Prof Juan Carlos Kaski, St George's, University of London, UK


Takotsubo syndrome (TTS), described initially by Sato et al in 1990 (1) has captured the attention of practicing physicians and researchers alike. TTS is characteristically associated with physical and emotional triggers. (2, 3) Among the latter, severe “negative” stress such as grief, anger, or fear are among the most common triggers.  TTS is also known as ‘stress cardiomyopathy’ and ‘broken heart syndrome’. Stress is known to activate neuroendocrine responses that affect the heart muscle and the coronary vessels. Increased sympathetic nervous system activity and parasympathetic withdrawal have been described in situations of severe emotional stress and these are associated with asymmetric brain activation, which may, in turn, trigger cardiac arrhythmias. (4) Wittstein et al. (5) reported increased levels of circulating catecholamines in patients with TTS compared with those in patients with CAD related myocardial infarction. This finding suggests that  in TTS, stressful events affect the cardiovascular system via an over-activation of the sympathetic neurohormonal axis. Interestingly, TTS associated with positive emotional triggers has been also described, albeit in a minority of patients. (6) The effect of positive emotions on the heart is less well known. Positive emotions activate the autonomic nervous system in a similar fashion to that of negative emotions.(7) A recent study analysed the prevalence and characteristics of TTS triggered by positive emotions (‘happy heart syndrome’). In the Ghadri et al study (6) TTS patients with preceding pleasant events were compared to those with negative emotional triggers. Of 1750 TTS patients, 485 had an emotional trigger and of these, only 4.1% had positive emotional triggers and 95.9% reported unequivocal negative emotional events. Of interest, the clinical presentation was similar in patients with ‘happy heart syndrome’ and ‘broken heart syndrome’. The main difference between these two groups however was that a higher prevalence of midventricular TTS in ‘happy hearts’ compared with ‘broken hearts’ (35.0 vs. 16.3%, p=0.030), who had the classical apical LV ballooning.

The study confirmed the link between “positive” emotional stress and TTS. The authors have indicated that the molecular pathways and functional anatomy of the central nervous system involved in the emotional processes responsible for the ‘happy syndrome’, remain poorly understood. The availability and rapid development of functional neurological imaging that is taking place at present will most likely contribute to a better understanding of the mechanisms leading to TTS.

Understanding the pathophysiology and molecular mechanisms underlying the syndrome is likely to result in rational therapeutic measures, as well as the development of suitable strategies for disease prevention. It is time to move forward, beyond the fascination of the clinical features of TTS, into the realm of molecular mechanisms if we are to make real progress in the treatment and prevention of this puzzling condition.


  1. Sato HTH, Uchida T, Dote K, Ishihara M. Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm. In Kodama K, Haze K, Hori M, eds. Clinical Aspect of Myocardial Injury: From Ischemia to Heart Failure. Tokyo, Japan: Kagakuhyor- onsha Publishing Co.; 1990, pp. 56–64 (Article in Japanese).
  2. Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation 2008;118:2754–2762.
  3. Sharkey SW, Lesser JR, Zenovich AG, Maron MS, Lindberg J, Longe TF, Maron BJ. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 2005;111:472–479.
  4. Ziegelstein RC. Acute emotional stress and cardiac arrhythmias. JAMA 2007;298: 324 – 329.
  5. Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539–548.
  6. Ghadri J et al. Eur Heart J 2016; 37: 2823–2829
  7. Allen D, Parmar G, Ravandi A, Hussain F, Kass M. Happiness can break your heart: a rare case of takotsubo cardiomyopathy after good news. Can J Cardiol 2015;31: 228 e1–e2.