DM promoted atrial structural remodeling via the activation of the AGEs-RAGE system with upregulating CTGF. The inhibition of AGEs formation could be a novel upstream therapeutic approach for diabetes-related atrial fibrosis.

The present diabetic GK rat showed increased atrial arrhythmogenicity with intra-atrial conduction disturbance, and thus indicated that the structural remodeling of atrium characterized by diffuse interstitial fibrosis would be a major substrate for diabetes-related AF.

Background Atrial fibrillation (AF) is believed to occur first as paroxysmal, then be gradually perpetuated, and finally become chronic as the end result. However, this presumed clinical course has not been well confirmed. Methods and Results The clinical course of recurrent paroxysmal AF (PAF) from its onset was examined in 171 patients (mean follow-up period: 14.1±8.1 years). This study population consisted of patients with no structural heart disease (n=88), ischemic heart disease (n=28), dilated or hypertrophic cardiomyopathy (n=17), valvular heart disease (n=35) or other cardiac diseases. The mean age at the onset of AF was 58.3±11.8 years old. During the mean follow-up period of 14.1 years, PAF eventually developed into its chronic form in 132 patients under conventional antiarrhythmic therapy (77.2%, 5.5% of patients per year). The independent factors for early development into chronic AF were aging (hazard ratio (HR) 1.27 per 10 years, 95% confidence interval (CI) 1.06-1.47)), dilated left atrium (HR 1.39 per 10 mm, 95% CI 1.11-1.69), myocardial infarction (HR 2.33, 95% CI 1.13-4.81), and valvular diseases (HR 2.29, 95% CI 1.22-4.30). Conclusions The present long-term observations definitely and quantitatively revealed the progressive nature of PAF.