This study sought to define the invasive hemodynamic correlates of peak oxygen consumption (Vo) in both supine and upright exercise in heart failure with preserved ejection fraction (HFpEF) and evaluate its diagnostic role as a method to discriminate HFpEF from noncardiac etiologies of dyspnea (NCD).

Peak Vo is depressed in patients with HFpEF. The hemodynamic correlates of reduced peak Vo and its role in the clinical evaluation of HFpEF are unclear.

Consecutive patients with dyspnea and normal EF (N = 206) undergoing both noninvasive upright and invasive supine cardiopulmonary exercise testing were examined. Patients with invasively verified HFpEF were compared with those with NCD.

Compared with NCD (n = 72), HFpEF patients (n = 134) displayed lower peak Vo during upright and supine exercise. Left heart filling pressures during exercise were inversely correlated with peak Vo in HFpEF, even after accounting for known determinants of O transport according to the Fick principle. Very low upright peak Vo (<14 ml/kg/min) discriminated HFpEF from NCD with excellent specificity (91%) but poor sensitivity (50%). Preserved peak Vo (>20 ml/kg/min) excluded HFpEF with high sensitivity (90%) but had poor specificity (49%). Intermediate peak Vo cutoff points were associated with substantial overlap between cases and NCD.

Elevated cardiac filling pressure during exercise is independently correlated with reduced exercise capacity in HFpEF, irrespective of body position, emphasizing its importance as a novel therapeutic target. Noninvasive cardiopulmonary testing discriminates HFpEF and NCD at high and low values, but additional testing is required for patients with intermediate peak Vo.