Interplay between cardiomyocytes and nonmyocytes plays a vital role in cardiac metabolism and function: early-phase metabolic syndrome and short QT

The heart is a complex organ composed of diverse cell types, primarily cardiomyocytes and nonmyocytes, which engage in intricate intercellular communication. This dynamic multicellular network is essential for maintaining cardiac function and metabolic homeostasis under physiological conditions. However, in the context of early- and late-phase metabolic syndrome (MetS), particularly induced by a high-carbohydrate diet, this cellular crosstalk becomes differentially disrupted. Among them, the early phase of MetS, characterized by hyperglycemia, insulin resistance, and dyslipidemia, promotes structural and functional remodeling of the heart, including metabolic reprogramming and increased susceptibility to arrhythmia, characterized by a short QT interval (SQT) in electrocardiograms. Concurrently, SQT, a cardiac channelopathy affecting ventricular repolarization, can exacerbate these electrophysiological disturbances. Emerging evidence suggests that interactions between cardiomyocytes and nonmyocytes mainly regulate mitochondrial dynamics, substrate metabolism, and inflammatory signaling pathways, which are crucial processes involved in both the progression of MetS and arrhythmogenic remodeling. This review examines the role of cardiomyocyte–nonmyocyte interactions in maintaining cardiac metabolic balance. It highlights how their disruption contributes to arrhythmias, such as SQT, in the early phase of MetS. Understanding this cellular interplay offers potential therapeutic avenues to restore metabolic flexibility and preserve cardiac electrophysiological integrity in metabolic and channelopathic disease states.