Alveolar Dead Space Is Augmented During Exercise in Patients With Heart Failure With Preserved Ejection Fraction

Background: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit many cardiopulmonary abnormalities that could result in V˙/Q˙ mismatch, manifesting as an increase in alveolar dead space (VD_alveolar) during exercise. Therefore, we tested the hypothesis that VD_alveolar would increase during exercise to a greater extent in patients with HFpEF compared with control participants.

Research question: Do patients with HFpEF develop VD_alveolar during exercise?

Study design and methods: Twenty-three patients with HFpEF and 12 control participants were studied. Gas exchange (ventilation [V˙_E], oxygen uptake [V˙o₂], and CO₂ elimination [V˙co₂]) and arterial blood gases were analyzed at rest, twenty watts (20W), and peak exercise. Ventilatory efficiency (evaluated as the V˙_E/V˙co₂ slope) also was measured from rest to 20W in patients with HFpEF. The physiologic dead space (VD_physiologic) to tidal volume (VT) ratio (VD/VT) was calculated using the Enghoff modification of the Bohr equation. VD_alveolar was calculated as: (VD / VT × VT) - anatomic dead space. Data were analyzed between groups (patients with HFpEF vs control participants) across conditions (rest, 20W, and peak exercise) using a two-way repeated measures analysis of variance and relationships were analyzed using Pearson correlation coefficient.

Results: VD_alveolar increased from rest (0.12 ± 0.07 L/breath) to 20W (0.22 ± 0.08 L/breath) in patients with HFpEF (P < .01), whereas VD_alveolar did not change from rest (0.01 ± 0.06 L/breath) to 20W (0.06 ± 0.13 L/breath) in control participants (P = .19). Thereafter, VD_alveolar increased from 20W to peak exercise in patients with HFpEF (0.37 ± 0.16 L/breath; P < .01 vs 20W) and control participants (0.19 ± 0.17 L/breath; P = .03 vs 20W). VD_alveolar was greater in patients with HFpEF compared with control participants at rest, 20W, and peak exercise (main effect for group, P < .01). Moreover, the increase in VD_alveolar correlated with the V˙_E/V˙co₂ slope (r = 0.69; P < .01), which was correlated with peak V˙o_2peak (r = 0.46; P < .01) in patients with HFpEF.

Interpretation: These data suggest that the increase in V˙/Q˙ mismatch may be explained by increases in VD_alveolar and that increases in VD_alveolar worsens ventilatory efficiency, which seems to be a key contributor to exercise intolerance in patients with HFpEF.