PMID- 24337482
OWN - NLM
STAT- MEDLINE
DCOM- 20140811
LR  - 20240514
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 5
IP  - 215
DP  - 2013 Dec 11
TI  - Metabolic rates of ATP transfer through creatine kinase (CK Flux) predict 
      clinical heart failure events and death.
PG  - 215re3
LID - 10.1126/scitranslmed.3007328 [doi]
AB  - Morbidity and mortality from heart failure (HF) are high, and current risk 
      stratification approaches for predicting HF progression are imperfect. Adenosine 
      triphosphate (ATP) is required for normal cardiac contraction, and abnormalities 
      in creatine kinase (CK) energy metabolism, the primary myocardial energy reserve 
      reaction, have been observed in experimental and clinical HF. However, the 
      prognostic value of abnormalities in ATP production rates through CK in human HF 
      has not been investigated. Fifty-eight HF patients with nonischemic 
      cardiomyopathy underwent (3)(1)P magnetic resonance spectroscopy (MRS) to quantify 
      cardiac high-energy phosphates and the rate of ATP synthesis through CK (CK flux) 
      and were prospectively followed for a median of 4.7 years. Multiple-event 
      analysis (MEA) was performed for HF-related events including all-cause and 
      cardiac death, HF hospitalization, cardiac transplantation, and 
      ventricular-assist device placement. Among baseline demographic, clinical, and 
      metabolic parameters, MEA identified four independent predictors of HF events: 
      New York Heart Association (NYHA) class, left ventricular ejection fraction 
      (LVEF), African-American race, and CK flux. Reduced myocardial CK flux was a 
      significant predictor of HF outcomes, even after correction for NYHA class, LVEF, 
      and race. For each increase in CK flux of 1 mumol g(-)(1) s(-)(1), risk of HF-related 
      composite outcomes decreased by 32 to 39%. These findings suggest that reduced CK 
      flux may be a potential HF treatment target. Newer imaging strategies, including 
      noninvasive (3)(1)P MRS that detect altered ATP kinetics, could thus complement risk 
      stratification in HF and add value in conditions involving other tissues with 
      high energy demands, including skeletal muscle and brain.
FAU - Bottomley, Paul A
AU  - Bottomley PA
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins University School 
      of Medicine, Baltimore, MD 21287, USA.
FAU - Panjrath, Gurusher S
AU  - Panjrath GS
FAU - Lai, Shenghan
AU  - Lai S
FAU - Hirsch, Glenn A
AU  - Hirsch GA
FAU - Wu, Katherine
AU  - Wu K
FAU - Najjar, Samer S
AU  - Najjar SS
FAU - Steinberg, Angela
AU  - Steinberg A
FAU - Gerstenblith, Gary
AU  - Gerstenblith G
FAU - Weiss, Robert G
AU  - Weiss RG
LA  - eng
GR  - R01 HL056882/HL/NHLBI NIH HHS/United States
GR  - R01 HL061912/HL/NHLBI NIH HHS/United States
GR  - R01-HL61912/HL/NHLBI NIH HHS/United States
GR  - R01-HL056882/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
CIN - Circ Res. 2014 Apr 11;114(8):1228-30. PMID: 24723654
MH  - Adenosine Triphosphate/*metabolism
MH  - Adult
MH  - Cardiomyopathies/enzymology/mortality
MH  - Case-Control Studies
MH  - Creatine Kinase/*metabolism
MH  - Disease Progression
MH  - Female
MH  - Heart/physiopathology
MH  - Heart Failure/*enzymology/*mortality
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - Middle Aged
MH  - Myocardium/enzymology
MH  - Prospective Studies
MH  - Risk
MH  - Treatment Outcome
MH  - Ventricular Dysfunction, Left/physiopathology
PMC - PMC4440545
MID - NIHMS689598
EDAT- 2013/12/18 06:00
MHDA- 2014/08/12 06:00
PMCR- 2015/05/21
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/08/12 06:00 [medline]
PHST- 2015/05/21 00:00 [pmc-release]
AID - 5/215/215re3 [pii]
AID - 10.1126/scitranslmed.3007328 [doi]
PST - ppublish
SO  - Sci Transl Med. 2013 Dec 11;5(215):215re3. doi: 10.1126/scitranslmed.3007328.