Assessment of in vivo metabolism in failing hearts using hyperpolarised 13C magnetic resonance
Journal of Cardiovascular Magnetic Resonance volume 13, Article number: O79 (2011)
Increasingly, abnormal metabolic substrate utilisation is considered a cause of heart failure (HF). Hyperpolarised 13C MR, a technique in which the fate of 13C-labelled metabolites can be followed in vivo using MR imaging or spectroscopy, has enabled non-invasive assessment of cardiac substrate utilisation.
The aim of this study was to monitor carbohydrate metabolism alongside cardiac structure and function, throughout HF progression.
Dilated cardiomyopathy (DCM) was induced in pigs (n = 4) by rapid ventricular pacing at 188 bpm for 4-5 weeks. Pigs were examined at baseline and at weekly time points throughout DCM progression. At each time point, cine MRI was used to assess cardiac structure and function, 0.05 mmol/kg hyperpolarised 13C2-pyruvate was administered intravenously and MRS was used to assess Krebs cycle-mediated 13C-glutamate production, and hyperpolarised 13C1-pyruvate was administered to assess H13CO3- production from pyruvate dehydrogenase (PDH), and thus relative carbohydrate oxidation. A new cardiac and respiratory-gated 13C MRI sequence was used to image 13C1-pyruvate and H13CO3-. The chemical shift-specific pulse sequence used allowed temporally resolved imaging of 13C1-pyruvate and H13CO3- with 9 mm in-plane spatial resolution in multiple slices (two in these studies), all within a 23 s scan. Pigs were sacrificed after presentation of clinical symptoms or >25% increase in end diastolic volume (EDV).
At baseline, pigs had an EDV of 62 ± 5 ml. The maximum 13C-glutamate/13C2-pyruvate ratio was 4.9 ± 1.2% (Fig 1A), whereas the mean H13CO3-/13C1-pyruvate ratio across the anterior myocardium was 2.0 ± 0.3% (Fig 1B). After 1 week of pacing, the 13C-glutamate/13C2-pyruvate decreased significantly to 2.1 ± 0.8%, and was maintained at this level throughout DCM development. EDV increased linearly with pacing duration, and after 2-3 weeks of pacing was significantly elevated to 84 ± 12 ml. After 4-5 weeks of pacing (at the final time point), the ejection fraction (EF) was decreased by 40% compared with the baseline value, and the H13CO3-/13C1-pyruvate was decreased to 0.8±0.2%.
In conclusion, metabolism of 13C2-pyruvate to 13C-glutamate was reduced by 59% at an early stage in DCM, with no change to PDH flux. Reduced 13C-glutamate relative to H13CO3- production could be an early marker of disease. Carbohydrate oxidation via PDH was maintained until end-stage DCM, at which point PDH flux was reduced by 62%. With further development, metabolic imaging using hyperpolarised 13C MR may similarly characterize HF progression in patients.
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Schroeder, M.A., Lau, A., Chen, A. et al. Assessment of in vivo metabolism in failing hearts using hyperpolarised 13C magnetic resonance. J Cardiovasc Magn Reson 13 (Suppl 1), O79 (2011). https://doi.org/10.1186/1532-429X-13-S1-O79
- Dilate Cardiomyopathy
- Carbohydrate Oxidation
- Weekly Time Point
- Final Time Point
- Heart Failure Progression