Detection of increased pyruvate dehydrogenase flux in the human heart during adenosine stress test using hyperpolarized [1-¹³C]pyruvate cardiovascular magnetic resonance imaging

Background: Hyperpolarized (HP) [1-¹³C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-¹³C]pyruvate to either [1-¹³C]lactate or ¹³C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-¹³C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress. Methods: A prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1-¹³C]pyruvate CMR at rest and during adenosine stress. HP [1-¹³C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1-¹³C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress. Results: Six healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1-¹³C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2 ± 2.8 to 2.7 ± 1.3 s, p = 0.02. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (k_PL) for lactate increased from 11 ± 9 *10^–3 to 20 ± 10 * 10^–3 s⁻¹, p = 0.04. The pyruvate oxidation rate (k_PB) increased from 4 ± 4 *10^–3 to 12 ± 7 *10^–3 s⁻¹, p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R² = 0.44, p = 0.02). Conclusions: Adenosine stress testing combined with HP [1-¹³C]pyruvate CMR is feasible and well-tolerated in healthy subjects. We observed an increased pyruvate oxidation during cardiac stress. The present study is an important step in the translation of HP [1-¹³C]pyruvate CMR into clinical cardiac imaging. Trial registration EUDRACT, 2018-003533-15. Registered 4th of December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15.