Different Determinants of Ventilatory Inefficiency at Different Stages of Reduced Ejection Fraction Chronic Heart Failure Natural History.

Background: It is not known whether determinants of ventilation (VE)/volume of exhaled carbon dioxide (VCO) slope during incremental exercise may differ at different stages of reduced ejection fraction chronic heart failure natural history.

Methods And Results: VE/VCO slope was fitted up to lowest VE/VCO ratio, that is, a proxy of the VE/perfusion ratio devoid of nonmetabolic stimuli to ventilatory drive. VE/VCO 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 slopes in 2 different tertiles were selected. Determinants of VE/VCO slope changes across tertile pairs 1 versus 2, 2 versus 3, and 1 versus 3 were assessed by exploring changes in VE and VCO at lowest VE/VCO and those in VE/work rate (W) and VCO/W slope. Resting and peak cardiac output (CO) were calculated as VO/estimated arteriovenous O difference and the CO/W slope analyzed. Notwithstanding a progressively lower W with increasing tertile, VE at lowest VE/VCO and VE/W slope were significantly higher in tertiles 2 and 3 versus tertile 1. Conversely, VCO at lowest VE/VCO and CO/W slope significantly decreased across tertiles, whereas VCO/W slope did not. Difference (Δ) in VE/W slope between tertiles accounted for 71% of ΔVE/VCO slope variance, with ΔVCO/W slope explaining an additional 26% (model =0.99; =0.97; <0.0001). Similar results were obtained substituting ΔVCO/W slope with ΔCO/W slope.

Conclusions: Ventilatory overactivation is the predominant cause of VE/VCO slope increase at initial stages of chronic heart failure, whereas hemodynamic impairment plays an additional role at more-advanced pathophysiological stages.