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 (vco2) slope during incremental exercise may differ at different stages of reduced ejection fraction chronic heart failure natural history. methods and results- ve/vco2 slope was fitted up to lowest ve/vco2 ratio,that is,a proxy of the ve/perfusion ratio devoid of nonmetabolic stimuli to ventilatory drive. ve/vco2 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/vco2 slopes in 2 different tertiles were selected. determinants of ve/vco2 slope changes across tertile pairs 1 versus 2,2 versus 3,and 1 versus 3 were assessed by exploring changes in ve and vco2 at lowest ve/vco2 and those in ve/work rate (w) and vco2/w slope. resting and peak cardiac output (co) were calculated as vo2/estimated arteriovenous o2 difference and the co/w slope analyzed. notwithstanding a progressively lower w with increasing tertile,ve at lowest ve/vco2 and ve/w slope were significantly higher in tertiles 2 and 3 versus tertile 1. conversely,vco2 at lowest ve/vco2 and co/w slope significantly decreased across tertiles,whereas vco2/w slope did not. difference (δ) in ve/w slope between tertiles accounted for 71% of δve/vco2 slope variance,with δvco2/w slope explaining an additional 26% (model r=0.99; r2=0.97; p< 0.0001). similar results were obtained substituting δvco2/w slope with δco/w slope. conclusions- ventilatory overactivation is the predominant cause of ve/vco2 slope increase at initial stages of chronic heart failure,whereas hemodynamic impairment plays an additional role at more-advanced pathophysiological stages. © 2017 the authors.