Mohammed, S. F., Borlaug, B. A., McNulty, S., Lewis, G. D., Lin, G., Zakeri, R., Semigran, M. J., LeWinter, M., Hernandez, A. F., Braunwald, E., Redfield, M. M. Resting Ventricular-Vascular Function and Exercise Capacity in Heart Failure with Preserved Ejection Fraction: A RELAX Trial Ancillary Study Circ Heart Fail. 2014;NA(NA):NA.

BACKGROUND: -Exercise intolerance is a hallmark of heart failure (HF), but factors associated with impaired exercise capacity in HF with preserved EF (HFpEF) are unclear. We hypothesized that in HFpEF, the severity of resting ventricular and vascular dysfunction are associated with impairment in exercise tolerance as assessed by peak oxygen consumption (pVO2).

METHODS: -Subjects with HFpEF 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 magnetic resonance imaging. RELAX participants were elderly (median age 69 years) and 48% were women. EF (60%) and stroke volume (77 ml) were normal, while diastolic dysfunction (medial E/e' 16, deceleration time 185 msec, left atrial volume 44 ml/m2) and increased arterial load (arterial elastance (Ea) 1.51 mmHg/ml) were evident. PVO2 was reduced (11.7 ml/kg/min, 1141 ml/min) and age, sex, body mass index (BMI), hemoglobin and chronotropic response collectively explained 64% of the variance in raw pVO2 (ml/min). After adjustment for these variables, LV structure (diastolic dimension (1.5%, p=0.008) and LV mass (1.6%, p=0.008)), resting stroke volume (2.0%, p=0.002), LV diastolic dysfunction (deceleration time (0.9%, p=0.03) and E/e' (1.4%, p=0.009), and arterial function (Ea (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 pVO2.

CONCLUSIONS: -In HFpEF, 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.