Abstract 3828: Long-term Monotherapy With Ivabradine Improves Left Ventricular Function and Prevents Progressive Chamber Remodeling in Dogs With Moderate Heart Failure
Background: Basal heart rate (HR) increases in heart failure (HF)to maintain cardiac output. This increase, however, leads to increased myocardial oxygen consumption and a further decrease in cardiac function; a phenomenon termed “inverse force-frequency relationship”. This study tested the hypothesis that monotherapy with Ivabradine (IVA), a novel HR lowering agent that acts by selective and specific inhibition of the cardiac pacemaker current, will improve LV function and prevent progressive LV remodeling in dogs with moderate HF (LV ejection fraction, EF ~35%) produced by coronary microembolizations.
Methods: Studies were performed in 24 HF dogs randomized to 3 months oral monotherapy with high dose (HD) IVA (30 mg twice daily, n=8), low dose (LD) IVA (15 mg twice daily, n=8) or to no therapy at all (placebo control, n=8). Study primary end-points of LV end-systolic volume (ESV), end-diastolic volume (EDV) and EF were measured by ventriculography at time of randomization (PRE) and at the end of 3 months of therapy (POST). Ambulatory 24 hours ECG Holter monitoring studies were also performed at PRE and POST. Treatment effect delta (Δ) was calculated for each group as the difference between PRE and POST measures.
Results: The data are shown in the table⇓. In Control dogs, EF decreased and ESV and EDV increased significantly. LD IVA prevented the progressive increase of ESV and EDV and the decrease of EF seen with controls. HD IVA prevented the increase in EDV, significantly reduced ESV and significantly increased EF. Overall, HD-IVA was significantly more effective in improving EF and reducing LV size compared to LD-EVA. Average HR from Holters decreased from PRE to POST by 12±2 beats/min in HD IVA, by 8±3 beats/min in LD IVA and by 4±3 beats/min in controls.
Conclusions: The results indicate that in the absence of any background therapy, long-term treatment with IVA, through HR lowering, can elicit improvements in LV function and remodeling in dogs with chronic moderate HF.