Metabolic flux as a predictor of heart failure prognosis

Abstract

The creatine kinase (CK) system is thought to play an integral role in maintaining levels of chemical energy in the form of ATP, which is essential for normal cardiac function. In the failing heart, it has long been established that multiple components of CK energy metabolism are commonly impaired and that these correlate with disease severity. A recent study published in Science Translational Medicine adds significantly to this body of evidence by demonstrating that the rate of ATP transfer via CK, measured noninvasively by magnetic resonance spectroscopy, is an independent predictor of adverse clinical outcome in patients with nonischemic cardiomyopathy. This finding invites speculation on the future role of metabolic imaging for risk stratification in patients with heart failure. The authors further assert an implied causal role for energetics in disease progression. Although this is not supported by recent findings in loss-of-function mouse models, there is, nonetheless, a strong argument for the development of novel metabolic therapies for the failing heart.

Figure

³¹P spectra from a normal ex-vivo rat heart during a saturation transfer experiment (reproduced from ). Selective irradiation at the frequency corresponding to the γ-ATP peak (small arrow) effectively renders this phosphate group NMR-invisible. Under the action of creatine kinase (CK), this invisible phosphate group is interconverted to phosphocreatine (PCr), but remains NMR-invisible. The observed result is a reduction in the visible PCr peak. The extent of this reduction reflects the rate of phosphotransfer via CK, i.e. CK flux.