Novel fibro-inflammation markers in assessing left atrial remodeling in non-valvular atrial fibrillation

Abstract

BackgroundStructural remodeling is associated with the fibroinflammatory process in the atrial extracellular matrix. In the present study we aimed to investigate whether serum levels of new circulating remodeling markers differ in patients with atrial fibrillation (AF) compared to patients with sinus rhythm.Material/MethodsThe study population included 52 patients diagnosed with non-valvular AF and 33 age-matched patients with sinus rhythm. Serum levels of Galectin-3, matrix metalloproteinase-9 (MMP-9), lipocalin-2 (Lcn2/NGAL), N-terminal propeptide of type III procollagen (PIIINP), Hs-Crp, and neutrophil-to-lymphocyte ratio (NLR) were measured. The left atrial volume (LAV) was calculated by echocardiographic method and LAV index was calculated.ResultsGalectin-3, MMP-9, and PIIINP levels were significantly higher in AF patients except NGAL levels (1166 pg/ml (1126–1204) and 1204 pg/ml (1166–1362) p=0.001, 104 (81–179) pg/ml and 404 (162–564) pg/ml p<0.0001, and 1101 (500–1960) pg/ml and 6710 (2370–9950) pg/ml p<0.0001, respectively). The NLR and Hs-CRP levels were also higher in AF (2.1±1.0 and 2.7±1.1 p=0.02 and 4.2±1.9 mg/L and 6.0±4.7 mg/L p=0.04, respectively). In correlation analyses, NLR showed a strongly significant correlation with LAVi, but Hs-CRP did not (p=0.007 r=0.247, Pearson test and p=0.808 r=0.025, Pearson test, respectively). Moreover, Galectin-3, MMP-9, and PIIINP had a strong positive correlation with LAVi (p=0.021 r=640, Spearman test and p=0.004 r=0.319 Pearson test, and p=0.004 r=0.325 Pearson test, respectively).ConclusionsNovel fibrosis and inflammation markers in AF are correlated with atrial remodeling. Several unexplained mechanisms of atrial remodeling remain, but the present study has taken the first step in elucidating the mechanisms involving fibrosis and inflammation markers.

Galectin-3 and incidence of atrial fibrillation: The Atherosclerosis Risk in Communities (ARIC) study

“…Galectin-3 has been associated with atrial remodeling in AF patients 9 , with AF recurrence in patients who have undergone ablation, 11 with cardiometabolic disease 26 , and with AF prevalence in case-control studies. 9,27,28 On the other hand, 2 prior prospective epidemiological studies failed to find an independent association between galectin-3 levels and the incidence of AF. 12,15 In both studies, higher galectin-3 concentrations were associated with an increased risk of AF in individuals in unadjusted analyses, but not after adjustment for other AF risk factors.…”

“…7 Inhibition of galectin-3 has been shown to interfere with myocardial fibrogenesis, and some have suggested it might be a therapeutic target for AF. 8 Galectin-3 has been associated with atrial remodeling in AF patients 9 and outcomes after catheter ablation of atrial AF. 10,11 Recent epidemiologic studies have shown that blood levels of galectin-3 are associated positively with incident heart failure (HF) and coronary heart disease (CHD), 6,12–14 but to our knowledge, only 2 prospective studies of exclusively whites have tested whether galectin-3 concentrations are associated with incident AF.…”

Role of Inflammation in Atrial Fibrillation Pathophysiology and Management

“…41 Serum levels of the fibro-inflammatory biomarkers MMP-9, type III procollagen, and hs-CRP, were greater in persistent-AF patients than in SR controls, and positively correlated with echocardiographic left atrial volume, an index of atrial remodeling. 42 After AF ablation, serum levels of some fibro-inflammatory biomarkers (hs-CRP and IL-6) decreased in patients without AF recurrence, whereas others (tissue inhibitor of metalloproteinase-2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), carboxyl-terminal telopeptide of collagen type I) increased. 43 Baseline MMP-2 levels were greater in those with recurrence.…”

Atrial remodelling in heart failure: recent developments and relevance for heart failure with preserved ejection fraction

“…However, to date, the exact relation between the extent and severity of low‐voltage regions and the degree of LA fibrosis/remodelling needs further clarification. Biomarkers have been used as a surrogate for atrial remodelling, reflecting mechanical stress, fibrosis, or inflammation; but individual markers to date lack atrial specificity 13, 14, 15…”