Heart rate: The hummingbird effect

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with heart failure, in whom risk of all-cause mortality and sudden death mortality is markedly increased, betaadrenergic antagonists are part of the standard of care, which is defined by randomized prospective clinical trials to pharmacologically extend longevity. A meta-analysis of 23 beta-blocker trials in patients with heart failure demonstrated that the protective effect associated with these drugs was proportional to the heart rate reduction and not related to the dose of the beta-blocker. 7 Ivabradine is a new agent with a direct effect on the funny current (If,) which is an important determinant of the pacemaker potential and periodicity in the sinoatrial node. A randomized prospective trial of ivabradine in patients with heart failure demonstrated a reduction in the primary composite end point of cardiovascular death and heart failure hospital admissions associated with ivabradine treatment. 8 Both reports provide strong evidence of a direct connection between an improvement in cardiovascular outcomes and a pharmacological effect on the resting heart rate. In this issue of HeartRhythm, Teodorescu et al 9 provide more evidence for an important link between resting heart rate and sudden death risk in patients with known coronary artery disease. For their case-control analysis, they identified 378 cases of sudden cardiac death older than 35 years that had prior electrocardiograms (ECGs) available for analysis. Cases were identified from the ongoing Oregon Sudden Unexpected Death Study. The control cases were chosen from the same geographic region and sex and age matched to cases. All the control patients also had coronary artery disease. Resting heart rate was defined by a 12-lead ECG identified from medical records before the sudden death event. The patient characteristics in the 2 groups were remarkable for a number of statistically significant asymmetries. Among cases, diabetes mellitus, chronic obstructive pulmonary disease, chronic renal insufficiency, and severe left ventricular systolic dysfunction (LVSD) were more prevalent. Among heart rate-modulating drugs, only digoxin and beta2-agonists were more commonly used among cases. After adjustment for major comorbidities such as diabetes, pulmonary, and renal disease as well as the effects of heart rate-modulating drugs, the authors found a 26% increase in risk associated with each 10-beats/min increase in resting heart rate. Subsequent adjustment for the impact of LVSD attenuated this relationship to a minor degree. Digoxin use had the strongest predictive value for sudden death, but only 12 controls were on the drug as opposed to 62 controls, of