Exploring the Association Between Brain Lesions and Takotsubo Syndrome

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Frederic Schaper, MD, PhD, an instructor in neurology at Brigham and Women's Hospital, discussed the complex interplay between brain lesions and takotsubo syndrome, a heart condition caused by physical and emotional triggers.

Frederic Schaper, MD, PhD  (Credit: Harvard Catalyst)

Frederic Schaper, MD, PhD

(Credit: Harvard Catalyst)

Takotsubo syndrome is a type of acute heart failure syndrome that usually manifests as acute chest pain, dyspnea or syncope that mimics an acute myocardial infarction. In prior research, the understanding of the pathogenesis of this syndrome suggested that the sympathetic nervous system activation plays an important role.1 However, in recent years researchers have shifted their focus to exploring more on the role of the brain-heart connection in the pathogenesis of takotsubo syndrome.

A recent study presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, revealed that takotsubo cardiomyopathy caused by lesions could be mapped to a brain network.2 Presented by lead author Frederic Schaper, MD, PhD, lesions occurred in multiple heterogeneous locations across different cortical lobes and subcortex of left (n = 19), right (n = 25) or both hemispheres (n = 28) in cases of lesion-induced takotsubo cardiomyopathy (n = 72) from studies (n = 61). Furthermore, these same lesion areas were part of a specific brain network functionally connected with the vagal nucleus in the medulla (P <.01).

During the meeting, Schaper, a neuroscientist and an instructor in neurology at Brigham and Women's Hospital, sat down with NeurologyLive® in an interview to discuss the common emotional and physical triggers for takotsubo syndrome. In the conversation, Schaper further talked about how brain lesions contribute to the onset of takotsubo syndrome as observed in prior studies analyzed in the literature review. In addition, he spoke about the patient population who would be the most at risk for developing takotsubo syndrome and some other risk factors associated with the heart condition.

NeurologyLive: Could you provide an overview of your presentation on takotsubo syndrome?

Frederic Schaper, MD, PhD: I study broken heart syndrome, also known as takotsubo syndrome, which is a transient and often reversible left ventricular wall dysfunction, accompanied by wall motion abnormalities. It is often preceded by emotional or physical triggers. It was first described by the Japanese in 1990, who called it takotsubo syndrome because the shape this ballooning shape of the heart resembled a takotsubo pot, which is what the vase they used to catch octopus in.

Takotsubo syndrome is often preceded by emotional or physical triggers. Those can be negative, such as the death of a loved one, or they can also be positive, such as a surprise party or winning the lottery. These can be emotionally induced heart symptoms that are thought to be provoked by brain activity. There are multiple causes. So, these emotionally induced takotsubo syndrome is one but there's also physically induced, such as brain lesions. This is the rarer part of takotsubo syndrome what we studied. We are very interested at the Center for Brain Circuit Therapeutics at the Brigham and Women's Hospital in Boston in studying brain lesions as they provide a causal link between damage to a brain region and the symptom that is evoked. We hope to use these rare brain lesions that cause takotsubo syndrome to learn more about the brain regions and the networks involved in the brain heart connection.

Does takotsubo syndrome have a high risk of morality?

Top Clinical Takeaways

  • Takotsubo syndrome, also known as broken heart syndrome, is often triggered by unexpected emotional or physical stress.
  • Brain lesions causing takotsubo syndrome are distributed throughout various regions, indicating a complex network rather than a single causative area.
  • Postmenopausal women and individuals with psychiatric or neurological disorders are at higher risk for this condition, underscoring the importance of further research into the brain-heart connection.

Thankfully, the mortality is not high. It’s often transient and often reversible and well treated. Most cases don't end up in death. There are some reported cases though where, for instance in Boston, a police officer entered the wrong room and there was an elderly person there. Once they were so scared, and so surprised that they dropped dead. Those cases are reported but they are rare. Mostly, as I said, they are reversible and transient and well treated.

There are many risk factors that increase the risk of this happening and leading to death. The main risk factor for takotsubo syndrome is to be a postmenopausal female because the decline in estrogen and progesterone has negative effects on safety of the heart and heart health. We don't know yet what that means for brain health although there's some big research studies that are looking into that. This bidirectional relationship of the heart and the brain is very interesting and I’m happy to see that it's getting more and more attention.

Was there anything that you found surprising or unexpected in the results of the study?

We are very interested in specifically the cases where lesions induce takotsubo syndrome because they may teach us something about the regions and networks involved. To share a bit about what we did, we searched the literature and found all cases published where a brain lesion induced takotsubo syndrome. We found that these lesions are all over the place. We were expecting to find them localized to certain brain region because then you have a causal link between a lesion region that is damaged and the symptom evoked takotsubo syndrome. That is not what we found.

We found that these lesions are distributed throughout the brain in different cortical lobes, thalamus, basal ganglia, brainstem, cerebellum and medulla. So, that doesn't give you a localization of this symptom. The next thing we did was use the Human Connectome, which is a database of connectivity data of the average human brain. There are big research studies that have been done that have collated how does the normal and average connectivity in a normal brain looks like. We used that and leveraged that to see what that lesion is connected to. What we can then do is statistically test which regions are more connected to lesions that cause takotsubo syndrome than normal strokes or other brain lesions. That can give us the brain network that is connected to lesions causing takotsubo syndrome and that was what we did.

Is there any way to prevent takotsubo syndrome from occurring?

It often comes unexpected and the definition of it is that it needs to come unexpected. Often it can happen from a surprise party or a lottery or the death of a loved one, things that come unexpected and that evoke it. There are certain risk factors that increase your risk from it, as mentioned. Most people have a surprise party and don't have this reaction, but certain groups are at risk. One of those, for instance, postmenopausal women and patients with psychiatric or neurological disorders and a history of those.

Do you have closing remarks on the study findings you presented at AAN?

We found in our results that the network that seems to be most important is the network that is connected to medulla connections. We know that the medulla plays an important role in regulating the autonomic nervous system. There are both sympathetic and parasympathetic nuclei in the medulla. We are now trying to figure out is to see what regions in the medulla are really critical for a lesion to be connected to cause takotsubo syndrome and could use help from other experts in field. In that way, we hope to map the brain regions and networks that are involved in this symptom potentially in the future to prevent or treated better.

Transcript edited for clarity. Click here for more coverage of AAN 2024.

REFERENCES
1. Wang X, Pei J, Hu X. The Brain-Heart Connection in Takotsubo Syndrome: The Central Nervous System, Sympathetic Nervous System, and Catecholamine Overload. Cardiol Res Pract. 2020;2020:4150291. Published 2020 Mar 9. doi:10.1155/2020/4150291
2. Schaper F, Kim K, Morton-Dutton M, et al. Takotsubo Cardiomyopathy: A Brain Network that Breaks Your Heart. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
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