The cardiac conduction system: development, function and therapeutic targets

The cardiac conduction system (CCS) has a vital role in initiating and coordinating nearly 3 billion heartbeats throughout a person's lifetime. The CCS comprises two primary tissue types: the impulse-generating, slow-conducting nodes and the fast-conducting components of the ventricular conduction system. Dysfunction in this system can give rise to a spectrum of clinical symptoms, including palpitations, syncope, heart failure and even sudden cardiac death. Owing to the limited therapeutic options other than electronic pacemakers, substantial research efforts have been aimed at uncovering the root causes of conduction system disorders. A comprehensive investigative approach integrating genetics, transcriptomics and proteomics has been used to unravel the complex biology of these diseases. Advances in single-cell genomic and transcriptomic technologies, together with spatial transcriptomics, are offering new insights into the cellular microenvironments that govern conduction system function. In this Review, we examine the latest progress in understanding the biology of the CCS, situating new findings within both established and emerging scientific paradigms. Additionally, we discuss how these insights can be leveraged to improve clinical risk assessment, expand drug discovery efforts, accelerate technology aimed at promoting CCS regeneration and foster the development of innovative therapies, including biological pacemakers.