title: 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 CRT.
  
  
  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.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Departments of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota; Department of Analytical Chemistry, Faculty of Pharmacy, University of Hacettepe, Ankara, Turkey.
authors.forename: Emirhan
authors.initials: E
authors.lastname: Nemutlu
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Departments of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Xu
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Departments of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Departments of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Petras D
authors.initials: PD
authors.lastname: Dzeja
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: ycha@mayo.edu.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Cha
mesh_terms: D000368:Aged; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D017115:Catheter Ablation / Q000379:methods; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007532:Isoleucine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D013617:Tachycardia, Supraventricular / Q000601:surgery; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D007532:Isoleucine; D010649:Phenylalanine; D005947:Glucose
keywords: Heart failure; cardiac resynchronization therapy; metabolism