Advanced Glycation End-Products Paradox in Patients Undergoing Catheter Ablation of Atrial Fibrillation (2018)

Böhm A, Tothova L, Urban L, Slezak P, Musil P, Gazova A, Kyselovic J, Hatala R

Introduction: Oxidative stress (OS) is an important contributor to the pathophysiology of atrial fibrillation (AF), however its significance for the outcome of patients (pts) undergoing radio-frequency catheter pulmonary veins isolation (PVI) is unknown.

Objectives: To prospectively study the pattern of OS biomarkers (OSB) in pts undergoing radio-frequency catheter PVI for paroxysmal AF and to assess its possible role in predicting long-term outcome.

Methods: In this prospective cohort study we included 62 consecutive pts (mean age 55±8 years, 19% females) with paroxysmal AF and implanted ECG loop recorders who underwent PVI. Plasmatic concentrations of advanced glycation end-products (AGEs), fructosamine, advanced oxidation protein products and thiobarbituric-acid reacting substances were measured immediately before, 3 months after and 9 months after the PVI. AF burden (defined as percentage of time spent in AF) was assessed for corresponding time intervals and at the end of the follow–up (1063±273 days).

Results: 19 pts were defined as optimal responders (oR) with total AF burden < 0.5% after PVI. The remaining pts were defined as incomplete responders (iR) or non-responders (nR). In nR (20 pts) PVI was repeated. Using logistic regression model for OSB we found that only AGEs predicted significantly the outcome after PVI (OR: 1.4; p=0.008). After adjustment for age, sex, BMI, left atrial size and AF burden before PVI, high levels of AGEs remained significantly associated with AF recurrence (OR: 1.3; p=0.03). We identified optimal cut-off AGEs concentration of 14 mg/l, with 80% sensitivity and 68% specificity for predicting AF recurrence after PVI. However, the AGEs concentration 3 months after the PVI was significantly higher by 11.7 mg/l ([CI] = 0.5 to 23; p = 0.039) in oR as compared to iR and nR. There were no further significant differences in AGEs or other OSB.

Conclusion: Higher AGEs concentrations before PVI predicted AF recurrence in pts with paroxysmal AF and might contribute to optimal patient selection for PVI. Furthermore, higher AGEs concentrations 3 months after the PVI were associated with lower AF recurrence. It may be hypothesized that this apparent paradox is caused by the more efficient energy delivery into the left atrial tissue leading to higher fibrotic activity (expressed by the higher AGEs at the end of the 3 months blanking period) and subsequently to better electrical isolation in oR.