Prognostic Value of Galectin-3 for Adverse Outcomes in Chronic Heart Failure

Abstract

Background Clinical studies have suggested the prognostic value of galectin-3, a marker of fibrosis, in chronic heart failure. However, the specific role of galectin-3, compared with established biomarkers, remains uncertain. Methods and Results The Penn Heart Failure Study was an ambulatory heart failure cohort that included 1385 participants with reduced (1141), preserved (106), and recovered (138) left ventricular ejection fraction (LVEF). Cox regression models determined the association between galectin-3 and risk of all-cause mortality, cardiac transplantation, or placement of a ventricular assist device. Receiver operating characteristic curves compared the prognostic accuracy of galectin-3, high-sensitivity soluble Toll-like receptor 2 (ST2), troponin I, and B-type natriuretic peptide (BNP) at 1 and 5 years. Higher galectin-3 levels were associated with an increased risk of adverse events (adjusted hazard ratio of 1.96 for each doubling in galectin-3; P < .001). This association was most pronounced among participants with preserved LVEF (adjusted hazard ratio 3.30; P < .001). At 5 years, galectin-3 was the most accurate discriminator of risk among participants with preserved LVEF (area under the curve 0.782; P = .81 vs high-sensitivity ST2; P = .029 vs troponin I; P = .35 vs BNP). BNP was most accurate among participants with reduced and recovered LVEF (areas under the curves 0.716 and 0.728, respectively). Conclusions Galectin-3 could have prognostic value for long-term events among patients with heart failure and preserved ejection fraction.

β‐Adrenoceptor activation affects galectin‐3 as a biomarker and therapeutic target in heart disease

“…Clinical studies have suggested a role of increased circulating levels of Gal‐3 in predicting the severity of heart disease or a high risk of major adverse cardiovascular events (MACE) including HF (Ho et al, ; van der Velde et al, ), poor survival (Bayes‐Genis et al, ; Lok et al, ), post‐MI cardiac events (Di Tano et al, ; Grandin et al, ; Maiolino et al, ), as well as diastolic dysfunction (Wu, Li, et al, ) and severity of atrial fibrosis (Hernandez‐Romero et al, ; Takemoto et al, ; Wu, Su, et al, ). French et al reported in HF patients ( n = 1,385) that elevated Gal‐3 level was associated with a greater risk of MACE (hazard ratio = 1.96 for each doubling in Gal‐3) and that such association was most pronounced among patients diagnosed as HF with preserved ejection fraction (hazard ratio = 3.30; French et al, ). In chronic HF patients, high Gal‐3 level predicts increased risk of MACE, with the predictive power increased when Gal‐3 was persistently high (Motiwala et al, ).…”

“…among patients diagnosed as HF with preserved ejection fraction (hazard ratio = 3.30; French et al, 2016). In chronic HF patients, high…”

Galectin-3 mediates the pulmonary arterial hypertension–induced right ventricular remodeling through interacting with NADPH oxidase 4

“…12 Gal-3 is recognized as a promising new biomarker which has been proved to be effective for diagnosing and evaluating the prognosis of the left heart failure. [13][14][15] The level of Gal-3 was elevated in both idiopathic PAH and connective tissue diseases related to PAH patients 16 ; however, the role of Gal-3 in the PAH-induced right ventricular morphologic changes remains less known.…”

Galectin‐3 and risk of cardiovascular events and all‐cause mortality in type 2 diabetes

“…Galectin‐3 was upregulated in decompensated hearts, and in animal models, genetic and pharmacological inhibition of galectin‐3 prevented cardiac remodelling by interfering with myocardial fibrogenesis . Increased circulating concentration of galectin‐3 is associated with a higher risk of incident heart failure in the general population, and with adverse outcome and mortality in patients with heart failure . It has been shown that plasma galectin‐3 level is one of the best short‐term predictors of events, and galectin‐3 has been incorporated into risk scores for the management of patients with heart failure .…”

“…4,5 Increased circulating concentration of galectin-3 is associated with a higher risk of incident heart failure in the general population, 6 and with adverse outcome and mortality in patients with heart failure. 7 It has been shown that plasma galectin-3 level is one of the best short-term predictors of events, and galectin-3 has been incorporated into risk scores for the management of patients with heart failure. [6][7][8] Galectin-3 inhibitors are currently being developed as potential therapy for heart failure.…”