Title: Rate (and rhythm)-limiting steps in newly diagnosed atrial fibrillationAuthors: Romil Patel DO, Jeremiah Wasserlauf MD, MS, FHRSInstitution: Division of Cardiology, Endeavor Health – Northshore University HealthSystema, University of Chicago Pritzker School of MedicinebOriginal paper: Contemporary Study of New Onset Atrial Fibrillation Treatment Strategies at a Large Academic Tertiary Care CenterManuscript ID: JCE-24-1123.R1Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide that affects approximately 1 in 4 adults over the age of 40, leading to impaired quality of life and complications that include heart failure, stroke, and increased mortality (1). Management strategies include stroke prevention, rate control, and rhythm control.This study by Zghaib et al. included 24,990 patients with a new diagnosis of AF between 2018 and 2023 who were retrospectively included via the TriNetX database. Initial treatment lines were initiated within 4 weeks of diagnosis as either rate-control, rhythm-control, or neither. Following 4-weeks, alternative therapy lines could be initiated during patient follow-ups. This study answers an important question on how ‘real life’ treatment is determined for newly diagnosed AF rather than presumptions of following guidelines.In this observational study, by the end of follow-up, 17,860 of the 24,990 patients at this tertiary care center were treated with either rate control only (9,760 patients) or neither rate nor rhythm control (8,100 patients). The other 7,130 patients (29% of the total population studied) underwent rhythm control by the end of the follow-up period; 4,610 patients received anti-arrhythmic drug therapy only, and 2,530 patients underwent an ablation procedure with or without anti-arrhythmic drug therapy. When assessing patients who received any treatment, whether rate or rhythm control, these patients were younger and had a higher burden of pre-existing comorbidities such as heart failure, ischemic heart disease, and hypertension but not prior strokes. When looking at rhythm control as the therapy received, these patients were also younger but had fewer comorbidities.The authors of this study showed that in ‘real-life’ practice, most patients received only rate control or neither rate nor rhythm control with incident AF. From the entire patient population, 71% received rate control or neither rate nor rhythm control, while 29% underwent rhythm control with either anti-arrhythmic drugs or catheter ablation by the end of follow-up. This study brings forth a need to streamline patients to AF programs quickly following new diagnosis to promote earlier initiation of AF therapy, including early rhythm control.In the 2000s and 2010s, treatment for atrial fibrillation evolved drastically with the adoption of catheter ablation as a second line, and thereafter, in appropriate candidates, as a guideline-based first-line treatment strategy. Earlier studies such as AFFIRM and RACE demonstrated non-inferiority of rate control to rhythm control, while CABANA failed to show a significant reduction in death, stroke, or cardiac arrest with catheter ablation compared to anti-arrhythmic drug therapy (2,3,4). However, as catheter ablation for AF improved, including a shift towards earlier treatment, the role of rate and rhythm control evolved in parallel. In 2020, EAST-AFNET 4 showed that in patients with a new diagnosis of AF, early rhythm control was associated with reduced hospitalizations, stroke, heart failure, and cardiovascular mortality (5). Early intervention for AF prevents cardiac remodeling, improving overall clinical outcomes and disease progression (6). Treatment paradigms have accordingly shifted to recognize maintenance of sinus rhythm as a disease-modifying therapy in AF.There are several limitations to this study by Zghaib et al. One is that patients were studied before the 2020 EAST-AFNET 4 trial, which may limit the generalizability of the study relative to current practice. Additionally, in this database and retrospective analysis, symptom burden could not be obtained for patients, meaning symptoms’ impact on referral status was not assessed. Finally, as patients were followed for a varying duration of 6 months to 6 years from AF diagnosis, the study may underrepresent patients who went on to have rhythm control after the completion of the follow-up period.The authors should be commended for this large study of physician management of new AF diagnosis. Future studies are needed to determine how management has changed in the era of early rhythm control, and the extent to which specialized care pathways targeting earlier treatment of AF can ameliorate outcomes, cost, and be scaled broadly across practice settings.ReferencesChugh, S. S., Havmoeller, R., Narayanan, K., Singh, D., Rienstra, M., Benjamin, E. J., Gillum, R. F., Kim, Y. H., McAnulty, J. H., Jr, Zheng, Z. J., Forouzanfar, M. H., Naghavi, M., Mensah, G. A., Ezzati, M., & Murray, C. J. (2014). Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation , 129 (8), 837–847. https://doi.org/10.1161/CIRCULATIONAHA.113.005119Wyse, D. G., Waldo, A. L., DiMarco, J. P., Domanski, M. J., Rosenberg, Y., Schron, E. B., Kellen, J. C., Greene, H. L., Mickel, M. C., Dalquist, J. E., Corley, S. D., & Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators (2002). A comparison of rate control and rhythm control in patients with atrial fibrillation. The New England journal of medicine , 347 (23), 1825–1833. https://doi.org/10.1056/NEJMoa021328Van Gelder, I. C., Groenveld, H. F., Crijns, H. J., Tuininga, Y. S., Tijssen, J. G., Alings, A. M., Hillege, H. L., Bergsma-Kadijk, J. A., Cornel, J. H., Kamp, O., Tukkie, R., Bosker, H. A., Van Veldhuisen, D. J., Van den Berg, M. P., & RACE II Investigators (2010). Lenient versus strict rate control in patients with atrial fibrillation. The New England journal of medicine , 362 (15), 1363–1373. https://doi.org/10.1056/NEJMoa1001337Packer DL, Mark DB, Robb RA, et al. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019;321(13):1261–1274. doi:10.1001/jama.2019.0693Kirchhof, P., Camm, A. J., Goette, A., Brandes, A., Eckardt, L., Elvan, A., Fetsch, T., van Gelder, I. C., Haase, D., Haegeli, L. M., Hamann, F., Heidbüchel, H., Hindricks, G., Kautzner, J., Kuck, K. H., Mont, L., Ng, G. A., Rekosz, J., Schoen, N., Schotten, U., … EAST-AFNET 4 Trial Investigators (2020). Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. The New England journal of medicine , 383 (14), 1305–1316. https://doi.org/10.1056/NEJMoa2019422Melanie A Gunawardene, Stephan Willems, Atrial fibrillation progression and the importance of early treatment for improving clinical outcomes, EP Europace , Volume 24, Issue Supplement_2, June 2022, Pages ii22–ii28, https://doi.org/10.1093/europace/euab257