Galectin 3 – ABC CARDIOL

ABC

Original Article

Predictors of Total Mortality and Serious Arrhythmic Events in Non-Ischemic Heart Failure Patients: The Role of Galectin-3

Adriano Nunes Kochi et al. Mauricio Pimentel Michael Andrades Tiago Zimerman … Leandro Ioschpe Zimerman Luis Eduardo Rohde

Abstract

Background:

Risk stratification remains clinically challenging in patients with heart failure (HF) of non-ischemic etiology. Galectin-3 is a serum marker of fibrosis that might help in prognostication.

Objective:

To determine the role of galectin-3 as a predictor of major arrhythmic events and overall mortality.

Methods:

We conducted a prospective cohort study that enrolled 148 non-ischemic HF patients. All patients underwent a comprehensive baseline clinical and laboratory assessment, including levels of serum galectin-3. The primary outcome was the occurrence of arrhythmic syncope, appropriate implantable cardioverter defibrillator therapy, sustained ventricular tachycardia, or sudden cardiac death. The secondary outcome was all-cause death. For all statistical tests, a two-tailed p-value<0.05 was considered significant.

Results:

In a median follow-up of 941 days, the primary and secondary outcomes occurred in 26 (17.5%) and 30 (20%) patients, respectively. Serum galectin-3>22.5 ng/mL (highest quartile) did not predict serious arrhythmic events (HR: 1.98, p=0.152). Independent predictors of the primary outcome were left ventricular end-diastolic diameter (LVEDD)>73mm (HR: 3.70, p=0.001), exercise periodic breathing (EPB) on cardiopulmonary exercise testing (HR: 2.67, p=0.01), and non-sustained ventricular tachycardia (NSVT)>8 beats on Holter monitoring (HR: 3.47, p=0.027). Predictors of all-cause death were galectin-3>22.5 ng/mL (HR: 3.69, p=0.001), LVEDD>73mm (HR: 3.35, p=0.003), EPB (HR: 3.06, p=0.006), and NSVT>8 beats (HR: 3.95, p=0.007). The absence of all risk predictors was associated with a 91.1% negative predictive value for the primary outcome and 96.6% for total mortality.

Conclusions:

In non-ischemic HF patients, elevated galectin-3 levels did not predict major arrhythmic events but were associated with total mortality. Absence of risk predictors revealed a prevalent subgroup of HF patients with an excellent prognosis.

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ABC

Editorial

The Challenge of Assessing Sudden Cardiac Death Risk in Patients with Nonischemic Heart Failure

Pedro Pimenta de Mello Spineti et al. Rodrigo Souto da Silva Sá Bruno Reznik Wajsbrot

Sudden cardiac death (SCD) accounts for approximately 50% of deaths in patients with ischemic and nonischemic heart disease in the presence of severe left ventricular systolic dysfunction. Many clinical trials^– have evaluated the effectiveness of implantable cardioverter defibrillators (ICDs) in primary prevention of SCD in the last 20 years.

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure (SCD-HeFT) defined the principles for indication^, of ICDs in primary prophylaxis of SCD of patients with heart failure (HF) of ischemic etiology. On the other hand, clinical trials evaluating patients with HF of nonischemic origin^,^– have shown heterogeneous results and, so far, there are uncertainties on the best candidates for this type of therapy.

[…]

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ABC

Editorial

Does Galectin-3 (Myocardial Fibrosis Biomarker) Predict Progression in Chagas Disease?

Roberto Coury Pedrosa

In recent decades, the epidemiology of Chagas disease (Chd) has changed significantly as a consequence of urbanization and migration. In Brazil, to date, it is the neglected disease with the highest burden, of which ~30% of individuals will progress to the symptomatic tissue disruptive stage within 20 – 30 years after being infected (around 2% per year progress from the indeterminate to the cardiac form, according to a contemporary study).

Persistent myocardial inflammation and fibrosis represent the main pathological characteristics of Chd that would be correlated with its progression.^, The use of myocardial fibrosis biomarkers to predict progression in patients with normal or near normal LV function is certainly important in Chd, where traditional risk factors, such as LVEF, may not be as useful. Nevertheless, studies have shown the value of myocardial fibrosis biomarkers in the progression of Chd pathogenesis.

[…]

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ABC

Original Article

Galectin-3 Associated with Severe Forms and Long-term Mortality in Patients with Chagas Disease

Fábio Fernandes et al. Carlos Henrique Valente Moreira Lea Campos Oliveira Marcela Souza-Basqueira … Barbara Maria Ianni Claudia di Lorenzo Felix José Alvarez Ramires Luciano Nastari Edecio Cunha-Neto Antonio L. Ribeiro Renato Delascio Lopes Sheila M. Keating Ester Cerdeira Sabino Charles Mady

Abstract

Background

The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD.

Objectives

We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality.

Methods

We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman’s correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant.

Results

The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio – HR 3.11; 95%CI 1.21–8.04; p=0.019).

Conclusions

In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)

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ABC

Original Article

Galectin-3 Levels in Patients with Chronic Constrictive Pericarditis

Fábio Fernandes et al. Dirceu Thiago Pessoa de Melo Felix José Alvarez Ramires Ester Cerdeira Sabino … Carlos Henrique Valente Moreira Luiz Alberto Benvenutti Viviane Tiemi Hotta Ana Luiza Carrari Sayegh Francis Ribeiro de Souza Ricardo Ribeiro Dias Charles Mady

Abstract

Background

Galectin-3 (Gal-3) is a proinflammatory, profibrotic molecule implicated in the pathogenesis of heart failure. The role of Gal-3 in patients with chronic constrictive pericarditis (CCP) is not clear.

Objective

The aim of this study was to assess plasma Gal-3 in patients with CCP and correlate it with clinical, functional and histologic parameters.

Methods

We prospectively evaluated 25 symptomatic patients with CCP referred for pericardiectomy and 21 healthy controls. Patients underwent clinical assessment, Gal-3 and B-type natriuretic peptide (BNP) measurements, echocardiography, cardiac magnetic resonance imaging and cardiopulmonary exercise test (CPET) at baseline. Six months after pericardiectomy CPET was repeated. An alpha error < 5% was considered statistically significant, with a confidence interval of 95%.

Results

Twenty-five patients with a median age of 45 years were included. Etiology was mainly idiopathic (n = 19, 76%); and 14 (56%) patients had NYHA functional class III/IV. Median BNP and Gal-3 were 143 (89-209) pg/dL and 14.8 (9.7-17.2) ng/mL, respectively. Gal-3 levels were not significantly higher in CCP patients than in control (p = 0.22). There were no significant correlations of Gal-3 with BNP, echocardiographic and cardiac magnetic resonance measures and histological findings. After pericardiectomy, it was found a statistically significant correlation between Gal-3 and the CPTE measures test duration (r = –0.79; p < 0.001) and exercise time (r = –0.79; p < 0.001).

Conclusions

Patients with CCP had normal levels of Gal-3 as compared to the controls. Gal-3 did not correlate with morphological and functional measures before pericardiectomy. However, the associations between Gal-3 and exercise intolerance after pericardiectomy may suggest a role of Gal-3 in prognosis prediction after pericardiectomy. (Arq Bras Cardiol. 2020; 114(4):683-689)

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ABC

Editorial

Galectin-3 in Chronic Constrictive Pericarditis: Accurate Information for the Good Doctor

Wolney de Andrade Martins

Galectin-3 (Gal-3), which is now known as a new biomarker, has traveled the rigorous scientific pathway from discovery to validation. Experimental and clinical studies described its elevation in several situations, such as tumors, renal failure and heart failure. Its administration caused myocardial fibrosis and heart failure (HF). Its genetic suppression or inhibition prevented fibrosis and remodeling, that is, the cause-and-effect relationship had been proven. Elevated levels of Gal-3 show a worse prognosis, as they predict sudden death. Galectin-3 was an independent predictor in the short and medium term of hospitalizations and of mortality in patients with HF, especially those with heart failure with preserved ejection fraction (HFpEF).

The biomarker can assist the clinician in their diagnostic dilemmas, in assessing the prognosis and even guiding the therapy. The HFpEF is an example of condition where all help is welcome. Multiple comorbidities, less typical conditions, especially in the elderly and obese, can be confusing. HFpEF is one of the situations where Gal-3 can greatly assist in diagnostic confirmation.

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IJCS

Original Article

Evaluation of Galectin-3 and Myocardial Fibrosis in Patients with Hypertrophic Cardiomyopathy

Murillo de Oliveira Antunes et al. Edmundo Arteaga-Fernández Fabio Fernandes Carla David Soffiatti … Paula de Cássia Buck Ester Cerdeira Sabino Carlos Henrique Valente Moreira Charles Mady

Abstract

Background:

Galectin-3 is the designation given to the protein that binds to ß-galactosides, expressed by activated macrophages and described as a cardiac fibrosis mediator. In hypertrophic cardiomyopathy (HCM), myocardial fibrosis is an independent predictor of adverse outcome; however, the association between Galectin-3 and myocardial fibrosis has not been studied in this cardiopathy.

Objective:

To evaluate the association of Galectin-3 and the presence of myocardial fibrosis in a patient with hypertrophic cardiomyopathy.

Methods:

Galectin-3 was measured in automated equipment using the Elisa technique in 100 participants divided into two groups: 50 patients with hypertrophic cardiomyopathy and 50 healthy control subjects. All patients with hypertrophic cardiomyopathy underwent magnetic nuclear resonance with the late enhancement technique to investigate myocardial fibrosis. For the statistical analysis, p values < 0.05 were considered statistically significant.

Results:

Galectin-3 levels were low and did not show significant differences between patients with hypertrophic cardiomyopathy and the control group, 10.3 ± 3.1 ng/dL and 11.3 ± 2.6 ng/dL (p = 0.12) respectively. Myocardial fibrosis was a common finding and was identified in 84% (42/50) of patients with HCM, but no differences were observed between Galectin-3 levels when comparing patients with and without fibrosis, 10.3 ± 2.4 ng/dL and 10.1 ± 2.1 ng/dL (p = 0.59).

Conclusion:

The results did not show an association between Galectin-3 and myocardial fibrosis in patients with hypertrophic cardiomyopathy, suggesting that non-inflammatory mechanisms of myocardial fibrosis formation and cardiac remodeling are involved in this cardiopathy.

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ABC

Original Article

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

Gabriela da Silva Cruz et al. Ana Luiza Dias Angelo Ticiana Ferreira Larocca Carolina Thé Macedo … Márcia Noya-Rabelo Luís Claudio Lemos Correia Jorge Andion Torreão Bruno Solano de Freitas Souza Ricardo Ribeiro dos Santos Milena Botelho Pereira Soares

Abstract

Background:

Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated.

Objective:

The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.

Methods:

Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.

Results:

For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease.

Conclusion:

Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0)

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