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


ABSTRACT:

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 (kPL) for lactate increased from 11 ± 9 *10-3 to 20 ± 10 * 10-3 s-1, p = 0.04. The pyruvate oxidation rate (kPB) 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.

SUBMITTER: Joergensen SH 

PROVIDER: S-EPMC9169396 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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

Joergensen Steen Hylgaard SH   Hansen Esben Soevsoe S ESS   Bøgh Nikolaj N   Bertelsen Lotte Bonde LB   Staehr Peter Bisgaard PB   Schulte Rolf F RF   Malloy Craig C   Wiggers Henrik H   Laustsen Christoffer C  

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 20220606 1


<h4>Background</h4>Hyperpolarized (HP) [1-<sup>13</sup>C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-<sup>13</sup>C]pyruvate to either [1-<sup>13</sup>C]lactate or <sup>13</sup>C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-<sup>13</sup>C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate  ...[more]

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