Soluble ST2 in Ambulatory Patients with Heart Failure Association with Functional Capacity and Long-Term Outcomes

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

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

BackgroundST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) studya multicenter, randomized study of exercise training in HF. Methods and ResultsHF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6 31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. ConclusionsST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk.

Original languageEnglish (US)
Pages (from-to)1172-1179
Number of pages8
JournalCirculation: Heart Failure
Volume6
Issue number6
DOIs
StatePublished - 2013

Fingerprint

Heart Failure
Exercise
Hospitalization
Brain Natriuretic Peptide
Proportional Hazards Models
Stroke Volume
Multicenter Studies
Myocardium
Biomarkers
Mortality

Keywords

  • Biomarkers
  • Heart failure
  • Prognosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Felker, G. M., Fiuzat, M., Thompson, V., Shaw, L. K., Neely, M. L., Adams, K. F., ... O Connor, C. M. (2013). Soluble ST2 in Ambulatory Patients with Heart Failure Association with Functional Capacity and Long-Term Outcomes. Circulation: Heart Failure, 6(6), 1172-1179. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000207

Soluble ST2 in Ambulatory Patients with Heart Failure Association with Functional Capacity and Long-Term Outcomes. / Felker, G. Michael; Fiuzat, Mona; Thompson, Vivian; Shaw, Linda K.; Neely, Megan L.; Adams, Kirkwood F.; Whellan, David J.; Donahue, Mark P.; Ahmad, Tariq; Kitzman, Dalane W.; Pina, Ileana L.; Zannad, Faiez; Kraus, William E.; O Connor, Christopher M.

In: Circulation: Heart Failure, Vol. 6, No. 6, 2013, p. 1172-1179.

Research output: Contribution to journalArticle

Felker, GM, Fiuzat, M, Thompson, V, Shaw, LK, Neely, ML, Adams, KF, Whellan, DJ, Donahue, MP, Ahmad, T, Kitzman, DW, Pina, IL, Zannad, F, Kraus, WE & O Connor, CM 2013, 'Soluble ST2 in Ambulatory Patients with Heart Failure Association with Functional Capacity and Long-Term Outcomes', Circulation: Heart Failure, vol. 6, no. 6, pp. 1172-1179. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000207
Felker, G. Michael ; Fiuzat, Mona ; Thompson, Vivian ; Shaw, Linda K. ; Neely, Megan L. ; Adams, Kirkwood F. ; Whellan, David J. ; Donahue, Mark P. ; Ahmad, Tariq ; Kitzman, Dalane W. ; Pina, Ileana L. ; Zannad, Faiez ; Kraus, William E. ; O Connor, Christopher M. / Soluble ST2 in Ambulatory Patients with Heart Failure Association with Functional Capacity and Long-Term Outcomes. In: Circulation: Heart Failure. 2013 ; Vol. 6, No. 6. pp. 1172-1179.
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abstract = "BackgroundST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) studya multicenter, randomized study of exercise training in HF. Methods and ResultsHF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6 31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. ConclusionsST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk.",
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T1 - Soluble ST2 in Ambulatory Patients with Heart Failure Association with Functional Capacity and Long-Term Outcomes

AU - Felker, G. Michael

AU - Fiuzat, Mona

AU - Thompson, Vivian

AU - Shaw, Linda K.

AU - Neely, Megan L.

AU - Adams, Kirkwood F.

AU - Whellan, David J.

AU - Donahue, Mark P.

AU - Ahmad, Tariq

AU - Kitzman, Dalane W.

AU - Pina, Ileana L.

AU - Zannad, Faiez

AU - Kraus, William E.

AU - O Connor, Christopher M.

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N2 - BackgroundST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) studya multicenter, randomized study of exercise training in HF. Methods and ResultsHF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6 31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. ConclusionsST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk.

AB - BackgroundST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) studya multicenter, randomized study of exercise training in HF. Methods and ResultsHF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6 31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. ConclusionsST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk.

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KW - Prognosis

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