Background—The relationship between anti-β-adrenergic (anti-βR) and anti-M₂-cholinergic (anti-M2R) receptor antibodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated.

Methods and Results—We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas’ heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas’ heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-β₁RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for β₁,β₂-adrenergic receptors (cAMP increment) or M₂-cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-βRAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-βRAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol.

Conclusions—Our results demonstrate a strong correlation between anti-βRAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-βRAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.