{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T05:27:38Z","timestamp":1770182858765,"version":"3.49.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T00:00:00Z","timestamp":1117238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Chronic heart failure (CHF) patients complain of breathlessness and fatigue. Beta-blockers improve symptoms, echocardiograpahic variables and prognosis in CHF, but their effect on exercise capacity remains unclear. The aim of this study was to describe the effects of long-term beta-blocker therapy on metabolic gas exchange variables and ventilation during exercise in CHF patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>42 patients with symptomatic heart failure due to left ventricular systolic dysfunction (ejection fraction 33.2 (8.2)) on loop diuretics and angiotensin-converting enzyme inhibitors or angiotensin II antagonists, underwent exercise testing with metabolic gas exchange. They were then initiated onto and uptitrated to the maximum tolerated dose of beta-blockers. After 1 year of follow-up, patients were invited back for repeat testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>35 patients attended for repeat exercise testing. Four patients had died, and three had not tolerated beta-blockade. After 1 year, exercise time was increased (487 (221) vs. 500 (217), p&amp;lt;0.05), and peak oxygen consumption and VE\/VCO2 slope were unchanged (20.9 (5.0) vs. 20.0 (5.4), p=0.15 and 36.7 (8.3) vs. 37.3 (7.8), p=0.70). Peak ventilation, (61.5 (12.9) vs. 57.1 (13.4), p&amp;lt;0.05), peak carbon dioxide production (1629 (404) vs. 1496 (375), p&amp;lt;0.02) and hence respiratory exchange ratio (1.02 (0.08) vs. 0.98 (0.06) p&amp;lt;0.02) and p&amp;lt;0.05) were reduced. Submaximal oxygen consumption and carbon dioxide production were lower at matched workloads. The slope relating symptoms to ventilation (Borg\/VE slope) was less steep following beta-blockade (0.18 (0.09) vs. 0.15 (0.06), p&amp;lt;0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Long term beta-blocker therapy increases exercise time but not peak oxygen consumption, and reduces peak carbon dioxide production. CHF patients are less symptomatic for a given ventilation during exercise following beta-blocker treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.ejheart.2004.05.006","type":"journal-article","created":{"date-parts":[[2004,8,5]],"date-time":"2004-08-05T15:44:01Z","timestamp":1091720641000},"page":"612-617","source":"Crossref","is-referenced-by-count":37,"title":["The Effects of Long-Term \u03b2-Blockade on the Ventilatory Responses to Exercise in Chronic Heart Failure"],"prefix":"10.1093","volume":"7","author":[{"given":"Klaus K.A.","family":"Witte","sequence":"first","affiliation":[{"name":"Academic Cardiology, Castle Hill Hospital , Castle Road, Cottingham Hull, HU16 5JQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Thackray","sequence":"additional","affiliation":[{"name":"Academic Cardiology, Castle Hill Hospital , Castle Road, Cottingham Hull, HU16 5JQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolay P.","family":"Nikitin","sequence":"additional","affiliation":[{"name":"Academic Cardiology, Castle Hill Hospital , Castle Road, Cottingham Hull, HU16 5JQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Academic Cardiology, Castle Hill Hospital , Castle Road, Cottingham Hull, HU16 5JQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew L.","family":"Clark","sequence":"additional","affiliation":[{"name":"Academic Cardiology, Castle Hill Hospital , Castle Road, Cottingham Hull, HU16 5JQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,5,28]]},"reference":[{"key":"2026020203580709200_ejhf2004-05-006-bib-0001","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/eurheartj\/16.1.49","article-title":"Muscle fatigue and dyspnoea in chronic heart failure: two sides of the same coin=","volume":"16","author":"Clark","year":"1995","journal-title":"Eur. Heart J."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0002","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/S0735-1097(96)00323-3","article-title":"Exercise limitation in chronic heart failure: central role of the periphery","volume":"28","author":"Clark","year":"1996","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0003","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1136\/hrt.63.5.281","article-title":"Mechanism of the increased ventilatory response to exercise in patients with chronic heart failure","volume":"63","author":"Buller","year":"1990","journal-title":"Br. Heart J."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0004","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1136\/hrt.65.4.179","article-title":"A critical threshold of exercise capacity in the ventilatory response to exercise in chronic heart failure","volume":"65","author":"Davies","year":"1991","journal-title":"Br. Heart J."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0005","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S1388-9842(02)00093-4","article-title":"Is the elevated slope relating ventilation to carbon dioxide production in chronic heart failure a consequence of slow metabolic gas kinetics=","volume":"4","author":"Witte","year":"2002","journal-title":"Eur. J. Heart Fail."},{"issue":"Suppl VI","key":"2026020203580709200_ejhf2004-05-006-bib-0006","first-page":"40","article-title":"Plasma norephinephrine, plasma rennin activity and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II follow-up","volume":"87","author":"Francis","year":"1993","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0007","first-page":"H1428","article-title":"Muscle metaboreceptors in the hemodynamic, autonomic and ventilatory responses to exercise in man","volume":"269","author":"Piepoli","year":"1995","journal-title":"Am. J. Physiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0008","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1161\/01.CIR.93.5.940","article-title":"Contribution of muscle afferents to the hemodynamic, autonomic and ventilatory responses to exercise in patients with chronic heart failure","volume":"93","author":"Piepoli","year":"1996","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0009","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1161\/01.CIR.100.3.262","article-title":"Enhanced sympathetic and ventilatory responses to central chemoreflex activation in heart failure","volume":"100","author":"Narkiewicz","year":"1999","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0010","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/0735-1097(95)00523-4","article-title":"Relationship between chemosensitivity and the ventilatory response to exercise in chronic heart failure","volume":"27","author":"Chua","year":"1996","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0011","first-page":"98","article-title":"The effect of adrenaline and noradrenaline infusions on respiration in man","volume":"8","author":"Wheelan","year":"1953","journal-title":"Br. J. Pharmacol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0012","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1172\/JCI106943","article-title":"Effects of adrenergic stimulation on ventilation in man","volume":"51","author":"Heistad","year":"1972","journal-title":"J. Clin. Invest."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0013","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/j.1365-2125.1982.tb04961.x","article-title":"The selectivity of the \u03b2 adrenoceptor for ventilation in man","volume":"14","author":"Butland","year":"1982","journal-title":"Br. J. Clin. Pharmacol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0014","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1093\/oxfordjournals.eurheartj.a015179","article-title":"Catecholamines contribute to exertional dyspnoea and to the ventilatory response to exercise in normal humans","volume":"18","author":"Clark","year":"1997","journal-title":"Eur. Heart J."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0015","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJM199605233342101","article-title":"The effect of carvedilol on morbidity and mortality in patients with chronic heart failure","volume":"334","author":"Packer","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0016","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0140-6736(98)11181-9","article-title":"The cardiac insufficiency bisoprolol study II (CIBIS II)","volume":"353","author":"CIBIS II Investigators","year":"1999","journal-title":"Lancet"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0017","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(97)80008-6","article-title":"Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease","volume":"349","author":"Australia\/New Zealand Heart Failure Research Collaborative Group","year":"1997","journal-title":"Lancet"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0018","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0002-8703(99)70148-1","article-title":"Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol","volume":"138","author":"Guazzi","year":"1999","journal-title":"Am. Heart J."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0019","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1161\/01.CIR.94.11.2793","article-title":"Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure","volume":"94","author":"Packer","year":"1996","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0020","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1161\/01.CIR.94.11.2807","article-title":"Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure","volume":"94","author":"Bristow","year":"1996","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0021","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1161\/01.CIR.94.11.2800","article-title":"Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure","volume":"94","author":"Colucci","year":"1996","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0022","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1071-9164(97)90013-0","article-title":"Safety and efficacy of carvedilol in severe heart failure","volume":"3","author":"Cohn","year":"1997","journal-title":"J. Card. Fail."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0023","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1002\/clc.4960211208","article-title":"The impact of beta-receptor blocker addition to high-dose angiotensin-converting enzyme inhibitor-nitrate therapy in heart failure","volume":"21","author":"Levine","year":"1998","journal-title":"Clin. Cardiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0024","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/S1053-2498(01)00341-2","article-title":"Long-term effect of atenolol on ejection fraction, symptoms, and exercise variables in patients with advanced left ventricular dysfunction","volume":"20","author":"Hulsmann","year":"2001","journal-title":"J. Heart Lung Transplant."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0025","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1136\/heart.89.10.1169","article-title":"The effects of \u03b1- and \u03b2-blockade on ventilatory responses to exercise in chronic heart failure","volume":"89","author":"Witte","year":"2003","journal-title":"Heart"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0026","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1053\/euhj.2000.2457","article-title":"How do you measure exercise capacity in chronic heart failure=","volume":"22","author":"Clark","year":"2001","journal-title":"Eur. Heart J."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0027","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1152\/jappl.1986.60.6.2020","article-title":"A new method for detecting the anaerobic threshold by gas exchange","volume":"60","author":"Beaver","year":"1986","journal-title":"J. Appl. Physiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0028","first-page":"108","article-title":"Subjective effort and physical activities","volume":"6","author":"Borg","year":"1978","journal-title":"Scand. J. Rehabil."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0029","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1136\/heart.89.6.610","article-title":"The pattern of ventilation during exercise in chronic heart failure","volume":"89","author":"Witte","year":"2003","journal-title":"Heart"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0030","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0167-5273(99)00198-9","article-title":"The carvedilol hibernation reversible ischaemia trial, marker of success (CHRISTMAS) study. Methodology of a randomised, placebo controlled, multicentre study of carvedilol in hibernation and heart failure","volume":"72","author":"Pennell","year":"2000","journal-title":"Int. J. Cardiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0031","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/j.1440-1681.1997.tb02712.x","article-title":"Importance of the \u2018crossover\u2019 concept in exercise metabolism","volume":"24","author":"Brooks","year":"1997","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0032","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1152\/jappl.1994.76.6.2253","article-title":"Balance of carbohydrate and lipid utilization during exercise: the \u201ccrossover\u201d concept","volume":"76","author":"Brooks","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0033","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/BF01015225","article-title":"Muscle and liver glycogen, protein, and triglyceride in the rat. Effect of exercise and of the sympatho-adrenal system","volume":"52","author":"Richter","year":"1984","journal-title":"Eur. J. Appl. Physiol. Occup. Physiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0034","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0002-9149(86)90900-8","article-title":"Exercise ventilation and pulmonary artery wedge pressure in chronic stable congestive heart failure","volume":"57","author":"Fink","year":"1986","journal-title":"Am. J. Cardiol."},{"key":"2026020203580709200_ejhf2004-05-006-bib-0035","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1161\/01.CIR.64.6.1218","article-title":"Acute and long-term effects of vasodilator therapy on resting and exercise hemodynamics and exercise tolerance","volume":"64","author":"Massie","year":"1981","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0036","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/0002-9149(83)90525-8","article-title":"Acute inotropic stimulation with dopamine in severe congestive heart failure: beneficial hemodynamic effect at rest but not during maximal exercise","volume":"52","author":"Maskin","year":"1983","journal-title":"Am. J. Cardiol."},{"issue":"1","key":"2026020203580709200_ejhf2004-05-006-bib-0037","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1161\/01.CIR.62.1.55","article-title":"Cardiorespiratory responses of cardiac transplant patients to graded, symptom-limited exercise","volume":"62","author":"Savin","year":"1980","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0038","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1161\/01.CIR.94.11.2807","article-title":"Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure","volume":"94","author":"Bristow","year":"1996","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0039","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1161\/01.CIR.79.3.491","article-title":"Contrasting peripheral short-term and long term effects of converting enzyme inhibition in patients with congestive heart failure. A double-blind, placebo-controlled trial","volume":"79","author":"Drexler","year":"1989","journal-title":"Circulation"},{"key":"2026020203580709200_ejhf2004-05-006-bib-0040","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S1388-9842(02)00025-9","article-title":"Rationale and design of the carvedilol or metoprolol European trial in patients with chronic heart failure: COMET","volume":"4","author":"Poole-Wilson","year":"2002","journal-title":"Eur. J. Heart Fail."}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.ejheart.2004.05.006","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/7\/4\/612\/66652061\/eurjhf_7_4_612.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/7\/4\/612\/66652061\/eurjhf_7_4_612.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T08:58:18Z","timestamp":1770022698000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/7\/4\/612\/8445130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5,28]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2005,5,28]]},"published-print":{"date-parts":[[2005,6,1]]}},"URL":"https:\/\/doi.org\/10.1016\/j.ejheart.2004.05.006","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,6]]},"published":{"date-parts":[[2005,5,28]]}}}