Abstract Body: Introduction: Takotsubo syndrome (TTS), or stress cardiomyopathy, is a clinical syndrome of a peculiar, regional, and reversible left ventricular systolic dysfunction, often triggered by emotional or physical stress, implicating a brain-heart axis.

Hypothesis: Patients with TTS exhibit differences in structural and functional brain imaging, supporting an altered brain-heart axis.

Purpose: To systematically review literature for structural and functional brain imaging in patients with TTS.

Methods: We searched PubMed, Embase, and Cochrane Library through December 2025 for studies of structural and functional brain imaging in patients with TTS using the following search strategy: “Takotsubo Syndrome OR stress cardiomyopathy OR broken heart syndrome AND brain OR neural OR neuro* OR central nervous system OR autonomic AND imaging OR MRI OR fMRI OR PET OR SPECT OR FDG-PET.” Of 1451 articles identified, 1288 were screened after duplicates removal.

Results: We identified 14 studies including 284 patients with TTS and 295 controls. The most common reason for exclusion was for the wrong outcome or population. Controls were typically matched for age and sex, with some studies also considering handedness, stress, and comorbidities. Five studies assessed 113 patients during acute TTS admission, while 11 assessed 194 patients after cardiac recovery, including 2 studies with both acute and chronic assessments. Differences compared with controls involved the amygdala (showing increased metabolism, reduced volume, and reduced resting connectivity), the insula (resting-state function/connectivity and structural differences such as volume and cortical thickness), the frontal cortex (decreased resting connectivity and reduced surface area/gray matter volume), and the hippocampus (reduced volume, decreased structural connectivity, increased metabolism, and mixed resting connectivity). Gray-matter differences were mostly regional rather than globally.

Conclusions: Patients with TTS have structural and functional differences in brain regions involved in emotional processing and autonomic regulation, supporting that a brain-heart axis may be central to TTS.