PMID- 18191736
OWN - NLM
STAT- MEDLINE
DCOM- 20080205
LR  - 20161124
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 51
IP  - 2
DP  - 2008 Jan 15
TI  - Myocardial gene expression in heart failure patients treated with cardiac 
      resynchronization therapy responders versus nonresponders.
PG  - 129-36
LID - 10.1016/j.jacc.2007.07.087 [doi]
AB  - OBJECTIVES: We studied whether functional improvement after cardiac 
      resynchronization therapy (CRT) is associated with reversal of the heart failure 
      (HF) gene program. BACKGROUND: Cardiac resynchronization therapy improves 
      exercise tolerance and survival in patients with advanced congestive HF and 
      dyssynchrony. METHODS: Twenty-four patients referred for CRT underwent left 
      ventricular (LV) endomyocardial biopsies immediately before CRT implantation 
      (baseline). In addition, 17 of them underwent LV endomyocardial biopsy 
      procurement 4 months later (follow-up). In 6 control patients with normal LV 
      function, LV biopsies were obtained at the time of coronary artery bypass 
      grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and 
      calcium regulatory genes were measured by quantitative real time polymerase chain 
      reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The 
      HF patients showing an improvement in New York Heart Association (NYHA) 
      functional class by >1 score and a relative increase in LV ejection fraction > or 
      =25% at 4 months after CRT were considered as responders. RESULTS: The HF 
      patients were characterized by lower LV mRNA levels of alpha-myosin heavy chain 
      (alpha-MHC), beta-myosin heavy chain (beta-MHC), sarcoplasmic reticulum calcium 
      ATPase 2alpha (SERCA), phospholamban (PLN), and higher brain natriuretic peptide 
      (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) 
      showed an increase in LVEF (p < 0.001), a decrease in left ventricular 
      end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a 
      reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This 
      was associated with an increase in mRNA levels of alpha-MHC (p = 0.035), SERCA (p 
      = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio 
      of alpha-/beta-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes 
      in molecular profile were observed in nonresponders. CONCLUSIONS: In HF patients 
      with electromechanical cardiac dyssynchrony, functional improvement related to 
      CRT is associated with favorable changes in established molecular markers of HF, 
      including genes that regulate contractile function and pathologic hypertrophy.
FAU - Vanderheyden, Marc
AU  - Vanderheyden M
AD  - Cardiovascular Center, Molecular Cardiology Unit and Cardiovascular Research 
      Center, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium. 
      marc.vanderheyden@olvz-aalst.be
FAU - Mullens, Wilfried
AU  - Mullens W
FAU - Delrue, Leen
AU  - Delrue L
FAU - Goethals, Marc
AU  - Goethals M
FAU - de Bruyne, Bernard
AU  - de Bruyne B
FAU - Wijns, William
AU  - Wijns W
FAU - Geelen, Peter
AU  - Geelen P
FAU - Verstreken, Sofie
AU  - Verstreken S
FAU - Wellens, Francis
AU  - Wellens F
FAU - Bartunek, Jozef
AU  - Bartunek J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Genetic Markers)
RN  - 0 (RNA, Messenger)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
CIN - J Am Coll Cardiol. 2008 Jan 15;51(2):137-8. PMID: 18191737
CIN - J Am Coll Cardiol. 2008 Sep 30;52(14):1177; author reply 1177-8. PMID: 18804748
MH  - Aged
MH  - *Cardiac Pacing, Artificial
MH  - Case-Control Studies
MH  - Echocardiography, Doppler
MH  - Female
MH  - *Gene Expression
MH  - Gene Expression Profiling
MH  - Genetic Markers
MH  - Heart Failure/diagnostic imaging/*genetics/mortality/*therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Myocardium/metabolism/pathology
MH  - Myosin Heavy Chains/*genetics
MH  - Natriuretic Peptide, Brain/*genetics
MH  - Probability
MH  - Prognosis
MH  - RNA, Messenger/analysis
MH  - Reference Values
MH  - Risk Assessment
MH  - Severity of Illness Index
MH  - Statistics, Nonparametric
MH  - Survival Rate
MH  - Treatment Outcome
MH  - Ventricular Dysfunction, Left/diagnostic imaging/genetics/mortality/therapy
MH  - Ventricular Remodeling/genetics
EDAT- 2008/01/15 09:00
MHDA- 2008/02/06 09:00
CRDT- 2008/01/15 09:00
PHST- 2007/03/29 00:00 [received]
PHST- 2007/07/02 00:00 [revised]
PHST- 2007/07/03 00:00 [accepted]
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2008/02/06 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - S0735-1097(07)03345-1 [pii]
AID - 10.1016/j.jacc.2007.07.087 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2008 Jan 15;51(2):129-36. doi: 10.1016/j.jacc.2007.07.087.