Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure.

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.