Long-term effects of repeated oral dose of ivabradine on heart rate variability in dogs with asymptomatic degenerative mitral valve disease

Abstract

Degenerative mitral valve disease (DMVD) is the most common acquired cardiac disease in geriatric dogs
leading to impaired cardiac autonomic activity and functions. This study aimed to evaluate the heart rate (HR), blood
pressure (BP), myocardial oxygen consumption (MVO2) and heart rate variability (HRV) of dogs with DMVD stage B2
in response to long-term treatment with ivabradine, orally. Four beagles with naturally occurring DMVD stage B2 were
instrumented with a 24-h Holter recorder to obtain electrocardiography and HRV, an oscillometric device to acquire
blood pressure (BP), HR and myocardial oxygen consumption (MVO2) as assessed by rate-pressure product (RPP = HR
x Systolic BP). Dogs were given ivabradine (1.0 mg/kg, twice daily, orally) for 3 months. Data were obtained at baseline
and every 4 weeks for 12 weeks (M1 = 4 weeks, M2 = 8 weeks, and M3 = 12 weeks) after oral administration of
ivabradine. The results revealed that chronic administration of ivabradine significantly decreased HR, BP, and RPP
without adverse effects (P < 0.05). All indices of time- and frequency- domain of HRV at M3 were significantly increased
when compared with baseline values (P < 0.05). The findings of this study imply that long-term treatment with
ivabradine at a dose of 1.0 mg/kg twice daily in dogs with asymptomatic DMVD stage B2 decreased the HR, BP, MVO2
and improves HRV. This makes ivabradine potentially promising for management of elevated HR and impaired HRV
in asymptomatic dogs with DMVD stage B2.