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Targeting the Metabolic-Inflammatory Circuit in Heart Failure With Preserved Ejection Fraction

  • Translational Research in Heart Failure (M. Hoes, Section Editor)
  • Published:
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Abstract

Purpose of Review

Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality. The current mechanistic paradigm supports a comorbidity-driven systemic proinflammatory state that evokes microvascular and myocardial dysfunction. Crucially, diabetes and obesity are frequently prevalent in HFpEF patients; as such, we review the involvement of a metabolic-inflammatory circuit in disease pathogenesis.

Recent Findings

Experimental models of diastolic dysfunction and genuine models of HFpEF have facilitated discovery of underlying drivers of HFpEF, where metabolic derangement and systemic inflammation appear to be central components of disease pathophysiology. Despite a shared phenotype among these models, molecular signatures differ depending on type and combination of comorbidities present.

Summary

Inflammation, oxidative stress, hypertension, and metabolic derangements have been positioned as therapeutic targets to suppress the metabolic-inflammatory circuit in HFpEF. However, the stratification of unique patient phenogroups within the collective HFpEF subgroup argues for specific interventions for distinct phenogroups.

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Funding

Chrishan Ramachandra is supported by the Singapore Ministry of Health’s National Medical Research Council Open Fund-Young Individual Research Grant (NMRC/OFYIRG/0073/2018), the SingHealth Duke-NUS Academic Medicine Research Grant (AM/TP033/2020 [SRDUKAMR2033]), and the Khoo Bridge Funding Award (Duke-NUS-KBrFA/2022/0059). Myu Mai Ja Kp is supported by the National Heart Centre Singapore Centre Grant PROTECT Seed Fund (NHCS-CGSF/2022/003).

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  1. National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore

    En Ping Yap, Myu Mai Ja Kp & Chrishan J. Ramachandra

  2. Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore

    En Ping Yap & Chrishan J. Ramachandra

  3. Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore

    En Ping Yap

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  1. En Ping Yap
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  2. Myu Mai Ja Kp
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  3. Chrishan J. Ramachandra
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Correspondence to Chrishan J. Ramachandra.

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Yap, E.P., Kp, M.M.J. & Ramachandra, C.J. Targeting the Metabolic-Inflammatory Circuit in Heart Failure With Preserved Ejection Fraction. Curr Heart Fail Rep 19, 63–74 (2022). https://doi.org/10.1007/s11897-022-00546-1

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