recent severe emotional or physical stress.


No large studies have confirmed the etiology of stress cardiomyopathy, so determining the underlying cause has so far not been possible. Several pathological mechanisms have been proposed, including coronary artery vasospasm, coronary microcirculation dysfunction, obstruction of the left ventricular outflow tract (LVOT), and catecholamine overload. Published data suggest that substantially elevated plasma catecholamine levels seen in stress cardiomyopathy patients could be particularly relevant, and result in catecholamine-related toxic effects1. (Mechanisms of stress (Takotsubo) cardiomyopathy, 2010)).
Disturbance of the calcium regulatory system has been demonstrated in stress cardiomyopathy. This effect might be caused by supraphysiological levels of catecholamines, which stimulate β-adrenoceptors and alter the expression of calcium-regulatory protein genes.
Sarcolipin2 regulates sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) by lowering its affinity for Ca2+ and is frequently overexpressed in stress cardiomyopathy. Raised sarcolipin expression in stress cardiomyopathy could contribute to contractile dysfunction in the acute phase. The inhibitory effect of sarcolipin on SERCA2 is substantially increased if it binds via its related protein, phospholamban, rather than by direct binding.
Several authors emphasize the central role of catecholamines in an oestrogen-deficient situation. Moreover, the shown cardioregulatory role of the female sex hormones might contribute to the sudden occurrence of this disorder after an emotional or physical stress event.
As published by Grohe et al.,3 the expression of oestrogen receptor on cardiac myocytes might explain a direct effect of female hormones on cardiac contractility. Additionally, Bupha-Intr and Wattanapermpool4 showed the physiological significance of ovarian sex hormones in the regulation of the calcium uptake in myocytes. In ovariectomized rats, the sarcolemic Ca2+-ATPase (SERCA2a) expression was remarkably downregulated in comparison to sham animals. Moreover, the activity of the calcium pump was reduced due to dephosphorylated phospholamban (PLN). Indeed, the Tako-Tsubo cardiomyopathy is characterized by a similar phenomenon.
As previously said a significantly increased ventricular expression of sarcolipin (SLN) is crucial in Tako-Tsubo cardiomyopathy pathogenesis. In contrast, analysis of SLN expression in the normal heart showed that SLN is expressed predominantly in the atrial component and its ventricular expression is low or even absent.5,6 (Rona G. MacLennan DH).


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Tako-tsubo Cardiomyopathy is mostly caused by a catecholamine excess that affects intracellurar Ca++-pathways in cardiomyocites; its dominance in postmenopausal women could be related to their oestrogen deficiency, that plays a concomitant role in same pathways.


1. Holger M. Nef, Helge Möllmann, Yoshihiro J. Akashi & Christian W. Hamm. Mechanisms of stress (Takotsubo) cardiomyopathy. Nature Reviews Cardiology 7, 187-193 (April 2010).
2. Nef HM, Moellman H, Troidl C, Kostin S, Voss S, Hilpert P, Clostermann U, Rolf A, Rixe J, Weber M, Hamm C, Elsaesser A. Tako-Tsubo cardiomyopathy is associated with abnormalities in calcium-handling proteins. Eur Heart J 2009;30:2155-2164.
3. Grohe C, Kahlert S, Lobbert K, Stimpel M, Karas RH, Vetter H, Neyses L. Cardiac myocytes and fibroblasts contain functional estrogen receptors. FEBS Lett 1997;416:107-112.
4. Bupha-Intr T, Wattanapermpool J. Regulatory role of ovarian sex hormones in calcium uptake activity of cardiac sarcoplasmic reticulum. Am J Physiol Heart Circ Physiol 2006;291:H1101-H1108.
5. Rona G. Catecholamine cardiotoxicity. J Mol Cellular Cardiol 1985;17:291-306.
6. MacLennan DH, Asahi M, Tupling AR. The regulation of SERCA-type pumps by phospholamban and sarcolipin. Ann N Y Acad Sci 2003;986:472-480.

Alessandro Matteo Fili and Pietro Elias Fubini.

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