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<p>Fontan circulation is characterized by markedly reduced exercise capacity, historically attributed predominantly to impaired preload reserve and cardiac limitations. However, invasive cardiopulmonary exercise testing demonstrates that a subset of patients exhibit relatively preserved exercise cardiac output with a blunted arteriovenous oxygen difference, implicating impaired peripheral oxygen extraction. We propose that bile acid dysregulation associated with Fontan-related liver disease may contribute to skeletal muscle microvascular and mitochondrial dysfunction, and advocate for integrated physiologic and multi-omics phenotyping to identify actionable therapeutic targets.</p>

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Bile Acids, Mitochondria, and Impaired Oxygen Extraction: A Shared Mechanistic Pathway in Fontan Circulation and MASLD–HFpEF

  • 期刊论文

  • 发表日期：

    2026年4月24日

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  • Ashish H. Shah

摘要

Fontan circulation is characterized by markedly reduced exercise capacity, historically attributed predominantly to impaired preload reserve and cardiac limitations. However, invasive cardiopulmonary exercise testing demonstrates that a subset of patients exhibit relatively preserved exercise cardiac output with a blunted arteriovenous oxygen difference, implicating impaired peripheral oxygen extraction. We propose that bile acid dysregulation associated with Fontan-related liver disease may contribute to skeletal muscle microvascular and mitochondrial dysfunction, and advocate for integrated physiologic and multi-omics phenotyping to identify actionable therapeutic targets.