Dataset Information

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes.

ABSTRACT:

Objectives

To determine whether Gal-3 mediates sustained atrial fibrillation (AF)-induced atrial structural and electrical remodeling and contributes to AF perpetuation.

Background

Galectin-3 (Gal-3) mediates extracellular matrix remodeling in heart failure, but its role in AF progression remains unexplored.

Methods

We examined intracardiac blood samples from patients with AF (N=55) to identify potential biomarkers of AF recurrence. In a sheep model of tachypacing-induced AF (N=20), we tested the effects of Gal-3 inhibition during AF progression.

Results

In patients, intracardiac serum Gal-3 levels were greater in persistent than paroxysmal AF and independently predicted atrial tachyarrhythmia recurrences after a single ablation procedure. In the sheep model, both Gal-3 and TGF-β1 were elevated in the atria of persistent AF animals. The Gal-3 inhibitor GM-CT-01 (GMCT) reduced both Gal-3 and TGF-β1-induced sheep atrial fibroblast migration and proliferation in vitro. GMCT (12 mg/kg twice/week) prevented the increase in serum procollagen type III N-terminal peptide seen during progression to persistent AF, and also mitigated atrial dilatation, myocyte hypertrophy, fibrosis, and the expected increase in dominant frequency of excitation. Atria of GMCT-treated animals had significantly less TGF-β1-Smad2/3 signaling pathway activation and expression of α-smooth muscle actin and collagen than saline-treated animals. Ex-vivo hearts from GMCT-treated animals had significantly longer action potential durations and fewer rotors and wavebreaks during AF, and myocytes had lower functional expression of inward rectifier K⁺ channel (Kir2.3) than saline-treated animals. Importantly, GMCT increased the probability of spontaneous AF termination, decreased AF inducibility and reduced overall AF burden.

Conclusions

Inhibiting Gal-3 during AF progression might be useful as an adjuvant treatment to improve outcomes of catheter ablation for persistent AF. Gal-3 inhibition may be a potential new upstream therapy for prevention of AF progression.

SUBMITTER: Takemoto Y

PROVIDER: S-EPMC4979747 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes.

Takemoto Yoshio Y Ramirez Rafael J RJ Yokokawa Miki M Kaur Kuljeet K Ponce-Balbuena Daniela D Sinno Mohamad C MC Willis B Cicero BC Ghanbari Hamid H Ennis Steven R SR Guerrero-Serna Guadalupe G Henzi Bettina C BC Latchamsetty Rakesh R Ramos-Mondragon Roberto R Musa Hassan H Martins Raphael P RP Pandit Sandeep V SV Noujaim Sami F SF Crawford Thomas T Jongnarangsin Krit K Pelosi Frank F Bogun Frank F Chugh Aman A Berenfeld Omer O Morady Fred F Oral Hakan H Jalife José J

JACC. Basic to translational science 20160401 3

<h4>Objectives</h4>To determine whether Gal-3 mediates sustained atrial fibrillation (AF)-induced atrial structural and electrical remodeling and contributes to AF perpetuation.<h4>Background</h4>Galectin-3 (Gal-3) mediates extracellular matrix remodeling in heart failure, but its role in AF progression remains unexplored.<h4>Methods</h4>We examined intracardiac blood samples from patients with AF (<i>N=55</i>) to identify potential biomarkers of AF recurrence. In a sheep model of tachypacing-in ...[more]

PMID: 27525318

Similar Datasets

Project description:BackgroundThe echocardiographic parameters total atrial conduction time (PA-TDI duration), left atrial (LA) volume index (LAVI), and LA strain reflect adverse atrial remodeling and predict atrial fibrillation (AF).ObjectivesThe aim of this study was to investigate echocardiographic parameters indicating reverse LA remodeling and potential associations with AF recurrence after pulmonary vein isolation (PVI).MethodsThis prospective observational study consecutively enrolled patients scheduled for PVI for symptomatic AF. Electrocardiogram (ECG) test and transthoracic echocardiography were performed the day before and after PVI and again 3 months later. AF recurrence was determined by Holter ECG at 3 months, and telephone follow-up at 12 months, after PVI. The parameters of LA remodeling [PA-TDI, LAVI, and LA strain analysis: reservoir strain (LASr), conduit strain (LAScd), contraction strain (LASct)] were determined by transthoracic echocardiography.ResultsA total of 48 patients were included in the study (mean age: 61.4 ± 12.2 years). PA-TDI significantly decreased the day after PVI compared with the baseline (septal PA-TDI 103 ± 13 vs. 82 ± 14.9 ms, p ≤ 0.001; lateral PA-TDI 122.4 ± 14.8 vs. 106.9 ± 14.4 ms, p ≤ 0.001) and at the 3-month follow-up (septal PA-TDI: 77.8 ± 14.5, p ≤ 0.001; lateral PA-TDI 105.2 ± 16.1, p ≤ 0.001). LAVI showed a significant reduction at the 3-month follow-up compared with the baseline (47.7 ± 14.4 vs. 40.5 ± 9.7, p < 0.05). LASr, LAScd, and LASct did not change after PVI compared with the baseline. AF recurred in 10 patients after PVI (21%). Septal PA-TDI, septal a', and LAVI/a' determined the day after PVI were associated with AF recurrence.ConclusionChanges in echocardiographic parameters of LA remodeling and function indicate that functional electromechanical recovery preceded morphological reverse remodeling of the left atrium after PVI. Furthermore, these changes in echocardiographic parameters indicating LA reverse remodeling after PVI may identify patients at high risk of AF recurrence.

Dataset Information

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes.

Objectives

Background

Methods

Results

Conclusions

Publications

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes.

Similar Datasets

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