title: Heart rate reduction for 12 months with ivabradine reduces left ventricular mass in cardiac allograft recipients.
abstract: BACKGROUND
  Graft denervation in heart transplant recipients causes sinus tachycardia, occasionally requiring pharmacologic heart rate reduction. Currently, no 12-month data regarding effects of the novel I(f) channel antagonist ivabradine on heart rate control, effects on left ventricular mass, tolerability, and safety are available in patients after heart transplantation (HTX).
  
  
  METHODS
  Mean heart rate, left ventricular mass indexed (LVMI) to body surface area, tolerability, and safety of ivabradine therapy were evaluated at baseline and after 12 months in 30 HTX recipients with marked sinus tachycardia.
  
  
  RESULTS
  In three patients (10.0% of total), ivabradine medication was discontinued. Further analysis was based on 27 patients with 12-month drug exposure. Mean patient age was 53.3+/-11.3 years, and mean time after HTX was 5.0+/-4.8 years. Mean ivabradine dose was 12.5 mg/day (+/-3.3 mg). Mean heart rate was reduced from 96.2+/-8.6 beats per minute (bpm) at baseline to 80.9+/-8.1 bpm at follow-up (P<0.0001). A statistically significant effect of heart rate reduction on LVMI was observed (104.3+/-22.7 g at baseline vs. 95.9+/-18.5 g at follow-up, P=0.04). No statistically significant changes in immunosuppressive drug dosage or blood levels were observed, except from a lower mycophenolate mofetil dose at follow-up (P=0.01). Safety laboratory values were unchanged. No phosphenes were observed.
  
  
  CONCLUSIONS
  Heart rate reduction with ivabradine is effective and safe in heart transplant recipients. After 12 months, significant effects on LVMI were observed. Therefore, ivabradine may offer a beneficial effect on left ventricular remodelling in HTX patients.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. andreas.doesch@med.uni-heidelberg.de
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ammon
authors.forename: Mathias
authors.initials: M
authors.lastname: Konstandin
authors.forename: Sultan
authors.initials: S
authors.lastname: Celik
authors.forename: Arnt
authors.initials: A
authors.lastname: Kristen
authors.forename: Lutz
authors.initials: L
authors.lastname: Frankenstein
authors.forename: Sebastian
authors.initials: S
authors.lastname: Buss
authors.forename: Stefan
authors.initials: S
authors.lastname: Hardt
authors.forename: Falk-Udo
authors.initials: FU
authors.lastname: Sack
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dengler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation / Q000009:adverse effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007473:Ion Channels / Q000037:antagonists & inhibitors; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D013616:Tachycardia, Sinus / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D001552:Benzazepines; D007473:Ion Channels; D000077550:Ivabradine