Dynamics of Galectin-3 serum levels after percutaneous occlusion of the left atrial appendage: a new surrogate parameter for successful LAA closure?
Authors: Haertel F , Ijuin S , Lustermann P , Gruen K , Hamadanchi A , Schulze C , Franz M , Moebius-Winkler S 
Published: November 2020

Abstract

Introduction
Left atrial cardiac tissue remodeling following left atrial appendage closure (LAAC) is a scientifically neglected phenomenon until now but might have impact on functional outcome of patients suffering from atrial fibrillation (AF). Thus, our study is focused on quantification of key biomarkers reflecting fibrosis development as a major component within cardiovascular tissue remodeling.

Methods
Patients (CHA2DS2VASC score ≥1, HASBLED score ≥3) with bleeding complications under anticoagulation therapy and therefore eligible for LAAC were included in the present study. Serum levels of biomarkers of cardiac fibrosis and remodeling (Galectin-3, ST2/IL-2, ST2/IL-1, 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 functional outcome, all patients performed a 6-minutes walk test (6- MWT). Transesophageal echocardiography (TEE) was carried out to assess success of the LAAC procedure regarding peri-device leakage (PDL).

Results
We included 33 patients (age: 73.5±6.7 years; 21 men (64%) and 12 women (36%); BMI: 29.1±5.1 kg/m2; CHA2DS2VASC score: 4.2±1.2; left ventricular ejection fraction: 61.1±9.3%; mean occluder size: 25.9±3.9 mm; type of AF: 46% paroxysmal (15 patients), 55% permanent (18 patients)). Complete LAAC (without any residual low) was achieved in 60% (19 patients) after 45 days and in 87% (29 patients) after 6 months. 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, patients with PDL 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. The walking distance measured by the 6-MWT increased significantly from 298.5±89.5 meters at baseline to 335.5±95.1 meters (p=0.04) after 45d and remained significantly elevated after 6M (346.7±122.7 meters; p=0.02).

Conclusion
The implantation of an LAA occluder device is accompanied by significantly increased circulating levels of the fibrosis biomarker Galectin-3 after 45 days in patients with AF. The regression in serum levels after 6 months probably reflects a successful fibrotic remodeling in the left atrial appendage over time and might be used as surrogate parameter for LAAC success. Increased and stable exercise tolerance after 45 days can be observed.

Funding Acknowledgement
Type of funding source: None