Heart of the matter: NMR cardiac prognosis

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  • Published: Jan 1, 2014
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Heart of the matter: NMR cardiac prognosis

Metabolic risk

Metabolic Rates of ATP Transfer Through Creatine Kinase (CK Flux) Predict Clinical Heart Failure Events and Death

Researchers in the US have turned to magnetic resonance spectroscopy to find a novel approach to predicting whether the health of a patient that has suffered heart failure is likely to worsen or improve.

Paul Bottomley, Gurusher Panjrath, Shenghan Lai, Glenn Hirsch, Katherine Wu, Samer Najjar, Angela Steinberg, Gary Gerstenblith and Robert Weiss of Johns Hopkins University School of Medicine, in Baltimore, Maryland, USA, have taken the first steps towards the application of NMR spectroscopy (commonly referred to as magnetic resonance spectroscopy in the medical setting) to develop a clinical prognosis system for heart patients based on metabolic risk factors. The approach might be used in parallel with more conventional means of assessing the future risk of heart failure in such patients, which normally includes the patient's physical symptoms, how well their heart can now pump blood around the body, the so-called ejection fraction and other factors.

According to the team about half of the five million people that suffer heart failure in the USA each year have non-ischemic cardiomyopathy. This form of heart failure is due to changes other than the relatively common form of heart disease, atherosclerosis, or blocked arteries.

Tailored interventions

"It is difficult to predict which people with non-ischemic heart failure will do poorly and be at a higher risk of death," explains Weiss, a cardiologist and professor of medicine at Johns Hopkins and senior author of the current research. "Having a more precise way to determine a patient's risk would enable us to identify those at higher risk earlier and tailor their treatments more specifically. In addition, with a new target - impaired energy metabolism - we can also open the door to developing and testing new therapies for heart failure," he adds.

He and his colleagues have published details of their NMR work in the 11th December issue of Science Translational Medicine. They measured energy metabolism - the interaction of adenosine triphosphate (ATP) with the enzyme creatine kinase (CK) - in the heart muscle of 58 patients who had suffered heart failure. CK is essential to maintaining a constant energy supply in the beating heart. The researchers were able to measure the rate of ATP synthesis through the CK reaction within patients' heart cells non-invasively without the need for the contrast agents commonly used in the related magnetic resonance imaging and without the need for ionizing radiation, such as X-rays. They followed up those patients for a median of 4.7 years to track heart failure hospitalization, heart transplantation, the placement of ventricular assist devices and/or death from all causes.

"We found that the rate of energy metabolism in heart muscle was significantly lower in those heart failure patients whose conditions got worse and needed hospitalization, implantation of a ventricular assist device or a heart transplant, or had died from their weakened heart," explains team member Paul Bottomley. "We believe that the rate of ATP delivery to the cells by CK can be used along with established methods to better predict heart failure events and improve the timing of intensive interventions for patients."

The ATP factor

Conventional approaches to assessing heart patients, recommended by hearth health organizations usually involve categorizing a patient based on physical, rather than chemical factors, such as shortness of breath and chest pain. "The current methods used for prediction are not reflective of the underlying mechanism in the weak heart, and some of them are not very consistent in their predictive ability. That's why there's a need for new methods that could potentially be more specific," says team member Gurusher Panjrath, who has moved to the George Washington School of Medicine & Health Sciences in Washington, DC, since the work was carried out. The researchers say that even after correcting assessment for this classification, ejection fraction and race, a reduction in energy metabolism was a significant predictor of heart failure outcomes in their study.

"It makes sense that failing hearts with reduced energy supply are at increased risk of adverse outcomes, because the heart requires a lot of chemical energy to beat and function normally," explains Weiss. "Now that our study has shown that energy metabolism in the human heart can be measured with an MRI scanner to predict heart failure outcomes, future studies are needed to determine the factors that impair energy metabolism in heart failure."

About half of the people who develop heart failure die within five years of diagnosis. The cause of non-ischemic heart failure is usually idiopathic but high blood pressure, diabetes, infection and certain inherited conditions are known risk factors. The MR technique could provide new insights into the failing heart in such patients and allow doctors to make better informed interventions, whether surgical, device or pharmaceutical approaches.

"The next steps are to first replicate these findings in a larger population," Weiss told SpectroscopyNOW. "Secondly, to determine what impairs ATP flux through CK in human heart failure, and thirdly to identify and test new metabolic approaches to improve energy metabolism in failing hearts," he says. "Because heart failure is a common problem with high mortality and medical care costs, we hope to eventually evaluate whether metabolic treatments improve outcomes and prognosis in patients with heart failure," Weiss adds.

Related Links

Sci Translat Med, 2013, 5, 215re3: "Metabolic Rates of ATP Transfer Through Creatine Kinase (CK Flux) Predict Clinical Heart Failure Events and Death"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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