The Association of Inflammation and the Recurrence of Atrial Fibrillation after Catheter Ablation and its Pathophysiological Mechanisms

• Main Authors: Yu-Feng Hu, 胡瑜峰
• Other Authors: Shih-Ann Chen
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/82747593731705456116

博士 === 國立陽明大學 === 臨床醫學研究所 === 101 === Background: Inflammation is an important mechanism in the pathogenesis of atrial fibrillation (AF). It remains unclear if inflammation is associated with the outcome of AF after catheter ablation. Furthermore, the patho-physiological process of AF recurrence and its associated cytokines and inflammatory pathways are also not clear. Methods: We enrolled prospective patients receiving catheter ablation for AF and tracked the recurrence of AF for 1 to 2 years. Different inflammation associated pathways and cytokines were screened using different methods, such as flow cytometry, real-time polymerase chain reaction (RT-PCR), and ELISA. Monocyte expression of CD36 was determined by flow cytometry. Heat shock protein 27 (HSP27), tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and HSP70 were detected by ELISA. High-sensitivity CRP (HsCRP) was determined using particle-enhanced immunoturbidimetry. Hemoxygenase-1 (HO-1) gene promoter polymorphisms and mRNA were determined using RT-PCR. Results: Of the screened cytokines or biomarkers, lower levels of monocyte CD36 protein and lower serum levels of HSP27 were independently associated with AF, but these variables were not associated with changes in TNF-α, IL-10, C-reactive protein, HSP70, or hemoxygenase-1 (HO-1) gene promoter polymorphisms. Monocyte CD36, HSP27, and HO-1 gene promoter polymorphisms were independently associated with AF recurrence after catheter ablation using a Kaplan–Meier analysis from different cohorts. CD36 and HSP27 were associated with different electro-anatomic properties, such as left atrial diameter and left atrial mean voltage. HSP27 levels were associated with non-pulmonary ectopies and fractionated intervals. An analysis of mRNA levels from the buffy coat revealed that CD36 levels were positively correlated with IL-10 levels but were inversely correlated with PPAR-γ and TNF-α levels. Similarly, HSP27 levels were inversely associated with TNF-α and positively correlated with IL-10, as indicated by both ELISA and mRNA, indicating the role of anti-inflammation. However, CD36 did not interact with HSP27. CD36 regulated monocyte inflammation, and HSP27 was associated with different lymphocyte levels, but not neutrophil levels. These findings suggest that chronic inflammation plays a more important role than acute inflammation. From the literature, HO-1 gene promoter polymorphisms have been associated with different inflammatory statuses. However, in the present study, we did not see an association between the number of GT repeats and CRP, IL-10, or TNF-α, implying other inflammatory pathways or alternative mechanisms such as anti-apoptosis may be involved. Conclusions: Specific inflammatory pathways such as monocyte CD36, HSP27S levels, and HO-1 gene promoter polymorphisms correlated with electro-anatomical remodeling and predicted AF recurrence after catheter ablation.