Ivabradine Preserves Cardiac Structure and Reduces Cell Death in Four Dogs With Preclinical Mitral Valve Disease

Abstract

BACKGROUND: Ivabradine, a specific funny channel blocker, has shown cardiovascular benefits in humans and animals. However, its effects on haemodynamics, cardiac function, ventricular remodelling and cardiac apoptosis in asymptomatic dogs with myxomatous mitral valve disease (MMVD) stage B2 remain unclear. OBJECTIVE: To investigate the effect of long-term oral ivabradine on heart rate (HR), haemodynamics, cardiac function and apoptosis in dogs with MMVD stage B2. METHODS: Four dogs with MMVD stage B2 received ivabradine (1 mg/kg orally, q12h) for 3 months. Under general anaesthesia (propofol and isoflurane), electrocardiograms and invasive measurements of left ventricular, aortic, pulmonic, right atrial and pulmonary capillary wedge pressures were obtained at baseline and 3 months. Endomyocardial biopsies were collected at both timepoints for histopathology and immunohistochemical evaluation of Bcl-2 and Bax expression to assess apoptosis. RESULTS: Ivabradine decreased HR by 30.4% (p < 0.05) without significantly affecting systemic or pulmonary pressures, vascular resistance or systolic/diastolic function. Histopathological analysis showed significant reductions in myocyte vacuolization (68.5%), glycogen accumulation (47.6%), interstitial fibrosis (57.3%) and fibrofatty infiltration (77.8%) (p < 0.05). The apoptosis index was reduced by 17.0% (p < 0.05), and Bcl-2 expression tended to increase (p = 0.06). CONCLUSION: Chronic ivabradine treatment lowered HR and reduced cardiac structural remodelling and apoptosis without impairing cardiac function in dogs with MMVD stage B2. These findings support the potential of ivabradine as a therapeutic option for asymptomatic canine heart disease.