Histopathological substrate for chronic atrial fibrillation in humans

Bich Lien Nguyen, Michael C. Fishbein, Lan Chen, Peng-Sheng Chen, Saqib Masroor

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Background: There is a lack of understanding of the substrate for microreentrant circuits and triggered activity of the pulmonary vein (PV) muscle sleeves and atria in patients with atrial fibrillation (AF). Objective: This study sought to examine the histological substrate of patients with chronic AF. Methods: We stained 23 biopsies taken from the PV-left atrium (LA) junction and right atrial appendage from 5 chronic AF patients and 3 sinus rhythm (SR) patients undergoing mitral valve surgery using periodic acid-Schiff (PAS) test, and antibodies to hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4), CD117/c-kit, myoglobin, tyrosine hydroxylase (TH), growth-associated protein 43, cholineacetyltransferase, and synaptophysin, as well as trichrome. Results: As opposed to being clustered together in the subendocardial layer in SR patients, PAS-positive cells were separated from each other by inflammatory infiltrate and collagen fibers in AF patients. These cells stained positively for HCN4 and myoglobin, indicating they were cardiomyocytes that might have a potential pacemaking function, but different from CD117/c-kit-positive interstitial Cajal-like cells (ICLC). In AF patients, the intercellular space was occupied by a lymphomononuclear infiltrate (100% vs 33% in SR patients, P = .002), and a greater amount of interstitial fibrosis (37% ± 5.6% vs 7.4% ± 2.8%, P = .009). Nerve densities did not differ between AF and SR patients. However, the density of sympathetic nerve twigs in AF patients was significantly greater as compared to the others nerves (P = .03). Conclusion: HCN4-/PAS-positive cardiomyocytes and CD117/c-kit-positive ICLC scattered among abundant inflammatory infiltrate, fibrous tissue, and sympathetic nerve structures in the atria and at the PV-LA junctions might be a substrate for the maintenance of chronic AF.

Original languageEnglish
Pages (from-to)454-460
Number of pages7
JournalHeart Rhythm
Volume6
Issue number4
DOIs
StatePublished - Apr 2009

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Atrial Fibrillation
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Periodic Acid
Pulmonary Veins
Potassium Channels
Myoglobin
Heart Atria
Cardiac Myocytes
GAP-43 Protein
Nerve Tissue
Atrial Appendage
Synaptophysin
Extracellular Space
Tyrosine 3-Monooxygenase
Mitral Valve
Fibrosis
Collagen
Maintenance
Biopsy
Muscles

Keywords

  • Atrial fibrillation
  • Electrophysiology
  • Pathology
  • Remodeling
  • Substrate

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Histopathological substrate for chronic atrial fibrillation in humans. / Nguyen, Bich Lien; Fishbein, Michael C.; Chen, Lan; Chen, Peng-Sheng; Masroor, Saqib.

In: Heart Rhythm, Vol. 6, No. 4, 04.2009, p. 454-460.

Research output: Contribution to journalArticle

Nguyen, Bich Lien ; Fishbein, Michael C. ; Chen, Lan ; Chen, Peng-Sheng ; Masroor, Saqib. / Histopathological substrate for chronic atrial fibrillation in humans. In: Heart Rhythm. 2009 ; Vol. 6, No. 4. pp. 454-460.
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abstract = "Background: There is a lack of understanding of the substrate for microreentrant circuits and triggered activity of the pulmonary vein (PV) muscle sleeves and atria in patients with atrial fibrillation (AF). Objective: This study sought to examine the histological substrate of patients with chronic AF. Methods: We stained 23 biopsies taken from the PV-left atrium (LA) junction and right atrial appendage from 5 chronic AF patients and 3 sinus rhythm (SR) patients undergoing mitral valve surgery using periodic acid-Schiff (PAS) test, and antibodies to hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4), CD117/c-kit, myoglobin, tyrosine hydroxylase (TH), growth-associated protein 43, cholineacetyltransferase, and synaptophysin, as well as trichrome. Results: As opposed to being clustered together in the subendocardial layer in SR patients, PAS-positive cells were separated from each other by inflammatory infiltrate and collagen fibers in AF patients. These cells stained positively for HCN4 and myoglobin, indicating they were cardiomyocytes that might have a potential pacemaking function, but different from CD117/c-kit-positive interstitial Cajal-like cells (ICLC). In AF patients, the intercellular space was occupied by a lymphomononuclear infiltrate (100{\%} vs 33{\%} in SR patients, P = .002), and a greater amount of interstitial fibrosis (37{\%} ± 5.6{\%} vs 7.4{\%} ± 2.8{\%}, P = .009). Nerve densities did not differ between AF and SR patients. However, the density of sympathetic nerve twigs in AF patients was significantly greater as compared to the others nerves (P = .03). Conclusion: HCN4-/PAS-positive cardiomyocytes and CD117/c-kit-positive ICLC scattered among abundant inflammatory infiltrate, fibrous tissue, and sympathetic nerve structures in the atria and at the PV-LA junctions might be a substrate for the maintenance of chronic AF.",
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AB - Background: There is a lack of understanding of the substrate for microreentrant circuits and triggered activity of the pulmonary vein (PV) muscle sleeves and atria in patients with atrial fibrillation (AF). Objective: This study sought to examine the histological substrate of patients with chronic AF. Methods: We stained 23 biopsies taken from the PV-left atrium (LA) junction and right atrial appendage from 5 chronic AF patients and 3 sinus rhythm (SR) patients undergoing mitral valve surgery using periodic acid-Schiff (PAS) test, and antibodies to hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4), CD117/c-kit, myoglobin, tyrosine hydroxylase (TH), growth-associated protein 43, cholineacetyltransferase, and synaptophysin, as well as trichrome. Results: As opposed to being clustered together in the subendocardial layer in SR patients, PAS-positive cells were separated from each other by inflammatory infiltrate and collagen fibers in AF patients. These cells stained positively for HCN4 and myoglobin, indicating they were cardiomyocytes that might have a potential pacemaking function, but different from CD117/c-kit-positive interstitial Cajal-like cells (ICLC). In AF patients, the intercellular space was occupied by a lymphomononuclear infiltrate (100% vs 33% in SR patients, P = .002), and a greater amount of interstitial fibrosis (37% ± 5.6% vs 7.4% ± 2.8%, P = .009). Nerve densities did not differ between AF and SR patients. However, the density of sympathetic nerve twigs in AF patients was significantly greater as compared to the others nerves (P = .03). Conclusion: HCN4-/PAS-positive cardiomyocytes and CD117/c-kit-positive ICLC scattered among abundant inflammatory infiltrate, fibrous tissue, and sympathetic nerve structures in the atria and at the PV-LA junctions might be a substrate for the maintenance of chronic AF.

KW - Atrial fibrillation

KW - Electrophysiology

KW - Pathology

KW - Remodeling

KW - Substrate

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