Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease

Domenico Corradi, Sergio Callegari, Stefano Benussi, Roberta Maestri, Paolo Pastori, Simona Nascimbene, Silvia Bosio, Enrica Dorigo, Chiara Grassani, Raffaella Rusconi, Maria Vittoria Vettori, Rossella Alinovi, Ettore Astorri, Carlo Pappone, Ottavio Alfieri

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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 μm; not significant) but larger than in the controls (11.9 ± 0.8 and 12.1 ± 1.3 μm, 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.

Original languageEnglish
Pages (from-to)1080-1089
Number of pages10
JournalHuman Pathology
Volume36
Issue number10
DOIs
Publication statusPublished - Oct 2005

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Atrial Appendage
Mitral Valve
Atrial Fibrillation
Muscle Cells
Sarcomeres
DNA Nucleotidylexotransferase
Pulmonary Veins
Heart Atria
Smooth Muscle
Actins
Electron Microscopy
Fibrosis
Maintenance
Apoptosis
Light

Keywords

  • Apoptosis
  • Atrial fibrillation
  • Dedifferentiation
  • Myocyte remodeling
  • Ultrastructure

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease. / Corradi, Domenico; Callegari, Sergio; Benussi, Stefano; Maestri, Roberta; Pastori, Paolo; Nascimbene, Simona; Bosio, Silvia; Dorigo, Enrica; Grassani, Chiara; Rusconi, Raffaella; Vettori, Maria Vittoria; Alinovi, Rossella; Astorri, Ettore; Pappone, Carlo; Alfieri, Ottavio.

In: Human Pathology, Vol. 36, No. 10, 10.2005, p. 1080-1089.

Research output: Contribution to journalArticle

Corradi, D, Callegari, S, Benussi, S, Maestri, R, Pastori, P, Nascimbene, S, Bosio, S, Dorigo, E, Grassani, C, Rusconi, R, Vettori, MV, Alinovi, R, Astorri, E, Pappone, C & Alfieri, O 2005, 'Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease', Human Pathology, vol. 36, no. 10, pp. 1080-1089. https://doi.org/10.1016/j.humpath.2005.07.018
Corradi, Domenico ; Callegari, Sergio ; Benussi, Stefano ; Maestri, Roberta ; Pastori, Paolo ; Nascimbene, Simona ; Bosio, Silvia ; Dorigo, Enrica ; Grassani, Chiara ; Rusconi, Raffaella ; Vettori, Maria Vittoria ; Alinovi, Rossella ; Astorri, Ettore ; Pappone, Carlo ; Alfieri, Ottavio. / Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease. In: Human Pathology. 2005 ; Vol. 36, No. 10. pp. 1080-1089.
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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 μm; not significant) but larger than in the controls (11.9 ± 0.8 and 12.1 ± 1.3 μm, 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.",
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AU - Vettori, Maria Vittoria

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