Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy

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• 作者：Sebastian Obrzut (1) (3)
  Jay Tiongson (2)
  Neema Jamshidi (1)
  Huy Minh Phan (2)
  Carl Hoh (1)
  Ulrika Birgersdotter-Green (2)
  
• 关键词：Metabolism ; Fatty acids ; Cardiomyopathy
• 刊名：Journal of Cardiovascular Translational Research
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：3
• 期：6
• 页码：643-651
• 全文大小：181KB
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• 作者单位：Sebastian Obrzut (1) (3)
  Jay Tiongson (2)
  Neema Jamshidi (1)
  Huy Minh Phan (2)
  Carl Hoh (1)
  Ulrika Birgersdotter-Green (2)
  
  1. Division of Nuclear Medicine, University of California San Diego, La Jolla, CA, USA
  3. UCSD Medical Center, Hillcrest, Division of Nuclear Medicine, 200 West Arbor Drive, San Diego, CA, 92103-8758, USA
  2. Department of Cardiology, University of California San Diego, La Jolla, CA, USA
  
• ISSN：1937-5395

文摘

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56?±-6) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35%?±-7%) than responders [18?±-0%, p--.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho--.63, p--.0298; AUC--.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115?±-.112) than responders (0.034?±-.030, p--.0171; AUC--.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT.