Noting the need for better noninvasive predictive tools to combat the "worldwide public health problem" of sudden cardiac death (SCD), a study led by Johns Hopkins researchers has found that MRI techniques could be used to detect abnormal heart metabolism and predict SCD. Authors of the study, recently published in JCI Insight, believe this is the first time that impaired cardiac metabolism has been linked to an increased risk of life-threatening arrhythmias or sudden cardiac death (2022; https://doi.org/10.1172/jci.insight.157557).
The researchers also noted their study "could open a window for a whole new approach, a metabolic approach for treating or preventing severe arrhythmias," citing American Heart Association data showing that sudden cardiac death accounts for 50 percent of all cardiovascular deaths in the United States, claiming more than 300,000 American lives annually. As the investigators pointed out, a metabolic approach for treating or preventing SCD is not currently available in cardiology.
"Current guidelines for primary preventive SCD therapies, such as implantable cardioverter defibrillators (ICDs), are based on left ventricular ejection fraction (LVEF), but these guidelines are imprecise," the authors wrote in the journal article, noting that fewer than 5 percent of ICDs deliver lifesaving therapy per year. "Impaired cardiac metabolism and ATP depletion cause arrhythmias in experimental models, but to our knowledge a link between arrhythmias and cardiac energetic abnormalities in people has not been explored, nor has the potential for metabolically predicting clinical SCD risk."
Study Details
For this study, the research team prospectively measured myocardial energy metabolism noninvasively with phosphorus magnetic resonance spectroscopy (MRS) in patients with no history of significant arrhythmias prior to scheduled ICD implantation for primary prevention in the setting of reduced LVEF (<=35%).
By two different analyses, low myocardial ATP significantly predicted the composite of subsequent appropriate ICD firings for life-threatening arrhythmias and cardiac death over approximately 10 years, the authors noted, adding that life-threatening arrhythmia risk was approximately 3 times higher in patients with low ATP and independent of established risk factors, including LVEF. In patients with normal ATP, rates of appropriate ICD firings were several-fold lower than reported rates of ICD complications and inappropriate firings.
"To the best of our knowledge, these are the first data linking in vivo myocardial ATP depletion and subsequent significant arrhythmic events in people," the authors wrote, with these findings suggesting an "energetic component to clinical life-threatening ventricular arrhythmogenesis." The results also support investigation of metabolic strategies that limit ATP loss to treat or prevent life-threatening cardiac arrhythmias and "herald non-invasive metabolic imaging as a complementary SCD risk stratification tool," they added.
T. Jake Samuel, PhD, first author of the study and a fellow in cardiology at Johns Hopkins Medicine, noted that all patients in the study underwent routine imaging with other imaging modalities, "and we found that metabolic information from magnetic resonance spectroscopy complemented the conventional measures and provided new, better prediction of sudden death risk."
There is currently no other imaging modality that can measure ATP metabolism noninvasively in the human heart, he stated, adding that magnetic resonance spectroscopy can be performed on clinical MRI scanners and even be added to more typical MRI exams to measure heart function. "Unlike positron emission tomography or computed tomography, MRS does not require the injection of contrast agents or the consumption of radio tracers. Therefore, the patients are not exposed to ionizing radiation."
Given these results, MRI could prove to have an impact on how imaging and patient care teams approach the prevention and treatment of severe arrhythmias, noted Samuel, while cautioning that more studies are required to replicate these results in different and larger populations before any changes to clinical practice should be made.
However, the findings suggest a metabolic basis for some arrhythmias, at least in part, "which could open a whole new way of treating or preventing arrythmias metabolically," he said. "Second, noninvasive MRS could become a complementary risk stratification tool used in the clinic to identify individuals who would most benefit from ICDs for the primary prevention of sudden cardiac death. This research also opens the possibility of studying a new range of drugs that preserve and improve ATP metabolism, and whether they can be used to reduce sudden cardiac death risk in people."
Mark McGraw is a contributing writer.