Predicting heart failure through metabolic profiling

December 11, 2013 § Leave a comment

The illustration shows the major signs and symptoms of heart failure. Image from http://en.wikipedia.org/wiki/File:Heartfailure.jpg

The illustration shows the major signs and symptoms of heart failure. Image from http://en.wikipedia.org/wiki/File:Heartfailure.jpg

Researchers say they now have a reliable predictor for heart failure. In a paper just out in Science Translational Medicine, the investigators say monitoring the activity of an enzyme called creatine kinase in a magnetic resonance scanner may help clinicians identify patients at high risk of cardiac events. The work “suggests, but does not prove, that strategies which could improve cardiac energy metabolism should be evaluated and tested as a desperately needed new approach for treating heart failure,” says Robert Weiss of Johns Hopkins University School of Medicine who is one of the authors.

In the 1990s, Weiss and one of his coauthors, Paul Bottomley, who is also at Hopkins, noticed something was not quite right with creatine kinase in disease-stricken hearts. Creatine kinase is the main energy reserve of the heart and is found both in the mitochondria and in the cytoplasm. It is believed to play an important role in the transfer of ATP to the muscle tissue of the heart. Weiss and Bottomley noticed that the level of creatine phosphate, a precursor to ATP in the  creatine kinase reaction, was lower than normal.

The idea of compromised energy being a possible cause of heart failure isn’t new, says Bottomley. It’s been around since the 1940s. “However, identifying an actual energy defect has been elusive, especially since the ATP concentrations do not appear to be particularly depressed in heart failure,” he says. Perhaps, the investigators thought, it was the supply mechanism overseen by creatine kinase that was the problem.

In 2005, the investigators established that that the metabolic flux through creatine kinase was down about 50 percent in patients with dilated cardiomyopathy and heart failure compared with healthy people. “Weiss calculated that this could be enough to cause an energy shortfall in periods of high-energy demand and stress,” says Bottomley. “We studied more patients, this time with hypertrophic disease, and found that the creatine kinase rate was specifically reduced only in those patients with heart failure.”

In the current work, the investigators studied 58 heart-failure patients with a magnetic resonance imaging instrument by tracking the flux of naturally occurring creatine phosphate  through their hearts. They demonstrated that a reduced flux of creatine phosphate may help identify patients who need aggressive treatment for heart failure, including those who should be evaluated for a heart transplant, at an earlier stage.

“The story is almost an ideal example of real bench-to-bedside translational research,” says Bottomley.

Weiss says the investigators now will validate their approach in a larger group of patients as well as work out which factors specifically impair creatine kinase energy metabolism. More importantly, says Weiss, the investigators hope to “identify new treatment strategies and medications that can restore cardiac energy metabolism to normal levels in failing hearts.”

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