N-terminal pro–brain natriuretic peptide and exercise capacity in chronic heart failure: Data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study

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Objectives

To examine the relationship between N-terminal pro–brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure.

Background

Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied.

Methods

We analyzed the relationship between baseline NT-proBNP and peak oxygen uptake (peak Vo2) or distance in the 6-minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak Vo2 or distance in the 6-minute walk test in the context of other clinical variables. Receiver operator curve analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak Vo2 <12 mL/kg per minute.

Results

NT-proBNP was the most powerful predictor of peak Vo2 (partial R2 = 0.13, P < .0001) of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6-minute walk test, this relationship was weaker than that for peak Vo2 (partial R2 = 0.02, P < .0001). For both peak Vo2 and distance in the 6-minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. Receiver operator curve analysis suggested NT-proBNP had moderate ability to identify patients with peak Vo2 <12 mL/kg per minute (c-index, 0.69).

Conclusions

In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak Vo2 and a significant predictor of distance in the 6-minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak Vo2 who might be considered for cardiac transplantation. These data suggest that, although hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic variables.

Section snippets

Methods

Details of design, rationale, and primary results of HF-ACTION have been published elsewhere.12, 13 Briefly, HF-ACTION (clinicaltrials.gov, NCT00047437) was a randomized clinical trial evaluating the effect of exercise training on long term morbidity and mortality in patients with chronic heart failure due to left ventricular systolic dysfunction. Enrolled patients were randomized to exercise training in addition to usual care versus usual care alone. HF-ACTION was approved by local

Study cohort

Baseline characteristics for the study cohort are shown in Table I. Generally, the cohort in whom NT-proBNP data were available (n = 1383) was similar to the overall study population (n = 2331). The study cohort was diverse with regard to gender (29% women), race (34% African-American), and age (20% with age ≥70). The mean ejection fraction was 25% and most patients (66%) had New York Heart Association (NYHA) class II heart failure symptoms. Notably, patients enrolled in HF-ACTION were

Discussion

The primary finding of this analysis was that NT-proBNP levels were associated with both peak Vo2 and distance in the 6-minute walk test in a large well-treated contemporary cohort of patients with chronic heart failure. NT-proBNP was the most significant overall predictor of peak Vo2 even after adjustment for 35 demographic and clinical candidate variables. For distance in the 6-minute walk test, NT-proBNP was also a significant independent predictor of exercise capacity, although the

Conclusions

NT-proBNP was strongly associated with peak Vo2 in a large well-treated cohort of patients with heart failure due to left ventricular systolic dysfunction. NT-proBNP was the strongest predictor of peak Vo2, even after adjustment for multiple other demographic and clinical characteristics. NT-proBNP was also significantly associated with distance in the 6-minute walk test, although this relationship was substantially weaker than for peak Vo2. These data support the concept that hemodynamic

Disclosures

M. Felker, C. O'Connor, and K. Adams have received research funding and served as consultants to Roche Diagnostics. D. Whellan, W. Kraus, R. Clare, F. Zannad, M. Donahue, R. McKelvie, and I. Piña have no conflicts of interest to disclose.

References (32)

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ClinicalTrials.gov identifier: NCT00047437.

A complete list of the HF-ACTION investigators is available as an appendix in the introduction of this supplement. This research was supported by National Institutes of Health grants: 5U01HL063747, 5U01HL068973, 5U01HL066501, 5U01HL066482, 5U01HL064250, 5U01HL066494, 5U01HL064257, 5U01HL066497, 5U01HL068980, 5U01HL064265, 5U01HL066491, 5U01HL064264, 5U01HL066461, R37AG18915, P60AG10484.

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