Growing evidence supports therapeutic ketosis in heart failure with reduced ejection fraction though uncertainty exists regarding use with SGLT2i and dose-dependent effects. In a phase I trial of 2 ketone ester (KE) doses in 20 heart failure with reduced ejection fraction participants stratified by background SGLT2i the authors detailed pharmacokinetic parameters noting rapid ketosis and short half-life.
Description of methods used for collection/generation of data:
- Venous blood gas testing using a point-of-care analyzer (iSTAT Abbott)
- Quantitative metabolomic profiling of metabolites using tandem flow injection mass spectrometry with a Xevo TQD instrument (Waters Corporation). Quantification for MS-profiled metabolites using stable isotope-labeled internal standards
- Non-esterified fatty acids total ketone bodies and beta-hydroxybutyrate were quantified on a Beckman-Coulter DxC600 clinical chemistry analyzer
- Glucagon and insulin measured via electrochemiluminescent immunoassays from Meso Scale Discovery (MSD) using a QuickPlex SQ-120 imager
Quality control of values imputation and transformation are described in the manuscript.
Please see manuscript for further details: Selvaraj S Kwee L Thompson E. et al. Metabolic and Pharmacokinetic Profiling of a Ketone Ester by Background SGLT2 Inhibitor Therapy in HFrEF. J Am Coll Cardiol Basic Trans Science. https://doi.org/10.1016/j.jacbts.2024.10.014
Description of methods used for collection/generation of data:
- Venous blood gas testing using a point-of-care analyzer (iSTAT Abbott)
- Quantitative metabolomic profiling of metabolites using tandem flow injection mass spectrometry with a Xevo TQD instrument (Waters Corporation). Quantification for MS-profiled metabolites using stable isotope-labeled internal standards
- Non-esterified fatty acids total ketone bodies and beta-hydroxybutyrate were quantified on a Beckman-Coulter DxC600 clinical chemistry analyzer
- Glucagon and insulin measured via electrochemiluminescent immunoassays from Meso Scale Discovery (MSD) using a QuickPlex SQ-120 imager
Quality control of values imputation and transformation are described in the manuscript.
Please see manuscript for further details: Selvaraj S Kwee L Thompson E. et al. Metabolic and Pharmacokinetic Profiling of a Ketone Ester by Background SGLT2 Inhibitor Therapy in HFrEF. J Am Coll Cardiol Basic Trans Science. https://doi.org/10.1016/j.jacbts.2024.10.014