Efficacy of Long-term Flecainide Therapy in Patients with Paroxysmal Atrial Fibrillation —Analysis Based on Time of Onset—

This study sought to evaluate the efficacy of long-term flecainide therapy in maintaining sinus rhythms in patients with paroxysmal atrial fibrillation (AF. based on time of onset. Flecainide (150 mg/day. was administered as an antiarrhythmic drug to a total of 70 patients (54 men and 16 women: mean age 65 ± 10 years. after sinus rhythm was restored spontaneously or by electrical and/or pharmacological cardioversion. Paroxysmal AF was divided into three categories based on time of onset: diurnal type (N = 11), nocturnal type (N = 13), and mixed type (N = 46). The mean follow-up period was 37.7 ± 17.7 months. The duration of sinus rhythm maintenance in patients with diurnal and nocturnal paroxysmal AF was 32.4 ± 10.4 months and 20.8 ± 8.3 months, respectively; the duration of sinus rhythm maintenance in those with mixed paroxysmal AF was only 7.2 ± 2.1 months. Significant differences were observed in duration between diurnal and mixed cases (mean ± S.E., P < 0.05). Actuarial recurrence-free rates at 1, 3, 6, 9 and 12 months were 90.9%, 63.6%, 63.6%, 54.5%, and 54.5%, respectively, for diurnal cases; 84.6%, 76.9%, 53.8%, 38.5%, and 30.8%, respectively, for nocturnal cases; and 58.7%, 39.1%, 28.3%, 21.7%, and 15.2% respectively, for mixed cases. Significant differences in rates at 12 months were observed between diurnal and mixed cases (P < 0.05). These results suggest that flecainide is highly effective in preventing AF recurrence in patients with diurnal paroxysmal AF

Long-term Efficacy of Combination Therapy with Anti-arrhythmic Agents and Pravastatin in Patients with Paroxysmal Atrial Fibrillation

Objective: To investigate the long-term effects of combination therapy with antiarrhythmic agents and pravastatin (10 mg/day) in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation (AF) and hyperlipidemia. Method and Results: In all, 318 patients (mean age: 69 ± 12 years) with paroxysmal AF were divided into 2 groups, one receiving pravastatin for hyperlipidemia (pravastatin (+) group, N = 41) and the other not (pravastatin (−) group, N = 277). At 60 months, the survival rate for patients free from conversion to permanent AF was significantly greater in the pravastatin (+) group than in the pravastatin (−) group. The percentage of patients who eventually developed permanent AF despite anti-arrhythmic therapy was significantly lower in the pravastatin (+) group than in the pravastatin (−) group (9.8% vs. 25.3%). Left atrial dimensions were significantly increased in the pravastatin (−) group during the follow-up period (from 34.8 ± 6.6 mm to 37.6 ± 7.0 mm: p < 0.01). In contrast, in the pravastatin (+) group, left atrial dimensions remained unchanged between baseline and after treatment (34.4 ± 7.3 mm vs 35.5 ± 6.6 mm). Conclusion: In patients with paroxysmal AF and hyperlipidemia, addition of pravastatin to anti-arrhythmic agents seems to enhance the efficacy of these agents in maintaining sinus rhythm and preventing the development of structural remodeling in the myocardium

Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population

Background/Aims:Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.Methodology/Principal Findings:Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies).Conclusions/Significance:This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases