The Prognostic Value of Plasma Galectin 3 in HFrEF Depends on the Etiology of Heart Failure: a Cohort Study and Animal Experiment

Abstract

Background: Although plasma galectin 3 (Gal-3) has been investigated in many previous studies, its prognostic value has not yet been determined. However, many studies had found that plasma and cardiac levels of Gal-3 are different within different animal models of heart failure (HF). Aim: The aim of the present study was to evaluate the prognostic value of plasma Gal-3 for HF originating from different causes. Methods: We examined the plasma levels and expression of Gal-3 in cardiac tissues in two transgenic (TG) strains of mice with cardiomyocyte-restricted overexpression of either β2- adrenergic receptor (β2- AR TG) or Mammalian sterile 20-like kinase 1 (Mst1-TG) in the present study. Age-matched non-transgenic (nTG) littermates were used as controls. Additionally, 166 patients suffering from heart failure with reduced ejection fraction (HFrEF) in two hospitals within the Shaanxi province were included in the present study. These patients were treated in accordance with the Chinese HF guidelines of 2014. Subsequently, these patients were followed up for 50 months, during which we analyzed the prediction value of baseline Gal-3 to endpoints in these patients via Cox and Kapla-Meir analyses. Results: Gal-3 was localized in the cytoplasm and nucleus of cardiomyocytes, often forming aggregates in Mst1TG mice. Extracellular Gal-3 staining was uncommon in Mst1-TG hearts. However, in β2-AR TG mice, although Gal-3 was also expressed in myocardial cells, it is more highly expressed in interstitial cells (e.g., fibroblasts and macrophages). Plasma Gal-3 was comparable between nTG and Mst1 TG mice, However, plasma Gal-3 was higher in β2-AR TG mice than nTG mice. In HFrEF patients cohort, the median Gal-3 concentration was 158.42 pg/mL. All participants were divided into two groups according to their Gal-3 levels. There were no statistical differences between the two groups in terms of gender, hypertension history, diabetes history, treatments, death, re-hospitalization and composite endpoint events. However, patients with Gal-3 plasma concentrations above the median were older (P=0.043), had lower plasma hemoglobin(P = 0.002), but higher plasma creatinine (P=0.011), tissue inhibitor of metalloproteinases 1 (TIMP-1)(P=0.002), left ventricular end systolic diameter (L VESD) (P = 0.036), left ventricular end-systolic volumes (LVESV) (P=0.043)and end-diastolic, and left ventricular end-diastolic volumes (LVEDV) (P=0.036).Spearmen correlation analysis revealed that Gal-3 was positively correlated with TIMP-1 (r=0.396, P<0.001), LVESV (r=0.181, P=0.020) and LVEDV (r=0.190, P=0.015). During a 50-month follow-up, 43 deaths, 97 unplanned re-hospitalizations, and 111 composite endpoint events occurred. Cox analysis demonstrated that although Gal-3 did not provide any prognostic value in either total-HF subjects or coronary-heart-disease (CHD) patients, it did provide prognostic value in non-CHD patients.Conclusion: Although plasma concentrations of Gal-3 were associated with TIMP-1 and echocardiographic parameters, the prognostic value of plasma Gal-3 in HFrEF depended on the etiology of HF.