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

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.

Do patients with HFpEF develop VD_alveolar during exercise?

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.

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.

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.