Inappropriate sinus tachycardia and beta-receptor autoantibodies: A mechanistic breakthrough?

Abstract

Inappropriate sinus tachycardia is a challenging condition. Often quite symptomatic, its mechanisms and pathophysiology are elusive, it is not easily cured by ablation, and it can be difficult to distinguish from other clinical conditions, including anxiety disorders, which cause sinus tachycardias. Improved insights into underlying pathophysiology might help in understanding and treating inappropriate sinus tachycardia. In this issue of Heart Rhythm, Chiale et al 1 present a tantalizing new set of findings in patients with inappropriate sinus tachycardia, reporting that 52% have immunoglobulin G (IgG) -receptor autoantibodies. -Receptor autoantibodies enhanced the beating rate of neonatal rat cardiomyocytes and the production of cyclic adenosine monophosphate (cAMP) in COS-7 cells transfected with 1 -o r2-adrenoceptors, suggesting that they interact with and stimulate -adrenergic receptors. The tachycardic effect of -receptor autoantibodies was inhibited by propranolol. What is the relationship of these findings to previous clinical observations in patients with inappropriate sinus tachycardia? Previously proposed cardiac mechanisms include increased sympathetic tone, increased sympathetic receptor sensitivity, blunted parasympathetic tone, and sympathovagal imbalance. 2 Three of these four possibilities (increased sympathetic tone, blunted parasympathetic tone, and sympathovagal imbalance) could be caused by -receptor autoantibodies. -Adrenergic hypersensitivity has been described in inappropriate sinus tachycardia. 3 Classically, chronic -adrenergic stimulation causes receptor desensitization, 4 so perhaps -receptor-stimulating -receptor autoantibodies should cause desensitization. However, desensitization mechanisms occurring with small-molecule ligands, such as catecholamines, may not apply to -receptor autoantibodies. Patients with inappropriate sinus tachycardia are predominantly female, a previously unexplained observation. Women are more susceptible to autoimmune conditions than are men, 5 so an autoimmune etiology of inappropriate sinus tachycardia (such as -receptor autoantibody production) might account for female predominance. -Receptor blockers can be effective in patients with inappropriate sinus tachycardia, 4 a response consistent with the blockade of -receptor autoantibody-induced tachycardia by propranolol