Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure

Tariq Ahmad, Mona Fiuzat, Benjamin Neely, Megan L. Neely, Michael J. Pencina, William E. Kraus, Faiez Zannad, David J. Whellan, Mark P. Donahue, Ileana L. Pina, Kirkwood F. Adams, Dalane W. Kitzman, Christopher M. O'Connor, G. Michael Felker

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Objectives: The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure. Background: The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown. Methods: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP. Results: After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure. Conclusions: Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.

Original languageEnglish (US)
Pages (from-to)260-268
Number of pages9
JournalJACC: Heart Failure
Volume2
Issue number3
DOIs
StatePublished - 2014

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Sudden Cardiac Death
Galectin 3
Fibrosis
Heart Failure
Biomarkers
Exercise
Left Ventricular Dysfunction
Stroke Volume
pro-brain natriuretic peptide (1-76)
Patient Care
Randomized Controlled Trials

Keywords

  • Biomarker
  • Heart failure
  • Mode of death
  • Prognosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Ahmad, T., Fiuzat, M., Neely, B., Neely, M. L., Pencina, M. J., Kraus, W. E., ... Felker, G. M. (2014). Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure. JACC: Heart Failure, 2(3), 260-268. https://doi.org/10.1016/j.jchf.2013.12.004

Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure. / Ahmad, Tariq; Fiuzat, Mona; Neely, Benjamin; Neely, Megan L.; Pencina, Michael J.; Kraus, William E.; Zannad, Faiez; Whellan, David J.; Donahue, Mark P.; Pina, Ileana L.; Adams, Kirkwood F.; Kitzman, Dalane W.; O'Connor, Christopher M.; Felker, G. Michael.

In: JACC: Heart Failure, Vol. 2, No. 3, 2014, p. 260-268.

Research output: Contribution to journalArticle

Ahmad, T, Fiuzat, M, Neely, B, Neely, ML, Pencina, MJ, Kraus, WE, Zannad, F, Whellan, DJ, Donahue, MP, Pina, IL, Adams, KF, Kitzman, DW, O'Connor, CM & Felker, GM 2014, 'Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure', JACC: Heart Failure, vol. 2, no. 3, pp. 260-268. https://doi.org/10.1016/j.jchf.2013.12.004
Ahmad, Tariq ; Fiuzat, Mona ; Neely, Benjamin ; Neely, Megan L. ; Pencina, Michael J. ; Kraus, William E. ; Zannad, Faiez ; Whellan, David J. ; Donahue, Mark P. ; Pina, Ileana L. ; Adams, Kirkwood F. ; Kitzman, Dalane W. ; O'Connor, Christopher M. ; Felker, G. Michael. / Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure. In: JACC: Heart Failure. 2014 ; Vol. 2, No. 3. pp. 260-268.
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abstract = "Objectives: The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure. Background: The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown. Methods: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35{\%}). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP. Results: After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11{\%} for sudden cardiac death, but not pump failure. Conclusions: Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.",
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T1 - Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure

AU - Ahmad, Tariq

AU - Fiuzat, Mona

AU - Neely, Benjamin

AU - Neely, Megan L.

AU - Pencina, Michael J.

AU - Kraus, William E.

AU - Zannad, Faiez

AU - Whellan, David J.

AU - Donahue, Mark P.

AU - Pina, Ileana L.

AU - Adams, Kirkwood F.

AU - Kitzman, Dalane W.

AU - O'Connor, Christopher M.

AU - Felker, G. Michael

PY - 2014

Y1 - 2014

N2 - Objectives: The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure. Background: The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown. Methods: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP. Results: After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure. Conclusions: Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.

AB - Objectives: The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure. Background: The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown. Methods: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP. Results: After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure. Conclusions: Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.

KW - Biomarker

KW - Heart failure

KW - Mode of death

KW - Prognosis

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