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Is the Tako Tsubo syndrome a hyperadrenergic entity?

The Tako Tsubo syndrome (TT) (also named transient left ventricular apical ballooning syndrome, stress cardiomyopathy and broken heart syndrome) is an unusual form of myocardial "stunning" that occurs without obstructive coronary artery disease. It has been included among the "unclassified cardiomyopathies" in the recent European classification of cardiomyopathies (1). The pathogenesis is poorly understood, however the growing published experience seems to indicate that any emotional, physical or disease-related acute insult (including neurological, respiratory, metabolic or hemodynamic distress) may trigger apical (or mid-ventricular or basal) ballooning (2), and excessive sympathetic stimulation seems to be implicated.

An interesting case of a young woman presenting the typical features of the syndrome caused by a functional paraganglioma intimate with the aorta and vena cava has been published (3); similar cases of TT syndrome have been reported with adrenal phaeochromocytoma.

Two recent papers reported the findings from endomyocardial biopsies taken during the acute phase of the disease. Both showed histological patterns compatible with strong adrenergic stimulation. In one study 9 patients were biopsied and contraction band necrosis (in 4) and mononuclear cell infiltration (in 3), were documented, associated with elevated levels of norepinephrine and epinephrine peaking on admission (744±52 and 140±166 pg/mc respectively) (4).

Moreover a disproportion between a severely reduced uptake at the ventricular apex on F-18FDG PET image and a slightly reduced uptake of 201 Tl was noted, showing a metabolic defect much more severe than perfusion abnormality (4). Another study performed in TT patients showed intracellular vacuoles of glycogen, disorganisation of contractile and cytoskeletal proteins, while signs of oncotic and apoptotic cell death were absent (5).

After functional recovery of ventricular contractility all described alterations appeared nearly completely reversed. These alterations were interpreted as resulting from catecholamine excess followed by microcirculatory dysfunction and direct cardiotoxicity. A further study performed in 11 consecutive TT patients demonstrated an absence of improvement in contractile performance of the akinetic ventricular wall to low-dose dobutamine infusion (6); a response distinctly different from that expected in an ischemic stunned myocardium, and interpreted as compatible with a catecholamine mediated cardiac toxicity.


In summary, several sources of data seem to converge toward a hyperadrenergic origin of the peculiar TT pattern, possibly related to regional myocardial differences in sympathetic innervation or catecholamine sensitivity. A different interpretation of the regional distribution of myocardial asynergy in TT syndrome has been proposed by DL Brutsaert (7). By considering that the apical myocardium is the thinnest and most densely trabeculated part of the left ventricle thereby having the higher surface-to volume ratio and then the maximal exposition of the endomyocardial endothelial surface, this area may become a most vulnerable target when exposed to excessive plasma levels of substances, like catecholamines, known to affect or damage the endocardiac endothelial cells. Further studies are needed to explain the pathophysiology of this new fascinating biological entity.


1. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyoathies: a position statement from the European society of cardiology working group on myocardial and pericardial diseases. Eur Heart J. 2008;29(2):270-6.

2. Wittstein IS. Apical-ballooning syndrome. Lancet 2007; 370: 545-6

3. Van Spall HCG, Roberts DJ, Sawka Am et al. Not a broken heart . Lancet 2007; 370: 628.

4. Yoshida T, Hibino T, Kako N, et al. A pathophysiologic study of Tako-Tsubo cardiomyopathy with F-18 fluorodeoxyglucose positron emission tomography. Eur Heart J 2007 ; 28 : 2598-2604.

5. Nef HM, Möllmann H, Kostin S, et al. Tako-Tsubo cardiomyopathy: intraindividual structural analysis in the acute phase after functional recovery. Eur Heart J 2007; 28: 2456-64

6. Fujiwara S, Takeishi Y, Isoyama S, et al. Responsiveness to dobutamine in patients with left ventricular apical ballooning syndrome. Am J Cardiol 2007; 100; 1600-1603.

7. Brutsaert DL, Tako-Tsubo cardiomyopathy. Eur J Heart Failur 2007; 9: 854

Notes to editor

By Prof. Luigi Tavazzi, Head Division of Cardiology – University Hospital PAVIA- Italy
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.