Abstract
AIMS: Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇(E) /V̇CO(2) ) slope. The physiological correlates of the V̇(E) /V̇CO(2) slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (V(D) /V(T) ) and arterial CO(2) tension (PaCO(2) ) differentially contribute to the V̇(E) /V̇CO(2) slope in HFrEF vs. HFpEF. METHODS AND RESULTS: Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m(2) and 33 ± 6 kg/m(2) , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO(2) was measured via radial arterial catheterization. We calculated the V̇(E) /V̇CO(2) slope via linear regression, and V(D) /V(T) = 1 - [(863 × V̇CO(2) )/(V̇(E) × PaCO(2) )]. Resting V(D) /V(T) (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO(2) (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise V(D) /V(T) (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO(2) (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇(E) /V̇CO(2) slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇(E) /V̇CO(2) slope in HFrEF and HFpEF was explained by peak exercise V(D) /V(T) (R(2) = 0.30 and R(2) = 0.50, respectively) and PaCO(2) (R(2) = 0.64 and R(2) = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). CONCLUSIONS: Relationships between the V̇(E) /V̇CO(2) slope and both V(D) /V(T) and PaCO(2) are robust, but differ between HFpEF and HFrEF. Increasing V̇(E) /V̇CO(2) slope appears to be strongly explained by mechanisms influential in regulating PaCO(2) in HFrEF, which contrasts with the strong role of increased V(D) /V(T) in HFpEF.