{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:39:23Z","timestamp":1780321163170,"version":"3.54.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Background<\/jats:title>\n \n It is not known whether determinants of ventilation (\n VE<\/jats:styled-content>\n )\/volume of exhaled carbon dioxide (\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n ) slope during incremental exercise may differ at different stages of reduced ejection fraction chronic heart failure natural history.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n slope was fitted up to lowest\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n ratio, that is, a proxy of the\n VE<\/jats:styled-content>\n \/perfusion ratio devoid of nonmetabolic stimuli to ventilatory drive.\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n slope tertiles were generated from our database (<27.5 [tertile 1], \u226527.5 to <32.0 [tertile 2], and \u226532.0 [tertile 3]), and 147 chronic heart failure patients with repeated tests yielding\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n slopes in 2 different tertiles were selected. Determinants of\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n slope changes across tertile pairs 1 versus 2, 2 versus 3, and 1 versus 3 were assessed by exploring changes in\n VE<\/jats:styled-content>\n and\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n at lowest\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n and those in\n VE<\/jats:styled-content>\n \/work rate (W) and\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n \/W slope. Resting and peak cardiac output (\n CO<\/jats:styled-content>\n ) were calculated as\n VO<\/jats:styled-content>\n 2<\/jats:sub>\n \/estimated arteriovenous O\n 2<\/jats:sub>\n difference and the\n CO<\/jats:styled-content>\n \/W slope analyzed. Notwithstanding a progressively lower W with increasing tertile,\n VE<\/jats:styled-content>\n at lowest\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n and\n VE<\/jats:styled-content>\n \/W slope were significantly higher in tertiles 2 and 3 versus tertile 1. Conversely,\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n at lowest\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n and\n CO<\/jats:styled-content>\n \/W slope significantly decreased across tertiles, whereas\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n \/W slope did not. Difference (\u0394) in\n VE<\/jats:styled-content>\n \/W slope between tertiles accounted for 71% of \u0394\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n slope variance, with \u0394\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n \/W slope explaining an additional 26% (model\n r<\/jats:italic>\n =0.99;\n r<\/jats:italic>\n 2<\/jats:sup>\n =0.97;\n P<\/jats:italic>\n <0.0001). Similar results were obtained substituting \u0394\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n \/W slope with \u0394\n CO<\/jats:styled-content>\n \/W slope.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Ventilatory overactivation is the predominant cause of\n VE<\/jats:styled-content>\n \/\n VCO<\/jats:styled-content>\n 2<\/jats:sub>\n slope increase at initial stages of chronic heart failure, whereas hemodynamic impairment plays an additional role at more\u2010advanced pathophysiological stages.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.005278","type":"journal-article","created":{"date-parts":[[2017,5,9]],"date-time":"2017-05-09T20:10:32Z","timestamp":1494360632000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Different Determinants of Ventilatory Inefficiency at Different Stages of Reduced Ejection Fraction Chronic Heart Failure Natural History"],"prefix":"10.1161","volume":"6","author":[{"given":"Alessandro","family":"Mezzani","sequence":"first","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri Spa SB\u2013Scientific Institute of Veruno IRCCS","place":["Veruno (NO), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Giordano","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri Spa SB\u2013Scientific Institute of Veruno IRCCS","place":["Veruno (NO), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Komici","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri Spa SB\u2013Scientific Institute of Veruno IRCCS","place":["Veruno (NO), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Corr\u00e0","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri Spa SB\u2013Scientific Institute of Veruno IRCCS","place":["Veruno (NO), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/eurheartj\/ehi141","article-title":"Why ventilatory inefficiency matters in chronic heart failure","volume":"26","author":"Coats AJ","year":"2005","unstructured":"Coats AJ. 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