Suppression of Cardiogenic Edema with Sodium–Glucose Cotransporter-2 Inhibitors in Heart Failure with Reduced Ejection Fraction: Mechanisms and Insights from Pre-Clinical Studies

Ryan D. Sullivan, Mariana E. McCune, Michelle Hernandez, Guy L. Reed, Inna P. Gladysheva

Research output: Contribution to journalReview articlepeer-review

Abstract

In heart failure with reduced ejection fraction (HFrEF), cardiogenic edema develops from impaired cardiac function, pathological remodeling, chronic inflammation, endothelial dysfunction, neurohormonal activation, and altered nitric oxide-related pathways. Pre-clinical HFrEF studies have shown that treatment with sodium–glucose cotransporter-2 inhibitors (SGLT-2i) stimulates natriuretic and osmotic/diuretic effects, improves overall cardiac function, attenuates maladaptive cardiac remodeling, and reduces chronic inflammation, oxidative stress, and endothelial dysfunction. Here, we review the mechanisms and effects of SGLT-2i therapy on cardiogenic edema in various models of HFrEF. Overall, the data presented suggest a high translational importance of these studies, and pre-clinical studies show that SGLT-2i therapy has a marked effect on suppressing the progression of HFrEF through multiple mechanisms, including those that affect the development of cardiogenic edema.

Original languageEnglish (US)
Article number2016
JournalBiomedicines
Volume10
Issue number8
DOIs
StatePublished - Aug 2022
Externally publishedYes

Keywords

  • HFrEF
  • cardiac remodeling
  • dilated cardiomyopathy
  • edema
  • endothelial dysfunction
  • excessive extracellular fluid
  • fluid management
  • inflammation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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