Cardiac Substrate Utilization and Relationship to Invasive Exercise Hemodynamic Parameters in HFpEF

[Display omitted] •HFpEF is a complex clinical syndrome with incompletely understood pathophysiology. The recent demonstration of a beneficial impact of sodium glucose co-transporter 2 inhibitor therapy in HFpEF has drawn attention to the potential role of deranged cardiac metabolism, although this...

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Published in:JACC. Basic to translational science 2024-03, Vol.9 (3), p.281-299
Main Authors: O’Sullivan, John F., Li, Mengbo, Koay, Yen Chin, Wang, Xiao Suo, Guglielmi, Giovanni, Marques, Francine Z., Nanayakkara, Shane, Mariani, Justin, Slaughter, Eugene, Kaye, David M.
Format: Article
Language:English
Subjects:
cardiac energetics
heart failure with preserved ejection fraction
invasive hemodynamics
lipids
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Summary:[Display omitted] •HFpEF is a complex clinical syndrome with incompletely understood pathophysiology. The recent demonstration of a beneficial impact of sodium glucose co-transporter 2 inhibitor therapy in HFpEF has drawn attention to the potential role of deranged cardiac metabolism, although this remains poorly understood.•Arterial and coronary sinus blood samples were collected in nonfasted HFpEF patients and healthy control subjects, in conjunction with detailed physiologic phenotyping. Lipidomic and metabolomic analyses were performed to develop a comprehensive profile of myocardial metabolism.•The data identify the metabolic profile of the HFpEF heart in the nonfasted state as one of less free fatty acid use, with a concomitant transition to more complex lipid generation, and protein catabolism. This effect was more pronounced in female HFpEF hearts, which also displayed a narrower repertoire of lipid class use compared to male hearts. Finally, there was an interdependence of lipid use with cardiac hemodynamics, particularly pulmonary pressures and cardiac index.•Taken together, these data illustrate a complex pattern of metabolic remodeling in the HFpEF heart. Further studies are required to evaluate the impact of recently identified metabolic therapies on myocardial metabolism and their physiologic consequences. The authors conducted transcardiac blood sampling in healthy subjects and subjects with heart failure with preserved ejection fraction (HFpEF) to compare cardiac metabolite and lipid substrate use. We demonstrate that fatty acids are less used by HFpEF hearts and that lipid extraction is influenced by hemodynamic factors including pulmonary pressures and cardiac index. The release of many products of protein catabolism is apparent in HFpEF compared to healthy myocardium. In subgroup analyses, differences in energy substrate use between female and male hearts were identified.
ISSN:2452-302X
2452-302X
DOI:10.1016/j.jacbts.2023.11.006