Abstract Cardiac arrhythmias are increasingly recognized as dynamic clinical phenotypes arising from the interplay between myocardial substrate, systemic biology, and modifiable exposures rather than as isolated disorders of cardiac electrophysiology. Advances in the field have broadened the conceptual framework of arrhythmia medicine to include structural remodeling, inflammation, autonomic dysfunction, metabolic perturbation, endothelial injury, and aging-related vulnerability as central determinants of arrhythmic risk, progression, and treatment response. In parallel, diagnostic paradigms are evolving from rhythm classification alone toward multidimensional phenotyping that integrates clinical, physiological, and imaging-based markers to identify susceptibility earlier and with greater precision. These developments are also reshaping therapeutic strategy, supporting a shift from uniform treatment algorithms toward individualized care in which rhythm control, surveillance, risk-factor modification, anticoagulation, and antiarrhythmic drug selection are aligned with the underlying biological context. This more integrated view positions arrhythmias not simply as electrical events to be suppressed, but as manifestations of broader cardiovascular and systemic disease processes that require mechanistically informed and phenotype-directed management. References Martins, I.L.F.; Almeida, F.V.D.S.; de Souza, K.P.; de Brito, F.C.F.; Rodrigues, G.D.; Scaramello, C.B.V. Reviewing Atrial Fibrillation Pathophysiology from a Network Medicine Perspective: The Relevance of Structural Remodeling, Inflammation, and the Immune System. Life 2023, 13, 1364. [ Google Scholar] [ CrossRef] [ PubMed] McCauley, M.D.; Iacobellis, G.; Li, N.; Nattel, S.; Goldberger, J.J. 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[ Google Scholar] [ CrossRef] [ PubMed] Kalaydzhiev, P.; Ilieva, R.; Spasova, N.; Yakov, S.; Markov, D.; Georgieva, N.; Kinova, E.; Goudev, A. Impact of CPAP Therapy Adherence on Time to First Recurrence of Paroxysmal Atrial Fibrillation in Patients with Severe Obstructive Sleep Apnea. Life 2026, 16, 389. [ Google Scholar] [ CrossRef] [ PubMed] Jin, M.N.; Kim, Y.J.; Song, C. Diagonal Earlobe Crease and the Risk of New-Onset Atrial Fibrillation After Cavotricuspid Isthmus Ablation in Patients with Typical Atrial Flutter. Life 2026, 16, 508. [ Google Scholar] [ CrossRef] [ PubMed] Karakasis, P.; Grigoriou, K.; Theofilis, P.; Iliakis, P.; Vlachakis, P.K.; Ktenopoulos, N.; Apostolos, A.; Patoulias, D.; Antoniadis, A.P.; Fragakis, N. Flecainide in Structural Heart Disease: Reconsidering Its Role in Contemporary Arrhythmia Management. Life 2026, 16, 778. [ Google Scholar] [ CrossRef] [ PubMed] Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. Share and Cite Karakasis, P.; Antoniadis, A.P.; Fragakis, N. Cardiac Arrhythmias: Advances in Mechanisms, Diagnosis, and Treatment. Life 2026, 16, 968. https://doi.org/10.3390/life16060968 Karakasis P, Antoniadis AP, Fragakis N. Cardiac Arrhythmias: Advances in Mechanisms, Diagnosis, and Treatment. Life. 2026; 16(6):968. https://doi.org/10.3390/life16060968 Karakasis, Paschalis, Antonios P. Antoniadis, and Nikolaos Fragakis. 2026. "Cardiac Arrhythmias: Advances in Mechanisms, Diagnosis, and Treatment" Life 16, no. 6: 968. https://doi.org/10.3390/life16060968 Karakasis, P., Antoniadis, A. P., & Fragakis, N. (2026). Cardiac Arrhythmias: Advances in Mechanisms, Diagnosis, and Treatment. Life, 16(6), 968. https://doi.org/10.3390/life16060968 Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details . Article Metrics Article metric data becomes available approximately 24 hours after publication online. Funding This research received no external funding. Informed Consent Statement Not applicable. Data Availability Statement All data generated in this research is included within the article. Conflicts of Interest The authors declare no conflicts of interest. References Martins, I.L.F.; Almeida, F.V.D.S.; de Souza, K.P.; de Brito, F.C.F.; Rodrigues, G.D.; Scaramello, C.B.V. Reviewing Atrial Fibrillation Pathophysiology from a Network Medicine Perspective: The Relevance of Structural Remodeling, Inflammation, and the Immune System. Life 2023, 13, 1364. [ Google Scholar] [ CrossRef] [ PubMed] McCauley, M.D.; Iacobellis, G.; Li, N.; Nattel, S.; Goldberger, J.J. Targeting the Substrate for Atrial Fibrillation: JACC Review Topic of the Week. J. Am. Coll. Cardiol. 2024, 83, 2015–2027. [ Google Scholar] [ CrossRef] [ PubMed] Cismaru, G.; Negru, A.-G. Atrial Fibrillation and Heart Failure. Life 2024, 14, 572. [ Google Scholar] [ CrossRef] [ PubMed] Lobeek, M.; Middeldorp, M.E.; Van Gelder, I.C.; Rienstra, M. Multimorbidity in Patients with Atrial Fibrillation. Open Hear. 2024, 11, e002641. [ Google Scholar] [ CrossRef] [ PubMed] Karakasis, P.; Theofilis, P.; Vlachakis, P.K.; Apostolos, A.; Ktenopoulos, N.; Grigoriou, K.; Patoulias, D.; Antoniadis, A.P.; Fragakis, N. Arrhythmia-Induced Cardiomyopathy in Atrial Fibrillation: Pathogenesis, Diagnosis, and Treatment. Life 2025, 15, 1675. [ Google Scholar] [ CrossRef] [ PubMed] Karakasis, P.; Tzeis, S.; Pamporis, K.; Schuermans, A.; Theofilis, P.; Milaras, N.; Tsiachris, D.; Efremidis, M.; Antoniadis, A.P.; Fragakis, N. Impact of Catheter Ablation Timing According to Duration of Atrial Fibrillation History on Arrhythmia Recurrences and Clinical Outcomes: A Meta-Analysis. EP Eur. 2025, 27, euaf110. [ Google Scholar] [ CrossRef] [ PubMed] Schach, C.; Lavall, D.; Voßhage, N.; Körtl, T.; Meindl, C.; Ücer, E.; Hamer, O.; Maier, L.S.; Wachter, R.; Sossalla, S. Time to Recovery from Systolic Dysfunction Correlates with Left Ventricular Fibrosis in Arrhythmia-Induced Cardiomyopathy. Life 2024, 14, 330. [ Google Scholar] [ CrossRef] [ PubMed] Bobu, A.M.; Duca, Ș.T.; Cucu, A.I.; Avieriței, D.A.; Ponor, C.G.; Cepoi, M.R.; Cucută, S.; Dmour, B.A.; Costea, C.F.; Botnariu, G.; et al. From Beat to Risk: How Heart Rate Variability Predicts Arrhythmias in Type 2 Diabetes. Life 2026, 16, 520. [ Google Scholar] [ CrossRef] [ PubMed] Tanasescu, M.-D.; Rosu, A.-M.; Minca, A.; Grigorie, M.-M.; Timofte, D.; Ionescu, D. Inflammation, Endothelial Dysfunction, and Platelet Dysregulation in Atrial Fibrillation with Chronic Kidney Disease: Toward a Biology-Informed Anticoagulation Strategy. Life 2026, 16, 547. [ Google Scholar] [ CrossRef] [ PubMed] Morales-Vazquez, H.N.; Cardona-Müller, D.; Grover-Paez, F.; Ramos-Becerra, C.G.; Cardona-Muñoz, E.G.; Ramos-Zavala, M.G.; Carmona-Huerta, J.; Hernandez-del-Rio, J.E.; Miranda-Aquino, T.; Gonzalez-Padilla, C.; et al. Arrhythmias as Part of Long COVID Syndrome in Hospitalized Patients That Survived a Severe COVID-19 Infection and the Potential Protective Role of Metformin in These Patients. Life 2026, 16, 319. [ Google Scholar] [ CrossRef] [ PubMed] Gammaldi, V.; Pucci, M.; La Rocca, F.; Megaro, P.; Paoletta, D.; Pontoriero, M.; Capece, L.M.; Luise, R.; Iacono, M.; Esposito, R. Transthoracic Echocardiography as a Tool for Early Detection of Atrial Fibrillation in Patients Receiving Ibrutinib. Life 2026, 16, 324. [ Google Scholar] [ CrossRef] [ PubMed] Kalaydzhiev, P.; Ilieva, R.; Spasova, N.; Yakov, S.; Markov, D.; Georgieva, N.; Kinova, E.; Goudev, A. Impact of CPAP Therapy Adherence on Time to First Recurrence of Paroxysmal Atrial Fibrillation in Patients with Severe Obstructive Sleep Apnea. Life 2026, 16, 389. [ Google Scholar] [ CrossRef] [ PubMed] Jin, M.N.; Kim, Y.J.; Song, C. Diagonal Earlobe Crease and the Risk of New-Onset Atrial Fibrillation After Cavotricuspid Isthmus Ablation in Patients with Typical Atrial Flutter. Life 2026, 16, 508. [ Google Scholar] [ CrossRef] [ PubMed] Karakasis, P.; Grigoriou, K.; Theofilis, P.; Iliakis, P.; Vlachakis, P.K.; Ktenopoulos, N.; Apostolos, A.; Patoulias, D.; Antoniadis, A.P.; Fragakis, N. Flecainide in Structural Heart Disease: Reconsidering Its Role in Contemporary Arrhythmia Management. Life 2026, 16, 778. [ Google Scholar] [ CrossRef] [ PubMed] Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
