Heart rate following short‐term beta‐blocker titration predicts all‐cause mortality in elderly chronic heart failure patients: insights from the CIBIS‐ELD trial

Abstract

AimsBeta-blockers (BBs) improve outcomes in heart failure. Results from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial previously demonstrated the feasibility of heart rate, not maximum dose, as a treatment goal. In this pre-specified analysis, we investigated the prognostic value of achieved heart rate after BB optimization on long-term mortality. Methods and resultsElderly heart failure patients from the CIBIS-ELD trial were invited to participate in a follow-up examination 4 years after the initial 12-week BB up-titration period. The relationship between all-cause mortality, BB dose, and heart rate after titration and potentially confounding clinical variables was analysed by multivariable Cox regression. In total, 728 patients (38% women; mean age 72.9 ± 5.4 years) were included. During a mean follow-up period of 45 ± 9 months, 134 patients (19%) died, thus accumulating 2268 patient-years at risk. There was no significant difference in baseline heart rate for survivors and non-survivors (P = 0.19). In models adjusting for age, sex, BB pre-treatment, ventricular function, heart rate, and NYHA class at baseline, a heart rate increase by 10 b.p.m. following up-titration was associated with a subsequent mortality hazard ratio of 1.19 (95% confidence interval 1.02-1.38, P = 0.023). The heart rate range with the lowest mortality and the fewest treatment-related adverse events was 55-64 b.p.m. The achieved BB dose was not associated with mortality risk.

Validation of the FEW16 questionnaire for the assessment of physical well‐being in patients with heart failure with reduced ejection fraction: results from the CIBIS‐ELD study

“…The achieved betablocker dose level on the other hand did not predict mortality. 8 Our result that a lower heart rate was associated with better physical well-being seems to point into the same direction. The severity of HF expressed by LVEF and NYHA did not significantly correlate with any of the FEW16 scores, although we found a weak correlation between NYHA class and Resilience.…”

“…Heart rate reduction is a therapeutic target of betablocker treatment of HF patients and lower heart rate correlated positively with lower mortality in elderly patients during the CIBIS‐ELD trial. The achieved betablocker dose level on the other hand did not predict mortality . Our result that a lower heart rate was associated with better physical well‐being seems to point into the same direction.…”

“…The questions ask how often the patients suffer from different types of discomfort on a scale ranging from '0' ('not at all') to '3' ('almost every day'). The points from all questions are summed up, yielding a score that indicates no depression/healthy (<5), mild or subliminal depression, [6][7][8][9] or major depression with the distinction of medium, 10-14 pronounced, [15][16][17][18][19] or severe. [20][21][22][23][24][25][26][27] The PHQ-D questionnaire can be answered quickly, is easy to interpret, and has been recognized as valid and reliable.…”

“…Patient's health status significantly impacts on QoL, which includes mental, physical, and social aspects of life. Impairment of QoL through illness may lead to depression, social isolation, and diminished adherence to therapy . On the other hand, the potentially causal associations are bi‐directional: treatment itself (e.g.…”

“…Impairment of QoL through illness may lead to depression, social isolation, and diminished adherence to therapy. 7,8 On the other hand, the potentially causal associations are bidirectional: treatment itself (e.g. betablocker therapy) may affect QoL, and 'objective clinical improvement' may differ from the 'subjective well-being' of patients.…”