Tissue Substrate of Rheumatic Atrial Fibrillation: Atrial Fibrosis and Cajal-Like Interstitial Cells at the Left Atrial–Pulmonary Vein Junction

Introduction: Atrial fibrillation (AF) is a frequent complication of rheumatic mitral valve disease and is based on a complex substrate of atrial remodeling. The pulmonary veins represent a key site for AF initiation; however, the cellular and histological determinants involved remain incompletely understood. By analogy with their pacemaker role in the gastrointestinal tract, interstitial cells of Cajal (ICCs) have been proposed as potential modulators of atrial electrical activity. Objectives: To investigate the histological and immunohistochemical characteristics of the left atrium–pulmonary vein junction, with particular emphasis on the presence of interstitial cells of Cajal (ICCs), in patients undergoing surgery for rheumatic mitral valve disease, and to analyze their association with atrial fibrillation. Methods: This was a prospective study conducted from August 2023 to July 2024 including 11 patients undergoing surgery for rheumatic mitral valve disease at Fann Teaching Hospital (Dakar). Tissue samples were obtained from the junction between the left atrium and the right superior pulmonary vein. Analyses included standard histological examination and immunohistochemical studies using CD34 and DOG1 markers. Clinical, electrocardiographic, and echocardiographic data were correlated with the anatomopathological findings. Results: The study population was predominantly young and female, with a high prevalence of advanced rheumatic heart disease. Four patients presented with atrial fibrillation, predominantly permanent. Histological analysis revealed diffuse interstitial fibrosis and marked architectural disorganization in nearly all specimens, regardless of cardiac rhythm. Interstitial cells of Cajal were identified at low density but more frequently in patients with atrial fibrillation, mainly within fibrotic areas and in close proximity to the atrial myocardial sleeve. CD34 staining was widely positive in all samples, indicating nonspecific fibro-interstitial remodeling, whereas DOG1 expression was negative in all patients. Conclusion: in this limited series, interstitial cells of Cajal were present at low density at the left atrium–pulmonary vein junction and appeared to be preferentially associated with atrial fibrillation in the context of chronic atrial remodeling. These cells seem to be integrated into a remodeled fibro-interstitial microenvironment without constituting a specific histological marker of atrial fibrillation. These findings support the hypothesis of a mainly modulatory role of Cajal-like interstitial cells in valvular atrial arrhythmogenesis and justify further studies combining morphological and functional analyses.