title: Ivabradine treatment prevents dobutamine-induced increase in heart rate in patients with acute decompensated heart failure.
abstract: BACKGROUND
  Ivabradine is a heart rate (HR)-lowering agent acting by inhibiting the If-channel. Dobutamine does increase the HR and has some deleterious effects on myocardium. So, we aimed to evaluate whether ivabradine treatment blunts a dobutamine-induced increase in HR.
  
  
  METHODS
  The main study population consisted of 58 acute decompensated heart failure patients requiring inotropic support with left-ventricular ejection fraction below 35%, who were randomized to ivabradine (n = 29) or control (n = 29). All patients underwent Holter recording for 6 h and then dobutamine was administered at incremental doses of 5, 10 and 15 μg/kg/min, with 6-h steps. Holter recording was continued during dobutamine infusion. Ivabradine 7.5 mg was given at the initiation of dobutamine and readministered at 12 h of infusion. Also, a nonrandomized beta-blocker group with 15 patients receiving beta-blocker was included in the analysis. Control and beta-blocker groups did not receive ivabradine.
  
  
  RESULTS
  In the control group, mean HR gradually and significantly increased at each step of dobutamine infusion (81 ± 11, 90 ± 16, 97 ± 14 and 101 ± 16 b.p.m., respectively; P = 0.001), whereas no significant increase in HR was observed in the ivabradine group (82 ± 17, 82 ± 15, 85 ± 14 and 83 ± 12 b.p.m., respectively; P = 0.439). Mean HR was also found to significantly increase during dobutamine infusion in the beta-blocker group (75 ± 13, 82 ± 13, 86 ± 14 and 88 ± 13 b.p.m., respectively; P = 0.001). The median increase in HR from baseline was significantly higher in the control group compared to those in the ivabradine group (5 vs. 2 b.p.m.; P = 0.007 at first step, 13 vs. 5 b.p.m.; P = 0.001 at second step and 18 vs. 6 b.p.m.; P = 0.0001 at third step of dobutamine, respectively).
  
  
  CONCLUSIONS
  Ivabradine treatment prevents dobutamine-induced increase in HR and may be useful in reducing HR-related adverse effects of dobutamine.
authors.affiliation: aCardiology Department bBiostatistic Department, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: Yuksel
authors.initials: Y
authors.lastname: Cavusoglu
authors.forename: Ugur
authors.initials: U
authors.lastname: Mert
authors.forename: Aydin
authors.initials: A
authors.lastname: Nadir
authors.forename: Fezan
authors.initials: F
authors.lastname: Mutlu
authors.forename: Bektas
authors.initials: B
authors.lastname: Morrad
authors.forename: Taner
authors.initials: T
authors.lastname: Ulus
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004280:Dobutamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D000077550:Ivabradine; D004280:Dobutamine