Zhang YF, Yang WX, Li XW. Letter to the Editor: Ca2+/calmodulin-dependent protein kinase II in heart failure and the role of sodium-glucose-cotransporter 2 inhibitors. World J Cardiol 2026; 18(4): 116558 [DOI: 10.4330/wjc.v18.i4.116558]
Corresponding Author of This Article
Xue-Wen Li, PhD, Chief Physician, Professor, Department of Cardiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99 Longcheng Street, Taiyuan 030032, Shanxi Province, China. xuewenli1010@126.com
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Cardiac & Cardiovascular Systems
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Correspondence
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Apr 26, 2026 (publication date) through Apr 14, 2026
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World Journal of Cardiology
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1949-8462
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Zhang YF, Yang WX, Li XW. Letter to the Editor: Ca2+/calmodulin-dependent protein kinase II in heart failure and the role of sodium-glucose-cotransporter 2 inhibitors. World J Cardiol 2026; 18(4): 116558 [DOI: 10.4330/wjc.v18.i4.116558]
World J Cardiol. Apr 26, 2026; 18(4): 116558 Published online Apr 26, 2026. doi: 10.4330/wjc.v18.i4.116558
Letter to the Editor: Ca2+/calmodulin-dependent protein kinase II in heart failure and the role of sodium-glucose-cotransporter 2 inhibitors
Yi-Fei Zhang, Wu-Xiao Yang, Xue-Wen Li
Yi-Fei Zhang, Xue-Wen Li, Department of Cardiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
Wu-Xiao Yang, Department of Cardiology, Shanxi Provincial People’s Hospital, Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Author contributions: Zhang YF was responsible for the initial draft preparation and creation of figures; Yang WX was responsible for the overall conceptualization and structural design of the manuscript; Li XW oversaw the entire writing project, provided critical revisions to the final manuscript, and was responsible for ensuring overall scientific rigor; and all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 8217022047.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Xue-Wen Li, PhD, Chief Physician, Professor, Department of Cardiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99 Longcheng Street, Taiyuan 030032, Shanxi Province, China. xuewenli1010@126.com
Received: November 14, 2025 Revised: December 4, 2025 Accepted: January 8, 2026 Published online: April 26, 2026 Processing time: 151 Days and 11 Hours
Core Tip
Core Tip: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have revolutionized the treatment of heart failure, but their direct molecular effects in cardiomyocytes, which express little sodium-glucose cotransporter-2, have not been fully described. This letter summarizes current evidence and presents a conceptual framework in which Ca2+/calmodulin-dependent protein kinase II is a central target. We hypothesize that many of the cardioprotective effects of SGLT2i are mediated by the dampening of Ca2+/calmodulin-dependent protein kinase II activity through synergistic modulation of ionic balance, relief of oxidative stress and inflammatory signaling suppression. Together, these processes may provide a unified explanation for the observed improvements in electrical stability, ventricular performance, and cardiac remodeling associated with SGLT2i treatment.
