Myocardial ATP depletion detected noninvasively predicts sudden cardiac death risk in patients with heart failure

BACKGROUND. Sudden cardiac death (SCD) remains a worldwide public health problem in need of better noninvasive predictive tools. 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: fewer than 5% 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. METHODS. We prospectively measured myocardial energy metabolism noninvasively with phosphorus magnetic resonance spectroscopy in patients with no history of significant arrhythmias prior to scheduled ICD implantation for primary prevention in the setting of reduced LVEF (<= 35%). RESULTS. By 2 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. Life-threatening arrhythmia risk was approximately 3-fold 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. CONCLUSION. To the best of our knowledge, these are the first data linking in vivo myocardial ATP depletion and subsequent significant arrhythmic events in people, suggesting an energetic component to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of metabolic strategies that limit ATP loss to treat or prevent life-threatening cardiac arrhythmias and herald noninvasive metabolic imaging as a complementary SCD risk stratification tool. TRIAL REGISTRATION. ClinicalTrials.gov NCT00181233.

Automated summary

Noninvasive measurement of myocardial ATP levels in patients with reduced LVEF prior to ICD implantation revealed a significant association between low ATP and subsequent life-threatening arrhythmias and cardiac death over a 10-year period. Patients with low ATP had a 3-fold higher risk of life-threatening arrhythmias, independent of established risk factors. These findings suggest the importance of myocardial energy metabolism in predicting clinical life-threatening arrhythmias and support further investigation into metabolic strategies for prevention and treatment.