Heart failure
Reproducibility of Peak Oxygen Uptake and Other Cardiopulmonary Exercise Testing Parameters in Patients With Heart Failure (from the Heart Failure and A Controlled Trial Investigating Outcomes of exercise traiNing)

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Peak oxygen uptake (pVo2) is an important parameter in assessing the functional capacity and prognosis of patients with heart failure. In heart failure trials, change in pVo2 was often used to assess the effectiveness of an intervention. However, the within-subject variability of pVo2 on serial testing may limit its usefulness. This study was designed to evaluate the within-subject variability of pVo2 over 2 baseline cardiopulmonary exercise tests. As a substudy of the HF-ACTION trial, 398 subjects (73% men, 27% women; mean age 59 years) with heart failure and left ventricular ejection fraction ≤35% underwent 2 baseline cardiopulmonary exercise tests within 14 days. Mean pVo2 was unchanged from test 1 to test 2 (15.16 ± 4.97 vs 15.18 ± 4.97 ml/kg/min; p = 0.78). However, mean within-subject absolute change was 1.3 ml/kg/min (10th, 90th percentiles 0.1, 3.0), with 46% of subjects increasing and 48% decreasing on the second test. Other parameters, including the ventilation-to-carbon-dioxide production slope and Vo2 at ventilatory threshold, also showed significant within-subject variation with minimal mean differences between tests. In conclusion, pVo2 showed substantial within-subject variability in patients with heart failure and should be taken into account in clinical applications. However, on repeated baseline cardiopulmonary exercise tests, there appears to be no familiarization effect for Vo2 in patients with HF. Therefore, in multicenter trials, there is no need to perform >1 baseline cardiopulmonary exercise test.

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Methods

Enrollment criteria and study design for the HF-ACTION have been previously published.1 Subjects had a left ventricular ejection fraction ≤35% (caused by ischemic or nonischemic cardiomyopathy) and were on stable doses (i.e., the same dose for ≥6 weeks before enrollment) of optimal drug therapy, including an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a β blocker unless a contraindication was present. Of subjects enrolled in HF-ACTION, 94% were using an

Results

Table 1 lists baseline demographics and pVo2 for the 398 subjects in the study. On the first cardiopulmonary exercise test, mean pVo2 was 15.2 ± 5.0 ml/kg/min.

As listed in Table 2, mean exercise time increased significantly from test 1 to test 2. Conversely, mean pVo2 was virtually identical on the 2 tests. pVo2 was nearly as likely to increase from test 1 to test 2 (46% of subjects) as it was to decrease (48% of subjects). Moreover, pVo2 had substantial within-subject variability, averaging

Discussion

As a prespecified substudy of the HF-ACTION, we evaluated the reproducibility of pVo2 and other important cardiopulmonary exercise parameters in 398 subjects with HF who underwent 2 tests within 14 days of each other to assess the need for repeated baseline testing in all subjects. The major findings were (1) significant within-subject variability in pVo2 between the 2 tests (average coefficient of variation 6.6%), but the mean was the same between the 2 tests; (2) similar variability in other

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This work was supported by Grant No. 5U01HL063747 from the National Institutes of Health, Bethesda, Maryland.

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