The Present and Future
JACC State-of-the-Art Review
Pathophysiology of Takotsubo Syndrome: JACC State-of-the-Art Review

https://doi.org/10.1016/j.jacc.2020.10.060Get rights and content
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Highlights

  • The pathophysiology of the Takotsubo form of acute heart failure is incompletely understood.

  • Excessive release of cardiac neuronal and systemic catecholamines contributes to acute myocardial dysfunction in patients with Takotsubo syndrome, but impaired microvascular perfusion, myocardial inflammation, and electrophysiological derangements contribute to its clinical manifestations.

  • Takotsubo stunning, which involves both catecholaminergic and ischemic mechanisms, is the pathophysiological framework underlying this syndrome, which is critical to the development of effective diagnostic and therapeutic strategies.

Abstract

Takotsubo syndrome (TTS) has been a recognized clinical entity for 31 years, since its first description in 1990. TTS is now routinely diagnosed in patients who present with acute chest pain, electrocardiographic changes, troponin elevation, unobstructed coronary arteries, and a typical pattern of circumferential left ventricular wall motion abnormalities that usually involve the apical and midventricular myocardium. Increasing understanding of this intriguing syndrome stems from wider recognition, possible increasing frequency, and a rising number of publications focused on the pathophysiology in clinical and laboratory studies. A comprehensive understanding of TTS pathophysiology and evidence-based treatments are lacking, and specific and effective treatments are urgently required. This paper reviews the pathophysiology of this fascinating syndrome; what is known from both clinical and preclinical studies, including review of the evidence for microvascular dysfunction, myocardial beta-adrenergic signaling, inflammation, and electrophysiology; and where focused research needs to fill gaps in understanding TTS.

Key Words

β-adrenergic signaling
catecholamines
inflammation
pathophysiology
stress
Takotsubo stunning
Takotsubo syndrome

Abbreviations and Acronyms

ANS
autonomic nervous system
APD
action potential duration
ATP
adenosine triphosphate
βAR
β-adrenoreceptor
cAMP
cyclic adenosine monophosphate
ECG
electrocardiography
iPSC-CMs
inducible pluripotent stem cell-derived cardiomyocytes
LV
left ventricle
MIBG
123I-metaiodo-benzylguanidine
NO
nitric oxide
PCr
phosphocreatine
SERCA2a
sarcoplasmic reticulum (SR) Ca2+-adenosine-triphosphatase 2a
TTS
Takotsubo syndrome

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