{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T08:24:52Z","timestamp":1768638292520,"version":"3.49.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T00:00:00Z","timestamp":1568937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Cardiac Arrhythmia Network of Canada","award":["15-P01-001"],"award-info":[{"award-number":["15-P01-001"]}]},{"name":"CANet"},{"name":"Network of Centres of Excellence"},{"DOI":"10.13039\/501100000161","name":"NCE","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000161","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John and Leslie Bissett"},{"name":"Apotex"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40\u2009mg (n\u2009=\u200927) or matched placebo (n\u2009=\u200929)] 12\u2009h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35\u2009\u00b1\u200914\u2009years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10\/29 vs. 19\/27; P\u2009=\u20090.003; risk ratio 0.49 (confidence interval 0.28\u20130.86)], but equal numbers of patients developed presyncope or syncope (23\/29 vs. 21\/27). Of patients who developed only presyncope, 87% (13\/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39\u2009\u00b1\u200918 vs. 69\u2009\u00b1\u200918\u2009mmHg, P\u2009&lt;\u20090.0001), and this was due to lower trough HRs in subjects with syncope (67\u2009\u00b1\u200930 vs. 103\u2009\u00b1\u200932 b.p.m., P\u2009=\u20090.006) and insignificantly lower cardiac index (2.20\u2009\u00b1\u20091.36 vs. 2.84\u2009\u00b1\u20091.05 L\/min\/m2, P\u2009=\u20090.075). There were no significant differences in stroke volume index (32\u2009\u00b1\u20096 vs. 35\u2009\u00b1\u20095\u2009mL\/m2, P\u2009=\u20090.29) or systemic vascular resistance index (2156\u2009\u00b1\u2009602 vs. 1790\u2009\u00b1\u2009793 dynes*s\/cm5*m2, P\u2009=\u20090.72).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euz250","type":"journal-article","created":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T15:11:49Z","timestamp":1565881909000},"page":"1733-1741","source":"Crossref","is-referenced-by-count":32,"title":["A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI"],"prefix":"10.1093","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0742-8379","authenticated-orcid":false,"given":"Robert S","family":"Sheldon","sequence":"first","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Lei","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan C","family":"Guzman","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Kus","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Universite de Montreal, and Hopital du Sacre-Coeur, Montreal, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix A","family":"Ayala-Paredes","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital of Sherbrooke, Sherbrooke, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Angihan","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahana","family":"Safdar","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connor","family":"Maxey","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Bennett","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satish R","family":"Raj","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, 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