PMID- 20842468 OWN - NLM STAT- MEDLINE DCOM- 20110321 LR - 20211020 IS - 1937-5395 (Electronic) IS - 1937-5387 (Print) IS - 1937-5387 (Linking) VI - 3 IP - 6 DP - 2010 Dec TI - Assessment of metabolic phenotypes in patients with non-ischemic dilated cardiomyopathy undergoing cardiac resynchronization therapy. PG - 643-51 LID - 10.1007/s12265-010-9223-5 [doi] AB - 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 +/- 16) 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% +/- 17%) than responders [18 +/- 10%, p = 0.0098, 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 = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 +/- 0.112) than responders (0.034 +/- 0.030, p = 0.0171; AUC = 0.8593, 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. FAU - Obrzut, Sebastian AU - Obrzut S AD - Division of Nuclear Medicine, University of California-San Diego, UCSD Medical Center-Hillcrest, 200 West Arbor Drive, San Diego, CA 92103-8758, USA. sobrzut@ucsd.edu FAU - Tiongson, Jay AU - Tiongson J FAU - Jamshidi, Neema AU - Jamshidi N FAU - Phan, Huy Minh AU - Phan HM FAU - Hoh, Carl AU - Hoh C FAU - Birgersdotter-Green, Ulrika AU - Birgersdotter-Green U LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100915 PL - United States TA - J Cardiovasc Transl Res JT - Journal of cardiovascular translational research JID - 101468585 RN - 0 (Amino Acids) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Fatty Acids, Nonesterified) RN - 33X04XA5AT (Lactic Acid) RN - 8558G7RUTR (Pyruvic Acid) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - S88TT14065 (Oxygen) SB - IM MH - Adenosine Triphosphate/metabolism MH - Adult MH - Aged MH - Amino Acids/blood MH - Biomarkers/blood MH - Blood Glucose/metabolism MH - *Cardiac Resynchronization Therapy MH - Cardiomyopathy, Dilated/blood/physiopathology/*therapy MH - *Energy Metabolism MH - Fatty Acids, Nonesterified/blood MH - Female MH - Heart Failure/blood/physiopathology/*therapy MH - Humans MH - Lactic Acid/blood MH - Male MH - Middle Aged MH - Mitochondria, Heart/metabolism MH - Myocardial Contraction MH - Myocardium/*metabolism MH - Oxygen/blood MH - *Oxygen Consumption MH - Phenotype MH - Prospective Studies MH - Proteomics MH - Pyruvic Acid/blood MH - Stroke Volume MH - Time Factors MH - Treatment Failure MH - *Ventricular Function, Left PMC - PMC2993897 EDAT- 2010/09/16 06:00 MHDA- 2011/03/22 06:00 PMCR- 2010/09/15 CRDT- 2010/09/16 06:00 PHST- 2010/05/27 00:00 [received] PHST- 2010/09/01 00:00 [accepted] PHST- 2010/09/16 06:00 [entrez] PHST- 2010/09/16 06:00 [pubmed] PHST- 2011/03/22 06:00 [medline] PHST- 2010/09/15 00:00 [pmc-release] AID - 9223 [pii] AID - 10.1007/s12265-010-9223-5 [doi] PST - ppublish SO - J Cardiovasc Transl Res. 2010 Dec;3(6):643-51. doi: 10.1007/s12265-010-9223-5. Epub 2010 Sep 15.