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To investigate whether the mortality of patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) is more strongly related to beta-blocker dose or to heart rate. It is known that beta-blockers reduce mortality in patients with CHF and LVSD, but the primary mechanism of action is uncertain.Patients with an ejection fraction ≤40%, who were in sinus rhythm both at an initial (visit 1) and at a 4-month clinic review (visit 2), were followed for a maximum of 36 months. The relationships between heart rate, beta-blocker dose, and survival in a multivariable model were examined. Of 654 eligible patients, 381 (58%) were started on beta-blockers prior to the initial visit, increasing to 537 (82%) by visit 2. During follow-up, 142 (22%) patients died. Neither resting heart rate nor beta-blocker dose at visit 1 predicted mortality (P = 0.09 and P = 0.99), but resting heart rate at visit 2 did (P = 0.02). Beta-blocker use at visit 2 was associated with better outcome (P = 0.03) but with little variation in outcome according to dose. Patients with a heart rate of 58–64 b.p.m. at visit 2 had the best prognosis.The use of beta-blockers and resting heart rate at visit 2 both independently indicated prognosis, but beta-blocker dose did not. Beta-blockers may reduce mortality by several mechanisms; one that may be specific to blockade of adrenergic receptors and another related to heart rate reduction. Achieving a target heart rate range may be an appropriate therapeutic goal for patients with CHF.