Beta-blockade in CHF: pathophysiological considerations

Sympathetic activation leading to raised levels of catecholamines is one of the earliest responses to the fall in cardiac output that occurs in chronic heart failure (CHF). Raised catecholamine levels have numerous adverse effects that can be counteracted by beta-blockers. For example, the increased heart rate associated with sympathetic activation is associated with a poor prognosis in CHF. In the major beta-blocker trials in CHF, a reduction in mortality of about 35% was consistently demonstrated with beta-blockade, which was associated with a reduction in heart rate of 10–15 bpm. The resting heart rate predicts longevity in many mammalian species. A limited ability to increase heart rate during exercise (chronotropic incompetence) in left ventricular (LV) dysfunction and CHF also predicts mortality. Beta-blockers increase heart rate variability by rebalancing the sympatho-vagal axis. Beta-blockers also reduce remodelling in CHF, increase LV ejection fraction, reduce end-systolic volume, and improve ventricular filling time. They are also believed to have a direct anti-arrhythmic action that protects against sudden cardiac death and to have additional effects at the cellular level on myocyte hypertrophy and apoptosis.