Importance of Heart Rate in Chronic Heart Failure
Importance of Heart Rate in Chronic Heart Failure
Resting heart rate is a modifiable risk factor both in the general population and in patients with cardiovascular (CV) disease. The reasons for this increased risk are not fully understood and may have several explanations. Elevated heart rate is associated with reduced myocardial function in experimental settings and various pathophysiological mechanisms exist for the development of CV and myocardial dysfunction by tachycardia. In heart failure and systolic dysfunction, the myocardium is energetically starving. Elevated heart rate has then added negative consequences, including progressive mechanical dyssynchrony and reduced inotropy. The importance of heart rate in chronic heart failure (CHF) was recently explored in SHIFT (The Systolic Heart failure Treatment with the If inhibitor Ivabradine Trial).
In SHIFT, eligible patients who had CHF and ejection fraction <35% were in sinus rhythm and on recommended therapy and were randomized to ivabradine or placebo. Heart rate at baseline was analysed in relation to various outcomes. When the placebo group was divided by quintiles based on baseline heart rate, the incidence of the primary composite endpoint (CV death or hospitalization for worsening heart failure) and its components was greatest in patients with high heart rates. Patients in the group with the highest heart rate at baseline (≥87 b.p.m.) were at more than a two-fold increased risk for primary composite endpoint events compared with those in the lowest heart rate group (70 to ≤72 b.p.m.; P < 0.0001). Analysis with heart rate as a continuous variable showed that for every beat increase in heart rate at baseline, the risk of the primary composite endpoint event increased by 3% (P < 0.0001).
Treatment with a β-blocker will reduce heart rate, a reduction thought to be the important mechanism to account for why β-blockers exert their beneficial effects in systolic CHF. However, β-blockers have several effects on the CV system, which today are of unclear importance. Further support for the relationship between changes in heart rate and improved myocardial function after treatment with β-blockers and outcome has been presented by Flannery et al. in a meta-regression analysis of β-blocker trials. In 35 trials with a mean follow-up duration of 9.6 months, there was a close relation between all-cause annualized mortality rate and achieved heart rate (adjusted r = 0.51, P = 0.004). In a meta-analysis of 23 trials on β-blockers in heart failure that included 19 209 patients in which mortality was reported, McAlister et al. could present data on heart rate vs. other variables for outcome. In a multivariable analysis, the degree of heart rate reduction by β-blockers was the only significant variable remaining of prognostic importance. For every 5 b.p.m. reduction, the risk of death decreased by 18%. By contrast, the dose of the β-blocker treatment in 17 trials was not predictive of outcome.
Abstract and Introduction
Introduction
Resting heart rate is a modifiable risk factor both in the general population and in patients with cardiovascular (CV) disease. The reasons for this increased risk are not fully understood and may have several explanations. Elevated heart rate is associated with reduced myocardial function in experimental settings and various pathophysiological mechanisms exist for the development of CV and myocardial dysfunction by tachycardia. In heart failure and systolic dysfunction, the myocardium is energetically starving. Elevated heart rate has then added negative consequences, including progressive mechanical dyssynchrony and reduced inotropy. The importance of heart rate in chronic heart failure (CHF) was recently explored in SHIFT (The Systolic Heart failure Treatment with the If inhibitor Ivabradine Trial).
In SHIFT, eligible patients who had CHF and ejection fraction <35% were in sinus rhythm and on recommended therapy and were randomized to ivabradine or placebo. Heart rate at baseline was analysed in relation to various outcomes. When the placebo group was divided by quintiles based on baseline heart rate, the incidence of the primary composite endpoint (CV death or hospitalization for worsening heart failure) and its components was greatest in patients with high heart rates. Patients in the group with the highest heart rate at baseline (≥87 b.p.m.) were at more than a two-fold increased risk for primary composite endpoint events compared with those in the lowest heart rate group (70 to ≤72 b.p.m.; P < 0.0001). Analysis with heart rate as a continuous variable showed that for every beat increase in heart rate at baseline, the risk of the primary composite endpoint event increased by 3% (P < 0.0001).
Treatment with a β-blocker will reduce heart rate, a reduction thought to be the important mechanism to account for why β-blockers exert their beneficial effects in systolic CHF. However, β-blockers have several effects on the CV system, which today are of unclear importance. Further support for the relationship between changes in heart rate and improved myocardial function after treatment with β-blockers and outcome has been presented by Flannery et al. in a meta-regression analysis of β-blocker trials. In 35 trials with a mean follow-up duration of 9.6 months, there was a close relation between all-cause annualized mortality rate and achieved heart rate (adjusted r = 0.51, P = 0.004). In a meta-analysis of 23 trials on β-blockers in heart failure that included 19 209 patients in which mortality was reported, McAlister et al. could present data on heart rate vs. other variables for outcome. In a multivariable analysis, the degree of heart rate reduction by β-blockers was the only significant variable remaining of prognostic importance. For every 5 b.p.m. reduction, the risk of death decreased by 18%. By contrast, the dose of the β-blocker treatment in 17 trials was not predictive of outcome.
