Serum amine-based metabolites and their association with outcomes in primary prevention implantable cardioverter-defibrillator patients

Yiyi Zhang, Elena Blasco-Colmenares, Amy C. Harms, Barry London, Indrani Halder, Madhurmeet Singh, Samuel C. Dudley, Rebecca Gutmann, Eliseo Guallar, Thomas Hankemeier, Gordon F. Tomaselli, Alan Cheng

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Aims Heart failure patients are at increased risk of ventricular arrhythmias and all-cause mortality. However, existing clinical and serum markers only modestly predict these adverse events.We sought to use metabolic profiling to identify novel biomarkers in two independent prospective cohorts of patients with implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death (SCD). Methods and results Baseline serum was quantitatively profiled for 42 known biologically relevant amine-based metabolites among 402 patients from the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD) Study (derivation group) and 240 patients from the Genetic Risk Assessment of Defibrillator Events (GRADE) Study (validation group) for ventricular arrhythmia-induced ICD shocks and all-cause mortality. Three amines, N-methyl-Lhistidine, symmetric dimethylarginine (SDMA), and L-kynurenine, were derived and validated to be associated with all-cause mortality. The hazard ratios of mortality in PROSE-ICD and GRADE were 1.48 (95% confidence interval 1.14-1.92) and 1.67 (1.22-2.27) for N-methyl-L-histidine, 1.49 (1.17-1.91) and 1.77 (1.27-2.45) for SDMA, 1.31 (1.06-1.63) and 1.73 (1.32-2.27) for L-kynurenine, respectively. L-Histidine, SDMA, and L-kynurenine were associated with ventricular arrhythmia-induced ICD shocks in PROSE-ICD, but they did not reach statistical significance in the GRADE cohort. Conclusion Utilizing metabolic profiling in two independent prospective cohorts of patients undergoing ICD implantation for primary prevention of SCD, we identified several novel amine markers that were associated with appropriate shock and mortality. These findings shed insight into the potential biologic pathways leading to adverse events in ICD patients. Further studies are needed to confirm the prognostic value of these findings.

Original languageEnglish (US)
Pages (from-to)1383-1390
Number of pages8
Issue number9
StatePublished - Sep 2016

Bibliographical note

Funding Information:
This work was supported by the Donald W. Reynolds Foundation, and the National Institutes of Health (R01 HL091062 to G.F.T., R01 HL103946 to A.C., and R01 HL077398 to B.L.)

Publisher Copyright:
© The Author 2016.


  • Amine
  • Implantable cardioverter-defibrillator
  • Metabolomics
  • Mortality
  • Ventricular arrhythmia


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