Key result
Cardiac leukocytes modulate electrical conduction via connexin-43 and drive arrhythmogenesis through inflammation and fibrosis.
Why the study?
Conduction disorders and arrhythmias remain difficult to treat, and a knowledge gap exists between electrophysiology and immunology regarding how the newly discovered functions of cardiac immune cells relate to conduction and arrhythmogenesis.
This review integrates electrophysiology and immunology to highlight how cardiac immune cells directly interact with cardiomyocytes via gap junctions and contribute to both normal cardiac conduction and arrhythmogenesis.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The evidence is no longer exploratory but is compelling and clinically actionable. The time for taking action has now arrived.”
Supports electroimmunology framework; hypothesis-generating for immunomodulatory arrhythmia therapies pending clinical validation.
Conduction disorders and arrhythmias remain difficult to treat and are increasingly prevalent owing to the increasing age and body mass of the general population, because both are risk factors for arrhythmia. Many of the underlying conditions that give rise to arrhythmia — including atrial fibrillation and ventricular arrhythmia, which frequently occur in patients with acute myocardial ischaemia or heart failure — can have an inflammatory component. In the past, inflammation was viewed mostly as an epiphenomenon associated with arrhythmia; however, the recently discovered inflammatory and non-canonical functions of cardiac immune cells indicate that leukocytes can be arrhythmogenic either by altering tissue composition or by interacting with cardiomyocytes; for example, by changing their phenotype or perhaps even by directly interfering with conduction. In this Review, we discuss the electrophysiological properties of leukocytes and how these cells relate to conduction in the heart. Given the thematic parallels, we also summarize the interactions between immune cells and neural systems that influence information transfer, extrapolating findings from the field of neuroscience to the heart and defining common themes. We aim to bridge the knowledge gap between electrophysiology and immunology, to promote conceptual connections between these two fields and to explore promising opportunities for future research.
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Grune et al. (2021) conducted a review in Cardiac conduction disorders and arrhythmias. Cardiac leukocytes and inflammatory pathways was evaluated. Cardiac leukocytes directly modulate electrical conduction via connexin-43 gap junctions and promote arrhythmias through cytokines, fibrosis, and autoantibodies.
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