The prognostic value of the heart rate response during exercise and recovery in patients with heart failure: Influence of beta-blockade

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Abstract

Background

The heart rate increase during exercise (ΔHR) and heart rate recovery (HRR) have demonstrated prognostic value in several investigations, but its application in the heart failure (HF) population is limited, particularly in a beta-blocked (BB) cohort.

Methods

Five-hundred and twenty subjects with HF underwent cardiopulmonary exercise testing to determine peak oxygen consumption (VO2), the minute ventilation/carbon dioxide production (VE/VCO2) slope, ΔHR and HRR at 1 min (HRR1).

Results

There were 79 cardiac-related deaths during the tracking period. A HRR1 threshold of </≥ 16 beats/min was a significant prognostic marker in the overall group (hazard ratio: 4.6, 95% CI: 2.8–7.5, p < 0.001) as well as no-BB (hazard ratio: 9.1, 95% CI: 4.1–20.2, p < 0.001) and BB (hazard ratio: 2.9, 95% CI: 1.6–5.4, p < 0.001) subgroups. The ΔHR was a significant univariate predictor in the overall group and no-BB subgroup only. Multivariate Cox regression analysis revealed HRR1 was the strongest prognostic marker (chi-square: 39.9, p < 0.001). The VE/VCO2 slope (residual chi-square: 21.8, p < 0.001) and LVEF (residual chi-square: 9.6, p = 0.002) were also retained in the regression.

Conclusions

These results indicate that HRR maintains prognostic value in HF irrespective of BB use. The routine inclusion of HRR in the prognostic assessment of patients with HF may be warranted.

Introduction

The cardiopulmonary exercise test (CPX) is a primary clinical evaluation tool in the heart failure (HF) population [1], [2], [3]. Although peak oxygen consumption (VO2) is the primary CPX variable analyzed by clinicians, other ventilatory expired gas measures, such as the minute ventilation (VE)-carbon dioxide production (VCO2) slope have demonstrated robust prognostic value [4], [5][6], [7], [8], [9]. In fact, some evidence indicates that the combination of an increase in HR from rest to maximal exercise (ΔHR) and heart rate recovery (HRR) provides greater prognostic strength than either variable alone. However, most of the investigations examining the prognostic value of the HR response to exercise have done so in cohorts at risk for or diagnosed with coronary artery disease rather than HF. Our group is aware of only one investigation that has reported on the prognostic value of ΔHR in patients with HF. Cohen-Solal et al. [10] found ΔHR was a significant prognostic marker in 175 patients with HF. Additionally, two investigations have examined the ability of HRR to predict adverse events in patients with HF. Arena et al. [11] reported that HRR predicted a composite endpoint of hospitalization and mortality in a small group (n < 100) of patients with HF. Additionally, HRR added prognostic value to the VE/VCO2 slope in a multivariate regression. Lipinski et al. [7] likewise demonstrated that HRR was a significant predictor of mortality, again in a small HF cohort (n < 100). In this latter investigation, ventilatory expired gas analysis was not performed during exercise testing. Clearly, further inquiry into the prognostic value of the HR response to exercise in the HF population is warranted. Moreover, given its widespread use and unique impact on HR, the influence of beta-blocker (BB) therapy on the prognostic value of the HR response to exercise in patients with HF requires further study.

Given the present scientific gaps in understanding of the prognostic importance of the HR response to exercise in patients with HF, the primary objectives of the present investigation were to: 1) propose prognostically applicable threshold values for the ΔHR and HRR; 2) examine the prognostic significance of ΔHR and HRR in combination with established ventilatory expired gas variables in a large HF cohort; and 3) examine the influence of beta-blocker use on the prognostic value of ΔHR and HRR.

Section snippets

Methods

This study was a multi-center analysis including HF patients from the CPX laboratories at San Paolo Hospital, Milan, Italy, Virginia Commonwealth University, Richmond, Virginia, USA, LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina, USA and the VA Palo Alto Health Care System and Stanford University, Palo Alto, California, USA. A total of 520 patients with chronic HF and tested between 1994 and 2007 were included. Inclusion criteria consisted of a diagnosis of HF15 and

Results

Overall group characteristics as well as BB subgroup comparisons are listed in Table 1. In the BB subgroup, 83% were prescribed Carvedilol (mean dose: 35 mg/day), 14% were prescribed Metoprolol (mean dose: 75 mg/day) and 3% were prescribed another agent (Bispropolol, Toprol or Sotalol). All subjects prescribed a BB were maintained on their prescribed dose during CPX. None of the subjects in this study was prescribed a calcium channel blocker. Left ventricular ejection fraction, resting and

Discussion

One previous investigation has demonstrated HRR was prognostically significant in patients with HF without consideration of measures obtained from ventilatory expired gas [7]. Our group has previously demonstrated HRR and the VE/VCO2 slope are important prognostic markers in a small HF cohort [11]of these studies were too small to meaningfully assess subjects according to BB use. The present investigation confirms our earlier findings in a larger HF cohort, using a hard endpoint (mortality),

Acknowledgement

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [35]

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