Background
It is not known whether determinants of ventilation (
VE
)/volume of exhaled carbon dioxide (
VCO
2
) slope during incremental exercise may differ at different stages of reduced ejection fraction chronic heart failure natural history.
Methods and Results
VE
/
VCO
2
slope was fitted up to lowest
VE
/
VCO
2
ratio, that is, a proxy of the
VE
/perfusion ratio devoid of nonmetabolic stimuli to ventilatory drive.
VE
/
VCO
2
slope tertiles were generated from our database (<27.5 [tertile 1], ≥27.5 to <32.0 [tertile 2], and ≥32.0 [tertile 3]), and 147 chronic heart failure patients with repeated tests yielding
VE
/
VCO
2
slopes in 2 different tertiles were selected. Determinants of
VE
/
VCO
2
slope changes across tertile pairs 1 versus 2, 2 versus 3, and 1 versus 3 were assessed by exploring changes in
VE
and
VCO
2
at lowest
VE
/
VCO
2
and those in
VE
/work rate (W) and
VCO
2
/W slope. Resting and peak cardiac output (
CO
) were calculated as
VO
2
/estimated arteriovenous O
2
difference and the
CO
/W slope analyzed. Notwithstanding a progressively lower W with increasing tertile,
VE
at lowest
VE
/
VCO
2
and
VE
/W slope were significantly higher in tertiles 2 and 3 versus tertile 1. Conversely,
VCO
2
at lowest
VE
/
VCO
2
and
CO
/W slope significantly decreased across tertiles, whereas
VCO
2
/W slope did not. Difference (Δ) in
VE
/W slope between tertiles accounted for 71% of Δ
VE
/
VCO
2
slope variance, with Δ
VCO
2
/W slope explaining an additional 26% (model
r
=0.99;
r
2
=0.97;
P
<0.0001). Similar results were obtained substituting Δ
VCO
2
/W slope with Δ
CO
/W slope.
Conclusions
Ventilatory overactivation is the predominant cause of
VE
/
VCO
2
slope increase at initial stages of chronic heart failure, whereas hemodynamic impairment plays an additional role at more‐advanced pathophysiological stages.
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