Heart rate as a target of treatment of chronic heart failure

Cardiovascular risk of increased heart rate (HR) was first reported in the Framingham study. Thereafter, the risk of increased HR for mortality has been extensively studied, suggesting the higher risk in clinical outcomes with increased HR in the general population and in patients with coronary artery disease or heart failure (HF). In a long-term follow-up study in Framingham, the general population in this cohort showed an increase in all-cause mortality by 14% at every 10 bpm increase in HR. In patients with heart failure, resting HR of more than 80 bpm could cause myocardial dysfunction which further deteriorates HF. Downregulation of β-adrenoreptor receptors with suppressed signal transductions, impaired intracellular Ca homeostasis, and excitation–contraction coupling may play a role in myocardial dysfunction. These subcellular alterations are mimicked in the pacing-induced HF in large animals; however, exact mechanisms of cardiac deterioration by increased HR are not fully understood. β-Blocker treatment is the most effective therapy for long-term survival of patients with chronic HF. Meta-analysis of HR reduction and improvement in survival in patients with chronic HF indicates that HR reduction is more important than the titrated dose of β-blockers, although the relative importance of HR reduction in improvement of prognosis is not clear. A recent study in which ivabradine decreased the hospitalization from HR deterioration in patients with chronic HF, demonstrated that further HR reduction with optimal treatment for HF is beneficial for clinical outcomes of the patients. These findings strongly suggest that HR reduction should be a pivotal target of the treatment in patients with HF.