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

Natalia Lopez-Andrés, Patrick Rossignol, Wafae Iraqi, Renaud Fay, Josette Nuée, Stefano Ghio, John G F Cleland, Faiez Zannad, Patrick Lacolley

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Aims Circulating 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 results Serum levels of ECCM biomarkers [galectin-3 (Gal-3), 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 (1.436.22), P = 0.004] with death or HF hospitalization, along with left ventricular end-systolic volume >200 mL [3.42 (OR: 1.657.10), P = 0.001]. The outcome death or left ventricular ejection fraction (LVEF) ≤35% was associated with MMP-1 [≤3 ng/mL: 3.04 (1.376.71), P 0.006]. No significant interaction was observed between the tested biomarkers and the treatment group. Conclusions Increased 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.

Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalEuropean Journal of Heart Failure
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Galectin 3
Cardiac Resynchronization Therapy
Left Ventricular Dysfunction
Fibrosis
Heart Failure
Extracellular Matrix
Biomarkers
Matrix Metalloproteinase 1
Stroke Volume
Hospitalization
Matrix Metalloproteinase 3
Collagen Type III
Collagen Type I
Serum
Collagen
Randomized Controlled Trials

Keywords

  • Cardiac resynchronization therapy
  • Collagen biomarkers
  • Dyssynchrony
  • Galectin-3
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Lopez-Andrés, Natalia; Rossignol, Patrick; Iraqi, Wafae; Fay, Renaud; Nuée, Josette; Ghio, Stefano; Cleland, John G F; Zannad, Faiez; Lacolley, Patrick.

In: European Journal of Heart Failure, Vol. 14, No. 1, 01.2012, p. 74-81.

Research output: Contribution to journalArticle

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abstract = "Aims Circulating 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 results Serum levels of ECCM biomarkers [galectin-3 (Gal-3), 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 (1.436.22), P = 0.004] with death or HF hospitalization, along with left ventricular end-systolic volume >200 mL [3.42 (OR: 1.657.10), P = 0.001]. The outcome death or left ventricular ejection fraction (LVEF) ≤35{\%} was associated with MMP-1 [≤3 ng/mL: 3.04 (1.376.71), P 0.006]. No significant interaction was observed between the tested biomarkers and the treatment group. Conclusions Increased 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.",
keywords = "Cardiac resynchronization therapy, Collagen biomarkers, Dyssynchrony, Galectin-3, Heart failure",
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T1 - Association of galectin-3 and fibrosis markers with long-term cardiovascular outcomes in patients with heart failure, left ventricular dysfunction, and dyssynchrony

T2 - Insights from the CARE-HF (Cardiac Resynchronization in Heart Failure) trial

AU - Lopez-Andrés, Natalia

AU - Rossignol, Patrick

AU - Iraqi, Wafae

AU - Fay, Renaud

AU - Nuée, Josette

AU - Ghio, Stefano

AU - Cleland, John G F

AU - Zannad, Faiez

AU - Lacolley, Patrick

PY - 2012/1

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N2 - Aims Circulating 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 results Serum levels of ECCM biomarkers [galectin-3 (Gal-3), 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 (1.436.22), P = 0.004] with death or HF hospitalization, along with left ventricular end-systolic volume >200 mL [3.42 (OR: 1.657.10), P = 0.001]. The outcome death or left ventricular ejection fraction (LVEF) ≤35% was associated with MMP-1 [≤3 ng/mL: 3.04 (1.376.71), P 0.006]. No significant interaction was observed between the tested biomarkers and the treatment group. Conclusions Increased 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.

AB - Aims Circulating 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 results Serum levels of ECCM biomarkers [galectin-3 (Gal-3), 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 (1.436.22), P = 0.004] with death or HF hospitalization, along with left ventricular end-systolic volume >200 mL [3.42 (OR: 1.657.10), P = 0.001]. The outcome death or left ventricular ejection fraction (LVEF) ≤35% was associated with MMP-1 [≤3 ng/mL: 3.04 (1.376.71), P 0.006]. No significant interaction was observed between the tested biomarkers and the treatment group. Conclusions Increased 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.

KW - Cardiac resynchronization therapy

KW - Collagen biomarkers

KW - Dyssynchrony

KW - Galectin-3

KW - Heart failure

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