Effects of Persistent Atrial Fibrillation on Serum Galectin-3 Levels

doi:10.1016/j.amjcard.2014.12.021

The American Journal of Cardiology

Volume 115, Issue 5, 1 March 2015, Pages 647-651

https://doi.org/10.1016/j.amjcard.2014.12.021 Get rights and content

Galectin-3 is known to play an important role in a number of fibrotic conditions, including cardiac fibrosis. Many studies have focused on the association between galectin-3 levels and cardiac fibrosis in heart failure. However, the role of galectin-3 in the pathogenesis of atrial fibrillation (AF) has not been evaluated thoroughly yet. The aim of this study was to determine whether serum galectin-3 levels were elevated in patients with AF and preserved left ventricular function. Seventy-six patients with paroxysmal or persistent AF and preserved left ventricular systolic function and 75 age- and gender-matched control subjects were enrolled in this observational study. Galectin-3 levels were measured by enzyme-linked immunosorbent assay. Serum galectin-3 (median 0.6 ng/ml [interquartile range 0.2 to 1.4] vs 0.5 ng/ml [interquartile range 0.1 to 0.7], p <0.001) and left atrial volume index (LAVI) (mean 29.5 ± 3.5 vs 26.5 ± 2.5 ml/m², p <0.001) were significantly greater in patients with AF compared with the control group. Serum galectin-3 levels were also significantly higher in patients with persistent AF than those with paroxysmal AF (median 0.8 ng/ml [interquartile range 0.4 to 1.4] vs 0.5 ng/ml [interquartile range 0.2 to 0.9], p <0.001). Multivariate regression analysis demonstrated that serum galectin-3 (odds ratio 87.53, 95% confidence interval 6.06 to 1,265.03, p = 0.001) and LAVI (odds ratio 1.38, 95% confidence interval 1.19 to 1.60, p <0.001) were independent predictors of AF. Only LAVI was independently correlated with serum galectin-3 levels in patients with AF in linear regression analysis. In conclusion, serum galectin-3 is significantly elevated and is also significantly correlated with LAVI in patients with AF with preserved left ventricular function.

Section snippets

Methods

Seventy-six patients with paroxysmal or persistent AF and preserved LV function and 75 age- and gender-matched control subjects were enrolled in this observational study. AF episodes either lasting >7 days or requiring termination by cardioversion, either with drugs or by direct-current cardioversion, were defined as persistent, whereas AF episodes self-terminating within 7 days were defined as paroxysmal.¹³ The control group consisted of subjects without histories of any disease who underwent

Results

Seventy-six patients with AF with preserved LV function and 75 age- and gender-matched control subjects were included in the study. Baseline demographic, clinical, laboratory, and echocardiographic parameters of the study population are listed in Table 1. Serum galectin-3 (median 0.6 ng/ml [IQR 0.2 to 1.4] vs 0.5 ng/ml [0.1 to 0.7], p <0.001) and LAVI (mean 29.5 ± 3.5 vs 26.5 ± 2.5 ml/m², p <0.001) were significantly elevated in patients with AF compared with the control group.

Serum galectin-3

Discussion

In this observational study, we demonstrated that serum galectin-3 was significantly elevated in patients with AF with preserved LV function. Galectin-3 levels were also higher in patients with persistent AF compared with those with paroxysmal AF and were independently correlated with LAVI. This is the first study to investigate this relation.

Electrical, contractile, and structural remodeling are known to be important contributors to the AF substrate,15, 16, 17 and fibrosis is the hallmark of

Disclosures

The authors have no conflicts of interest to disclose.

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Cited by (63)

L1 cell adhesion molecule may be a protective molecule for atrial fibrillation in patients with valvular heart disease
2023, Heliyon
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia. L1 cell adhesion molecule (L1CAM) served as a crucial regulator of signaling pathways. This research sought to examine the clinical value and functions of soluble L1CAM in the serum of AF patients.
In total, 118 patients (valvular heart disease patients [VHD, total: n = 93; AF: n = 47; sinus rhythm (SR): n = 46] and healthy controls [n = 25]) were recruited in this retrospective study. Plasma levels of L1CAM were detected by enzyme-linked immunosorbent assays. The Pearson's correlation approach, as applicable, was used for analyzing the correlations. The L1CAM was shown to independently serve as a risk indicator of AF in VHD after being analyzed by the multivariable logistic regression. To examine the specificity and sensitivity of AF, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used. A nomogram was developed for the visualisation of the model. We further evaluate the prediction model for AF using calibration plot and decision curve analysis.
The plasma level of L1CAM was substantially decreased in AF patients as opposed to healthy control and SR patients (healthy control = 46.79 ± 12.55 pg/ml, SR = 32.86 ± 6.11 pg/ml, AF = 22.48 ± 5.39 pg/ml; SR vs. AF, P < 0.001; control vs. AF, P < 0.001). L1CAM was significantly and negatively correlated with LA and NT-proBNP (LA: r = −0.344, P = 0.002; NT-proBNP: r = −0.380, P = 0.001). Analyses using logistic regression showed a substantial correlation between L1CAM and AF in patients with VHD (For L1CAM, Model 1: OR = 0.704, 95%CI = 0.607–0.814, P < 0.001; Model 2: OR = 0.650, 95% CI = 0.529–0.798, P < 0.001; Model 3: OR = 0.650, 95% CI = 0.529–0.798, P < 0.001). ROC analysis showed that inclusion of L1CAM in the model significantly improved the ability of other clinical indicators to predict AF. The predictive model including L1CAM, LA, NT-proBNP and LVDd had excellent discrimination and a nomogram was developed. The model had good the calibration and clinical utility.
L1CAM was shown to independently serve as a risk indicator for AF in VHD. In AF patients with VHD, the prognostic and predictive effectiveness of models incorporating L1CAM was satisfactory. Collectively, L1CAM may be a protective molecule for atrial fibrillation in patients with valvular heart disease.
Galectin-3 is an independent predictor of postoperative atrial fibrillation and survival after elective cardiac surgery
2022, Heart Rhythm
Citation Excerpt :
The present study extends current knowledge of galectin-3 and AF as well as of the pathogenesis of POAF in general. Galectin-3 levels are known to be elevated in patients with AF compared with control subjects and are particularly high in patients with persistent AF,18 LA enlargement,18 and advanced atrial fibrosis.13 Galectin-3 levels also predict future AF14 as well as the recurrence of AF after catheter ablation19,20 and after electrical cardioversion.21
Postoperative atrial fibrillation (POAF) is a frequent complication after heart surgery and is associated with thromboembolic events, prolonged hospital stay, and adverse outcomes. Inflammation and fibrosis are involved in the pathogenesis of atrial fibrillation.
The purpose of this study was to assess whether galectin-3, which reflects preexisting atrial fibrosis, has the potential to predict POAF and mortality after cardiac surgery.
Four hundred seventy-five consecutive patients (mean age 67.4 ± 11.8 years; 336 (70.7%) male) undergoing elective heart surgery at the Medical University of Vienna were included in this prospective single-center cohort study. Galectin-3 plasma levels were assessed on the day before surgery.
The 200 patients (42.1%) who developed POAF had significantly higher galectin-3 levels (9.60 ± 6.83 ng/mL vs 7.10 ± 3.54 ng/mL; P < .001). Galectin-3 significantly predicted POAF in multivariable logistic regression analysis (adjusted odds ratio per 1-SD increase 1.44; 95% confidence interval 1.15–1.81; P = .002). During a median follow-up of 4.3 years (interquartile range 3.4–5.4 years), 72 patients (15.2%) died. Galectin-3 predicted all-cause mortality in multivariable Cox regression analysis (adjusted hazard ratio per 1-SD increase 1.56; 95% confidence interval 1.16–2.09; P = .003). Patients with the highest-risk galectin-3 levels according to classification and regression tree analysis (>11.70 ng/mL) had a 3.3-fold higher risk of developing POAF and a 4.4-fold higher risk of dying than did patients with the lowest-risk levels (≤5.82 ng/mL).
The profibrotic biomarker galectin-3 is an independent predictor of POAF and mortality after cardiac surgery. This finding highlights the role of the underlying arrhythmogenic substrate in the genesis of POAF. Galectin-3 may help to identify patients at risk of POAF and adverse outcome after cardiac surgery.
Research progress on the role of gal-3 in cardio/cerebrovascular diseases
2021, Biomedicine and Pharmacotherapy
Citation Excerpt :
Recently, other studies found that the average value of gal-3 in the serum of patients with AF was significantly higher compared to those with sinus rhythm [23,24]. Further studies also found that levels of gal-3 were positively correlated with the duration of AF and with left atrial diameter [25]. Moreover, serum gal-3 levels were associated with the presence of spontaneous echo contrast (SEC) (P < 0.01) and left atrial thrombus (P = 0.08) [26].
Galectin-3 (gal-3), a member of the galectin family, is a glycoprotein with high affinity for β-galactoside. Gal-3 is a cytoplasmically synthesized protein that can shuttle between the cytoplasm and nucleus and can even be transported to the membrane and secreted into the extracellular environment. Cardio/cerebrovascular diseases generally refer to ischemic or hemorrhagic diseases occurring in the heart, brain and systemic tissues, which are characterized by high morbidity, high disability rates and high mortality rates. To date, considerable research has demonstrated that gal-3 expression is aberrantly increased and plays important roles in cardio/cerebrovascular diseases, such as acute ischemic stroke (AIS), myocardial fibrosis, acute coronary syndrome (ACS), and heart failure (HF). Hence, understanding the biological roles of gal-3 in these diseases may be essential for cardio/cerebrovascular disease treatment and diagnosis to improve patient quality of life. In this review, we summarize current research on the roles of gal-3 in human cardiovascular diseases and potential inhibitors of gal-3, which may provide new strategies for disease therapies.
The Atrium and Embolic Stroke: Myopathy Not Atrial Fibrillation as the Requisite Determinant?
2020, JACC: Clinical Electrophysiology
Citation Excerpt :
Similarly, Galectin (Gal)-3 a β-galactoside binding lectin, has also been implicated in cardiac fibrosis through its role in recruitment of macrophages and fibroblasts. Gal-3 is an independent predictor of AF, conversely an increased LA volume index was independently predictive of Gal-3 (92). Both TGF-β1 and Gal-3 are independently associated with LA fibrosis, and delayed enhancement CMR in patients with AF appear to support these findings (93).
Atrial fibrillation (AF) is well-recognized in the pathophysiology of left atrial thrombogenesis and resultant cardioembolic stroke. Subclinical AF is believed to account for a significant proportion of embolic stroke. However, recent randomized control trials failed to demonstrate a significant benefit for oral anticoagulation, in an unselected population with embolic stroke of undetermined source. This has reinvigorated the focus on finding robust markers to identify patients at risk of cardioembolic stroke. Several nonfibrillatory atrial electrical markers, along with structural and biochemical abnormalities, have been associated with ischemic stroke, independently of AF. An increasingly complex relationship exists among vascular risk factors, atrial remodeling, and thrombogenesis. Identifying robust markers of an underlying atrial myopathy may allow for early identification of patients at risk for cardioembolic stroke. This review outlines the inconsistencies in the evidence for AF as the prerequisite for left atrial thrombogenesis and embolic stroke. It will highlight the current evidence and controversies for adverse atrial remodeling, independent from rhythm, as a plausible mechanism for left atrial thrombogenesis and ischemic stroke.
The role of galectin-3 in atrial fibrillation
2023, Journal of Molecular Medicine
The Role of Galectin-3 in Heart Failure—The Diagnostic, Prognostic and Therapeutic Potential—Where Do We Stand?
2023, International Journal of Molecular Sciences

View all citing articles on Scopus

: This project was funded by Hacettepe University Scientific Research Projects Coordination Unit (grant number 1993).

: See page 650 for disclosure information.

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Arrhythmias and Conduction DisturbancesEffects of Persistent Atrial Fibrillation on Serum Galectin-3 Levels

Section snippets

Methods

Results

Discussion

Disclosures

Clin Chim Acta

J Am Coll Cardiol

J Card Fail

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Heart Rhythm

Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction

Circulation

Galectin-3: a novel blood test for the evaluation and management of patients with heart failure

Rev Cardiovasc Med

Plasma galectin 3 and heart failure risk in the Physicians' Health Study

Eur Heart Fail

Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: a pooled analysis of 3 clinical trials

Am Heart J

Histological substrate of atrial biopsies in patients with lone atrial fibrillation

Circulation

Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease

Heart

Arrhythmias and Conduction Disturbances
Effects of Persistent Atrial Fibrillation on Serum Galectin-3 Levels