Methylxanthine Derivatives in the Treatment of Sinus Node Dysfunction: A Systematic Review

While the chronotropic effects of theophylline and aminophylline are well-known, their clinical application in the treatment of sinus node dysfunction has not been established in a review. The purpose of this systematic review is to evaluate the efficacy and safety of methylxanthines in the treatment of bradyarrhythmias associated with sinus node dysfunction. A systematic review was conducted in accordance with PRISMA guidelines on Embase, PubMed, MEDLINE, Cochrane Central, Web of Science, SciELO, Korean Citation Index, Global Index Medicus, and CINAHL through June 2023. A total of 607 studies were identified through the literature search. After applying the inclusion and exclusion criteria, 14 studies were included in this review. The causes of bradyarrhythmias involving the sinoatrial node included acute cervical spinal cord injury, coronavirus disease of 2019, carotid sinus syncope, chronotropic incompetence, heart transplant, and chronic sinus node dysfunction. Theophylline and aminophylline were shown to be effective for increasing heart rate and reducing the reoccurrence of bradyarrhythmias. The data on symptom resolution was conflicting. While many case studies reported a resolution of symptoms, a randomized controlled trial reported no significant difference in symptom scores between the control, theophylline, and pacemaker groups in the treatment of sick sinus syndrome. The incidence of adverse effects was low across all study designs. The data suggests methylxanthines may be useful as an alternative or bridge to nonpharmacologic pacing; however, dosing has yet to be established for various indications. Overall, methylxanthines proved safe and effective as a pharmacologic therapy for bradyarrhythmic manifestations of sinus node dysfunction.