title: Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease.
abstract: It has been found that the pulmonary veins and adjacent left atrial posterior wall (LAPW) are deeply involved in both the initiation and maintenance of atrial fibrillation (AF), and the identification of these high-risk sites has aroused great interest in investigating their histopathologic substrate. We used light and conventional electron microscopy to evaluate the differential myocyte and interstitial changes in LAPW and left atrial appendage (LAA) samples from 28 patients with chronic AF undergoing mitral valve surgery and from 12 autoptic controls. There were always more myocytes with loss of sarcomeres in the LAPW than in the LAA (19.9% +/- 7.7% versus 8.2% +/- 5.0%; P < .0001), and the LAPW showed more marked immunohistochemical evidence of dedifferentiation, characterized by the reexpression of smooth muscle actin. In pathological left atria, myocyte diameter in the LAPW and LAA was comparable (19.0 +/- 1.5 versus 18.5 +/- 2.0 microm; not significant) but larger than in the controls (11.9 +/- 0.8 and 12.1 +/- 1.3 microm, respectively; P < .0001). A terminal deoxynucleotidyltransferase assay did not reveal any myocyte apoptosis. The LAPW also showed more interstitial fibrosis than the LAA (7.49% +/- 3.34% versus 2.80% +/- 1.35%; P < .0001). Ultrastructural examination confirmed the presence of myocyte myocytolysis in the perinuclear area and showed changes in mitochondrial shape. In conclusion, the LAPW in patients with chronic AF related to mitral valve disease seems to be a particular anatomical site in which major myocyte and interstitial changes are concentrated, whereas the LAA is more protected. This remodeling may increase the heterogeneity of LAPW electrical conduction, thus confirming this location as an elective target for the ablation treatment of AF.
authors.affiliation: Pathology Section, Department of Pathology and Laboratory Medicine, University of Parma, 43100 Parma, Italy. domenico.corradi@unipr.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Corradi
authors.forename: Sergio
authors.initials: S
authors.lastname: Callegari
authors.forename: Stefano
authors.initials: S
authors.lastname: Benussi
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestri
authors.forename: Paolo
authors.initials: P
authors.lastname: Pastori
authors.forename: Simona
authors.initials: S
authors.lastname: Nascimbene
authors.forename: Silvia
authors.initials: S
authors.lastname: Bosio
authors.forename: Enrica
authors.initials: E
authors.lastname: Dorigo
authors.forename: Chiara
authors.initials: C
authors.lastname: Grassani
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rusconi
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Vettori
authors.forename: Rossella
authors.initials: R
authors.lastname: Alinovi
authors.forename: Ettore
authors.initials: E
authors.lastname: Astorri
authors.forename: Carlo
authors.initials: C
authors.lastname: Pappone
authors.forename: Ottavio
authors.initials: O
authors.lastname: Alfieri
mesh_terms: D000328:Adult; D000368:Aged; D020517:Atrial Appendage / Q000473:pathology / Q000648:ultrastructure; D001281:Atrial Fibrillation / Q000473:pathology* / Q000503:physiopathology; D002908:Chronic Disease; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006325:Heart Atria / Q000473:pathology* / Q000648:ultrastructure; D006349:Heart Valve Diseases / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000473:pathology* / Q000648:ultrastructure; D008953:Models, Anatomic; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000648:ultrastructure