Tariq Ahmad1, Jacob P Kelly2, Robert W McGarrah3, Anne S Hellkamp4, Mona Fiuzat4, Jeffrey M Testani5, Teresa S Wang6, Amanda Verma7, Marc D Samsky7, Mark P Donahue7, Olga R Ilkayeva8, Dawn E Bowles9, Chetan B Patel2, Carmelo A Milano9, Joseph G Rogers2, G Michael Felker2, Christopher M O'Connor10, Svati H Shah3, William E Kraus3. 1. Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut; Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina. Electronic address: tariq.ahmad@yale.edu. 2. Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina. 3. Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina. 4. Duke Clinical Research Institute, Duke University, Durham, North Carolina. 5. Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. 6. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 7. Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina. 8. Duke Molecular Physiology Institute, Duke University, Durham, North Carolina. 9. Division of Cardiac Surgery, Duke University Medical Center, Durham, North Carolina. 10. Duke Clinical Research Institute, Duke University, Durham, North Carolina; Inova Heart and Vascular Institute, Falls Church, Virginia.
Abstract
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 toexercise 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).
RCT Entities:
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 HFpatients 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).
Authors: Tariq Ahmad; Teresa Wang; Emily C O'Brien; Marc D Samsky; John A Pura; Yuliya Lokhnygina; Joseph G Rogers; Adrian F Hernandez; Damian Craig; Dawn E Bowles; Carmelo A Milano; Svati H Shah; James L Januzzi; G Michael Felker; Chetan B Patel Journal: JACC Heart Fail Date: 2014-11-12 Impact factor: 12.035
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Authors: Marat Fudim; Jacob P Kelly; Aaron D Jones; Omar F AbouEzzeddine; Andrew P Ambrosy; Stephen J Greene; Yogesh N V Reddy; Kevin J Anstrom; Brooke Alhanti; Gregory D Lewis; Adrian F Hernandez; G Michael Felker Journal: Am Heart J Date: 2019-11-16 Impact factor: 4.749
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