What is the clinical evidence from this study?

Study design: Observational. Population: chronic heart failure with reduced ejection fraction (EF < 35%) (n=1118). Intervention: Chronotropic index (CI) and resting heart rate (HR). Primary outcome: all-cause mortality or hospitalization.

January 12, 2013Open Access

Association between resting heart rate, chronotropic index, and long-term outcomes in patients with heart failure receiving β-blocker therapy: data from the HF-ACTION trial

Q: What are the key findings of this study?

Each 0.1 unit decrease in chronotropic index <0.6 was associated with a 17% increased risk of all-cause mortality (HR 1.17; 95% CI 1.01-1.36; P=0.036) in HF patients on beta-blockers.

Key Result

Each 0.1 unit decrease in chronotropic index <0.6 was associated with a 17% increased risk of all-cause mortality (HR 1.17; 95% CI 1.01-1.36; P=0.036) in HF patients on beta-blockers.

Study Design

Type

Observational (n=1,118)

PICO

Population

chronic heart failure with reduced ejection fraction (EF < 35%) (n=1,118)

Intervention / Comparator

Chronotropic index (CI) and resting heart rate (HR)

Primary Outcome

all-cause mortality or hospitalization

Abstract

AIMS: The aim of this study was to assess the association between resting heart rate (HR), chronotropic index (CI), and clinical outcomes in optimally treated chronic heart failure (HF) patients on β-blocker therapy. METHODS AND RESULTS: We performed a sub-study in 1118 patients with HF and reduced ejection fraction (EF < 35%) included in the HF-ACTION trial. Patients in sinus rhythm who received a β-blocker and who performed with maximal effort on the exercise test were included. Chronotropic index was calculated as an index of HR reserve achieved, by using the equation (220-age) for estimating maximum HR. A sensitivity analysis using an equation developed for HF patients on β-blockers was also performed. Cox proportional hazards models were fit to assess the association between CI and clinical outcomes. Median (25th, 75th percentiles) follow-up was 32 (21, 44) months. In a multivariable model including resting HR and CI as continuous variables, neither was associated with the primary outcome of all-cause mortality or hospitalization. However, each 0.1 unit decrease in CI <0.6 was associated with 17% increased risk of all-cause mortality (hazard ratio 1.17, 95% confidence interval 1.01-1.36; P = 0.036), and 13% increased risk of cardiovascular mortality or HF hospitalization (hazard ratio 1.13, 1.02-1.26; P = 0.025). Overall, 666 of 1118 (60%) patients had a CI <0.6. Chronotropic index did not retain statistical significance when dichotomized at a value of ≤ 0.62. CONCLUSION: In HF patients receiving optimal medical therapy, a decrease in CI <0.6 was associated with adverse clinical outcomes. Obtaining an optimal HR response to exercise, even in patients receiving optimal β-blocker therapy, may be a therapeutic target in the HF population.