Hemodynamic Correlates and Diagnostic Role of Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction

Objectives: This study sought to define the invasive hemodynamic correlates of peak oxygen consumption (VO₂) 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). Background: Peak VO₂ is depressed in patients with HFpEF. The hemodynamic correlates of reduced peak VO₂ and its role in the clinical evaluation of HFpEF are unclear. Methods: 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. Results: Compared with NCD (n = 72), HFpEF patients (n = 134) displayed lower peak VO₂ during upright and supine exercise. Left heart filling pressures during exercise were inversely correlated with peak VO₂ in HFpEF, even after accounting for known determinants of O₂ transport according to the Fick principle. Very low upright peak VO₂ (<14 ml/kg/min) discriminated HFpEF from NCD with excellent specificity (91%) but poor sensitivity (50%). Preserved peak VO₂ (>20 ml/kg/min) excluded HFpEF with high sensitivity (90%) but had poor specificity (49%). Intermediate peak VO₂ cutoff points were associated with substantial overlap between cases and NCD. Conclusions: 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 VO₂.