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

Abstract

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.

Keywords: HFpEF; diagnosis; exercise; heart failure; hemodynamics.

Figure 1

Peak O₂ consumption (VO₂) in HFpEF (red) and NCD (black) indexed to body weight [A] and after converting to percent predicted peak VO₂ by the Wasserman nomogram [B,C]. [D] Correlation between peak VO₂ measured during invasive hemodynamic testing in the supine and upright position.

Figure 2

Correlation between peak VO₂ in both upright (black) and supine (red) positions and exercise pulmonary capillary wedge pressure (PCWP), pulmonary artery (PA) pressure, cardiac output (CO) and PCWP indexed to work performed in Watts (W).

Figure 3

As compared to HFpEF patients with peak VO₂≥14 ml/kg/min (black), patients with severely decreased peak VO₂ (<14 ml/kg/min, red) display [A] worse CO response relative to metabolic demand (ΔCO/ΔVO₂), [B] higher PCWP, [C] higher PCWP relative to cardiac output reserve, and [D] higher PCWP relative to ergometric work performed.

Figure 4

Proposed diagnostic algorithm for Cardiopulmonary exercise testing (CPET) for unexplained dyspnea. When obvious causes have been excluded, measurement of peak VO₂ by CPET allows for discrimination of HFpEF from non-cardiac dyspnea at very low (<14 ml/kg/min) or relatively peak VO₂ (>20 ml/kg/min), respectively. However, given the substantial overlap in the intermediate range, additional testing, as with hemodynamic exercise testing, is required in patients with peak VO₂ 14–20 ml/kg/min.