Serum Levels of Caspase-3 Decrease in Patients with Long-Term Arrhythmia Suppression after PVI

Background: The success of pulmonary vein isolation (PVI) is limited with more advanced disease of the atrial myocardium which may develop due to aging, atrial fibrillation (AF), cardiac diseases and comorbidities leading to elevated atrial pressure. Our group has recently reported on long-term decrease in the levels of different biomarkers after PVI, potentially reflecting a reversal of the fibrotic process in the atria with arrhythmia control. Whether the presence of baseline comorbidities has a significant impact on long-term changes in the serum concentration of these substances is unknown. Aim: Herein, we compared the levels of 4 biomarkers (CA-125, Caspase-3, Cathepsin L and Galectin-3) before and 3 years after successful PVI in patients with versus without comorbidities at baseline. Methods: Serum concentrations of the 4 biomarkers were measured prospectively in consecutive patients undergoing PVI with any of 3 different techniques for paroxysmal/permanent AF 24 hours before and 3 years after ablation. Only patients free of AF recurrence at 3-year follow-up were included in this analysis. Results: 28 men and 9 women (age 56.5 +/- 9.2 years) were enrolled. Caspase-3 concentrations decreased significantly by the end of follow-up in patients without (from 500.9 (345.7-719.5) to 340.5 (255.9-387.3); p=0.016 as well as with comorbidities: from 623.8 (476.9-751.4) to 447.7 (327.6-636.9) p=0.039. Caspase-3 concentrations (pg/mL) were higher at 3-year follow-up in patients with versus without comorbidities: 447.7 (327.6-636.9) vs 340.5 (255.9-387.3); p=0.038. For Caspase-3, a significant overall time effect was observed (beta=-0.437, p=0.010), consistent with lower concentrations at 3-year follow-up after adjustment for age, sex, AF type, and ablation technique. No differences were measured with the other biomarkers. Conclusion: Serum levels of Caspase-3 decreased in patients maintaining sinus rhythm after PVI regardless of the presence or absence of comorbidities, suggesting that it might be a sensitive biomarker indicating long-term arrhythmia suppression.