From ischaemia to heart failure: Heart rate - Actor or stamper?

The heart rate in sinus rhythm depends on I-f current-induced automaticity of sinus node cells. Such a current is activated by hyperpolarisation and is modulated by influences from sympathetic and para-sympathetic tones. There are established prognostic values for the baseline heart rate and its variability in coronary heart disease and heart failure. However. heart rate per se directly modulates myocardial oxygen consumption and cardiac contractility by interfering with the excitation-contraction coupling. The therapeutic implications of pharmacological modulation of the heart rate are important mainly for slowing the heart rate, as illustrated by the use of calcium antagonists in coronary heart disease and beta-blockers in both coronary heart disease and heart failure. The possibility of a direct action on sinusal automaticity by drugs such as ivabradine, an I-f channel blocker, reveals new therapeutic perspectives. Indeed, a benefit of combination therapy with these drugs and beta-blockers should be lower heart rate values than can be attained with maximally tolerated doses of beta-blockers.