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 associate d with increased resting heart rate. The resting heart rate is an index of dominant sympathetic nervous activity which may increase coronary vasoconst riction, enhance myocardial oxygen consumption, reduce diastolic perfusion time, increase endothelial shear stress and platelet aggregation, release g rowth factors and increase plaque instability. Reduction of heart rate by b eta-receptor blockade has been shown to delay and limit enzyme release duri ng acute myocardial infarction. Reduction in heart rate by at least 15 beat s. min(-1) during. infarct evolution has been associated with a reduction i n infarct size of between 25 and 30%. However. it is suggested that a reduc tion in heart rate of less than 8 beats.min(-1) has no effect. In large con trolled clinical trials beta-blockade has reduced mortality by 15% during a cute myocardial infarction. The benefit is larger among patients with left ventricular dysfunction, enlarged hearts, symptomatic heart failure and ele vated heart rates. The effect is improved if treatment is started early dur ing infarct evolution, (less than 4 h after onset of symptoms): however, no ne 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 hear t rate and the percentage reduction of mortality obtained in each trial. be ta-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 efficac y. These results suggest that the beneficial effect of beta-blockers in heart failure is related to the blocking of the sympathetic activity, as reflecte d in a quantitative reduction in heart rate and increase in diastolic time.