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

Hyperpolarized (HP) [1- C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1- C]pyruvate to either [1- C]lactate or C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine st...

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Published in:	Journal of cardiovascular magnetic resonance 2022-06, Vol.24 (1), p.34-34, Article 34
Main Authors:	Joergensen, Steen Hylgaard, Hansen, Esben Soevsoe S, Bøgh, Nikolaj, Bertelsen, Lotte Bonde, Staehr, Peter Bisgaard, Schulte, Rolf F, Malloy, Craig, Wiggers, Henrik, Laustsen, Christoffer
Format:	Article
Language:	eng
Subjects:	Adenosine Adult Bicarbonate Bicarbonates Carbohydrate metabolism Carbohydrates Carbonates Cardiac metabolism Cardiac stress tests Cardiovascular disease Conversion Dehydrogenases Electrical equipment and supplies industry Electrocardiography Exercise Test Female Glucose Heart Heart beat Heart rate Humans Image acquisition Ischemia Lactates Lactic acid Magnetic resonance imaging Magnetic Resonance Imaging - methods Magnetic Resonance Imaging, Cine Male Medical tests Metabolic imaging Metabolism Metabolites Myocardial Perfusion Imaging - methods Oxidation Oxidation rate Oxidoreductases Perfusion Physiological aspects Predictive Value of Tests Prospective Studies Pyruvic Acid Resonance Stress Stress test Ventricle Young Adult
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Summary:	Hyperpolarized (HP) [1- C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1- C]pyruvate to either [1- C]lactate or C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1- C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress. A prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1- C]pyruvate CMR at rest and during adenosine stress. HP [1- C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1- C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress. Six healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1- C]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 ) for lactate increased from 11 ± 9 10 to 20 ± 10 10 s , p = 0.04. The pyruvate oxidation rate (k ) increased from 4 ± 4 10 to 12 ± 7 10 s , p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R = 0.44, p = 0.02). Adenosine stress testing combined with HP [1- C]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- C]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.
ISSN:	1532-429X 1097-6647 1532-429X