Pathophysiologic Insights into Heart Rate Reduction in Heart Failure: Implications in the Use of Beta-Blockers and Ivabradine.

OPINION STATEMENT: In patients with heart failure, an elevated heart rate is associated with worse cardiovascular outcomes and is increasingly recognized as a modifiable risk factor. Beta-blockers are the mainstay of therapy for heart failure. However, up-titration of beta-blockers in response to persistently elevated heart rate can be associated with increased risk of adverse reactions besides negative chronotropism. Recently, the specific heart rate-lowering agent, ivabradine, which acts by directly and selectively inhibiting the I f current in the sinoatrial node, generated renewed interest in potential benefits of pharmacologic modification of heart rate in heart failure. Several placebo-controlled, multicenter clinical trials showed the benefits of ivabradine in patients with angina and heart failure, which is largely confined to those with left ventricular systolic dysfunction. In addition, the other potential effects of ivabradine have been proposed.