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Research links abnormal heart metabolism to abrupt cardiac mortality in future

Adults with abnormal heart metabolism are up to three times more likely to experience life-threatening arrhythmias (an irregular heart rhythm), according to a small but rigorous study led by Johns Hopkins Medicine researchers, and MRI techniques could be used to detect the condition and predict future sudden cardiac death (SCD).

“We think this is the first time that poor cardiac metabolism in individuals has been related to an increased risk of life-threatening arrhythmias or sudden cardiac death,” says research senior author and Johns Hopkins University School of Medicine professor of medicine Robert Weiss, M.D.

“This might pave the way for a whole new technique, a metabolic method for treating or avoiding severe arrhythmias, which is now unavailable in cardiology.” According to the American Heart Association, sudden cardiac death accounts for 50% of all cardiovascular fatalities in the United States, taking more than 300,000 American lives each year. Currently, the primary approach of avoiding SCD in high-risk individuals is an implanted cardioverter-defibrillator (ICD) – a tiny, battery-powered device put in the chest to detect and halt abnormal heart beats. The gadget continually monitors the heart rhythm and, if necessary, delivers electric shocks to restore a normal heart rhythm. An ICD’s battery life is normally five to seven years.

“Over a seven-year period, 60 percent to 70 percent of these devices never discharge to save a life,” says T. Jake Samuel, PhD, the study’s first author and a fellow in cardiology at Johns Hopkins Medicine. “We spend billions of dollars each year on implanted ICDs with procedural and postprocedural dangers. Noninvasive techniques to determining who requires or does not need an ICD to avoid sudden cardiac death in persons are needed.”

Samuel and colleagues evaluated adenosine triphosphate (ATP), the basic chemical cellular energy source, in the hearts of 46 persons before they received an ICD for primary prevention.

To establish whether patients had aberrant ATP metabolism, cardiac ATP levels were evaluated on clinical magnetic resonance imaging (MRI) scanners using a magnetic resonance spectroscopy (MRS) technology developed at Johns Hopkins Medicine by Paul Bottomley, PhD, a co-author of the work. For an average of ten years, all patients were followed up on every three to six months to assess whether patients had appropriate ICD firings for life-threatening arrhythmias.

People with low cardiac ATP levels (impaired metabolism) had a three-fold greater risk of sudden cardiac mortality (if not spared by ICD intervention) than those with normal ATP metabolism, according to the findings.

When corrected for low left ventricular ejection fraction, the parameter presently used to establish the requirement for a primary prevention ICD, this remained true.

“The ICD was never required in around 80% of patients with normal cardiac ATP levels over the research period,” Samuel and colleagues write. According to the researchers, the study findings might supplement current methodologies and lead to better forecasts of who will or will not require an ICD. They emphasise, however, that further research is needed to analyse diverse and bigger groups.

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“But we’re delighted about these very novel discoveries, possibly the first in humans, and feel they can revolutionise how clinicians estimate the risk of sudden cardiac death,” Weiss adds.

“Once we’ve established that metabolism and SCD are connected, we intend to investigate which medications retain and improve ATP metabolism and if they may be utilised to lower SCD risk.”

In addition to Weiss, other Johns Hopkins University School of Medicine researchers include T. Jake Samuel, Michael Schar, Katherine Wu, Angela Steinberg, Mark Anderson, Gary Gerstenblith, and Paul Bottomley; An-Chi Wei from National Taiwan University in Taipei, Taiwan; and Gordon Tomaselli from Albert Einstein College of Medicine in the Bronx, New York.

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