{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:59:12Z","timestamp":1787623152299,"version":"build-2736575974"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (\u22651000\/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (\u226550% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non\u2013ion channel\u2013based therapeutic strategy targeting the cardiac glutamatergic system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT06501638.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.079023","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T09:00:21Z","timestamp":1773910821000},"page":"1196-1209","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Memantine for Premature Atrial Contractions: A Phase 2 Randomized Clinical Trial"],"prefix":"10.1161","volume":"153","clinical-trial-number":[{"clinical-trial-number":"nct06501638","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Yunli","family":"Shen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China (C.Z., B. Zhou, J. Zeng, X.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-899X","authenticated-orcid":true,"given":"Yingxian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Hospital of China Medical University, Shenyang (Y.S., G.S., S.Z., X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4583-3204","authenticated-orcid":true,"given":"Jian\u2019an","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Transvascular Implantation Devices, Heart Regeneration and Repair Key Laboratory of Zhejiang Province, and Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (J.W., Xinyang Hu, Yaping Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5955-6332","authenticated-orcid":true,"given":"Bo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, China (B. Yu, S.L., N.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6287-3128","authenticated-orcid":true,"given":"Xiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.C., M.Z., Yiyi Wang, Xiajun Hu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6754-1432","authenticated-orcid":true,"given":"Xiaogang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (X.G., C.Z., K.W., J.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (D.W.W., Y.W., J. Lai, L.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2353-4078","authenticated-orcid":true,"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, China (Y. Li, D.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0078-2105","authenticated-orcid":true,"given":"Wei","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4305-5418","authenticated-orcid":true,"given":"Bingqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China (C.Z., B. Zhou, J. Zeng, X.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhuan","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Affiliated Hospital of Nantong University, Medical School of Nantong University, China (H.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5873-5697","authenticated-orcid":true,"given":"Zhaoqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Affiliated Hospital of Guangzhou Medical University, China (Z.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3007-7212","authenticated-orcid":true,"given":"Yigang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China (Y.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-0717","authenticated-orcid":true,"given":"Guosheng","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China (G.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jidong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, China (J. Zhang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duanyang","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-8996","authenticated-orcid":true,"given":"Dandan","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-9305","authenticated-orcid":true,"given":"Bing","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. 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Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhang","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"He","sequence":"additional","affiliation":[{"name":"Department of Health Statistics, Second Military Medical University, Shanghai, China (J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Shanghai Arrhythmia Research Center, and Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, China (Y.S., W.H., D.X., D.L., Y. Liu, B. Yang, Q.Z., R.D., H.L., B. Zhang, Yizhang Wu, L.Z., S.L., K.X., G.W., Q.Z., B.S., Z.C., Yahan Wu, J. Leng, Y.-H.C.)."},{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, China (B. Yu, S.L., N.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7057-9340","authenticated-orcid":true,"given":"Dechun","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, China (Y. Li, D.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8373-1049","authenticated-orcid":true,"given":"Guozhe","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Hospital of China Medical University, Shenyang (Y.S., G.S., S.Z., X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5521-1679","authenticated-orcid":true,"given":"Shu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Hospital of China Medical University, Shenyang (Y.S., G.S., S.Z., X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7687-0825","authenticated-orcid":true,"given":"Xiaofan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Hospital of China Medical University, Shenyang (Y.S., G.S., S.Z., X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.C., M.Z., Yiyi Wang, Xiajun Hu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1168-1731","authenticated-orcid":true,"given":"Yiyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.C., M.Z., Yiyi Wang, Xiajun Hu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1625-2029","authenticated-orcid":true,"given":"Xiajun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.C., M.Z., Yiyi Wang, Xiajun Hu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China (C.Z., B. 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Lai, L.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (D.W.W., Y.W., J. Lai, L.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7975-2693","authenticated-orcid":true,"given":"Luyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (D.W.W., Y.W., J. 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