RSNA News - April 2005

MRS Supports "Energy Starvation" Hypothesis in Heart Failure

Using MR spectroscopy (MRS), researchers at Johns Hopkins University School of Medicine have directly measured the rate at which the human heart produces adenosine triphosphate (ATP) through the creatine kinase (CK) reaction.

Writing in the January 18 issue of the Proceedings of the National Academy of Sciences, the research team concluded that "these direct measures of ATP synthesis through CK in the human heart demonstrate a deficit in energy supply in clinical heart failure. This reduction … is cardiac specific and occurs in mild to moderate heart failure before a significant reduction in ATP can be detected."

These findings support the "energy starvation" hypothesis of heart failure and could lead to new therapies for heart failure patients, said senior author, Paul A. Bottomley, Ph.D., director of the Division of MR Research in the Russell H. Morgan Department of Radiology and Radiological Science at Johns Hopkins.

In a group of 14 healthy controls, four angle saturation transfer (FAST) studies revealed that the rate of ATP flux remained constant, regardless of exercise status. "We did a pharmaceutical stress at 200 percent of the workload of the heart, doubling the heart rate and blood pressure, and the energy flux stayed the same. This means that the supply of ATP from CK is not unlimited," said Dr. Bottomley.

He compared these in vivo processes to gasoline reaching an automobile engine. "When you put your foot to the floor, the engine will choke if it's not getting enough fuel or energy. Similarly, you can't just keep ratcheting up exercise," he explained. "In our group of patients with heart failure studied at rest, we found that the energy supply was reduced by about half, which was quite surprising. So if the energy supply is halved, could it be that there would not be enough energy to meet demand? When we did the calculations it appears that energy supply could well be limited during stress or exercise in patients with mild-to-moderate heart failure, or even at rest in very severe cases."

This would be another explanation why patients live longer when they're given ACE inhibitors and ß-blockers that inhibit humoral response and reduce energy needs, said Dr. Bottomley, who is anxious to begin further research into the effects of linking improvement in energy supply with improvement in clinical symptoms.

"From the viewpoint of research, we think this is a major step forward in linking reduced energy supply and heart failure," he said. "A lot of MR studies just involve development and applications of techniques in direct clinical, diagnostic or therapeutic studies. Of course, that's a very worthy and valid approach to radiology research, but in addition, we can also use such techniques to find some new understanding of disease and its underlying causes."

To view the abstract of the article, go to www.pnas.org, click on Archives and then choose the January 18, 2005, issue pages 808-813.

Cardiac MR imaging and 31-P spectra from FAST studies of a normal subject acquired at rest (a and b) and during dobutamine stress (c); and of a 37-year-old patient with NYHA class III heart failure at rest (d and e).

Images courtesy of Paul A. Bottomley, Ph.D. © 2005 by The National Academy of Sciences, U.S.A.