{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:22:40Z","timestamp":1785147760980,"version":"3.55.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":2153,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Clinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM-HF), increase of vagal tone in heart failure (INOVATE-HF), and neural cardiac therapy for heart failure (NECTAR-HF) for hypothesis generation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Descriptive statistics were used to analyse data from the public domain for differences in proportions using Pearson's chi-square test, differences in mean values using Student's unpaired t-test, and differences in changes of mean values using two-sample t-tests.<\/jats:p>\n                    <jats:p>Guideline-directed medical therapy recommendations were similar across studies. Fewer patients were in New York Heart Association 3, and baseline heart rate (HR) was higher in ANTHEM-HF. In INOVATE-HF, VNS was aimed at peripheral neural targets, using closed-loop delivery that required synchronization of VNS to R-wave sensing by an intracardiac lead. Pulse frequency was low (1\u20132 Hz) because of a timing schedule allowing \u22643 pulses of VNS following at most 25% of detected R waves. NECTAR-HF and ANTHEM-HF used open-loop VNS delivery (i.e. independent of any external signal) aimed at both central and peripheral targets. In NECTAR-HF, VNS delivery at 20 Hz caused off-target effects that limited VNS up-titration in a majority of patients. In ANTHEM-HF, VNS delivery at 10 Hz allowed up-titration until changes in HR dynamics were confirmed. Six months after VNS titration, significant improvements in both HR and HR variability occurred only in ANTHEM-HF. When ANTHEM-HF and NECTAR-HF were compared, greater improvements from baseline were observed in ANTHEM-HF in standard deviation in normal-to-normal R-R intervals (94 \u00b1 26 to 111 \u00b1 50 vs. 146 \u00b1 48 to 130 \u00b1 52 ms; P &amp;lt; 0.001), left ventricular ejection fraction (32 \u00b1 7 to 37 \u00b1 0.4 vs. 31 \u00b1 6 to 33 \u00b1 6; P &amp;lt; 0.05), and Minnesota Living with Heart Failure mean score (40 \u00b1 14 to 21 \u00b1 10 vs. 44 \u00b1 22 to 36 \u00b1 21; P &amp;lt; 0.002). When compared with INOVATE-HF, greater improvement in 6-min walk distance was observed in ANTHEM-HF (287 \u00b1 66 to 346 \u00b1 78 vs. 304 \u00b1 111 to 334 \u00b1 111 m; P &amp;lt; 0.04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this post-hoc analysis, differences in patient demographics were seen and may have caused the differential responses in symptoms and function observed in association with VNS. Major differences in technology platforms, neural targets, VNS delivery, and HR and HR variability responses could have also potentially played a very important role. Further study is underway in a randomized controlled trial with these considerations in mind.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12592","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T03:09:25Z","timestamp":1580094565000},"page":"76-84","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Comparison of Symptomatic and Functional Responses to Vagus Nerve Stimulation in ANTHEM-HF, INOVATE-HF, and NECTAR-HF"],"prefix":"10.1093","volume":"7","author":[{"given":"Inder S.","family":"Anand","sequence":"first","affiliation":[{"name":"Division of Cardiology, University of Minnesota , Minneapolis, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin A.","family":"Konstam","sequence":"additional","affiliation":[{"name":"The CardioVascular Center at Tufts Medical Center , Boston, MA 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Boston University , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Libbus","sequence":"additional","affiliation":[{"name":"LivaNova USA Incorporated , Houston, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo A.","family":"DiCarlo","sequence":"additional","affiliation":[{"name":"LivaNova USA Incorporated , Houston, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John James E.","family":"Udelson","sequence":"additional","affiliation":[{"name":"The CardioVascular Center at Tufts Medical Center , Boston, MA 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