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The myocardial sleeves of the systemic venous tributaries and the pulmonary veins are known to be common anatomic substrates for atrial fibrillation. Rapidly evolving evidence has shown that a substantial part of the paroxysmal variant of this abnormal rhythm has a familial heritage, and the number of genes found to be involved is increasing. One of the mechanisms underlying the condition is ectopic pacemaking activity. Knowledge of the normal embryological development of the atrial myocardium, in particular the myocardial sleeves clothing the systemic venous tributaries and the pulmonary veins at their junctions with the atrial chambers, may contribute to the understanding of the origins of such ectopic pacing. In this respect, it is now well established that the myocardial sleeves of the systemic venous tributaries have a distinct origin and program of gene expression when compared with the pulmonary venous myocardium. The myocardium clothing the pulmonary veins, however, is particularly susceptible to changes in the levels of gene expression, with the changes then favoring the presence of genes responsible for pacemaking. Only recently has interest developed in the genetic and heritable bases of atrial fibrillation, and much is still to be learned. Better understanding of both the developmental and genetic factors, nonetheless, will surely be helpful in the diagnosis, prevention, and treatment of this troublesome arrhythmia. With this in mind, therefore, we have reviewed the current knowledge concerning the initial development of the pulmonary venous myocardium, emphasizing its crucial differences from the systemic venous myocardium.

Original publication




Journal article


Heart Rhythm

Publication Date





1818 - 1824


Atrial Fibrillation, Genetic Variation, Heart Atria, Heart Conduction System, Humans, Mutation, Myocardium, Phenotype, Pulmonary Veins, Sinoatrial Node