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Review Open Access

Takotsubo syndrome: Unraveling the mystery behind its triggers (Review)

  • Authors:
    • Xuehui Fan
    • Yanlin Yuan
    • Zuchuan Huang
    • Liulu Zhang
    • Binyi Zhao
    • Dechou Zhang
    • Yong Liu
    • Guiquan Chen
    • Ping Liu
    • Guoqiang Yang
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Luzhou, Sichuan 646000, P.R. China, Department of Acupuncture and Rehabilitation, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Cardiovascular Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Magnetic Resonance Imaging, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany, Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
    Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 174
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    Published online on: August 22, 2025
       https://doi.org/10.3892/ijmm.2025.5615
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Abstract

Takotsubo syndrome (TTS) is a clinical condition characterized by left ventricular dysfunction, clinically mimicking acute coronary syndrome. Despite significant advancements in understanding TTS, more questions about its underlying pathological mechanisms remain unresolved. The present review offered current data on the underlying pathological mechanisms of TTS, including central nervous system structural and functional alterations, sympathetic nervous system overstimulation, excessive catecholamine secretion, shifts in adrenergic receptors (ARs) distribution and balance, hormone influences, epicardial vasospasm, endothelial dysfunction and genetic predispositions. For example, stressors from physical or emotional triggers induce central neurohumoral activation by influencing the hippocampus and amygdala, which results in excessive local or systemic secretion. This catecholamine surge affects the myocardium by altering cellular metabolism, disrupting signaling pathways and impairing endothelial function. The regional myocardial effects are influenced by the modified ARs distribution and the density of autonomic innervation, which are pivotal in the onset of TTS. These insights suggest potential therapeutic strategies, including cognitive behavioral therapy, endothelin A antagonists and β‑blockers. However, the complex interplay of these factors in TTS onset remains poorly understood. Further research is essential to elucidate the intricate mechanisms and interactions underlying this syndrome, paving the way for improved prevention and treatment approaches.
View Figures

Figure 1

Epidemiology and clinical features of
TTS. TTS, Takotsubo syndrome; ACS, acute coronary syndrome; CAD,
coronary artery disease; LV, left ventricle; ECG,
electrocardiography.

Figure 2

Underlying mechanisms of TTS. The
underlying mechanisms of TTS are predominantly triggered by
emotional or physical stress and encompass structural and
functional alterations in the CNS, overstimulation of the SNS,
excessive catecholamine secretion, modulation of ARs, epicardial
vasospasm or dysfunction, endothelial dysfunction, hormone-mediated
changes and genetic predispositions. TTS, Takotsubo syndrome; CNS,
central nervous system; SNS, sympathetic nervous system; ARs,
adrenergic receptors; LV, left ventricle.

Figure 3

The potential pathophysiological
mechanisms of TTS. Current pathological mechanisms underlying TTS,
encompass CNS structural and functional alterations, SNS
overstimulation, excessive catecholamine secretion, ARs
distribution and balance shifts, hormonal influences, epicardial
vasospasm, endothelial dysfunction and genetic predispositions.
TTS, Takotsubo syndrome; CNS, central nervous system; SNS,
sympathetic nervous system; ARs, adrenergic receptors; CBF,
cerebral blood flow; FMD, flow-mediated; MINOCA, MI with
non-obstructive coronary arteries; LV, left ventricle.

Figure 4

TTS prognosis and clinical
implications. Illustration of the natural course of TTS and factors
influencing patient outcomes. Initial triggers such as emotional or
physical stress, the role of cardiovascular complications and
comorbidities during the acute phase are associated with clinical
prognosis. TTS, Takotsubo syndrome; ACS, acute coronary
syndrome.

Figure 5

Overview of potential therapeutic
approaches for TTS. Representation of therapeutic strategies for
TTS, emphasizing pharmacological interventions, stress management
and supportive care. Highlighted treatments include β-blockers,
ACEI and therapies targeting SNS regulation alongside emerging
approaches for managing severe complications. TTS, Takotsubo
syndrome; ACEI, angiotensin-converting enzyme inhibitors; SNS,
sympathetic nervous system; ARB, angiotensin-converting enzyme
inhibitors/Angiotension II receptor blockers; CBT, cognitive
behavioral therapy; ECMO, extracorporeal membrane oxygenation; LV,
left ventricle.
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Copy and paste a formatted citation
Spandidos Publications style
Fan X, Yuan Y, Huang Z, Zhang L, Zhao B, Zhang D, Liu Y, Chen G, Liu P, Yang G, Yang G, et al: Takotsubo syndrome: Unraveling the mystery behind its triggers (Review). Int J Mol Med 56: 174, 2025.
APA
Fan, X., Yuan, Y., Huang, Z., Zhang, L., Zhao, B., Zhang, D. ... Yang, G. (2025). Takotsubo syndrome: Unraveling the mystery behind its triggers (Review). International Journal of Molecular Medicine, 56, 174. https://doi.org/10.3892/ijmm.2025.5615
MLA
Fan, X., Yuan, Y., Huang, Z., Zhang, L., Zhao, B., Zhang, D., Liu, Y., Chen, G., Liu, P., Yang, G."Takotsubo syndrome: Unraveling the mystery behind its triggers (Review)". International Journal of Molecular Medicine 56.5 (2025): 174.
Chicago
Fan, X., Yuan, Y., Huang, Z., Zhang, L., Zhao, B., Zhang, D., Liu, Y., Chen, G., Liu, P., Yang, G."Takotsubo syndrome: Unraveling the mystery behind its triggers (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 174. https://doi.org/10.3892/ijmm.2025.5615
Copy and paste a formatted citation
x
Spandidos Publications style
Fan X, Yuan Y, Huang Z, Zhang L, Zhao B, Zhang D, Liu Y, Chen G, Liu P, Yang G, Yang G, et al: Takotsubo syndrome: Unraveling the mystery behind its triggers (Review). Int J Mol Med 56: 174, 2025.
APA
Fan, X., Yuan, Y., Huang, Z., Zhang, L., Zhao, B., Zhang, D. ... Yang, G. (2025). Takotsubo syndrome: Unraveling the mystery behind its triggers (Review). International Journal of Molecular Medicine, 56, 174. https://doi.org/10.3892/ijmm.2025.5615
MLA
Fan, X., Yuan, Y., Huang, Z., Zhang, L., Zhao, B., Zhang, D., Liu, Y., Chen, G., Liu, P., Yang, G."Takotsubo syndrome: Unraveling the mystery behind its triggers (Review)". International Journal of Molecular Medicine 56.5 (2025): 174.
Chicago
Fan, X., Yuan, Y., Huang, Z., Zhang, L., Zhao, B., Zhang, D., Liu, Y., Chen, G., Liu, P., Yang, G."Takotsubo syndrome: Unraveling the mystery behind its triggers (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 174. https://doi.org/10.3892/ijmm.2025.5615
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