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In HFrEF, abnormal autonomic and cardiopulmonary responses arising from locomotor muscle group III\/IV afferent feedback is one of the primary mechanisms contributing to exercise intolerance. HFrEF patients also have pulmonary system and respiratory muscle abnormalities that impair exercise tolerance. Thus, the primary impetus for this review was to describe the mechanistic consequences of locomotor muscle group III\/IV afferent feedback and respiratory muscle work in HFrEF. To address this, we first discuss the abnormal autonomic and cardiopulmonary responses mediated by locomotor muscle afferent feedback in HFrEF. Next, we outline how respiratory muscle work impairs exercise tolerance in HFrEF through its effects on locomotor muscle O\n                    <jats:sub>2<\/jats:sub>\n                    delivery. We then discuss the direct and indirect evidence supporting an interaction between locomotor muscle group III\/IV afferent feedback and respiratory muscle work during exercise in HFrEF. Last, we outline future research directions related to locomotor and respiratory muscle abnormalities to progress the field forward in understanding the pathophysiology of exercise intolerance in HFrEF.\n                  <\/jats:p>","DOI":"10.1113\/ep090755","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:41:56Z","timestamp":1695343316000},"page":"1351-1365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Consequences of group III\/IV afferent feedback and respiratory muscle work on exercise tolerance in heart failure with reduced ejection fraction"],"prefix":"10.1113","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3687-6261","authenticated-orcid":false,"given":"Joshua R.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Mayo Clinic  Rochester MN 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