Van Iterson EH, Johnson BD, Borlaug BA, Olson TP

Eur J Heart Fail. 2017 Oct 8. doi: 10.1002/ejhf.913. [Epub ahead of print]

AIMS: Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF)
ejection fraction demonstrate an increased ventilatory equivalent for carbon
dioxide (V̇E /V̇CO2 ) slope. The physiological correlates of the V̇E /V̇CO2 slope
remain unclear in the two HF phenotypes. We hypothesized that changes in the
physiological dead space to tidal volume ratio (VD /VT ) and arterial CO2 tension
(PaCO2 ) differentially contribute to the V̇E /V̇CO2 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. PaCO2
was measured via radial arterial catheterization. We calculated the V̇E /V̇CO2
slope via linear regression, and VD /VT  = 1 - [(863 × V̇CO2 )/(V̇E  × PaCO2 )].
Resting VD /VT (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO2
(38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak
exercise VD /VT (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO2 (33 ± 6 mmHg
vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇E /V̇CO2 slope
was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance
associated with the V̇E /V̇CO2 slope in HFrEF and HFpEF was explained by peak
exercise VD /VT (R(2)  = 0.30 and R(2)  = 0.50, respectively) and PaCO2 (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 V̇E /V̇CO2 slope and both VD /VT and PaCO2
are robust, but differ between HFpEF and HFrEF. Increasing V̇E /V̇CO2 slope
appears to be strongly explained by mechanisms influential in regulating PaCO2 in
HFrEF, which contrasts with the strong role of increased VD /VT in HFpEF.