Baseline differences in the HF-ACTION trial by sex

Am Heart J. 2009 Oct;158(4 Suppl):S16-23. doi: 10.1016/j.ahj.2009.07.012.


Background: In patients with heart failure (HF), assessment of functional capacity plays an important prognostic role. Both 6-minute walk and cardiopulmonary exercise testing have been used to determine physical function and to determine prognosis and even listing for transplantation. However, as in HF trials, the number of women reported has been small, and the cutoffs for transplantation have been representative of male populations and extrapolated to women. It is also well known that peak VO(2) as a determinant of fitness is inherently lower in women than in men and potentially much lower in the presence of HF. Values for a female population from which to draw for this important determination are lacking.

Methods: The HF-ACTION trial randomized 2,331 patients (28% women) with New York Heart Association class II-IV HF due to systolic dysfunction to either a formal exercise program in addition to optimal medical therapy or to optimal medical therapy alone without any formal exercise training. To characterize differences between men and women in the interpretation of final cardiopulmonary exercise testing models, the interaction of individual covariates with sex was investigated in the models of (1) VE/VCO(2), (2) VO(2) at ventilatory threshold (VT), (3) distance on the 6-minute walk, and (4) peak VO(2).

Results: The women were younger than the men and more likely to have a nonischemic etiology and a higher ejection fraction. Dose of angiotensin converting enzyme inhibitor (ACEI) was lower in the women, on average. The lower ACEI dose may reflect the higher use of angiotensin II receptor blocker (ARB) in women. Both the peak VO(2) and the 6-minute walk distance were significantly lower in the women than in the men. Perhaps the most significant finding in this dataset of baseline characteristics is that the peak VO(2) for women was significantly lower than that for men with similar ventricular function and health status.

Conclusion: Therefore, in a well-medicated, stable, class II-IV HF cohort of patients who are able to exercise, women have statistically significantly lower peak VO(2) and 6-minute walk distance than men with similar health status and ventricular function. These data should prompt careful thought when considering prognostic markers for women and listing for cardiac transplant.

Trial registration: NCT00047437.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Data Collection / statistics & numerical data
  • Exercise Test / statistics & numerical data*
  • Exercise Therapy
  • Exercise Tolerance
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology*
  • Heart Transplantation / standards
  • Humans
  • Male
  • Multicenter Studies as Topic
  • Oxygen Consumption / physiology
  • Prognosis
  • Sex Distribution
  • Stroke Volume / physiology
  • Ventricular Dysfunction, Left / physiopathology


  • Angiotensin-Converting Enzyme Inhibitors

Associated data