Introduction

Left atrial cardiac tissue remodeling following left atrial appendage closure (LAAC) might have impact on functional outcome of patients suffering from atrial fibrillation (AF). It means implanting foreign material into the left atrium with the possibility of deteriorating cardiac function Our study is focused on quantification of key biomarkers reflecting fibrosis development as a major component within cardiovascular tissue remodeling.

Methods

We included patients (CHA₂DS₂VASC score ≥ 1, HASBLED score ≥ 3) with bleeding complications under anticoagulation therapy and LAAC. Serum levels of certain biomarkers of cardiac fibrosis and remodelling (Galectin-3, ST2/IL-2, ST2/IL1, B domain containing Tenascin-C (B⁺ Tn-C), C domain containing Tenascin-C (C⁺ Tn-C)) were determined before device implantation (baseline), 45 days (45d) and 6 months (6M) after LAAC using commercially available ELISAs. To quantify cardiopulmonary exercise testing, all patients performed a spiroergomertry (oxygen uptake at the anaerobic threshold = VO₂; maximum oxygen uptake= VO₂max). Transesophageal echocardiography (TEE) was carried out to assess success of the LAAC procedure.

Results

We included 49 patients (73.5 ± 7.1 years; 31 (64%) male; 28.7 ± 4.9 kg/m²; CHA₂DS₂VASC score: 3.9 ± 0.9; HAS-BLED score: 5.0 ± 0.8; left ventricular ejection fraction: 59.1 ± 11.3%). At baseline, Galectin-3 levels did not show a relevant difference regarding the type of AF (paroxysmal AF: 14.7 ± 5.4 ng/ml vs. permanent AF: 13.1 ± 6.3 ng/ml; p= 0.45). We observed a significant increase of serum levels of Galectin-3 [ng/ml] after 45 days vs. baseline (baseline: 13.3 ± 5.8 vs. 45d: 18.3 ± 10.6; p= 0.005) with a return to baseline levels after 6 months (baseline: 13.3 ± 5.8 vs. 6M: 12.5 ± 5.4; p= 0.28).  Compared to patients with successful LAAC (44 (87%)), patients with a persisting gap (5 (13%)) had a trend towards higher levels of Galectin -3 after 6 months (11.3 ± 5.5 ng/ml vs. 16.1 ± 4.1 ng/ml, p= 0.09). Measurements of other fibrosis markers were statistically not significantly different. Exercise testing showed a relevant and stable increase in oxygen uptake at the anaerobic threshold (VO₂: 11.2 ± 2.7 ml/kg/min (baseline) vs.12.3 ± 2.6 ml/kg/min (45d), p= 0.02). Even though no relevant further increase of the VO₂ could be observed beyond 45 days (12.3 ± 2.6 ml/kg/min (45d) vs. 12.6 ml/kg/min (6M), p= 0.09), we could measure an ongoing increase in maximum oxygen uptake after 45 days following LAAC (VO₂max: 13.5 ± 2.7 ml/kg/min (baseline) vs. 15.3 ± 2.4ml/kg/min (45d) p= 0.001 vs. 16.4 ± 3.9ml/kg/min (6M), p= 0.001). We found a significant negative correlation between Galectin-3 levels and exercise capacity after 6M (VO₂: r= - 0.54, p= 0.009; VO₂max: r=-0.53, p=0.01).  

Conclusion

The implantation of an LAA occluder device is accompanied by significantly increased circulating levels of the fibrosis biomarker Galectin-3 after 45 days. The regression in serum levels after 6 months probably reflects a successful fibrotic remodeling in the left atrial appendage over time as aimed by the closure concept. Additionally, increased and stable exercise tolerance after 45 days can be observed meaning no limitation of the cardiopulmonary system after LAAC. This effect is associated with absence of bleeding recurrence / need for hospitalization after LAAC in the follow up period.