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Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure.

Publication ,  Journal Article
Selvaraj, S; Kelly, DP; Margulies, KB
Published in: Circulation
June 2, 2020

Despite existing therapy, patients with heart failure (HF) experience substantial morbidity and mortality, highlighting the urgent need to identify novel pathophysiological mechanisms and therapies, as well. Traditional models for pharmacological intervention have targeted neurohormonal axes and hemodynamic disturbances in HF. However, several studies have now highlighted the potential for ketone metabolic modulation as a promising treatment paradigm. During the pathophysiological progression of HF, the failing heart reduces fatty acid and glucose oxidation, with associated increases in ketone metabolism. Recent studies indicate that enhanced myocardial ketone use is adaptive in HF, and limited data demonstrate beneficial effects of exogenous ketone therapy in studies of animal models and humans with HF. This review will summarize current evidence supporting a salutary role for ketones in HF including (1) normal myocardial ketone use, (2) alterations in ketone metabolism in the failing heart, (3) effects of therapeutic ketosis in animals and humans with HF, and (4) the potential significance of ketosis associated with sodium-glucose cotransporter 2 inhibitors. Although a number of important questions remain regarding the use of therapeutic ketosis and mechanism of action in HF, current evidence suggests potential benefit, in particular, in HF with reduced ejection fraction, with theoretical rationale for its use in HF with preserved ejection fraction. Although it is early in its study and development, therapeutic ketosis across the spectrum of HF holds significant promise.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

June 2, 2020

Volume

141

Issue

22

Start / End Page

1800 / 1812

Location

United States

Related Subject Headings

  • Stroke Volume
  • Sodium-Glucose Transporter 2 Inhibitors
  • Rats, Inbred Dahl
  • Myocardial Reperfusion Injury
  • Mice
  • Liver
  • Ketosis
  • Ketones
  • Ketone Bodies
  • Humans
 

Citation

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Selvaraj, S., Kelly, D. P., & Margulies, K. B. (2020). Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure. Circulation, 141(22), 1800–1812. https://doi.org/10.1161/CIRCULATIONAHA.119.045033
Selvaraj, Senthil, Daniel P. Kelly, and Kenneth B. Margulies. “Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure.Circulation 141, no. 22 (June 2, 2020): 1800–1812. https://doi.org/10.1161/CIRCULATIONAHA.119.045033.
Selvaraj S, Kelly DP, Margulies KB. Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure. Circulation. 2020 Jun 2;141(22):1800–12.
Selvaraj, Senthil, et al. “Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure.Circulation, vol. 141, no. 22, June 2020, pp. 1800–12. Pubmed, doi:10.1161/CIRCULATIONAHA.119.045033.
Selvaraj S, Kelly DP, Margulies KB. Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure. Circulation. 2020 Jun 2;141(22):1800–1812.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

June 2, 2020

Volume

141

Issue

22

Start / End Page

1800 / 1812

Location

United States

Related Subject Headings

  • Stroke Volume
  • Sodium-Glucose Transporter 2 Inhibitors
  • Rats, Inbred Dahl
  • Myocardial Reperfusion Injury
  • Mice
  • Liver
  • Ketosis
  • Ketones
  • Ketone Bodies
  • Humans