Abstract
INTRODUCTION: Patients with systolic heart failure often have concomitant left ventricular (LV) diastolic dysfunction. Although in animal models diastolic dysfunction is associated with worsening exercise capacity and prognosis, information regarding these relationships in patients with established systolic heart failure (HF) is sparse. METHODS: HF-ACTION was a large, multicenter National Institutes of Health-funded trial of exercise training in systolic HF (LV ejection fraction [LVEF] < or = 35%) and included detailed Doppler-echocardiographic (echo) and cardiopulmonary exercise testing at baseline. We tested the hypothesis that echo measures of LV diastolic function predict key cardiopulmonary exercise outcomes, including aerobic exercise capacity (peak exercise oxygen consumption, VO(2)), distance in the 6-minute walk test (6MWD), and ventilatory efficiency (VE/VCO(2) slope) in patients with systolic HF. RESULTS: Overall, 2,331 patients (28% women, median age 59 years, median LVEF 25%) were enrolled. There were significant bivariate correlations between echo diastolic function variables and peak VO(2) (inverse) and VE/VCO(2) slope (direct) that were strongest for ratio of early diastolic peak transmitral (MV) to myocardial tissue velocity (E/E'), peak MV early-to-late diastolic velocity ratio (E/A), and left atrial dimension (range of absolute r = 0.16-0.28). Both MV E/A and E/E' were more strongly related to all 3 exercise variables than was LVEF. The relationships of E/A and E/E' with 6MWD were weaker than with peak VO(2) or VE/VCO(2) slope. A multivariable model with peak VO(2) as the dependent variable, which included MV E/A and 9 demographic predictors including age, sex, race, body mass index, and New York Heart Association class, explained 40% of the variation in peak VO(2), with MV E/A explaining 6% of the variation. Including LVEF in the model explained less than an additional 1% of the variance in peak VO(2). In a multivariable model for VE/VCO(2) slope, MV E/A was the strongest independent echo predictor, explaining 10% of the variance. The relationship of LV diastolic function variables with 6MWD was weaker than with peak VO(2) or VE/VCO(2) slope. CONCLUSION: In patients with systolic HF, LV early diastolic function is a modest independent predictor of aerobic exercise capacity and appears to be a better predictor than LVEF.