Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac β andrenergic receptors

BackgroundThe mechanisms underlying inappropriate sinus tachycardia are not fully known. An autonomic imbalance seems to play a role, but no attempts have been made to investigate a relationship between this arrhythmia and the antiautonomic membrane receptor antibodies found in other heart disorders and arrhythmias.ObjectiveThe purpose of this study was to investigate the prevalence and the functional and biochemical effects of circulating antiautonomic receptor antibodies in patients with inappropriate sinus tachycardia.MethodsWe studied 21 patients with inappropriate sinus tachycardia and 15 healthy volunteers. The chronotropic effects of the IgG fractions (also of affinity-purified anti-β1 adrenergic receptor antibodies in selected cases) were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The effects of the IgG fractions from five patients and five healthy volunteers on cAMP production were evaluated in COS-7 cells transfected with genes encoding for β1 or β2 adrenergic receptor.ResultsThe IgG fractions from patients with inappropriate sinus tachycardia exerted a positive chronotropic action with a high prevalence of anti-β receptor antibodies (52%) and induced a clear-cut and long lasting increment of cAMP. No anti-M2 cholinergic receptor antibodies were found. The IgG fractions from healthy volunteers did not contain antiautonomic receptor antibodies.ConclusionsOur results suggest, for the first time, a link between inappropriate sinus tachycardia and circulating anti-β adrenergic receptor antibodies that induce a persistent increment in cAMP production. This finding offers new insight into the physiopathology of inappropriate sinus tachycardia with potential therapeutic consequences.