Frederic Schaper1, Kyuree Kim2, Mae Morton-Dutton2, Ona Wu3, Natalia Rost4, Michael Fox5
1Neurology, Brigham and Women's Hospital, Harvard Medical School, 2Brigham and Women's Hospital, Harvard Medical School, 3MGH Stroke Research Center, 4Massachusetts General Hospital, 5Brigham and Women's Hospital / Harvard Medical School
Objective:
To test whether lesions causing takotsubo cardiomyopathy map to a common brain network.
Background:
Takotsubo cardiomyopathy - also known as broken-heart syndrome - is a type of acute heart failure that can lead to sudden death. It is commonly triggered by intense emotional or physical distress such as a divorce, earthquakes, or a surprise party; leading to a surge of the sympathetic nervous system. However, takotsubo cardiomyopathy can also be caused by brain lesions, potentially lending insight into the brain regions and networks involved in nervous system control of the heart.
Design/Methods:
We performed a systematic literature search and collected all published cases of brain lesions causing takotsubo cardiomyopathy. Lesions were mapped to a common brain template and the brain network functionally connected to each lesion location was computed using resting state functional MRI data of 1000 healthy participants (human connectome), a method termed ‘lesion network mapping’. Functional connections specific to lesions causing takotsubo cardiomyopathy were identified using control lesions causing other non-specific symptoms (n = 490) and a whole-brain voxel-wise t-test with 10,000 permutations, controlling for lesion volume as a covariate.
Results:
We identified 61 publications describing 72 cases of lesion-induced takotsubo cardiomyopathy (50 [69%] females, mean [SD] age, 52.9 [24.9] years). Lesions causing takotsubo cardiomyopathy occurred in multiple heterogeneous locations spanning different cortical lobes and subcortex of left (n=19), right (n=25) or both hemispheres (n=28). However, these same lesion locations were part of a specific brain network functionally connected to the vagal nucleus in the medulla (p<0.01). Repeating this analysis excluding lesions directly involving the medulla gave a similar result (p<0.05), suggesting a diaschisis-like network effect.
Conclusions:
The findings in this study indicate that lesions causing takotsubo cardiomyopathy map to a brain network defined by functional connectivity to the vagal nucleus, a brain region previously implicated in parasympathetic nervous system control of the heart.