Brain heart interfaces: Takotsubo- and Stroke-heart syndrome: two sides of the same coin?

Takotsubo- or the Broken-Heart syndrome is often triggered by an episode of severe stress followed by acute heart failure in the absence of coronary obstruction, which may also occur in the so- called Stroke-heart syndrome early after stroke. Both cause significant mortality and lack a specific therapy. They also share other aspects, including brain regions typically affected, high levels of stress hormones, and myocardial inflammation. We propose that both syndromes are driven by overlapping as well as distinct pathophysiology. We will compare the functional and molecular features of animal models of both syndromes and dissect the role of inflammatory and other cell types in the heart by single-cell sequencing and cell culture studies. The results will be confirmed by clinical data and heart biopsies of Takotsubo patients, acquired in this study. A treatment approach will then be tested in both animal and cellular models with the potential for human therapy.. Takotsubo syndrome (TTS) is often triggered by an episode of stress followed by acute heart failure in the absence of coronary obstruction, which may also occur in Stroke-heart syndrome (SHS) early after stroke. Both cause significant mortality and lack a specific therapy. They also share other aspects, including brain regions typically affected, high levels of catecholamines, and myocardial inflammation. We propose that both syndromes are driven by overlapping and distinct pathophysiology. We will compare the functional and molecular features of murine models of TTS and of SHS and dissect the role of inflammatory, myocardial and endothelial cells in the heart by single nucleus RNA-sequencing and human-induced pluripotent stem cell modelling in co-culture studies. The results will be confirmed clinically and with myocardial biopsies of TTS patients. Pharmacological treatment will then be tested in both animal and cellular models with translational potential for an early clinical trial.