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| Item Type: | Review |
|---|---|
| Title: | Excess and dysfunctional fat as a primary driver of heart failure with preserved ejection fraction: from institutional recognition to clinical integration |
| Creators Name: | Packer, Milton, Ho, Jennifer, Petrie, Mark C., Schiattarella, Gabriele G., Butler, Javed, Lam, Carolyn S.P., Vaduganathan, Muthiah, Zannad, Faiez and Borlaug, Barry A. |
| Abstract: | Epidemiological and Mendelian randomization studies demonstrate a strong link between central obesity, visceral adiposity, and heart failure with preserved ejection fraction (HFpEF). The AHA (American Heart Association) has specifically identified excess and dysfunctional fat as the primary upstream cause of the “cardiovascular-kidney-metabolic” syndrome, noting that biologically abnormal adipose tissue exerts adverse effects through its action to secrete proinf lammatory adipokines. Experimental studies confirm the causal role of these adipose tissue secretions in the pathogenesis of HFpEF. The earliest clinical evidence of excess and dysfunctional fat is the presence of abdominal obesity, and HFpEF represents the advanced stage of the cardiovascular-kidney-metabolic syndrome for many patients. The AHA also recognizes excess and dysfunctional fat as the major upstream driver of hypertension, type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and chronic kidney disease—the common comorbidities of HFpEF. Adipose signaling may amplify the development of HFpEF, even when caused experimentally by other disorders (such as pressure overload), because the hemodynamically stressed heart can signal to adipose tissue, whose secretions act on the heart to reinforce the severity of cardiac injury. Additional work is needed to validate clinical, imaging, and biomarker approaches for identifying biologically active (ie, inflamed) visceral adiposity in individual patients. Ongoing and anticipated clinical trials favor the development of adipose biological modulators for use in a broad population of HFpEF. In conclusion, the role of excess and dysfunctional fat in the genesis of HFpEF is well recognized, likely representing a primary or major upstream contributing cause in the large majority of patients. |
| Keywords: | Adipokines, Dysfunctional Fat, Heart Failure with Preserved Ejection Fraction |
| Source: | JACC: Heart Failure |
| ISSN: | 2213-1787 |
| Publisher: | Elsevier |
| Page Range: | 103046 |
| Date: | 29 March 2026 |
| Official Publication: | https://doi.org/10.1016/j.jchf.2026.103046 |
| PubMed: | View item in PubMed |
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