title: Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial.
abstract: BACKGROUND
  The improvement in left-ventricular ejection fraction (LVEF) in response to beta blockers is heterogeneous in patients with heart failure due to ischaemic heart disease, possibly indicating variations in the myocardial substrate underlying left-ventricular dysfunction. We investigated whether improvement in LVEF was associated with the volume of hibernating myocardium (viable myocardium with contractile failure).
  
  
  METHODS
  We did a double-blind, randomised trial to compare placebo and carvedilol for 6 months in individuals with stable, chronic heart failure due to ischaemic left-ventricular systolic dysfunction. We enrolled 489 patients, of whom 387 were randomised. Patients were designated hibernators or non-hibernators according to the volume of hibernating myocardium. The primary endpoint was change in LVEF, measured by radionuclide ventriculography, in hibernators versus non-hibernators, on carvedilol compared with placebo. Analysis was by intention to treat.
  
  
  RESULTS
  82 patients dropped out of the study because of adverse events, withdrawal of consent, or failure to complete the investigation. Thus, 305 (79%) were analysed. LVEF was unchanged with placebo (mean change -0.4 [SE 0.9] and -0.4 [0.8] for non-hibernators and hibernators, respectively) but increased with carvedilol (2.5 [0.9] and 3.2 [0.8], respectively; p<0.0001 compared with baseline). Mean placebo-subtracted change in LVEF was 3.2% (95% CI 1.8-4.7; p=0.0001) overall, and 2.9% (0.7-5.1; p=0.011) and 3.6% (1.7-5.4; p=0.0002) in non-hibernators and hibernators, respectively. Effect of hibernator status on response of LVEF to carvedilol was not significant (0.7 [-2.2 to 3.5]; p=0.644). However, patients with more myocardium affected by hibernation or by hibernation and ischaemia had a greater increase in LVEF on carvedilol (p=0.0002 and p=0.009, respectively).
  
  
  CONCLUSIONS
  Some of the effect of carvedilol on LVEF might be mediated by improved function of hibernating or ischaemic myocardium, or both. Medical treatment might be an important adjunct or alternative to revascularisation for patients with hibernating myocardium.
authors.affiliation: Castle Hill Hospital, Kingston-upon-Hull, UK. g.m.porter@hull.ac.uk
authors.forename: J G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: D J
authors.initials: DJ
authors.lastname: Pennell
authors.forename: S G
authors.initials: SG
authors.lastname: Ray
authors.forename: A J
authors.initials: AJ
authors.lastname: Coats
authors.forename: P W
authors.initials: PW
authors.lastname: Macfarlane
authors.forename: G D
authors.initials: GD
authors.lastname: Murray
authors.forename: J Dalle
authors.initials: JD
authors.lastname: Mule
authors.forename: Z
authors.initials: Z
authors.lastname: Vered
authors.forename: A
authors.initials: A
authors.lastname: Lahiri
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017682:Myocardial Stunning / Q000150:complications; D011412:Propanolamines / Q000627:therapeutic use*; D013318:Stroke Volume / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol