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

Abstract

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.