The developmental basis of adult arrhythmia: atrial fibrillation as a paradigm

Normal cardiac rhythm is one of the most fundamental physiologic phenomena, emerging early in the establishment of the vertebrate body plan. The developmental pathways underlying the patterning and maintenance of stable cardiac electrophysiology must be extremely robust, but are only now beginning to be unraveled. The step-wise emergence of automaticity, AV delay and sequential conduction are each tightly regulated and perturbations of these patterning events is now known to play an integral role in pediatric and adult cardiac arrhythmias. Electrophysiologic patterning within individual cardiac chambers is subject to exquisite control and is influenced by early physiology superimposed on the underlying gene networks that regulate cardiogenesis. As additional cell populations migrate to the developing heart these too bring further complexity to the organ, as it adapts to the dynamic requirements of a growing organism. A comprehensive understanding of the developmental basis of normal rhythm will inform not only the mechanisms of inherited arrhythmias, but also the differential regional propensities of the adult heart to acquired arrhythmias. In this review we use atrial fibrillation as a generalizable example where the various factors are perhaps best understood.