Histological evidence of inflammatory reaction associated with fibrosis in the atrial and ventricular walls in a case-control study of patients with history of atrial fibrillation.

AIMS: Chronic inflammation in the atrial myocardium was shown to play an important role in the development of atrial fibrosis in patients with atrial fibrillation (AF). However, it is not clear to what extent atrial inflammatory reaction associated with AF extends on the ventricular myocardium. Our aim was to assess the extent of fibrosis and lymphomononuclear infiltration in human ventricular myocardium and explore its association with AF. METHODS AND RESULTS: Medical records from consecutive autopsies were checked for presence of AF. Heart specimens from 30 patients died from cardiovascular causes (64 ± 12 years, 17 men) were collected in three equal groups: no AF, paroxysmal AF, and permanent AF. Tissue samples were taken from the Bachmann's bundle, crista terminalis, posterior left atrium, left ventricle and right ventricle free walls and stained with Masson's trichrome for analysis of fibrosis extent. Immunohistochemistry was performed using antibodies against CD3- and CD45-antigens and quantified as number of antigen-positive cells per 1 mm2. Fibrosis extent, CD3+ and CD45+ cell counts were elevated in AF patients at all sites (P < 0.001 for all). Fibrosis extent demonstrated correlation with both CD3+ and CD45+ cell counts in the right (r = 0.781, P < 0.001 for CD45+ and r = 0.720, P < 0.001 for CD3+) and the left (r = 0.515, P = 0.004 for CD45+ and r = 0.573, P = 0.001 for CD3+) ventricles. Neither fibrosis nor inflammatory cell count showed association with either age or comorbidities. CONCLUSION: Histological signs of chronic inflammation affecting ventricular myocardium are strongly associated with AF and demonstrate significant correlation with fibrosis extent that cannot be explained by cardiovascular comorbidities otherwise.

P-wave characteristics and histological atrial abnormality.

BACKGROUND: Fibro-fatty transformation is believed to be the leading cause of deteriorated atrial conduction; however, any direct assessment in relation to P-wave characteristics is lacking. We sought to assess P-wave morphology (PWM) and duration (PWD) in relation to histology of the atrial myocardium. OBJECTIVE: Atrial specimens were collected from 11 patients who died from cardiovascular causes (7 men; median age 73 years). METHODS: Tissue samples were taken at the level of superior and inferior PVs, center of posterior left atrial wall, terminal crest (CT) and Bachmann's bundle (BB) for assessment of fibro-fatty tissue extent. Standard 12-lead ECGs in sinus rhythm recorded during hospital stay were used for manual assessment of P-wave. Partial interatrial block (pIAB) was defined as a prolonged (≥ 120 ms) and bimodal P-wave in any lead on 12-lead ECG. RESULTS: The median PWD was 160 (120-200) ms. Fibrosis extent in CT highly correlated to PWD (r=0.914, p<0.001). The combination of fibrosis extent and fatty tissue in BB (16%, range 1%-41%), CT (18%, range 3%-47%) or superior PV (15%, range 6%-24%) correlated to PWD (r=0.627, p=0.039; r=0.795, p=0.003; and r=0.668, p=0.025, respectively). pIAB pattern was observed in 10 subjects; however, it was not associated with either fibrosis or fatty tissue content at any sampling location. CONCLUSIONS: Our findings further support causal association between PWD and the extent of structural abnormalities in the atrial myocardium and the major atrial conduction routes.

Structural abnormalities in atrial walls are associated with presence and persistency of atrial fibrillation but not with age.

OBJECTIVES: The purpose of this study was to assess the association between structural changes in human atria, age, and history of atrial fibrillation (AF). BACKGROUND: Development of fibrosis in atrial walls is associated with deterioration of atrial conduction and predisposes to AF in experiment. Human data, however, are scarce, and whether fibrosis is a cause or consequence of AF is not known. METHODS: Medical records for consecutive autopsies were checked for AF history and duration. Atrial specimens from 30 patients (ages 64 ± 12 years) were collected in 3 equal age-matched groups as patients without AF history, with paroxysmal AF, or with permanent AF. Tissue samples were obtained at the level of superior pulmonary veins, inferior pulmonary veins, center of posterior left atrial wall, terminal crest, and Bachmann's bundle. Histology sections were assessed for extent of fibrosis, fatty tissues, and inflammatory infiltration at each location. RESULTS: No correlation was observed between age and fibrosis at any location. Fibrosis extent and fatty infiltration were twofold to threefold higher at all locations in patients with history of AF and correlated with lymphomononuclear infiltration. Patients with permanent AF had greater fibrosis extent than did patients with paroxysmal AF. CONCLUSIONS: In post-mortem material, structural changes in the atria were not associated with age, but were significantly correlated with presence of AF and its severity. Our findings suggest that age-related changes per se are unlikely to be the sole cause of advanced fibrosis underlying AF.