title: The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers.
abstract: BACKGROUND
  Beta-blockers are effective for the treatment of heart failure, but their mechanism of action is unresolved. Heart rate reduction may be a central mechanism or a troublesome side effect.
  
  
  METHODS
  A randomized, double-blind, parallel group study comparing chronic higher-rate (80 pulses per minute) with lower-rate (60 pulses per minute) pacing in pacemaker-dependent patients with symptomatic left ventricular (LV) systolic dysfunction, receiving beta-blockers. Gated radionuclide ventriculography (RNVG) was performed at baseline and after at least 9 months. The primary outcome was change in LV volumes, as a marker of beneficial reverse remodeling, from baseline to follow-up.
  
  
  RESULTS
  Forty-nine patients were randomized. Mean age was 74 +/- 6 years and with LV ejection fraction of 26% +/- 9% at baseline. During 14 +/- 13 months of follow-up, 21 patients (43%) died and 25 (51%) completed the study protocol: 12 in the higher-rate and 13 in the lower-rate group. Mean LV end-diastolic (higher rate +20 +/- 104 mL vs lower rate -65 +/- 92 mL, P = .03) and systolic (higher rate +29 +/- 83 mL vs lower rate -60 +/- 74 mL, P = .006) volumes increased with higher-rate versus lower-rate pacing, whereas LV ejection fraction declined (higher rate -4.2% +/- 4.4% vs lower rate +2.2% +/- 5.4%, P = .002).
  
  
  CONCLUSIONS
  Reversal of beta-blocker-induced bradycardia has deleterious effects on ventricular function, suggesting heart rate reduction is an important mediator of their effects. The prognosis of patients with pacemakers and heart failure is poor.
authors.affiliation: Department of Academic Cardiology, University of Hull, Castle Hill Hospital, Kingston-upon-Hull, United Kingdom. simonthackray@hotmail.com
authors.forename: Simon D R
authors.initials: SD
authors.lastname: Thackray
authors.forename: Justin M
authors.initials: JM
authors.lastname: Ghosh
authors.forename: Graham A
authors.initials: GA
authors.lastname: Wright
authors.forename: Klaus K A
authors.initials: KK
authors.lastname: Witte
authors.forename: Nikolay P
authors.initials: NP
authors.lastname: Nikitin
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Kaye
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Clark
authors.forename: Ann
authors.initials: A
authors.lastname: Tweddel
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D001919:Bradycardia / Q000139:chemically induced / Q000517:prevention & control; D002303:Cardiac Output, Low / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D004311:Double-Blind Method; D005500:Follow-Up Studies; D015637:Gated Blood-Pool Imaging; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D013318:Stroke Volume; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists