Heart rate lowering with ivabradine and burden of symptoms in patients with postural orthostatic tachycardia syndrome

Abstract Background Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic form of orthostatic intolerance, characterized by an excessive increase in heart rate (HR) of ≥30 beats per minute (bpm) (≥40 bpm in individuals under 20 years) within 10 minutes of standing, in the absence of orthostatic hypotension. The pathophysiology of POTS remains unclear, with recent data linking it to postacute sequelae of COVID-19. Patients experience a broad range of chronic symptoms contributing to significant functional impairment and reduced quality of life. Ivabradine, a selective If channel blocker, lowers HR without impacting blood pressure and has been suggested as a potential treatment for POTS. Methods We herein report the changes in POTS symptoms in 10 patients with established POTS who were prescribed ivabradine as part of their routine clinical management, with doses ranging from 5 mg to 7.5 mg twice daily. The Malmö POTS Symptom Score (Malmö score), a validated tool for assessing symptom burden, was used to measure clinical changes. Data are reported as n (%) or median (interquartile range). Statistical analyses included the Wilcoxon test for paired comparisons and Spearman’s correlation to assess relationships between HR changes and Malmö score. The local institutional review board determined the study to be exempt. Results The median age was 28 years (20-36 years) and seven (70%) patients were females. Time from initial diagnosis to prescription of ivabradine was 14 months (4-27 months), duration of ivabradine therapy was 7 months (4-22 months). Following ivabradine treatment there was a significant reduction in ΔHR (orthostatic HR response) from 40 (30-70) bpm to 15 (8-19) bpm (p=0.011), without significant changes in blood pressure. The Malmö score, reflecting overall symptom burden, decreased from 86 (74-92) to 39 (32-66) (p=0.005), with statistically significant improvements across most individual symptoms, including palpitations, dizziness, chest pain, and fatigue. Muscle pain was the only symptom that did not significantly improve. The ΔHR correlated strongly with the Malmö score (R=+0.828; p0.001), suggesting a direct link between HR regulation and POTS symptomatology. No adverse effects were reported. Conclusions Although limited by its small sample size and observational design, this study suggests that ivabradine effectively reduces the excessive tachycardic response and is associated with substantial symptomatic relief. The findings reinforce the hypothesis that excessive HR response is not merely a compensatory mechanism but plays a central role in POTS pathophysiology, potentially contributing to a self-perpetuating cycle of sympathetic overactivation. By blunting tachycardia, ivabradine may interrupt this cycle and lead to sustained symptomatic improvement.Correlation HR response - Malmö score Expanded paradigm for POTS management