Autoimmune channelopathies as a novel mechanism in cardiac arrhythmias

Abstract

Cardiac arrhythmias confer a considerable burden of morbidity and mortality in industrialized countries. Although coronary artery disease and heart failure are the prevalent causes of cardiac arrest, in 5-15% of patients, structural abnormalities at autopsy are absent. In a proportion of these patients, mutations in genes encoding cardiac ion channels are documented (inherited channelopathies), but, to date, the molecular autopsy is negative in nearly 70% of patients. Emerging evidence indicates that autoimmunity is involved in the pathogenesis of cardiac arrhythmias. In particular, several arrhythmogenic autoantibodies targeting specific calcium, potassium, or sodium channels in the heart have been identified. Experimental and clinical studies demonstrate that these autoantibodies can promote conduction disturbances and life-threatening tachyarrhythmias by inducing substantial electrophysiological changes. In this Review, we propose the term 'autoimmune cardiac channelopathies' to define this novel pathogenic mechanism of cardiac arrhythmias, which could be more frequent and clinically relevant than previously appreciated. Indeed, pathogenic autoantibodies against ion channels are detectable not only in patients with manifest autoimmune disease, but also in apparently healthy individuals, which suggests a causal role in some cases of unexplained arrhythmias and cardiac arrest. Considering this possibility and performing specific testing in patients with 'idiopathic' rhythm disturbances could create novel treatment opportunities.