Heart Rate Reduction by If-Channel Inhibition and its Potential Role in Heart Failure with Reduced and Preserved Ejection Fraction

Selective heart rate (HR) reduction by If-channel inhibition is a recently developed pharmacological principle in cardiovascular therapy. Among these newly identified HR-lowering drugs, only ivabradine has now become approved for clinical use. If-channel inhibition mainly reduces HR, thereby improving myocardial oxygen supply, energy balance, and cardiac function. Ivabradine was well tolerated and revealed a good safety profile in the investigated study populations. The guiding experimental and clinical results of If-channel inhibition were compared to those of β-blockade as a HR reducing principle as well as cornerstone of heart failure standard therapy. Beside its use in therapy of coronary artery disease, If-channel inhibition potentially exhibits beneficial effects in systolic and diastolic heart failure as well. Therefore, hemodynamic effects of ivabradine and its limitations in heart failure together with the biological impact of HR reduction will be considered in this context. Because no clinical data with specific heart-rate-reducing agents are available in heart failure patients until now, the prospective significance of If-channel inhibition can only be speculated on. However, the presented results and considerations are encouraging: ivabradine may play a therapeutic role in the future protecting left ventricular function and structure from early deterioration in heart failure with reduced and preserved ventricular ejection fraction.