Identification of novel pulmonary vein nodes as generators of ectopic arrhythmic foci for atrial fibrillation: an immunohistochemical proof

Purpose The atrial muscle sleeve (AMS) of the pulmonary vein is the most common source of the arrhythmogenic triggers in atrial fibrillation (AF). Anatomical substrate generating these ectopic currents is still elusive. The present study was designed to study the AMS of pulmonary veins with an emphasis on the structural basis which might govern AF initiation and perpetuation. Methods The study was conducted on a longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric nondiseased hearts. Tissue was studied histologically using H&E and Gomori trichrome stain. The pacemaker channels were identified by immunohistochemistry using monoclonal HCN4 and HCN1 antibodies. Results The AMS was identified in each pulmonary vein, located between the tunica adventitia and tunica media. A node-like arrangement of myocytes was seen within the AMS in 30% of veins. It had a compact zone limited by a fibrous capsule and contained much smaller, paler and interconnected myocytes. Outside the capsule, there was a zone of dispersed, singly placed myocytes separating the compact zone from the working myocytes of the AMS. HCN4 and HCN1 antibodies were expressed on the cell membrane of nodal myocytes, while the working myocytes demonstrated none to minimal staining. Conclusion Pulmonary veins nodes are similar to the specialized cardiac conductive tissue in the histological arrangement of compact and transitional zones, cellular characteristics and the presence of pacemaker channels. They might be the anatomical basis of ectopic arrhythmogenic foci. To our knowledge, these nodes are being described for the first time in human.