Takotsubo: a Japanese contribution to cardiology

Patients with an acute coronary syndrome either with 1 or without 2 ST-segment elevations in the ECG presenting with chest pain as well as acute heart failure typically associated with dyspnoea 3 are common in emergency departments today. They still account for the bulk of the mortality in Western countries. 4 More recently, a hitherto unknown new entity decribed by the Japanese cardiologist H.T.M. Sato, 5 the so-called Takotsubo syndrome, has also become more and more common in the Western world. 6 Takotsubo is a relatively novel disease entity in female patients with clinical and ECG presentation of an ST-segment elevation myocardial infarction, normal coronary arteries, and commonly apical ballooning of the left cardiac chamber resembling the shape of a Japanese octopus trap. Since the first description, the syndrome has been increasingly recognized, but mainly reported in single case reports. 7 With the introduction of primary percutaneous coronary intervention, it became obvious that Takotsubo syndrome is much more common than anticipated. Also, it has been discussed in depth as to whether this is a novel form of an acute coronary syndrome or a transient cardiomyopathy. In their Editor’s Note ‘ Is Takotsubo a microvascular acute coronary syndrome? Towards a new definition’ , Thomas F. Lüscher and Christian Templin from the University of Zürich in Switzerland shed light on this matter and argue that it most probably represents a microvascular form of an acute coronary syndrome. 8 Takotsubo cardiomyopathy is typically provoked by negative stressors such as grief, anger, or fear, leading to the popular term ‘broken heart syndrome’. However, the role of positive emotions triggering Takotsubo syndrome remains unknown. In their article entitled ‘Happy heart syndrome: role of positive emotional stress in Takotsubo cardiomyopathy’ Jelena-Rima Ghadri and colleagues from the University Hospital Zurich in Switzerland investigated this matter. 9 They analysed the incidence and characteristics of patients with Takotsubo cardiomyopathy following pleasant events, which are distinct from the stressful or undesirable episodes commonly associated with Takotsubo syndrome. In certain patients, the syndrome is indeed preceded by pleasant events. Out of 1750 patients from the International Takotsubo Registry, they identified a total of 485 individuals with a definite emotional trigger. Out of these, 4% presented with pleasant preceding events and 96% with unequivocal negative emotional events. Interestingly, the clinical presentation of patients with ‘happy hearts’ was similar to that of those with ‘broken heart syndrome’, including symptoms such as angina. Similarly, ECG and laboratory findings did not differ. However, in a post-hoc analysis, midventricular involvement was twice as common in ‘happy hearts’ compared with ‘broken hearts’. The authors conclude that Takotsubo syndrome can be triggered not only by negative, but also by positive life events. While patient characteristics were similar between groups, the midventricular Takotsubo cardiomyopathy type was more prevalent among the ‘happy hearts’. Presumably, despite their distinct nature, happy and sad life events may share a similar final common emotional pathway, which can ultimately result in Takotsubo syndrome. The fact that such a clinical presentation may be as old as Western culture is illustrated by the Viewpoint entitled ‘ Positive emotions and Takotsubo syndrome: ‘happy heart’ or ‘Diagoras’ syndrome?’ by Gerasimos Filippatos and colleagues from the Attikon University Hospital in Athens, Greece. 10 Diagoras lived in the city of Ialysus on the island of Rhodes in the fifth century BC; he was a crowned Olympic boxing champion twice and had victories in numerous other major athletic events. In 448 BC, during the 83rd Olympics, Diagoras watched as his oldest son Damagetos won the pankration wrestling games for the second time in a row, and his second son Akousilaos won the boxing games. According to the story, Diagoras died on the spot, possibly overwhelmed by the joy and the Takotsubo associated with it. Further, in an EHJ Brief Communication ‘ Takotsubo cardiomyopathy and neurogenic stunned myocardium: similar albeit different ’, Paolo G. Camici and colleagues from the Vita-Salute University and Scientific Institute San Raffaele Milan in Italy demonstrate that in patients with stress cardiomyopathy the type of triggering event is associated with different clinical, instrumental, and laboratory features that characterize the phenotype at presentation. 11 In spite of all the attention that Takotsubo syndrome has received lately, coronary artery disease due to plaque rupture remains the most common acute cardiac presentation. Although sympathic activation may also play a role here as a trigger, inflammation of the plaque is considered essential to make the lesion vulnerable and prone to rupture. 12,13 In a Basic Science paper ‘ Intracoronary dual-modal optical coherence tomography-near-infrared fluorescence structural–molecular imaging with a clinical dose of indocyanine green for the assessment of high-risk plaques and stent-associated inflammation in a beating coronary artery ’, Jin Won Kim and colleagues from Korea University in the Republic of Korea aimed to examine whether intracoronary dual-modal optical coherence tomography-near-infrared fluorescence structural–molecular imaging with indocyanine green can estimate inflammation in swine coronary arteries. 14 After administration of clinically approved near-infrared fluorescence-enhancing indocyanine green or saline, rapid coronary imaging using a fully integrated optical coherence tomography-near-infrared fluorescence catheter was safely performed in atheromatous Yucatan minipigs and in those in which a drug-eluting stent had been implanted. Of note, stronger near-infrared fluorescence activity was identified in high-risk plaques compared with controls, which was validated on ex vivo fluorescence reflectance imaging. The in vivo plaque target-to-background ratio was much higher in inflamed lipid-rich plaques compared with fibrous plaques. In vivo and ex vivo peak target-to-background ratios correlated significantly. In vitro cellular indocyanine green uptake and histological validations corroborated the optical coherence tomography-near-infrared fluorescence findings in vivo . Indocyanine green co-localization with macrophages and lipids of human plaques was further confirmed with autopsy atheroma specimens. Two weeks after deployment of a drug-euting stent, optical coherence tomography-near-infrared fluorescence imaging detected strong near-infrared fluorescence signals along stent struts. Histologically, near-infrared fluorescence signals in peri-strut tissue co-localized with macrophages. Thus, optical coherence tomography-near-infrared fluorescence imaging with a clinically applicable dose of indocyanine green accurately assessed inflammation of plaques and that associated with the implantation of stents in a beating coronary artery. This highly translatable dual-modal molecular–structural imaging strategy could be relevant for clinical intracoronary estimation of high-risk plaques and vascular reactions to stent implantation. In vivo optical coherence tomography-near-infrared fluorescence (OCT-NIRF) imaging. ( A ) Image of contoured 2-D NIRF map overlaid on angiography. ( B ) Corresponding longitudinal OCT-NIRF image. ( B , a) Weak NIRF activity on fibrotic OCT signal pattern. ( B , b) Strong NIRF activity on fibroffaty OCT signal pattern. ( C ) Saline-injected control. ( D ) Normal-looking artery. ( E ) Comparisons of peak pTBR. Equally windowed. (from Kim S, Lee MW, Kim TS, Song JW, Nam HS, Cho HS, Jang S-J, Ryu J, Oh DJ, Gweon D-G, Park SH, Park K, Oh W-Y, Yoo H, Kim JW. Intracoronary dual-modal optical coherence tomography-near-infrared fluorescence structuralmolecular imaging with a clinical dose of indocyanine green for the assessment of high-risk plaques and stent-associated inflammation in a beating coronary artery. See pages 2833–2844.) The editors hope that this issue of the European Heart Journal will be of interest to its readers.