Addition of ivabradine to betablockers in patients with atrial fibrillation: Effects on heart rate and exercise tolerance

Abstract

Atrial fibrillation (AF) is one of the most common arrhythmias and is often responsible for impaired exercise tolerance and quality of life. Traditionally, in patients with persistent and/or permanent AF, heart rate (HR) control is obtained by using drugs that prolong atrioventricular (AV) node refractoriness such as β-adrenergic receptor blockers (βBs), nondihydropyridine calcium channel blockers, and digitalis glycosides. However a significant proportion of subjects with AF has poor HR control. According to current evidences βBs, the most effective drugs in achieving HR control, fail to obtain their goal in about 30% of cases [1]. Ivabradine, according to the traditional view, is a HR reducing agent that selectively inhibits the If current in the sinus node, without affecting heart contractility, relaxation and peripheral vascular resistance [2]. Recent studies conducted mainly in animal models support the hypothesis that ivabradine could have clinically valuable effects on AF by slowing the AV node conduction [3–5]. The goal of the present study was to test whether the addition of ivabradine to patients with persistent/permanent AF already taking βBs could be capable of improving HR control and clinical conditions of these patients. We evaluated 6 patients, mean age 66.4, (SD = 7), males/females: 4/2, with persistent or permanent AF already treated with βBs. Patients were considered suitable for this study if they fulfilled the following inclusion criteria: 1) they were taking the highest tolerated dose of a βB and no further increase were possible; 2) patients had HR N 110 bpy ata restingECG[6]; and3)they had dyspnea arisingfor mild efforts. Exclusion criteria were unstable clinical conditions (hospital admission in the last three months) or a previous diagnosis of pre-excitation. The study protocol was conform to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by San Raffaele Ethics Committee. After the enrollment and before starting ivabradine administration, all subjects underwent a 24/h ambulatory ECG monitoring (AEM) and asixminutewalkingtest(6MWT)withevaluationofthesubjectiveperceptionofdyspneathroughtheBorg'sscalescore.AEMand6MWTwere repeated after one, two and three months. The starting dose of