{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:31:53Z","timestamp":1789767113487,"version":"4.0.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Patients with sympathetic excess are those most likely to benefit from novel interventions targeting the autonomic nervous system. To inform such personalized therapy, we identified determinants of augmented muscle sympathetic nerve activity (MSNA) in heart failure, versus healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We compared data acquired in 177 conventionally-treated, stable non-diabetic patients in sinus rhythm, aged 18\u201379\u2009years (149 males; 28 females; left ventricular ejection fraction [LVEF] 25\u2009\u00b1\u200911% [mean\u2009\u00b1\u2009standard deviation]; range 5\u201360%), and, concurrently, under similar conditions, in 658 healthy, normotensive volunteers (398 males; aged 18\u201381\u2009years). In heart failure, MSNA ranged between 7 and 90 bursts\u00b7min\u22121, proportionate to heart rate (p\u2009&amp;lt;\u20090.0001) and body mass index (BMI) (p = 0.03), but was unrelated to age, blood pressure, or drug therapy. Mean MSNA, adjusted for age, sex, BMI, and heart rate, was greater in heart failure (+14.2 bursts\u00b7min\u22121; 95% confidence interval [CI] 12.1\u201316.3; p\u2009&amp;lt;\u20090.0001), but lower in women (\u22125.0 bursts\u00b7min\u22121; 95% CI 3.4\u20136.6; p\u2009&amp;lt;\u20090.0001). With spline modeling, LVEF accounted for 9.8% of MSNA variance; MSNA related inversely to LVEF below an inflection point of \u223c21% (p\u2009&amp;lt;\u20090.006), but not above. Burst incidence was greater in ischaemic than dilated cardiomyopathy (p = 0.01), and patients with sleep apnoea (p = 0.03). Burst frequency correlated inversely with stroke volume (p\u2009&amp;lt;\u20090.001), cardiac output (p\u2009&amp;lt;\u20090.001), and peak oxygen consumption (p = 0.002), and directly with norepinephrine (p\u2009&amp;lt;\u20090.0001) and peripheral resistance (p\u2009&amp;lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Burst frequency and incidence exceeded normative values in only \u223c53% and \u223c33% of patients. Such diversity encourages selective deployment of sympatho-modulatory therapies. Clinical characteristics can highlight individuals who may benefit from future personalized interventions targeting pathological sympathetic activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2749","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T09:53:07Z","timestamp":1669974787000},"page":"201-210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Normal and Excessive Muscle Sympathetic Nerve Activity in Heart Failure: Implications for Future Trials of Therapeutic Autonomic Modulation"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7809-0729","authenticated-orcid":false,"given":"Mark B.","family":"Badrov","sequence":"first","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Keir","sequence":"additional","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]},{"name":"School of Kinesiology, Western University , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine F.","family":"Notarius","sequence":"additional","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Millar","sequence":"additional","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Human Health and Nutritional Science, University of Guelph , Guelph, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek S.","family":"Kimmerly","sequence":"additional","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]},{"name":"Division of Kinesiology, School of Health and Performance, Dalhousie University , Halifax, Nova Scotia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Kevin","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Western University , London, Ontario ,","place":["Canada"]},{"name":"Department of Physiology and Pharmacology, Western University , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Keys","sequence":"additional","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Floras","sequence":"additional","affiliation":[{"name":"University Health Network and Sinai Health Division of Cardiology, Department of Medicine, University of Toronto and the Toronto General Hospital Research Institute , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"2026010913083099300_ejhf2749-bib-0001","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1093\/eurheartj\/ehv087","article-title":"The sympathetic\/parasympathetic imbalance in heart failure with reduced ejection fraction","volume":"36","author":"Floras","year":"2015","journal-title":"Eur Heart J"},{"key":"2026010913083099300_ejhf2749-bib-0002","first-page":"609","article-title":"Cardiovascular autonomic disturbances in heart failure with preserved ejection fraction","volume":"37","author":"Badrov","year":"2021","journal-title":"Can J Cardiol"},{"key":"2026010913083099300_ejhf2749-bib-0003","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/ejhf.921","article-title":"The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology","volume":"19","author":"van Bilsen","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2026010913083099300_ejhf2749-bib-0004","doi-asserted-by":"crossref","first-page":"R338","DOI":"10.1152\/ajpregu.00143.2021","article-title":"The 2021 Carl Ludwig lecture. 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