Heart rate reduction for 12 months with ivabradine reduces left ventricular mass in cardiac allograft recipients.
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.
Doesch
Andreas O
AO
Department of Cardiology, University of Heidelberg, Heidelberg, Germany. andreas.doesch@med.uni-heidelberg.de
Ammon
Kerstin
K
Konstandin
Mathias
M
Celik
Sultan
S
Kristen
Arnt
A
Frankenstein
Lutz
L
Buss
Sebastian
S
Hardt
Stefan
S
Sack
Falk-Udo
FU
Katus
Hugo A
HA
Dengler
Thomas J
TJ
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
D001552:Benzazepines; D007473:Ion Channels; D000077550:Ivabradine