Abstract #1434

A Multi-Nuclear MRI/MRS Study Exploring the Impact of a Novel Cardiac Mitotrope in the Treatment of Diabetic Cardiomyopathy

Damian Tyler¹, Moritz Hundertmark¹, Adrienne Siu¹, Violet Matthews², Andrew Lewis¹, James Grist^1,2, Jai Patel³, Paul Chamberlin³, Rizwan Sarwar¹, Arash Yavari^1,3, Hakim-Moulay Dehbi⁴, Michael Frenneaux⁵, Ladislav Valkovič^1,6, Jack Miller^1,7, Stefan Neubauer¹, and Oliver Rider¹

¹University of Oxford, Oxford, United Kingdom, ²Oxford University Hospitals NHS Foundations Trust, Oxford, United Kingdom, ³Imbria Pharmaceuticals, Boston, MA, United States, ⁴University College London, London, United Kingdom, ⁵Hamad Medical Corporation, Doha, Qatar, ⁶Slovak Academy of Sciences, Bratislava, Slovakia, ⁷Aarhus University, Aarhus, Denmark

Synopsis

Keywords: Heart, Diabetes, Multi-nuclear SpectroscopyPatients with Type 2 Diabetes (T2D) are at a significantly increased risk of heart failure (HF) with the development of HF driven by energetic, metabolic, structural, and functional cardiac changes. In this study we have used a multi-nuclear MRI/MRS approach to demonstrate that the novel metabolic modulator, ninerafaxstat, can significantly improve myocardial energetics, cardiac steatosis and diastolic function in patients with T2D and obesity. In addition, using cardiac hyperpolarized [1-¹³C]pyruvate MRS, we have identified a potential signal for increased pyruvate dehydrogenase flux upon treatment with ninerafaxstat.

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