Relationship of Doppler-Echocardiographic left ventricular diastolic function to exercise performance in systolic heart failure: The HF-ACTION study

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] ≤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, VO2 ), distance in the 6-minute walk test (6MWD), and ventilatory efficiency (VE/VCO2 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 VO2 (inverse) and VE/VCO2 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 VO2 or VE/VCO2 slope. A multivariable model with peak VO2 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 VO2 , 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 VO2 . In a multivariable model for VE/VCO2 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 VO2 or VE/VCO2 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.