# Cardiac Nuclear Imaging Findings in Atypical Variants of Takotsubo Cardiomyopathy
###### Abstract  
Background: In addition to the typical form resembling the classical Japanese octopus trap, atypical variants of Takotsubo cardiomyopathyopathy (TTC) sparing the left ventricular apex have emerged over the years. The aim of this systematic review is to provide a comprehensive overview of the cardiac nuclear imaging findings in atypical variants. Methods: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The literature research was carried out online on the Pubmed, Scopus, Central (Cochrane Library), and Web Of Science databases. Results: A total of 14 articles were ultimately selected. Myocardial perfusion scintigraphy was performed in nine studies, followed by 123I-mIBG scintigraphy, 123I-BMIIP scintigraphy, and 18F-FDG PET. In seven cases, a single cardiac nuclear imaging technique was performed, while in the remaining five and two cases, two and three different imaging modalities were, respectively, used. The most common atypical variant of our selection was the midventricular form, followed by reverse/inverted/basal TTC, with only a single case reported of a focal pattern. Conclusions: As the reason why TTC variants occur is still not clear, a deeper understanding of the current knowledge could be the basis for providing more insights into this fascinating disorder and its uncommon manifestations. Keywords:takotsubo; 123I-mIBG; 123I-BMIIP; 18F-FDG PET; cardiac nuclear imaging; TTC; myocardial perfusion scintigraphy +
Footnote †: journal: Medical  
0.6/100,000 in males [7; 8]. Up to 90% of TC patients are women and 80% are over the age of 50 years; the mean age is 67 years, as reported in the International Takotsubo Registry [9]. Although the mechanisms underlying TTC are not fully understood, with several postulated hypotheses existing, including transient multivessel epicardial coronary spasm and microvascular dysfunction [10], a link to sudden stressors and high catecholamine levels has been established [11; 12; 13]. The interaction between adrenergic hyperactivation and cardiovascular system response to the peak of catecholamines plays a central role in the pathophysiology of TTC. The large majority of patients diagnosed with TC have experienced either significant emotional, physical, or environmental stress [3; 14; 15; 16], suggesting how the release of large quantities of norepinephrine from the sympathetic nervous system and epinephrine from the adrenal medulla could be a major mechanism underlying this syndrome [17; 18]. Stressors vary widely among reports of TTC cases and include natural disasters to weddings and surprise parties, from surgery and anesthesia to thyrotoxicosis [19] and sepsis, from the postpartum period [20; 21] to COVID-19 infection [22], from subarachnoid hemorrhage and stroke to pancreatitis and cholecystitis, from pheochromocytoma to neoplasm and cancer-related therapies, and so on [23]. The reaction to stressors depends on individual factors influencing both catecholamine production and myocyte and microvascular response to sympathetic stimulation [24], with estrogen deficiency, genetic factors, and neurologic and psychiatric disorders being predisposing factors to mental and physical triggers [25; 26; 27; 28; 29]. Despite the clinical presentation usually mimicking ACS [30], with patients often presenting with chest pain, followed by dyspnea and syncope [31], having electrocardiographic abnormalities (ST-segment elevation, ST-segment depression, T-wave negative conversion, and QT prolongation) [32] and showing a mild elevation of myocardiumecrosis enzyme levels, as well as the marked elevation of brain natriuretic peptide (BNP) and N-terminal pro-BNP [33; 34; 35; 36], TTC is formally considered a benign self-limiting state presenting a favorable prognosis [37] and it is generally characterized by a temporary impairment with complete recovery within 3 weeks.