Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Abstract Background Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value regarding the response to...

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Bibliographic Details
Published in:Journal of cardiac failure 2015-06, Vol.21 (6), p.460-469
Main Authors: Nemutlu, Emirhan, PhD, Zhang, Song, PhD, Xu, Yi-Zhou, MD, Terzic, Andre, MD, PhD, Zhong, Li, MD, Dzeja, Petras D., PhD, Cha, Yong-Mei, MD
Format: Article
Language:English
Subjects:
Aged
cardiac resynchronization therapy
Cardiac Resynchronization Therapy - methods
Cardiovascular
Catheter Ablation - methods
Energy Metabolism - physiology
Female
Gas Chromatography-Mass Spectrometry - methods
Glucose - metabolism
Heart failure
Heart Failure - metabolism
Heart Failure - physiopathology
Heart Failure - therapy
Humans
Isoleucine - metabolism
Magnetic Resonance Spectroscopy - methods
Male
metabolism
Metabolomics - methods
Middle Aged
Myocardium - metabolism
Phenylalanine - metabolism
Predictive Value of Tests
Prognosis
Prospective Studies
Tachycardia, Supraventricular - surgery
Ventricular Dysfunction, Left - metabolism
Ventricular Dysfunction, Left - physiopathology
Ventricular Dysfunction, Left - therapy
Ventricular Remodeling - physiology
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Summary:Abstract Background Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value regarding the response to CRT. Methods and Results This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed with the use of gas chromatography–mass spectrometry and nuclear magnetic resonance. The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolomic profile. The succinate-glutamate ratio, an index of Krebs cycle activity, improved from 0.58 ± 0.13 to 2.84 ± 0.60 ( P < .05). The glucose-palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96 ± 0.05 to 1.54 ± 0.09 ( P < .01). Compared with nonresponders to CRT, responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline ( P < .05). Conclusions CRT improves the plasma metabolomic profile of HF patients, indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolomic profile as a potential biomarker for predicting CRT outcome.
ISSN:1071-9164
1532-8414
DOI:10.1016/j.cardfail.2015.04.005