Association of galectin‐3 and fibrosis markers with long‐term cardiovascular outcomes in patients with heart failure, left ventricular dysfunction, and dyssynchrony: insights from the CARE‐HF (Cardiac Resynchronization in Heart Failure) trial

Abstract

AimsCirculating biomarkers of collagen turnover reflect extracellular cardiac matrix (ECCM) remodelling. The extent to which the success of cardiac resynchronization therapy (CRT) is influenced by the degree of cardiac fibrosis and whether CRT can influence matrix remodelling has yet to be studied. Our aim was to determine, in patients with heart failure (HF) and cardiac dyssynchrony, whether ECCM biomarkers are influenced by CRT and can predict cardiovascular outcomes and response to CRT. Methods and resultsSerum levels of ECCM biomarkers , N-terminal propeptides of type I and III procollagens (PINP and PIIINP), type I collagen telopeptide (ICTP), and matrix metalloproteinase 1 (MMP-1)] were measured in 260 patients, in a substudy of CARE-HF, a randomized controlled trial which evaluated the effects of CRT in patients with left ventricular systolic dysfunction and cardiac dyssynchrony. ECCM biomarkers did not change throughout the 18-month follow-up period. In age-and gender-adjusted analyses, Gal-3 and PIIINP were associated with death or HF hospitalization. In a further multivariate model, Gal-3 .30 ng/mL was associated [OR (95% CI): 2.98 (1.43-6.22), P ¼ 0.004] with death or HF hospitalization, along with left ventricular end-systolic volume .200 mL [3.42 (OR: 1.65 -7.10), P ¼ 0.001]. The outcome death or left ventricular ejection fraction (LVEF) ≤35% was associated with MMP-1 [≤3 ng/mL: 3.04 (1.37-6.71), P ¼ 0.006]. No significant interaction was observed between the tested biomarkers and the treatment group. ConclusionsIncreased Gal-3 and PIIINP, and low MMP-1 are associated with adverse long-term cardiovascular outcomes but did not predict response to CRT. CRT did not favourably affect serum concentrations of ECCM markers.--

Galectin-3 in Patients with Acute Heart Failure: Preliminary Report on First Polish Experience

“…Recent studies have revealed that Gal-3 appears to be a promising prognostic biomarker in HF patients [3,6,7,21,23,24]. In our study, patients who died during the follow-up period presented significantly higher baseline Gal-3 levels than the survivors, which is in line with some previous reports [3,6,7,21,23,24].…”

“…In our study, patients who died during the follow-up period presented significantly higher baseline Gal-3 levels than the survivors, which is in line with some previous reports [3,6,7,21,23,24]. Nevertheless, the clinical utility of this particle in the diagnostics as well as monitoring of therapy still needs to be addressed in large, prospective trials.…”

“…High levels of Gal-3 are expressed on activated macrophages, basophils, and mast cells. Many authors suggest a significant role of galectin in the pathogenesis and pathophysiology of cardiovascular diseases, in particular atherosclerosis, stroke, myocardial infarction, and heart failure [5,7,15]. Gal-3 is a member of the β-galactoside-binding animal lectin family, and its interaction with several ligands at the extracardiac matrix (ECM), including laminin, synexin, integrins, and collagens, could modulate inflammation and immunity [8].…”

“…Its elevated serum levels were measured not only in such fibrotic conditions as pancreatitis, cirrhosis, idiopathic lung fibrosis and renal failure, but also in adverse cardiac remodeling. As a consequence, it constitutes an attractive biomarker in HF patients [6][7][8][9][10][11].…”

New possibilities of diagnostics and control of efficacy of drug therapy for chronic heart failure

“…Данные нескольких когортных исследований под-тверждают способность галектина-3 прогнозировать риск развития крупных сердечно-сосудистых событий у пациентов с ХСН, таких как смерть и частота госпита-лизаций [6][7][8].…”