Heart rate as a therapeutic target in heart failure

Resting heart rate has prognostic importance regarding late cardiovascular mortality and morbidity. Hypertension and heart failure are often associated with increased resting heart rate. The resting heart rate is an index of dominant sympathetic nervous activity which may increase coronary vasoconstriction, enhance myocardial oxygen consumption, reduce diastolic perfusion time, increase endothelial shear stress and platelet aggregation, release growth factors and increase plaque instability. Reduction of heart rate by beta-receptor blockade has been shown to delay and limit enzyme release during acute myocardial infarction. Reduction in heart rate by at least 15 beats. min(-1) during. infarct evolution has been associated with a reduction in infarct size of between 25 and 30%. However. it is suggested that a reduction in heart rate of less than 8 beats.min(-1) has no effect. In large controlled clinical trials beta-blockade has reduced mortality by 15% during acute myocardial infarction. The benefit is larger among patients with left ventricular dysfunction, enlarged hearts, symptomatic heart failure and elevated heart rates. The effect is improved if treatment is started early during infarct evolution, (less than 4 h after onset of symptoms): however, none of the trials have specifically tested early intervention during infarct evolution. Comparison between placebo and drug intervention in patients with signs of heart failure suggests a relationship between the reduction of resting heart rate and the percentage reduction of mortality obtained in each trial. beta-blocker treatment has the largest potential to reduce heart rate. Confounding properties of a beta-blocker, such as intrinsic sympatomimetic activity or prolongation of the QT interval, may reduce its overall efficacy. These results suggest that the beneficial effect of beta-blockers in heart failure is related to the blocking of the sympathetic activity, as reflected in a quantitative reduction in heart rate and increase in diastolic time.