Out ahead of print in @CircAHA and displaying the first 2.5 years of my DPhil @RDMOxford @UniofOxford : EMPA-VISION RCT, investigating the hypothesis that #sglt2i mediate their benefits in #heartfailure via augmentation of cardiac energy metabolism

doi.org/10.1161/CIRCUL…

As SGLT2i induce glucosuria and thus, increase lipolysis and formation of ketone bodies like b-OHB, it was assumed that this effect might mediate their benefits in HF. But is this true? Well, we’ve tested it

We enrolled 36 patients with #HFrEF and 36 with #HFpEF and randomly assigned them #empagliflozin or placebo.

We then investigated them with #WhyCMR 31P-MRS for 🫀 energetics, MRI for 🫀function+vols and LC-MS for targeted serum metabolomics.

We know that myocardial energy supply is 🔻 in HFrEF and have recently shown that severity of diastolic dysfunction correlates nicely with energetic impairments, e.g. HFpEF as well doi.org/10.1161/CIRCUL…
@cardiolewis @DrMattBurrage

Following 12 weeks of treatment, there was no significant difference in resting or dobutamine 🥵measurements of cardiac energetics. Neither in #HFrEF nor in #HFpEF . Likewise, we did not see any changes in a panel of 19 targeted serum metabolites or circulating ketones

So, is the substrate hypothesis of #SGLT2i in HF dead? Not necessarily. There are limitations, like the length of therapy or exclusion of ischemia due (energetics only work in non-scarred myocardium). Lots more to do for smart people with interest in the 🫀 and 🦀🚲 (or TCA)

All credit goes to my mentors Stefan Neubauer, Ladislav Valkovič and @Ollie__Rider as well as my amazing colleagues who are way smarter than me (like @DrJackMiller) the patients and everyone who made this possible despite COVID.

@juanbadimon @SantosGallegoMD @DLBHATTMD @ChristophMaack @ImmunoCardioLab @LopaschukLab @EylemLevelt @SCMRorg @MassarOmard @MayooranShan @mvaduganathan @ChristophWanne4 @ChrisKramerMD @cardiolewis @DrMattBurrage @DrWillWatson @StefanFrantz @jochen_dutzmann @DjawidHashemi

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