Targeted metabolomics in Out-of-Hospital Cardiac arrest (OHCA)

Abstract

Abstract Background Out-of-hospital cardiac arrest is a leading cause of death. Even if successfully resuscitated, mortality and morbidity remain high due to ischemic and reperfusion injury (I/R). The oxygen deprivation leads to a metabolic derangement amplified upon reperfusion resulting in an uncontrolled generation of reactive oxygen species, triggering cell death mechanisms and organ damage. Understanding the I/R damage in humans following OHCA remains sparse, with no existing treatment to attenuate the reperfusion injury. Aim Describe metabolic derangement in patients following OHCA. Methods Blood samples from consecutive resuscitated unconscious OHCA patients drawn at hospital admission were analyzed using ultra-performance liquid mass-spectrometry. Sixty-one metabolites of the ∼3000 compounds detected were prespecified for quantification and analyzed in the current study. We used hierarchical cluster data analysis to identify metabolic clusters/phenotypes. Results In total, 163 patients were included, of which 143 (88%) were men, and the median age was 62 years (53–68). All measured metabolites from the tricarboxylic (TCA) cycle were significantly higher in non-survivors vs. survivors (180-days survival). Hierarchical clustering identified four (A-D) phenotypes of patients with distinct metabolic profiles. The mortality was significantly different in two phenotypes; A and B (A: 62% and B: 59% vs. C: 21% and D: 24%, p<0.001). There were no significant differences in age between the four phenotypes (p=0.35). Phenotype A and B had longer time to ROSC (A: 33 min (21–43), B: 27 min (24–35), C: 18 min (13–28), and D: 18 min (12–25), p<0.001). Phenotype A and D, who both had higher levels of free fatty acids, also a higher prevalence of ST-elevation or acute left bundle branch block in first ECG as compared to phenotype B and C (A: 76%, B: 55%, C: 36% and D: 75%, p<0.001. Conclusion Circulating levels of metabolites from the TCA cycle best described the variance between survivors and non-survivors. Four different metabolic phenotypes were identified. These phenotypes had significantly different mortality. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk Foundation