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Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing.

Publication ,  Journal Article
Limkakeng, AT; Henao, R; Voora, D; O'Connell, T; Griffin, M; Tsalik, EL; Shah, S; Woods, CW; Ginsburg, GS
Published in: PLoS One
2019

BACKGROUND: The heart is a metabolically active organ, and plasma acylcarnitines are associated with long-term risk for myocardial infarction. We hypothesized that myocardial ischemia from cardiac stress testing will produce dynamic changes in acylcarnitine and amino acid levels compared to levels seen in matched control patients with normal stress tests. METHODS: We analyzed targeted metabolomic profiles in a pilot study of 20 case patients with inducible ischemia on stress testing from an existing prospectively collected repository of 357 consecutive patients presenting with symptoms of Acute Coronary Syndrome (ACS) in an Emergency Department (ED) observation unit between November 2012 and September 2014. We selected 20 controls matched on age, sex, and body-mass index (BMI). A peripheral blood sample was drawn <1 hour before stress testing and 2 hours after stress testing on each patient. We assayed 60 select acylcarnitines and amino acids by tandem mass spectrometry (MS/MS) using a Quattro Micro instrument (Waters Corporation, Milford, MA). Metabolite values were log transformed for skew. We then performed bivariable analysis for stress test outcome and both individual timepoint metabolite concentrations and stress-delta metabolite ratios (T2/T0). False discovery rates (FDR) were calculated for 60 metabolites while controlling for age, sex, and BMI. We built multivariable regularized linear models to predict stress test outcome from metabolomics data at times 0, 2 hours, and log ratio between these two. We used leave-one-out cross-validation to estimate the performance characteristics of the model. RESULTS: Nine of our 20 case subjects were male. Cases' average age was 55.8, with an average BMI 29.5. Bivariable analysis identified 5 metabolites associated with positive stress tests (FDR < 0.2): alanine, C14:1-OH, C16:1, C18:2, C20:4. The multivariable regularized linear models built on T0 and T2 had Area Under the ROC Curve (AUC-ROC) between 0.5 and 0.55, however, the log(T2/T0) model yielded 0.625 AUC, with 65% sensitivity and 60% specificity. The top metabolites selected by the model were: Ala, Arg, C12-OH/C10-DC, C14:1-OH, C16:1, C18:2, C18:1, C20:4 and C18:1-DC. CONCLUSIONS: Stress-delta metabolite analysis of patients undergoing stress testing is feasible. Future studies with a larger sample size are warranted.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

2

Start / End Page

e0211762

Location

United States

Related Subject Headings

  • Prospective Studies
  • Pilot Projects
  • Middle Aged
  • Male
  • Humans
  • General Science & Technology
  • Female
  • Exercise Test
  • Emergency Service, Hospital
  • Carnitine
 

Citation

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Limkakeng, A. T., Henao, R., Voora, D., O’Connell, T., Griffin, M., Tsalik, E. L., … Ginsburg, G. S. (2019). Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing. PLoS One, 14(2), e0211762. https://doi.org/10.1371/journal.pone.0211762
Limkakeng, Alexander T., Ricardo Henao, Deepak Voora, Thomas O’Connell, Michelle Griffin, Ephraim L. Tsalik, Svati Shah, Christopher W. Woods, and Geoffrey S. Ginsburg. “Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing.PLoS One 14, no. 2 (2019): e0211762. https://doi.org/10.1371/journal.pone.0211762.
Limkakeng AT, Henao R, Voora D, O’Connell T, Griffin M, Tsalik EL, et al. Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing. PLoS One. 2019;14(2):e0211762.
Limkakeng, Alexander T., et al. “Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing.PLoS One, vol. 14, no. 2, 2019, p. e0211762. Pubmed, doi:10.1371/journal.pone.0211762.
Limkakeng AT, Henao R, Voora D, O’Connell T, Griffin M, Tsalik EL, Shah S, Woods CW, Ginsburg GS. Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing. PLoS One. 2019;14(2):e0211762.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

2

Start / End Page

e0211762

Location

United States

Related Subject Headings

  • Prospective Studies
  • Pilot Projects
  • Middle Aged
  • Male
  • Humans
  • General Science & Technology
  • Female
  • Exercise Test
  • Emergency Service, Hospital
  • Carnitine