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Ivabradine is a novel heart rate (HR) lowering agent acting by inhibiting the If current in the sino-atrial node and has been shown to improve clinical outcomes in chronic heart failure (HF). Inotropic stimulation with dobutamine (DOB) has been known to increase HR and the incidence of cardiac arrhythmias in patients with HF. However, the effects of ivabradine specifically on cardiac arrhythmias are unknown. In this prospective study, we compared the effects of ivabradine treatment with β blocker therapy on the increase in HR and incidence of ventricular arrhythmias during DOB infusion using holter monitoring.
Sixty nine patients with acute decompensated HF requiring inotropic support, LVEF <35% and in sinus rhythm were included in the present study. All patients underwent holter recording for 6 h before the initiation of DOB infusion. Following baseline recording, 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 initiation of DOB and readministered at 12 h of DOB infusion in 26 patients not receiving β blocker therapy (ivabradine group). 15 patients under β blocker therapy (β blocker group) and 28 patients not taking β blocker therapy (control group) did not receive ivabradine during DOB infusion. Holter recordings were analyzed for change in HR, the median number of ventricular premature contractions (VPC), ventricular couplets, episodes of non sustained ventricular tachycardia (NSVT) and total ventricular arrhythmia for each step of study protocol.
Mean HR gradually and significantly increased at each step of DOB infusion in both control (81±11, 90±16, 97±14 and 101±16 respectively, p=0.001) and β blocker groups (75±13, 82±13, 86±14 and 88±13 respectively, p=0.001), while no significant increase in HR was observed in ivabradine group (82±17, 82±15, 85±14 and 83±12 respectively, p=0.439). The median number of VPCs, ventricular couplets and total ventricular arrhythmia significantly increased in ivabradine group (p<0.001, p<0.003 and p<0.015, respectively). In control group, VPCs and total ventricular arrhythmia increased significantly (p<0.01 and p<0.018, respectively). However, in β blocker group, no statistically significant increase was found in VPCs, couplets and total ventricular arrhythmias (Table). The incidence of NSVT did not significantly change in three groups.
Ivabradine effectively prevents HR increase during DOB infusion, however, it has almost no effect on DOB-induced ventricular arrhythmias. In contrast, β blocker therapy fails to blunt DOB-induced increase in HR, but it prevents DOB-induced increase in ventricular arrhythmias.
|VPCs Control||VPCs Ivabradine||VPCs|
|Total Arrhythmia Control||Total Arrhythmia Ivabradin||Total Arrhythmia|
|Baseline||149 (42-340)||132 (23-271)||45 (7-245)||128 (42-322)||158 (48-312)||49 (7-249)|
|DOB 5 μg/kg/min||256 (55-508)||147 (30-538)||22 (11-448)||258 (58-469)||205 (55-722)||38 (11-565)|
|DOB 10 μg/kg/min||251 (57-549)||158 (47-588)||96 (7-820)||241 (59-446)||226 (112-739)||99 (7-900)|
|DOB 15 μg/kg/min||208 (44-446)||198 (47-503)||123 (21-634)||212 (45-438)||261 (74-493)||135 (21-847)|