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Eur Heart J. 2019 Apr 14;40(15):1183-1187. doi: 10.1093/eurheartj/ehz068.

Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome.

Author information

1
University Heart Center, Department of Cardiology, University Hospital Zurich, Raemistrasse 100, Zurich, Switzerland.
2
Division Neuropsychology, Department of Psychology, University of Zurich, Binzmuehlestrasse 14, Zurich, Switzerland.
3
Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, Schlieren, Switzerland.
4
Royal Brompton and Harefield Hospitals Trust and Imperial College, Cardiology, Sydney Street, London, UK.
5
University Research Priority Program (URPP), Dynamic of Healthy Aging, University of Zurich, Andreasstrasse 15, Zurich, Switzerland.

Abstract

AIMS:

Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction often triggered by emotional or physical stress. Severe activation of the sympathetic nervous system with catecholamine release caused by a dysfunctional limbic system has been proposed as a potential mechanism. We hypothesize that brain regions responsible for autonomic integration and/or limbic processing might be involved in the development of TTS. Here, we investigated alterations in resting state functional connectivity in TTS patients compared with healthy controls.

METHODS AND RESULTS:

Using brain functional magnetic resonance imaging (fMRI), resting state functional connectivity has been assessed in 15 subjects with TTS and 39 healthy controls. Network-based statistical analyses were conducted to identify subnetworks with altered resting state functional connectivity. Sympathetic and parasympathetic networks have been constructed in addition to the default mode network and whole-brain network. We found parasympathetic- and sympathetic-associated subnetworks both showing reduced resting state functional connectivity in TTS patients compared with controls. Important brain regions constituting parasympathetic- and sympathetic-associated subnetworks included the amygdala, hippocampus, and insula as well as cingulate, parietal, temporal, and cerebellar regions. Additionally, the default mode network as well as limbic regions in the whole-brain analysis demonstrated reduced resting state functional connectivity in TTS, including the hippocampus, parahippocampal, and medial prefrontal regions.

CONCLUSION:

For the first time, we demonstrate hypoconnectivity of central brain regions associated with autonomic functions and regulation of the limbic system in patients with TTS. These findings suggest that autonomic-limbic integration might play an important role in the pathophysiology and contribute to the understanding of TTS.

KEYWORDS:

Sympathetic; Autonomic-limbic integration; Brain–heart connection; Parasympathetic; Resting state fMRI; Takotsubo syndrome

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