A total-body PET scanner will track two distinct biological processes—fibroblast activation and platelet clotting—in the hearts and bloodstreams of 10 patients with takotsubo syndrome, a poorly understood condition that mimics a heart attack. This matters because takotsubo syndrome carries a 2–4-fold higher risk of death and major cardiovascular complications than the general population, and systemic thromboembolism is 5–6 times more common than in heart attack patients. Yet no one knows whether activated fibroblasts drive the heart’s long-term damage, or where the dangerous blood clots originate. Current treatments are guesswork. If the scans reveal activated fibroblasts in the left ventricle, or clots forming there or elsewhere in the body, it would provide the first direct evidence of these mechanisms in takotsubo syndrome. That could open the door to clinical trials of anti-fibrotic or anti-thrombotic drugs—potentially the first targeted treatments for this neglected condition. The work is exploratory and small-scale, but it addresses two fundamental unknowns in a disease that currently has no evidence-based therapy.
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Takotsubo syndrome is characterised by acute transient left ventricular systolic dysfunction which often presents like acute myocardial infarction and has a 2-4-fold increased risk of all-cause mortality and major adverse cardiovascular events compared to the general population. The causes and consequences of takotsubo cardiomyopathy are unknown. Almost all cardiomyopathic conditions are associated with adverse left ventricular remodelling, which is in part mediated by activated fibroblasts. This has not been explored in takotsubo syndrome. In addition, systemic thromboembolism is an important complication of takotsubo syndrome and is 5-6-fold more prominent than in patients with myocardial infarction. The origin and clinical course of these cerebrovascular events are currently unknown. I propose to address these two key unknown questions using a highly novel approach of total body positron emission tomography. In 10 patients with acute takotsubo cardiomyopathy, I will perform gallium-68 fibroblast activation protein inhibitor ([68Ga]FAPI; marker of activated myocardial fibroblasts) and fluorine-18 GP1 ([18F]GP1; marker of activated glycoprotein IIb/IIIa receptor on activated platelets) positron emission tomography to assess for evidence of activated fibroblasts in the left ventricle or left ventricular and/or systemic thrombosis respectively, both at baseline and after 3-6 months of convalescence. This would be the first of its kind, to examine the role of activated fibroblasts and thrombosis in the pathophysiology of takotsubo syndrome and has the potential to inform clinical practice and treatment decisions (eg: anti-fibrotic or anti-thrombotic agents) as a step to identify the first treatment for this neglected and under researched condition.
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