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Activation of the sympathetic nervous system can also provoke arrhythmias by increasing the automaticity of cardiac cells, increasing triggered activity in the heart, and promoting the development of hypokalemia. Norepinephrine can also increase heart rate and potentiate the activity and actions of other neurohormonal systems.

Finally, by stimulating growth and oxidative stress in terminally differentiated cells, norepinephrine can trigger programmed cell death or apoptosis.

These deleterious effects are mediated through actions on alpha-1-, beta-1-, and beta-2- adrenergic receptors.

Beta-blockers that have been shown to be effective in the treatment of HF, including those that selectively block beta-1-receptors (e.g., bisoprolol and metoprolol) and those that block alpha-1, beta-1-, and beta-2-adrenergic receptors (e.g., carvedilol).

Effect of beta-blockers in the management of HF

Beta-blockers have been evaluated in more than 10,000 patients with HF who participated in more than 20 published placebo-controlled clinical trials. All trials enrolled patients with systolic dysfunction (ejection fraction less than 0.35 to 0.45) who had already been treated with diuretics and an ACE inhibitor, with or without digitalis.

These trials recruited many types of patients, including women and the elderly, as well as patients with a wide range of causes and severity of left ventricular dysfunction, but patients with preserved systolic function, low heart rates (less than 65 beats per min), or low systolic blood pressure (less than 85 mm Hg) were not recruited or represented a small proportion of the patients who participated in these published studies. A recent prospective trial with carvedilol, carried out in clinically stable patients with severe symptoms (class IV HF), demonstrated a reduction in mortality also in patients with such advanced disease.

This collective experience indicates that long-term treatment with beta-blockers can lessen the symptoms of HF, improve the clinical status of patients, and enhance the overall sense of well-being71,72. In addition, like ACE inhibitors, beta-blockers can reduce the risk of death and the combined risk of death or hospitalization.

These benefits of beta-blockers were seen in patients with or without coronary artery disease and in patients with or without diabetes.

71 Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-8.

72 Fisher ML, Gottlieb SS, Plotnick GD, et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol 1994;23:943-50.

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