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.

A multicenter registry for the purpose of research collaboration of this rare disease was established, with the University of Michigan serving as the coordinating center for this study. This registry was © 2014 American Heart Association, Inc. Original Article Circ Arrhythm ElectrophysiolBackground-The purpose of this study was to assess whether delayed enhancement (DE) on MRI is associated with ventricular tachycardia (VT)/ventricular fibrillation or death in patients with cardiac sarcoidosis and left ventricular ejection fraction >35%. Methods and Results-Fifty-one patients with cardiac sarcoidosis and left ventricular ejection fraction >35% underwent DE-MRI. DE was assessed by visual scoring and quantified with the full-width at half-maximum method. The patients were followed for 48.0±20.2 months. Twenty-two of 51 patients (63%) had DE. Forty patients had no prior history of VT (primary prevention cohort). Among those, 3 patients developed VT and 2 patients died. DE was associated with risk of VT/ventricular fibrillation or death (P=0.0032 for any DE and P<0.0001 for right ventricular DE). The positive predictive values of the presence of any DE, multifocal DE, and right ventricular DE for death or VT/ventricular fibrillation at mean follow-up of 48 months were 22%, 48%, and 100%, respectively. Among the 11 patients with a history of VT before the MRI, 10 patients had subsequent VTs, 1 of whom died. approved by all institutional review boards with data use agreements in place. Using previously published criteria, 5,6 patients who met diagnostic criteria for CS were identified. Patients from the University of Michigan, Henry Ford Hospital, University of Colorado, Johns Hopkins University, and Virginia Commonwealth University were included. Medical records were reviewed to identify patients who had cardiac MRIs, a left ventricular (LV) ejection fraction >35%, and ≥6 months of follow-up. Stored electrograms documenting arrhythmia episodes were reviewed to confirm appropriateness of ICD therapies (antitachycardia pacing or ICD discharge). Electrocardiograms and stored electrograms were analyzed, and ventricular arrhythmias were classified as monomorphic ventricular tachycardia (VT), polymorphic VT, or ventricular fibrillation (VF). Ventricular arrhythmia in the non-ICD group was defined as cardiac arrest, VT lasting ≥30 seconds or requiring defibrillation. VT/VF storm was defined as ≥3 episodes of VT/VF in a 24-hour period. Conclusions-RV DE in patients with cardiac sarcoidosis is associated with a risk of adverse events in patients with Cardiac MRIAll patients underwent cardiac MRI, including cine imaging of cardiac morphology and function and DE-MRI. All studies were performed on 1.5 Tesla scanners (Signa Excite CV/i; General Electric; Milwaukee, Wisconsin; Magnetom Sonata; Siemens Medical Solutions; Erlangen, Germany, Philips Healthcare, Best, The Netherlands). Cine imaging was performed in ventricular short-and long-axis planes using a segmented 2D steady-statefree-precession pulse sequence (repetition time,...

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• Increased epicardial fat is associated with presence and chronicity of atrial fibrillation • Extensive epicardial fat is associated with earlier recurrences of AF after ablation • Extensive epicardial fat may reduce transmurality of ablation by affecting current dynamics.