The aim of this viewpoint/commentary on a recent contribution by the Gothenburg takotsubo syndrome (TTS) laboratory, in which the authors provide a comprehensive review/state of the art report on the animal models, currently employed in the elucidation of the pathophysiology of TTS, is to intensify the debate as to what constitutes a suitable TTS animal model with as promising as possible translational potential to the human TTS.

The pathophysiology of TTS is still elusive. This viewpoint proposes that TTS is an acute coronary syndrome, engendered by an ASNS/catecholamine-induced LVOTO, which results in an enhanced wall stress and afterload-based supply/demand mismatch, culminating in a segmental myocardial ischemic injury state, in susceptible individuals. Such individuals are felt to be particularly women with chronic hypertension, known or latent HCM, or non-HCM segmental myocardial hypertrophy, and certain structural abnormalities involving the LV and the MV apparatus. Recommendations are provided to explore further this hypothesis, while maintaining our focus on all other advanced TTS pathophysiology hypotheses for all patients, or those who do not experience LVOTO, men, the young, and patients with reverse, mid-ventricular, or right ventricular TTS, in whom more prolonged hyperadrenergic stimulation and/or larger amounts of blood-ridden catecholamines, segmental particularities of cardiac innervation and/or density of α-, and β-adrenergic receptors, pheochromocytoma, neurological chronic or acute comorbidities/catastrophies, coronary epicardial/microvascular vasospasm, and CMD.

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UNASSIGNED: Release of norepinephrine (NE) from neuronal cardiac nerve endings and/or blood-borne catecholamines (CATs), mainly epinephrine (EPI), may mediate TTS. The aim of this study was to document the levels of NE, EPI, and dopamine (DA) in patients with TTS.
UNASSIGNED: A qualitative/quantitative meta-analysis of CATs and their relationship to age, gender, and triggers, was carried out, employing the world literature on TTS, published in PubMed.
UNASSIGNED: NE/EPI/DA in108 patients with TTS, 65.2 ± 16.4 years old, 89 (82.4%) women, revealed that: NE was measured more frequently than EPI, and EPI than DA; the timing of the measurements was variable; CATs were reported variably (qualitatively/quantitatively/with/without upper limits of normal); NE/EPI or NE/EPI/DA rose to the same degree; CATs were normal, or mildly/moderately elevated, with only 6 patients showing markedly elevated NE/EP/DA; NE, EPI, and DA were similar in patients with physical triggers and NE was similar in patients with physical, emotional, or no triggers (p = 0.47); EPI was higher than NE in patients with emotional triggers and EPI was higher in patients with emotional than physical triggers (p = 0.012); NE, EPI, and DA rose to the same proportion in men and women; types of TTS triggers were distributed proportionally in men and women.
UNASSIGNED: NE, EPI, and DA rise proportionally in patients with TTS; CATs are mildly/moderately, and rarely markedly elevated; measurements of CATs should become more systematised; although CATs may not be essential for TTS diagnosis, they may contribute to prognosis and elucidation of the pathophysiology of TTS.

The pathophysiology of takotsubo syndrome (TTS) and its recurrence (REC-TTS) is still elusive. Various ventriculographic \"ballooning\" patterns in response to a variety of triggers are observed in patients with REC-TTS. Although patients with and without REC-TTS have been previously compared, no comparison of patients\' 1st TTS episode (1stTTS) with the 1st REC-TTS episode (1stREC-TTS) has been attempted.
All patients with ≥1 REC-TTS episodes with patient-based data (45 variables) from the world literature, retrieved via PubMed, were meta-analyzed, and the patients\' 1st REC-TTS and stREC-TTS were compared.
The time interval between the 1stTTS and 1stREC-TTS of the meta-analyzed 128 patients, 117 (91.4%) female, was 30.4 ± 36.1 months, with 47 (36.7%) patients having a neurological and/or psychiatric comorbidity(ies). Among 113 patients with paired 1stTTS and 1stREC-TTS data on the ventriculographic \"ballooning\" appearance, 101 (78.9%) had a different variant during the 1stTTS as compared with the 1stREC-TTS. Six patients (4.7%) died during hospitalization. Thirty patients (23.4%) were taking a β-blocker prior to their 1strTTS. Among 19 variables compared between the 1st TTS and 1st REC-TTS episodes, only mean age (by 2.5 years) and use of β-blockers were statistically significantly different. The precipitating triggers, and the in-hospital adverse events were similar in the 1st TTS and 1st REC-TTS episodes.
A comparison of the 1st TTS and 1st REC-TTS episodes of patients with REC-TTS, revealed large variation in the ventriculographic \"ballooning\" patterns, similarity in the TTS triggers, and no difference in the in-hospital adverse events. There was no protective effect for imparted by β-blockers in REC-TTS.

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