Autoimmune cardiac channelopathies and heart rhythm disorders: A contemporary review

Cardiac arrhythmias still represent a major health problem worldwide, at least in part because the fundamental pathogenic mechanisms are not fully understood, thus affecting the efficacy of therapeutic measures. In fact, whereas cardiac arrhythmias are in most cases due to structural heart diseases, the underlying cause remains elusive in a significant number of patients despite intensive investigations even including postmortem examination and molecular autopsy. A large body of data progressively accumulated during the last decade provides strong evidence that autoimmune mechanisms may be involved in a significant number of such unexplained or poorly explained cardiac arrhythmias. Several proarrhythmic anti–cardiac ion channel autoantibodies have been discovered, in all cases able to directly interfere with the electrophysiologic properties of the heart but leading to different arrhythmic phenotypes, including long QT syndrome, short QT syndrome, and atrioventricular block. These autoantibodies, which may develop independent of a history of autoimmune diseases, could help explain a percentage of arrhythmic events of unknown origin, thereby opening new frontiers for diagnosis and treatment of heart rhythm disorders. Based on this evidence, the novel term autoimmune cardiac channelopathies was coined in 2017. Since then, the interest in the field of cardioimmunology has shown a tumultuous growth, so much so that the number of arrhythmogenic anti–ion channel autoantibodies reported has significantly increased, also in association with not previously described arrhythmic phenotypes, such as atrial fibrillation, Brugada syndrome, and ventricular fibrillation/cardiac arrest. Thus, an updated reassessment of this topic, also highlighting perspectives and unmet needs, has become necessary and represents the main objective of this review.