Heterogeneity in Cardiac Electrophysiology: novel understandings and solutions

Heterogeneity in myocardial electrical conduction is the core link of arrhythmogenesis. Abnormalities in cellular electrophysiology, cell-to-cell communication, interstitia, and cardiac structure lead to enhanced non-uniform anisotropy. They also lead to the initiation and maintenance of reentry, contributing to sustained arrhythmias including atrial fibrillation, ventricular tachycardia, and atrioventricular nodal reentrant tachycardia.

Cardiac conduction heterogeneity may be the result of one or a number of complex factors. At the cellular or subcellular level, ion channels dysfunction, ionic remodeling, dysfunction of protein kinases and phosphatases and/or cell hypertrophy could trigger ectopic activity, regional heterogeneity, and form the basis for reentry. Connexins play a vital role in the intercellular electrical propagation due to their low-resistance electrical property. On the contrary, fibrotic scars increase conduction heterogeneity due to their high resistivity.

Noncardiogenic disorders or conditions can indirectly cause cardiomyocyte dysfunction and remodeling. Other conditions including: inflammation, metabolic factors, and anticancer therapies may also lead to electrical conduction heterogeneity.

Although therapies aimed at improving cardiac pump function, or reducing arrhythmia susceptibility, are booming, correction in electrical conduction heterogeneity is less specifically developed. Recently, the advent of many new techniques, ideas, and tools may aid in understanding and rescuing such problems. There is an urgency to develop novel biomaterials, such as hydrogels and cardiac patches, to decrease the risk of arrhythmogenic conduction heterogeneity. The induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) bring new avenues for testing pharmacological cardiotoxicity and efficacy, building patient-specific models, and developing personalized drugs. Optogenetically-paced iPSC-CMs may change the game in electrical conduction heterogeneity. We also need to learn more about the formation of electrical conduction heterogeneity to drive drug innovation, and to prevent drug-induced electrical conduction heterogeneity in cardiogenic and noncardiogenic disorders.

In this research topic, original research articles, review articles, and other article types that relate to cardiac electrical conduction heterogeneity will be particularly welcomed. Basic and clinical studies focusing on understanding the pathophysiology and developing novel therapies including biomaterials, stem cells, and pharmaceutic approaches are highly encouraged. Submissions to the topic could include, but are not limited to, the following themes:

- Understanding the formation of pathological substrates including fibrosis, connexins, or other factors involved in cardiac electrical conduction heterogeneity
- Therapeutic approaches to correct relevant factors and to improve conduction heterogeneity using novel biomaterials, stem cells therapies, and pharmaceutical approaches
- Computer modeling in the pattern of cardiac electrical conduction heterogeneity
- Non-cardiogenic factors that cause cardiac electrical conduction heterogeneity including, but not limited to, the use of chemotherapies, endurance exercise, sleep apnea, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and drugs side effects

Topic editor Matthijs Cluitmans is employed by Phillips Research. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: fibrosis, Electrical heterogeneity, Connexins, Reentry, Ion channels, Tissue engineering, Biomaterials, Stem cells

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.