Impaired energy metabolism has been implicated in the pathogenesis of heart failure. Hyperpolarized ¹³C magnetic resonance (MR), in which ¹³C‐labelled metabolites are followed using MR imaging (MRI) or spectroscopy (MRS), has enabled non‐invasive assessment of pyruvate metabolism. We investigated the hypothesis that if we serially examined a model of heart failure using non‐invasive hyperpolarized [¹³C]pyruvate with MR, the profile of in vivo pyruvate oxidation would change throughout the course of the disease.

Dilated cardiomyopathy (DCM) was induced in pigs (n = 5) by rapid pacing. Pigs were examined using MR at weekly time points: cine‐MRI assessed cardiac structure and function; hyperpolarized [2‐¹³C]pyruvate was administered intravenously, and ¹³C MRS monitored [¹³C]glutamate production; ³¹P MRS assessed cardiac energetics [phosphocreatine (PCr)/ATP]; and hyperpolarized [1‐¹³C]pyruvate was administered for MRI of pyruvate dehydrogenase complex (PDC)‐mediated pyruvate oxidation via [¹³C]bicarbonate production. Early in pacing, the cardiac index decreased by 25%, PCr/ATP decreased by 26%, and [¹³C]glutamate production decreased by 51%. After clinical features of DCM appeared, end‐diastolic volume increased by 40% and [¹³C]bicarbonate production decreased by 67%. Pyruvate dehydrogenase kinase 4 protein increased by two‐fold, and phosphorylated Akt decreased by half. Peroxisome proliferator‐activated receptor‐α and carnitine palmitoyltransferase‐1 gene expression decreased by a half and a third, respectively.

Despite early changes associated with cardiac energetics and ¹³C incorporation into the Krebs cycle, pyruvate oxidation was maintained until DCM developed, when the heart's capacity to oxidize both pyruvate and fats was reduced. Hyperpolarized ¹³C MR may be important to characterize metabolic changes that occur during heart failure progression.