People with failing hearts don't have enough chemical energy to support normal pumping function, according to recently published research by a team of scientists and doctors at the Johns Hopkins University School of Medicine. These findings lend credence to the "energy starvation" hypothesis of heart failure and could lead to new therapies for heart failure patients.
The energy starvation hypothesis states that heart cells beat weakly because they do not have enough energy supply to sustain normal contraction beating.
Heart disease is currently the number one cause of death in the United States, according to the Centers for Disease Control.
In 2002 approximately 700,000 deaths, or 28.5 percent of all deaths, were caused by heart disease.
The researchers pioneered a new technology to measure the rate at which chemical energy sources were generated in living, beating heart tissue.
Coupling a Magnetic Resonance Imaging (MRI) machine with spectroscopic techniques, they were able to measure turnover of the ATP molecule in heart tissue.
ATP, or adenosine triphosphate, is frequently called the "energy currency of the cell" and is used to chemically power myriad cellular functions from muscular contractions to construction of cellular supporting structures.
In heart cells the ATP molecules are produced from several sources, including a reaction involving the enzyme Creatine Kinase (CK). Measuring the ATP production rate of this reaction allowed researchers to compare the energy supply in the normal heart with that of heart failure patients.
They studied 14 healthy volunteers, as well as 17 volunteers with a history of heart failure. The study was published in the January 18, 2005 issue of the Proceedings of the National Academy of Sciences under the title "ATP flux through creatine kinase in the normal, stressed, and failing human heart." The article was authored by Paul A. Bottomley PhD of the Nuclear Magnetic Resonance Research Division, The Johns Hopkins University School of Medicine as well as by Robert G. Weiss, M.D. and Gary Gerstenblith, M.D. of the Johns Hopkins Department of Medicine, Cardiology Division.
The team's findings indicate that healthy patients were able to produce ATP from CK at a sufficient rate for a range of different work levels, while for patients with mild to moderate heart failure energy supply was approximately halved.
According to Weiss, there were several previous conceptions how heart failure developed and progressed. "The older 'hemodynamic hypothesis' of heart failure proposed that making the heart beat stronger would treat heart failure. In the short term such approaches may improve symptoms and cardiac output but ultimately they do not reduce long-term mortality and in fact sometimes increase mortality. This may be because, in part," they increase energy demand in an energy deficient environment." If the heart is an "old tired horse pulling a cart up a hill," as Weiss explains, these treatments were akin to "whipping the tired horse."
More recently the "neurohormonal hypothesis," which current heart failure therapies are based on, holds that our bodies' natural response to heart failure, namely releasing chemicals like adrenaline into the blood helps in the short term but hurts more in the long term. Consequently drugs such as ACE-inhibitors and beta-blockers that are used to treat heart failure are designed to stop this ultimately damaging response.
These treatments, unlike those based on the earlier hemodynamic hypothesis, have resulted in greater survival rates for heart failure patients. In the horse cart analogy these treatments "slow down the horse [and] unload the wagon."
These treatments also lower the amount of energy required by the heart and may be working, in part, through the energy starvation hypothesis.
This recent study showing a problem in energy transfer in the failing heart may lead to new metabolic treatments for heart failure. These would be akin to "feeding" the tired horse pulling the cart and could complement current treatments.
This new MRI technique offers a new and potentially important way to study the energetic status of the normal and failing human heart.
