J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

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Review

Volume 12, Number 10, October 2020, pages 647-654

How Can Galectin-3 as a Biomarker of Fibrosis Improve Atrial Fibrillation Diagnosis and Prognosis?

**Table 1.** Studies About Galectin-3 and Its Association With Fibrosis in Patients With Atrial Fibrillation
Author and year of publication	LE	GR	Type of study	Sample size	Parameters age (mean ± SD)	Comparison of Gal-3 levels	Results and P value	Conclusions
^ang/mL; ^bpg/mL. LE: level of evidence; GR: grade of recommendation; Gal-3: galectin-3; AF: atrial fibrillation; SD: standard deviation; AMI: Acute myocardial infarction.
Stanojevic et al, 2019 [17]	3B	B	Case-control	51	66.33 ± 11.34	8.41 ± 2.76 vs. 10.53 ± 2.75^a, P = 0.011	Patients with AF presented higher levels of Gal-3 when compared to those without AF (P < 0.05).	Patients with AF presented higher levels of Gal-3 than those without AF. Gal-3, as a fibrosis marker, could be a potential target in the treatment of patients with AMI.
Kang et al, 2018 [18]	3B	B	Case-control	30	57.9 ± 1.09 (control G)/67 ± 3.02 (case G)	0.51 ± 0.03 vs. 1.05 ± 0.08^a, P < 0.05	Elevation in the levels of Gal-3 is associated with the population with AF (P < 0.05).	Gal-3 plays an important role in myocardial fibrosis. Its inhibition could prevent myocardial fibrosis, effectively preventing myocardial remodeling.
Berger et al, 2017 [19]	2B	B	Prospective cohort	98	59.8 ± 8.6	194 vs. 126^a, P = 0.011	The increase in the level of Gal-3 after ablation was associated to a higher AF recurrence rate during the 2-year period after ablation (P = 0.014). Gal-3 is an independent predictor for AF (P = 0.035).	Circulating Gal-3 alterations above the baseline value can reflect the change in the arrhythmogenic substrate and predict the results of thoracoscopic ablation for AF.
Fashanu et al, 2017 [12]	2B	B	Prospective cohort	8,436	61.4 ± 5.4 (Q1)/62.2 ± 5.6 (Q2)/62.7 ± 5.6 (Q3)/64 ± 5.7 (Q4)	1.37 (1.05 - 1.78) vs. 1.67 (1.29 - 2.16)^a, P = 0.004	Gal-3 was associated with all risk factors for AF. High levels of Gal-3 were associated with increased risk of developing AF (P < 0.0001).	High levels of Gal-3 are associated to an increase in the incidence of AF in the general population.
Hernandez-Romero et al, 2017 [20]	1B	A	Prospective cohort	115	65.1 ± 9.5	14.25 ± 4.15 vs. 17.61 ± 6.84^a, P = 0.02	There is difference in levels of Gal-3 in patients with and without AF (P = 0.05). There is association between Gal-3 and fibrosis (P = 0.02). Elevated serum levels of Gal-3 are considered an independent predictor for fibrosis (P = 0.022).	Gal-3 is a biomarker of cardiac fibrosis. Atrial fibrosis is considered the only independent predictor for the development of AF.
Chen et al, 2016 [21]	3B	B	Case-control	131	68 ± 11(new AF)/71 ± 12 (chronic AF)	9.4 ± 3.3 vs. 8 ± 3.3^a, P = 0.04	Patients with new onset AF have elevated levels of Gal-3 when compared to patients with chronic AF (P = 0.05).	Gal-3 can be used as a biomarker for AF chronicity. Elevated levels of Gal-3 can stratify these patients in risk groups for the development of AF.
Clementy et al, 2016 [22]	2B	B	Prospective cohort	160	61 ± 10	13.5 ± 4.8 vs. 16.1 ± 6.6 ^a, P = 0.01	Elevated serum levels of Gal-3 were associated with AF (P = 0.0006), and as a predictive factor for AF recurrence after ablation (P = 0.02).	Higher levels of Gal-3 in patients with AF after ablation can predict independently AF new episodes recurrence and identify patients with low, medium and high risk.
Selcoki et al, 2016 [5]	3B	B	Case-control	84	59.1 ± 7.7 (control G)/59.8 ± 7.3 (case G)	1.38 (1.21- 1.87) vs. 1.21 (0.88 - 1.37)^a, P < 0.001	AF was associated to elevated Gal-3 levels. Serum levels of Gal-3 predicted 89.7% of patients with paroxysmal AF (P < 0.001).	Gal-3 is a potential mediator of cardiac fibrosis. Results suggest that serum levels of Gal-3 can be an indicator for AF. It was shown that AF leads to atrial fibrosis and remodeling.
Gurses et al, 2015 [10]	3B	B	Case-control	151	57.6 ± 11.1 (control G)/58.6 ± 9.2 (case G)	0.8 (0.4 - 1.4) vs. 0.5 (0.2 - 0.9)^a, P < 0.001	Patients with permanent AF presented fibrosis more frequently than patients with paroxysmal AF (P < 0.001). Levels of Gal-3 were elevated in patients with AF (P < 0.001).	Serum Gal-3 is significantly elevated in patients with AF with preserved left ventricular function.
Wu et al, 2015 [23]	3B	B	Case-control	96	46.1 ± 10.7 (control G)/48.9 ± 7.8 (case G)	3.63 ± 1.18 vs. 5.4 ± 2.24^a, P < 0.001	Association between an increase in levels of Gal-3 with AF (P = 0.001). Patients with AF recurrence presented elevated Gal-3 (P = 0.007). An increase in levels of Gal-3 as an independent predictor for AF occurrence after ablation (P = 0.007).	Plasmatic concentrations of Gal-3 provide an independent prognostic value for the prediction of AF recurrence after catheter ablation.
Yalcin et al, 2015 [11]	2C	B	Ecological study	33	58	0.549 ± 7.745^a, P < 0.001	Serum levels of Gal-3 were independently correlated with the extension of the fibrosis in patients with AF (P < 0.001).	It is suggested that Gal-3 has a mechanical role in the atrial electrical and structural remodeling in patients with AF.
Sonmez et al, 2014 [24]	3B	B	Case-control	85	70 ± 10 for both groups	1,166 (1,166 - 1,204) vs. 1,204 (1,166 - 1,362)^b, P = 0.001	Gal-3 as a fibrosis marker can predict the onset of the atrial remodeling process (P = 0.001).	It is suggested that Gal-3 can contribute for clinical and therapeutic treatment of AF as a new target for therapies that aim to decrease fibrosis in the atriums.

Table 1. Studies About Galectin-3 and Its Association With Fibrosis in Patients With Atrial Fibrillation

Author and year of publication

Type of study

Sample size

Parameters age (mean ± SD)

Comparison of Gal-3 levels

Results and P value

Conclusions

^ang/mL; ^bpg/mL. LE: level of evidence; GR: grade of recommendation; Gal-3: galectin-3; AF: atrial fibrillation; SD: standard deviation; AMI: Acute myocardial infarction.

Stanojevic et al, 2019 [17]

Case-control

66.33 ± 11.34

8.41 ± 2.76 vs. 10.53 ± 2.75^a, P = 0.011

Patients with AF presented higher levels of Gal-3 when compared to those without AF (P < 0.05).

Patients with AF presented higher levels of Gal-3 than those without AF. Gal-3, as a fibrosis marker, could be a potential target in the treatment of patients with AMI.

Kang et al, 2018 [18]

Case-control

57.9 ± 1.09 (control G)/67 ± 3.02 (case G)

0.51 ± 0.03 vs. 1.05 ± 0.08^a, P < 0.05

Elevation in the levels of Gal-3 is associated with the population with AF (P < 0.05).

Gal-3 plays an important role in myocardial fibrosis. Its inhibition could prevent myocardial fibrosis, effectively preventing myocardial remodeling.

Berger et al, 2017 [19]

Prospective cohort

59.8 ± 8.6

194 vs. 126^a, P = 0.011

The increase in the level of Gal-3 after ablation was associated to a higher AF recurrence rate during the 2-year period after ablation (P = 0.014). Gal-3 is an independent predictor for AF (P = 0.035).

Circulating Gal-3 alterations above the baseline value can reflect the change in the arrhythmogenic substrate and predict the results of thoracoscopic ablation for AF.

Fashanu et al, 2017 [12]

Prospective cohort

8,436

61.4 ± 5.4 (Q1)/62.2 ± 5.6 (Q2)/62.7 ± 5.6 (Q3)/64 ± 5.7 (Q4)

1.37 (1.05 - 1.78) vs. 1.67 (1.29 - 2.16)^a, P = 0.004

Gal-3 was associated with all risk factors for AF. High levels of Gal-3 were associated with increased risk of developing AF (P < 0.0001).

High levels of Gal-3 are associated to an increase in the incidence of AF in the general population.

Hernandez-Romero et al, 2017 [20]

Prospective cohort

115

65.1 ± 9.5

14.25 ± 4.15 vs. 17.61 ± 6.84^a, P = 0.02

There is difference in levels of Gal-3 in patients with and without AF (P = 0.05). There is association between Gal-3 and fibrosis (P = 0.02). Elevated serum levels of Gal-3 are considered an independent predictor for fibrosis (P = 0.022).

Gal-3 is a biomarker of cardiac fibrosis. Atrial fibrosis is considered the only independent predictor for the development of AF.

Chen et al, 2016 [21]

Case-control

131

68 ± 11(new AF)/71 ± 12 (chronic AF)

9.4 ± 3.3 vs. 8 ± 3.3^a, P = 0.04

Patients with new onset AF have elevated levels of Gal-3 when compared to patients with chronic AF (P = 0.05).

Gal-3 can be used as a biomarker for AF chronicity. Elevated levels of Gal-3 can stratify these patients in risk groups for the development of AF.

Clementy et al, 2016 [22]

Prospective cohort

160

61 ± 10

13.5 ± 4.8 vs. 16.1 ± 6.6 ^a, P = 0.01

Elevated serum levels of Gal-3 were associated with AF (P = 0.0006), and as a predictive factor for AF recurrence after ablation (P = 0.02).

Higher levels of Gal-3 in patients with AF after ablation can predict independently AF new episodes recurrence and identify patients with low, medium and high risk.

Selcoki et al, 2016 [5]

Case-control

59.1 ± 7.7 (control G)/59.8 ± 7.3 (case G)

1.38 (1.21- 1.87) vs. 1.21 (0.88 - 1.37)^a, P < 0.001

AF was associated to elevated Gal-3 levels. Serum levels of Gal-3 predicted 89.7% of patients with paroxysmal AF (P < 0.001).

Gal-3 is a potential mediator of cardiac fibrosis. Results suggest that serum levels of Gal-3 can be an indicator for AF. It was shown that AF leads to atrial fibrosis and remodeling.

Gurses et al, 2015 [10]

Case-control

151

57.6 ± 11.1 (control G)/58.6 ± 9.2 (case G)

0.8 (0.4 - 1.4) vs. 0.5 (0.2 - 0.9)^a, P < 0.001

Patients with permanent AF presented fibrosis more frequently than patients with paroxysmal AF (P < 0.001). Levels of Gal-3 were elevated in patients with AF (P < 0.001).

Serum Gal-3 is significantly elevated in patients with AF with preserved left ventricular function.

Wu et al, 2015 [23]

Case-control

46.1 ± 10.7 (control G)/48.9 ± 7.8 (case G)

3.63 ± 1.18 vs. 5.4 ± 2.24^a, P < 0.001

Association between an increase in levels of Gal-3 with AF (P = 0.001). Patients with AF recurrence presented elevated Gal-3 (P = 0.007). An increase in levels of Gal-3 as an independent predictor for AF occurrence after ablation (P = 0.007).

Plasmatic concentrations of Gal-3 provide an independent prognostic value for the prediction of AF recurrence after catheter ablation.

Yalcin et al, 2015 [11]

Ecological study

0.549 ± 7.745^a, P < 0.001

Serum levels of Gal-3 were independently correlated with the extension of the fibrosis in patients with AF (P < 0.001).

It is suggested that Gal-3 has a mechanical role in the atrial electrical and structural remodeling in patients with AF.

Sonmez et al, 2014 [24]

Case-control

70 ± 10 for both groups

1,166 (1,166 - 1,204) vs. 1,204 (1,166 - 1,362)^b, P = 0.001

Gal-3 as a fibrosis marker can predict the onset of the atrial remodeling process (P = 0.001).

It is suggested that Gal-3 can contribute for clinical and therapeutic treatment of AF as a new target for therapies that aim to decrease fibrosis in the atriums.