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HRV markers were selected using a systematic literature screen and a data-driven approach. Reference values were determined from a healthy subsample. Clinical determinants of HRV were investigated via multivariable linear regression analyses, while their relationship with mortality was investigated by multivariable Cox regression analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Holter ECG recordings were available for analysis in 1001 study participants (mean age 64.5\u2009\u00b1\u200910.5\u00a0years; female sex 35.4%). While the most frequently reported HRV markers in literature were from time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Age, sex, dyslipidemia, family history of myocardial infarction or stroke, peripheral artery disease, and heart failure were strongly related to HRV in multivariable models. In a follow-up period of 6.5\u00a0years, acceleration capacity [HR\n                      <jats:sub>perSD<\/jats:sub>\n                      1.53 (95% CI 1.21\/1.93),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0004], deceleration capacity [HR\n                      <jats:sub>perSD<\/jats:sub>\n                      : 0.70 (95% CI 0.55\/0.88),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002], and time lag [HR\n                      <jats:sub>perSD<\/jats:sub>\n                      1.22 (95% CI 1.03\/1.44),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018] were the strongest predictors of all-cause mortality in individuals with heart failure independently of cardiovascular risk factors, comorbidities, and medication.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HRV markers are associated with the cardiovascular clinical profile and are strong and independent predictors of survival in heart failure. This underscores clinical relevance and interventional potential for individuals with heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ClinicalTrials.gov identifier<\/jats:title>\n                    <jats:p>NCT04064450.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00392-023-02248-7","type":"journal-article","created":{"date-parts":[[2023,7,9]],"date-time":"2023-07-09T04:01:19Z","timestamp":1688875279000},"page":"1317-1330","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Heart rate variability: reference values and role for clinical profile and mortality in individuals with heart failure"],"prefix":"10.1007","volume":"113","clinical-trial-number":[{"clinical-trial-number":"nct04064450","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Silav","family":"Zeid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Buch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Velmeden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"S\u00f6hne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Schuch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven-Oliver","family":"Tr\u00f6bs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc William","family":"Heidorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Strauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Coboeken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl J.","family":"Lackner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Gori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"M\u00fcnzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen H.","family":"Prochaska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-9752","authenticated-orcid":false,"given":"Philipp S.","family":"Wild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,9]]},"reference":[{"issue":"11","key":"2248_CR1","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1161\/CIRCRESAHA.114.302589","volume":"114","author":"VG Florea","year":"2014","unstructured":"Florea VG, Cohn JN (2014) The autonomic nervous system and heart failure. 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PLoS One 10(2):e0117332","journal-title":"PLoS One"}],"container-title":["Clinical Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-023-02248-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00392-023-02248-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-023-02248-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T11:04:37Z","timestamp":1725361477000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00392-023-02248-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,9]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["2248"],"URL":"https:\/\/doi.org\/10.1007\/s00392-023-02248-7","relation":{},"ISSN":["1861-0684","1861-0692"],"issn-type":[{"value":"1861-0684","type":"print"},{"value":"1861-0692","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,9]]},"assertion":[{"value":"21 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"P.S.W. reports for the submitted work grants from Bayer AG. Outside the submitted work, he reports on non-financial grants from Philips Medical Systems, grants and consulting fees from Boehringer Ingelheim, grants and consulting fees from Novartis Pharma, grants and consulting fees from Sanofi-Aventis, grants, consulting and lecturing fees from Bayer Health Care, grants and consulting fees from Daiichi Sankyo Europe, lecturing fees from Pfizer Pharma, lecturing fees from Bristol Myers Squibb, consulting fees from Astra Zeneca, consulting fees and non-financial support from Diasorin and non-financial support from I.E.M. P.S. Wild is principal investigator of the German Center for Cardiovascular Research (DZHK) and principal investigator of the DIASyM research core (BMBF DIASyM research core (BMBF 031L0217A) P.S. Wild was funded by the Ministry of Education and Research (BMBF 01EO1003 and 01EO1503). J.H.P. has received honoraria for lectures from Bayer AG, Boehringer Ingelheim, Daiichi Sankyo GmbH, and Sanofi-Aventis GmbH as well as research grants from the Federal Ministry of Education and Research (BMBF 01EO1503) and the German Center for Cardiovascular Research (DZHK) outside the topic of the present study. K.C. is an employee of Bayer AG. S.O.T. has received personal fees from Philips Health Care for a lecture outside the submitted work and is an employee of Boehringer Ingelheim and University Medical Center Mainz.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The local data protection officer and the responsible ethics committee approved the study protocol [reference number 837.319.12 (8420-F)] prior to study initiation. All study participants provided written informed consent prior to study enrolment. The Declaration of Helsinki [\n                      \n                      ] and the recommendations of good clinical practice and good epidemiological practice were followed in all study procedures.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}