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

ABSTRACT: 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.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.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.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.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).

SUBMITTER: Ahmad T

PROVIDER: S-EPMC5429585 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Ahmad Tariq T Kelly Jacob P JP McGarrah Robert W RW Hellkamp Anne S AS Fiuzat Mona M Testani Jeffrey M JM Wang Teresa S TS Verma Amanda A Samsky Marc D MD Donahue Mark P MP Ilkayeva Olga R OR Bowles Dawn E DE Patel Chetan B CB Milano Carmelo A CA Rogers Joseph G JG Felker G Michael GM O'Connor Christopher M CM Shah Svati H SH Kraus William E WE

Journal of the American College of Cardiology 20160101 3

<h4>Background</h4>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.<h4>Objectives</h4>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 systo ...[more]

PMID: 26796394

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Project description:ImportanceGiven the shortage of donor hearts and improvement in outcomes with left ventricular assist device (LVAD) therapy, a relevant but, to date, unanswered question is whether select patients with advanced heart failure should receive LVAD destination therapy as an alternative to heart transplant.ObjectiveTo determine whether a strategy of LVAD destination therapy is associated with similar survival benefit as wait-listing for heart transplant with or without LVAD therapy among patients with advanced heart failure.Design, setting, and participantsThis retrospective propensity-matched cohort analysis used data on heart transplants from the United Network for Organ Sharing registry and LVAD implants from the Interagency Registry for Mechanically Assisted Circulatory Support from January 1, 2010, to December 31, 2014. The matched LVAD destination therapy cohort included 3411 patients. Data analysis for this study was conducted from December 22, 2017, to May 24, 2019.Main outcomes and measuresSurvival at 5 years was analyzed using Cox proportional hazards models.ResultsIn total, 8281 patients had albumin level, creatinine level, and BMI data recorded and were included in the analysis. Despite propensity score matching, the 3411 patients receiving LVAD destination therapy still tended to be slightly older than the 3411 patients wait-listed for heart transplant (64.0 years [interquartile range, 55.0-70.0 years] vs 60.0 [interquartile range, 54.0-65.0 years]; P < .001), but there was no significant difference in sex (2701 men [79.2%] vs 2648 men [77.6%]; P = .13). After propensity score matching for age, sex, body mass index, renal function, and albumin level, 3411 patients were wait-listed for heart transplant. This included 1607 patients with bridge to transplant LVAD therapy and 1804 patients without LVAD. The strategy of wait-listing for heart transplant was associated with better 5-year survival than LVAD destination therapy (risk ratio, 0.42; 95% CI, 0.38-0.46) after matching and adjusting for key clinical factors. This survival advantage was associated with heart transplant (adjusted risk ratio for time-dependent transplant status, 0.27; 95% CI, 0.24-0.32).Conclusions and relevanceThe present analysis suggests that heart transplant with or without bridge to transplant LVAD therapy was associated with superior 5-year survival compared with LVAD destination therapy among patients matched on several relevant clinical factors. Continued improvement in LVAD technology, along with prospective comparative research, appears to be needed to amend this strategy.

Dataset Information

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

Publications

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

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