Author + information
- Yüksel Çavuşoğlu,
- Kadir Uğur Mert,
- Aydın Nadir,
- Fezan Mutlu,
- Erkan Gencer,
- Bektas Morrad and
- Taner Ulus
Ivabradine is a selective If channel inhibitor that results in heart rate (HR) reduction without affecting contractility. Beta-adrenergic stimulation increases intracellular cAMP that positively shifts the If channel activation curve, increases the slope of the diastolic depolarization and accelerates HR. Dobutamine (DOB) is well-known to increase HR and energy expenditure, and thereby may precipitate ischemia and myocyte damage. The aim of this study was to evaluate whether ivabradine treatment blunts DOB-induced increase in HR.
Seventy three acute decompensated heart failure (HF) patients requiring inotropic support, LVEF <35% and in sinus rhythm were included in the study. All patients underwent holter recording for 6-h before the initiation of DOB and then DOB was administered at incremental doses of 5, 10 and 15 μgr/kg/min, with 6-h steps. Holter monitoring was continued during 18 h of DOB infusion. Ivabradine 7.5 mg was given at the time of the initiation of DOB and readministered at 12 h of DOB infusion in 29 patients not receiving beta-blocker (Ivabradine group). 15 patients who were on beta-blocker therapy (beta-blocker group) and 29 patients not taking beta-blocker therapy (control group) did not receive ivabradine during DOB infusion. Holter recordings were analyzed for mean HR change for each step of study protocol.
Baseline mean HR was similar among three groups. In both control and beta-blocker groups, mean HR gradually and significantly increased at each step of DOB infusion (table). However, in ivabradine group, no significant change was observed in mean HR with incremental doses of DOB infusion. Mean HR during the two highest doses of DOB infusion was found to be significantly higher in control group among three groups. Two-way ANOVA analysis also suggested a significant rise in mean HR in control group (p<0.001), a slight but significant increase in beta-blocker group (p <0.001) and no significant increase in HR in ivabradine group (p=0.439).
This study showed that ivabradine treatment blunts DOB-induced increase in HR in patients with acute decompensated HF and may be useful in reducing heart rate-related adverse effects of DOB.
Mean HR, bpm
Mean HR, bpm
Mean HR, bpm
|DOB 5 μg/kg/min||90.3±16.6*||82.3±13.9‡||82.4±15.7||0.118|
|DOB 10 μg/kg/min||97.7±14.8†#||86.1±14.1†||85.1±14.9||0.003|
|DOB 15 μg/kg/min||101.7±16.9†§||88.7±13.5†α||83.5±12.4||0.001|
|P (Two-way ANOVA)||0.001||0.001||0.439|
*p=0.001, ‡p=0.009 and †p=0.0001 compared with baseline. αp=0.013, #p=0.006 and §p=0.0001 compared with DOB 5 μg/kg/min.