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Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support.

Publication ,  Journal Article
Ahmad, T; Kelly, JP; McGarrah, RW; Hellkamp, AS; Fiuzat, M; Testani, JM; Wang, TS; Verma, A; Samsky, MD; Donahue, MP; Ilkayeva, OR; Bowles, DE ...
Published in: J Am Coll Cardiol
January 26, 2016

BACKGROUND: Heart failure (HF) is characterized by perturbations in energy homeostasis and metabolism. The reversibility and prognostic value of circulating markers associated with these changes remain unclear. OBJECTIVES: This study sought to describe the metabolomic profiles of patients along the spectrum of systolic HF, determine their association with adverse outcomes in a clinical trial of HF, and evaluate whether identified metabolites change with treatment for end-stage systolic HF. METHODS: To assess association of metabolites with clinical outcomes, we evaluated a population of 453 chronic systolic HF patients who had been randomized to exercise training versus usual care. To assess change in metabolites with mechanical circulatory support, 41 patients with end-stage HF who underwent left ventricular assist device (LVAD) placement were studied. Targeted, quantitative profiling of 60 metabolites using tandem flow injection mass spectrometry was performed on frozen plasma samples obtained prior to randomization, as well as prior to and ≥90 days post-placement in the LVAD group. Principal components analysis was used for data reduction. RESULTS: Five principal components analysis-derived factors were significantly associated with peak Vo2 levels at baseline in fully adjusted models. Of these, factor 5 (composed of long-chain acylcarnitines) was associated with increased risk of all 3 pre-specified clinical trial outcomes: all-cause mortality/all-cause hospitalization, all cause-hospitalization, and cardiovascular death or cardiovascular hospitalization. Individual components of factor 5 were significantly higher in patients with end-stage HF prior to LVAD placement and decreased significantly post-implantation. CONCLUSIONS: In chronic HF patients, circulating long-chain acylcarnitine metabolite levels were independently associated with adverse clinical outcomes and decreased after long-term mechanical circulatory support. These metabolites may serve as potential targets for new diagnostics or therapeutic interventions. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

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Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

January 26, 2016

Volume

67

Issue

3

Start / End Page

291 / 299

Location

United States

Related Subject Headings

  • Statistics as Topic
  • Severity of Illness Index
  • Reproducibility of Results
  • Prognosis
  • Outcome Assessment, Health Care
  • North Carolina
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Humans
 

Citation

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Ahmad, T., Kelly, J. P., McGarrah, R. W., Hellkamp, A. S., Fiuzat, M., Testani, J. M., … Kraus, W. E. (2016). Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support. J Am Coll Cardiol, 67(3), 291–299. https://doi.org/10.1016/j.jacc.2015.10.079
Ahmad, Tariq, Jacob P. Kelly, Robert W. McGarrah, Anne S. Hellkamp, Mona Fiuzat, Jeffrey M. Testani, Teresa S. Wang, et al. “Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support.J Am Coll Cardiol 67, no. 3 (January 26, 2016): 291–99. https://doi.org/10.1016/j.jacc.2015.10.079.
Ahmad T, Kelly JP, McGarrah RW, Hellkamp AS, Fiuzat M, Testani JM, et al. Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support. J Am Coll Cardiol. 2016 Jan 26;67(3):291–9.
Ahmad, Tariq, et al. “Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support.J Am Coll Cardiol, vol. 67, no. 3, Jan. 2016, pp. 291–99. Pubmed, doi:10.1016/j.jacc.2015.10.079.
Ahmad T, Kelly JP, McGarrah RW, Hellkamp AS, Fiuzat M, Testani JM, Wang TS, Verma A, Samsky MD, Donahue MP, Ilkayeva OR, Bowles DE, Patel CB, Milano CA, Rogers JG, Felker GM, O’Connor CM, Shah SH, Kraus WE. Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support. J Am Coll Cardiol. 2016 Jan 26;67(3):291–299.
Journal cover image

Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

January 26, 2016

Volume

67

Issue

3

Start / End Page

291 / 299

Location

United States

Related Subject Headings

  • Statistics as Topic
  • Severity of Illness Index
  • Reproducibility of Results
  • Prognosis
  • Outcome Assessment, Health Care
  • North Carolina
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Humans