Takotsubo Syndrome Presents With Brain Volume, Thickness, Connectivity Changes

In takotsubo syndrome, patients present with smaller gray and white matter volumes and cortical surface areas and greater cortical thicknesses and tractography connectivity, according to study findings published in JACC: Heart Failure.

Takotsubo syndrome is an acute heart failure cardiomyopathy that typically occurs after a mental or physical stress event and mimics acute myocardial infarction (MI).

To investigate potential mechanisms of how emotional processing or stress may lead to takotsubo syndrome, researchers from Aberdeen University in the United Kingdom recruited 25 patients with takotsubo syndrome between 2020 and 2021. Features observed at magnetic resonance imaging (MRI) were compared with data from 25 matched controls individuals.

The patients and control individuals were mean age, 68 (interquartile range [IQR], 47-83) and 65 (IQR, 64-69) years, 96% and 96% were women, 32% and 24% had hypertension, and 24% and 16% psychiatric disease, respectively.

Among the patients, the triggers for takotsubo syndrome were emotional (40%), physical (28%), or no trigger (32%) and they underwent MRI a median of 5 (IQR, 2-8) days after diagnosis.

At MRI, the patients were found to have significantly reduced surface areas of the left rostral anterior cingulate, right and left insula, and total right and left white surface areas (all P ≤.007). They also had greater cortical thicknesses in the right insula and total right and left mean thicknesses (all P ≤.001). The researchers also noted different volumes in the total cerebral white matter, total gray matter, subcortical gray matter, right and left thalamus, right and left hippocampus, right and total caudate, right and total parahippocampus, right and left insula, and brainstem (all P ≤.039) compared with control individuals.

Patients with takotsubo syndrome had a functional connectivity profile featuring greater connectivity between right or left thalamus and the left caudate and left nucleus accumbens, the anterior cingulate cortex and the right cerebral cortex, and/or the left thalamus and posterior cerebellum. This was coupled with decreased connectivity between the right thalamus and right inferior frontal gyrus, left insula, visual lateral and visual medial lobes, orbitofrontal cortex, and inferior frontal gyrus and/or the left insula and left caudate and thalamus.

The patient group was also observed to have increased structural connectivity to temporal regions in general and the left insula was more connected to the right amygdala, right putamen, right posterior cingulate gyrus, and right rostral anterior cingulate gyrus.

Study limitations included the small sample size and observational design.

The researchers highlighted that “This is the largest cohort of takotsubo syndrome patients whose acute brain phenotype has been investigated.”

They concluded, “The abnormalities in the thalamus-amygdala-insula and basal ganglia support the concept of involvement of higher-level function centers in takotsubo syndrome, and interventions aimed at modulating these may be of benefit.”