Association of Heart Rate and Outcomes in a Broad Spectrum of Patients With Chronic Heart Failure: Results From the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity) Program

Study Questions:

Is elevated heart rate associated with worse outcome in all patients with chronic heart failure (HF)?

Methods:

This was secondary analysis of the CHARM (Candesartan in Heart Failure) study. Baseline heart rate was measured per standardized guidelines, and patients were then subgrouped by rhythm (sinus vs. atrial fibrillation) and ejection fraction (left ventricular ejection fraction [LVEF] >40% and ≤40%). The primary outcome (all-cause mortality ) was analyzed based on heart rate tertile in the total cohort, and in the subgroups of LVEF and baseline rhythm.

Results:

There were 7,597 patients in the cohort with a median heart rate of 72 (interquartile range, 64-80) bpm. Overall, patients with higher heart rates were higher risk: They had worse New York Heart Association (NYHA) class and were more likely to smoke, have diabetes, and to have had prior HF hospitalizations. Patients with higher heart rates were more likely to be on loop diuretics and digoxin, and were less likely to be on a beta-blocker (p < 0.001). Over a mean follow-up of 37.7 months, there were 1,831 (24%) deaths. Each 10 beat increase in heart rate increased the risk of death by 6% (adjusted hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02-1.1) overall. In patients with a reduced LVEF, mortality risk increased 6% (adjusted HR, 1.06; 95% CI, 1.02-1.1 per 10 beats) and tended to be higher in those with preserved LVEF (adjusted HR, 1.05; 95% CI, 0.98-1.05) and higher heart rates. Beta-blocker use did not appear to impact the association between heart rate and mortality (p > 0.10 for interaction). Higher heart rate was not associated with a significant risk increase in patients with atrial fibrillation (adjusted HR, 0.97; 95% CI, 0.90-1.05), but did afford increased risk in those in sinus rhythm (adjusted HR, 1.08; 95% CI, 1.04-1.12 per 10 beats).

Conclusions:

The authors concluded that a faster heart rate is associated with worse outcome in patients with chronic HF and sinus rhythm, regardless of LVEF. This correlation was not noted in patients in atrial fibrillation.

Perspective:

This analysis showed that a higher heart rate obtained as a ‘single snapshot’ portended worse long-term prognosis in patients with HF, correlations of which only trended toward significance in those with preserved LVEF. Overall, these results are not surprising. Patients with higher heart rates were clinically sicker—they had worse NYHA class, more diabetes, more diuretic and digoxin use, and less beta-blocker use. Pre-renal states (from either overdiuresis or low cardiac output) can lead to sympathetic nervous system and renin-angiotensin-system elevations, with subsequent tachycardia. The authors attempted to control for these baseline differences in patient clinical characteristics. Why this association was not seen in patients with atrial fibrillation is not clear. Perhaps they were on higher doses of beta-blockers or there was more subclinical atrial fibrillation.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents, Acute Heart Failure

Keywords: Follow-Up Studies, Chronic Disease, Diuretics, Renin-Angiotensin System, Heart Rate, New York, Tachycardia, Heart Diseases, Prognosis, Incidence, Benzimidazoles, Sympathetic Nervous System, Cardiology, Heart Failure, Ventricular Function, Diabetes Mellitus


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