Effect of ivabradine, a novel I_f current inhibitor, on dynamic obstruction of the left ventricular outflow tract in cats with preclinical hypertrophic cardiomyopathy: a single-dose study

A relevant subset of cats with hypertrophic cardiomyopathy (HCM) develop dynamic obstruction of the left ventricular outflow tract and mitral regurgitation secondary to hypertrophy of the left ventricle and systolic anterior motion (SAM) of the mitral valve. This leads to an increase in left ventricular systolic pressure, and thus wall stress, that may ultimately lead to progression of the disease. While prospective studies documenting the morbidity and mortality associated with dynamic obstruction have not been performed in feline HCM, it is possible that the results would be similar to human studies, in which SAM has been proven repeatedly to be a negative prognostic indicator in HCM, as well as an independent predictor of disease progression and sudden death. Beta-blockers are the primary medication used to reduce heart rate and relieve dynamic left ventricular outflow tract obstruction in cats with HCM, however, side effects or contraindications sometimes limit their use. Ivabradine is a highly selective I_f current inhibitor that exerts negative chronotropic effects without significant effects on inotropy, lusitropy, or dromotropy as documented in multiple species. Ivabradine has been studied in cats, and has been shown to have unique heart rate lowering properties. The drug is clinically well tolerated without any discernable side effects, has only minimal effects on central hemodynamics, has pharmacokinetic and pharmacodynamic properties that allow for twice daily dosing, and enhances left atrial function. The purpose of this study was to determine whether ivabradine, at a single dose of 0.3 mg/kg PO, could reduce or eliminate dynamic obstruction of the left ventricular outflow tract in cats with HCM.In this prospective, randomized, double-blind, active-control single dose study, 21 cats with preclinical HCM and dynamic left ventricular outflow tract obstruction received one dose of atenolol at approximately 2 mg/kg PO or one dose of ivabradine at 0.3 mg/kg PO. Baseline and 3-hour post-treatment heart rate, echocardiographic variables, and blood pressure were recorded. Statistical comparisons were made using analysis of covariance (ANCOVA).Peak velocity in the left ventricular outflow tract was significantly decreased compared to baseline for both drugs, however the mean change in velocity was more reduced for atenolol (2.54 m/s; 95% confidence interval 1.83 m/s to 3.25 m/s) compared to ivabradine (0.51 m/s; 95% confidence interval 0.01 m/s to 1.01 m/s; P<0.0001). Echocardiographic indices of systolic function were largely unchanged by ivabradine, but reduced by atenolol. Doppler systolic blood pressure was not affected by either drug. Predictably, heart rate was reduced by both drugs.These findings indicate that a single dose of ivabradine at 0.3 mg/kg mildly reduces dynamic left ventricular outflow tract obstruction in cats with HCM while preserving systolic function, but this reduction is inferior compared to that achieved by atenolol and is likely not clinically relevant. Further studies evaluating the utility of ivabradine in reducing dynamic obstruction over a longer time period are needed.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Veterinary Clinical Sciences

Grantor dc:publisher

The Ohio State University

Year dc:date

2013

Author dc:creator

• Blass, Keith Andrew

Contributors dc:contributor

• Schober, Karsten

• Veterinary Services
• Ivabradine
• Feline
• Hypertrophic Cardiomyopathy
• Systolic Anterior Motion
• Dynamic Left Ventricular Outflow Tract Obstruction
• Amyl Nitrite

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=osu1363981181

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1363981181