Resting Ventricular–Vascular Function and Exercise Capacity in Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study

Background—Exercise intolerance is a hallmark of heart failure, but factors associated with impaired exercise capacity in heart failure with preserved ejection fraction are unclear. We hypothesized that in heart failure with preserved ejection fraction, the severity of resting ventricular and vascular dysfunction are associated with impairment in exercise tolerance as assessed by peak oxygen consumption. Methods and Results—Subjects with heart failure with preserved ejection fraction enrolled in the PhosphodiesteRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart Failure (RELAX) clinical trial (n=216) underwent baseline Doppler echocardiography, cardiopulmonary exercise testing, and cardiac MRI. RELAX participants were elderly (median age 69 years) and 48% were women. Ejection fraction (60%) and stroke volume (77 mL) were normal, while diastolic dysfunction (medial E/e′, 16; deceleration time, 185 ms; left atrial volume, 44 mL/m2) and increased arterial load (arterial elastance, 1.51 mm Hg/mL) were evident. Peak oxygen consumption was reduced (11.7 mLkg−1min−1, 1141 mL/min) and age, sex, body mass index, hemoglobin, and chronotropic response collectively explained 64% of the variance in raw peak oxygen consumption (mL/min). After adjustment for these variables, left ventricular structure (diastolic dimension [1.5%, P=0.008] and left ventricular mass [1.6%, P=0.008]), resting stroke volume (2.0%, P=0.002), left ventricular diastolic dysfunction (deceleration time [0.9%, P=0.03] and E/e′ [1.4%, P=0.009]), and arterial function (arterial elastance [2.1%, P=0.002] and systemic arterial compliance [1.5%, P=0.007]), each explained only a small additional portion of the variance in peak oxygen consumption. Conclusions—In heart failure with preserved ejection fraction, potentially modifiable factors (obesity, anemia, and chronotropic incompetence) are strongly associated with exercise capacity, whereas resting measures of ventricular and vascular structure and function are not. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867