Heart failure is an important cause of cardiovascular morbidity and mortality. In the group of patients with heart failure with reduced ejection fraction (HFrEF) therapeutic manipulations of heart rate is associated with improved outcomes in these patients.

Heart failure is an important cause of cardiovascular morbidity and mortality

For example the BEATIFUL, SHIFT and EVEREST studies using ivabradine and vasopressin antagonist. However, less is known about the association of heart rate and outcomes in patients with heart failure with preserved ejection fraction (HFpEF).

Study 1

In this study, data was used from the OPTIMIZE-HF registry, a program to initiate life-saving treatment in hospitalised patients with heart failure. There were 8 873 hospitalised patients with heart failure with preserved ejection fraction and from those there were 6 286 who had a stable heart rate and of these there were 2 369 patients who had a heartbeat of <70 beats per minute (bpm) and the rest >70bpm. A propensity score using 58 baseline characteristics was used to assemble a cohort of 2031 pairs of patients (total 4062 patients) with heart failure with heart rate <70bpm vs >70bpm. During 6 years of follow-up, all-cause mortality was 65% in those patients with heart rate <70bpm and the mortality was 70% for those patients with heart rate of >70bpm. The hazard ratio: 0.86 (95% CI: 0.80-0.93), p <0.0001. Significant reduced mortality of 14% for those patients in heart failure with heart rate less than 70bpm.

Heart rate <70bpm was also associated with a lower risk of the combined end-point of heart failure readmission or all-cause mortality: Hazard Ratio: 0.90 (95%CI: 0.84-0.96), p= 0.002. Readmissions to hospital alone were not significantly different between those with heart rate <70 vs >70bpm.

In this study, hospitalised patients with heart failure with preserved ejection fraction with a heart rate of <70bpm on discharge, was associated with a reduced mortality.

Study 2

This study explored the relationship of heart rate in patients with heart failure with reduced ejection fraction in patients receiving beta-blockers. They did a meta-analysis of individual patient-level data which they obtained from 11 randomised controlled trials. They obtained the data from the principal investigators and the pharmaceutical companies who sponsored the original trials. The primary outcome of this study was all-cause mortality. A Cox proportional hazard ratios modelling heart rate measured at baseline and 6 months post-randomisation.

A higher heart rate at baseline was associated with increased mortality for patients with sinus rhythm: Adjusted HR: 1.11 per 10 beats per minute (95%CI: 1.07-1.15) p<0.0001. Those patients in atrial fibrillation did not show this association of increased heart rate and mortality.

Beta-blockers reduced heart rate in both those patients in sinus rhythm and in those in atrial fibrillation. Mortality in those patients in sinus rhythm on beta-blockers was significantly reduced: HR 0.73 (95%CI: 0.65-0.79) p< 0.001 regardless of the baseline heart rate.

Beta blockers had no effect on mortality in those patients in heart failure in atrial fibrillation at any heart rate level.

Author: Prof James Ker

Conclusion

Regardless of the baseline heart rate (pre-treatment) beta blockers reduced mortality in patients with heart failure with reduced ejection fraction in sinus rhythm.

Achieving a lower heart rate was associated with a better prognosis in this group of heart failure patients with reduced ejection fraction.

Patients with atrial fibrillation in heart failure with reduced ejection fraction did not benefit from beta blockers.

Whether clinicians should aim for a specific heart rate or a target dose of beta blockers remains unanswered.