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 journalArticle

2 Citations (Scopus)

Abstract

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
JournalEuropace
Volume18
Issue number9
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Implantable Defibrillators
Primary Prevention
Amines
Kynurenine
Serum
Defibrillators
Mortality
Observational Studies
Cardiac Arrhythmias
Shock
Biomarkers
Sudden Cardiac Death
Prospective Studies
Histidine
Validation Studies
Heart Failure
Confidence Intervals

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Zhang, Y., Blasco-Colmenares, E., Harms, A. C., London, B., Halder, I., Singh, M., ... Cheng, A. (2016). Serum amine-based metabolites and their association with outcomes in primary prevention implantable cardioverter-defibrillator patients. Europace, 18(9), 1383-1390. https://doi.org/10.1093/europace/euv342

Serum amine-based metabolites and their association with outcomes in primary prevention implantable cardioverter-defibrillator patients. / Zhang, Yiyi; Blasco-Colmenares, Elena; Harms, Amy C.; London, Barry; Halder, Indrani; Singh, Madhurmeet; Dudley, Samuel C.; Gutmann, Rebecca; Guallar, Eliseo; Hankemeier, Thomas; Tomaselli, Gordon F.; Cheng, Alan.

In: Europace, Vol. 18, No. 9, 01.01.2016, p. 1383-1390.

Research output: Contribution to journalArticle

Zhang, Y, Blasco-Colmenares, E, Harms, AC, London, B, Halder, I, Singh, M, Dudley, SC, Gutmann, R, Guallar, E, Hankemeier, T, Tomaselli, GF & Cheng, A 2016, 'Serum amine-based metabolites and their association with outcomes in primary prevention implantable cardioverter-defibrillator patients', Europace, vol. 18, no. 9, pp. 1383-1390. https://doi.org/10.1093/europace/euv342
Zhang, Yiyi ; Blasco-Colmenares, Elena ; Harms, Amy C. ; London, Barry ; Halder, Indrani ; Singh, Madhurmeet ; Dudley, Samuel C. ; Gutmann, Rebecca ; Guallar, Eliseo ; Hankemeier, Thomas ; Tomaselli, Gordon F. ; Cheng, Alan. / Serum amine-based metabolites and their association with outcomes in primary prevention implantable cardioverter-defibrillator patients. In: Europace. 2016 ; Vol. 18, No. 9. pp. 1383-1390.
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abstract = "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.",
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AU - Zhang, Yiyi

AU - Blasco-Colmenares, Elena

AU - Harms, Amy C.

AU - London, Barry

AU - Halder, Indrani

AU - Singh, Madhurmeet

AU - Dudley, Samuel C.

AU - Gutmann, Rebecca

AU - Guallar, Eliseo

AU - Hankemeier, Thomas

AU - Tomaselli, Gordon F.

AU - Cheng, Alan

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N2 - 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.

AB - 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.

KW - Amine

KW - Implantable cardioverter-defibrillator

KW - Metabolomics

KW - Mortality

KW - Ventricular arrhythmia

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