High Plasma Concentrations of Transforming Growth Factor-.BETA. and Tissue Inhibitor of Metalloproteinase-1 - Potential Non-Invasive Predictors for Electroanatomical Remodeling of Atrium in Patients With Non-Valvular Atrial Fibrillation -

Abstract

Background:The degree of electroanatomical remodeling of the left atrial (LA) affects the clinical outcome after rhythm control of atrial fibrillation (AF). Our hypothesis was that plasma concentrations of transforming growth factor (TGF)-β and tissue inhibitor of metalloproteinase (TIMP)-1 reflect LA voltage and structural remodeling in patients with non-valvular AF. Methods and Results:In the study, 242 patients (male 79.4%, 55.1±11.0 years old) with AF (155 paroxysmal AF, 87 persistent AF) underwent catheter ablation. Pre-ablation plasma concentrations of TGF-β and TIMP-1 and the degree of electroanatomical remodeling quantified by LA voltage map (NavX) and 3D-CT were evaluated. The mean LA voltage and volume were compared in patients with high TGF-β (≥10.0 ng/ml, H-TGF) vs. low TGF-β (<10.0 ng/ml, L-TGF) and high TIMP-1 (≥1.1 ng/ml, H-TIMP) vs. low TIMP-1 (<1.1 ng/ml, L-TIMP). Patients with H-TGF had lower mean LA voltage (P=0.014) and greater LA volume (P=0.022), particularly, posterior venous LA volume (P=0.005) than those with L-TGF. In patients with H-TIMP, the mean LA voltage (P=0.019) was lower than those with L-TIMP. LA volume was significantly higher (P<0.001) in patients with ejection fraction ≤58% than those with >58%. Conclusions:In patients with non-valvular AF, high plasma concentrations TGF-β and TIMP-1 and low ejection fraction were closely related with electroanatomical remodeling of LA. (Circ J 2011; 75: 557 - 564)

Triggered Firing and Atrial Fibrillation in Transgenic Mice With Selective Atrial Fibrosis Induced by Overexpression of TGF-β1

“…14–16 Transgenic (Tx) mice with cardiac-restricted expression of a constitutively active form of TGF- β 1 (MHC-TGFcys 33 ser mice) have increased atrial fibrosis 17 and significantly increased vulnerability to AF by rapid pacing. 18 However, it is unclear if fibrosis promotes spontaneous (non-paced) AF, and whether or not CTTF is important in spontaneous AF in this model.…”

Association of Plasma Transforming Growth Factor-β1 Levels and the Risk of Atrial Fibrillation: A Meta-Analysis

“…TGF-β1 is a major factor promoting collagen production in cardiac fibroblasts [ 27 ]. It is also considered to be a key factor in the signal cascade reaction during the process of tissue fibrosis [ 28 , 29 ]. Multiple studies have found increased atrial fibrosis on biopsy or autopsy specimens of patients with AF and concurrently elevated plasma level of TGF-β1 [ 30 , 31 , 32 ].…”

Mitochondrial DNA 4977bp Deletion Mutation in Peripheral Blood Reflects Atrial Remodeling in Patients with Non-Valvular Atrial Fibrillation

“…This is especially true in chronic degenerative diseases like AF. Several protein biomarkers have been shown to reflect various aspects of AF, such as electro-anatomical remodeling 37 or chronicity. 38 However, multiple confounding factors, such as transient inflammation and associated systemic disease, affect plasma levels of these protein biomarkers and ultimately prevent effective and accurate use in the clinic.…”