Elevated Sera sST 2 Is Associated With Heart Failure in Men ≤50 Years Old With Myocarditis

Michael J. Coronado, Katelyn A. Bruno, Lori A. Blauwet, Carsten Tschöpe, Madeleine W. Cunningham, Sabine Pankuweit, Sophie van Linthout, Eun Seok Jeon, Dennis M. McNamara, Jan Krejčí, Julie Bienertová-Vašků, Erika J. Douglass, Eric D. Abston, Adriana Bucek, J. Augusto Frisancho, Merci S. Greenaway, Anneliese R. Hill, Heinz Peter Schultheiss, Leslie T Jr. Cooper, DeLisa Fairweather

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Abstract

Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST 2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78% male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST 2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST 2 levels were higher in healthy men ( P=8×10-6) and men with myocarditis ( P=0.004) compared with women. sST 2 levels were elevated in patients with myocarditis and New York Heart Association class III - IV heart failure ( P=0.002), predominantly in men ( P=0.0003). Sera sST 2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( r=0.231, P=0.0006), but not in women ( r=0.172, P=0.57). Sera sST 2 levels were also significantly higher in male mice with myocarditis ( P=0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( P<0.001), but not estradiol ( P=0.32), increased sera sST 2 levels in male mice with myocarditis. Conclusions We show in a well-characterized subset of heart failure patients with clinically suspected and biopsy-confirmed myocarditis that elevated sera sST 2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old.

Original languageEnglish (US)
Pages (from-to)e008968
JournalJournal of the American Heart Association
Volume8
Issue number2
DOIs
StatePublished - Jan 22 2019

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Myocarditis
Heart Failure
Serum
Sex Characteristics
Testosterone
Estradiol
Transplantation
Enzyme-Linked Immunosorbent Assay
Hormones
Inflammation
Biopsy
Mortality

Keywords

  • biomarkers
  • heart failure
  • myocarditis
  • sex differences
  • sST2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Elevated Sera sST 2 Is Associated With Heart Failure in Men ≤50 Years Old With Myocarditis. / Coronado, Michael J.; Bruno, Katelyn A.; Blauwet, Lori A.; Tschöpe, Carsten; Cunningham, Madeleine W.; Pankuweit, Sabine; van Linthout, Sophie; Jeon, Eun Seok; McNamara, Dennis M.; Krejčí, Jan; Bienertová-Vašků, Julie; Douglass, Erika J.; Abston, Eric D.; Bucek, Adriana; Frisancho, J. Augusto; Greenaway, Merci S.; Hill, Anneliese R.; Schultheiss, Heinz Peter; Cooper, Leslie T Jr.; Fairweather, DeLisa.

In: Journal of the American Heart Association, Vol. 8, No. 2, 22.01.2019, p. e008968.

Research output: Contribution to journalArticle

Coronado, MJ, Bruno, KA, Blauwet, LA, Tschöpe, C, Cunningham, MW, Pankuweit, S, van Linthout, S, Jeon, ES, McNamara, DM, Krejčí, J, Bienertová-Vašků, J, Douglass, EJ, Abston, ED, Bucek, A, Frisancho, JA, Greenaway, MS, Hill, AR, Schultheiss, HP, Cooper, LTJ & Fairweather, D 2019, 'Elevated Sera sST 2 Is Associated With Heart Failure in Men ≤50 Years Old With Myocarditis', Journal of the American Heart Association, vol. 8, no. 2, pp. e008968. https://doi.org/10.1161/JAHA.118.008968
Coronado, Michael J. ; Bruno, Katelyn A. ; Blauwet, Lori A. ; Tschöpe, Carsten ; Cunningham, Madeleine W. ; Pankuweit, Sabine ; van Linthout, Sophie ; Jeon, Eun Seok ; McNamara, Dennis M. ; Krejčí, Jan ; Bienertová-Vašků, Julie ; Douglass, Erika J. ; Abston, Eric D. ; Bucek, Adriana ; Frisancho, J. Augusto ; Greenaway, Merci S. ; Hill, Anneliese R. ; Schultheiss, Heinz Peter ; Cooper, Leslie T Jr. ; Fairweather, DeLisa. / Elevated Sera sST 2 Is Associated With Heart Failure in Men ≤50 Years Old With Myocarditis. In: Journal of the American Heart Association. 2019 ; Vol. 8, No. 2. pp. e008968.
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abstract = "Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST 2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78{\%} male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST 2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST 2 levels were higher in healthy men ( P=8×10-6) and men with myocarditis ( P=0.004) compared with women. sST 2 levels were elevated in patients with myocarditis and New York Heart Association class III - IV heart failure ( P=0.002), predominantly in men ( P=0.0003). Sera sST 2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( r=0.231, P=0.0006), but not in women ( r=0.172, P=0.57). Sera sST 2 levels were also significantly higher in male mice with myocarditis ( P=0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( P<0.001), but not estradiol ( P=0.32), increased sera sST 2 levels in male mice with myocarditis. Conclusions We show in a well-characterized subset of heart failure patients with clinically suspected and biopsy-confirmed myocarditis that elevated sera sST 2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old.",
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T1 - Elevated Sera sST 2 Is Associated With Heart Failure in Men ≤50 Years Old With Myocarditis

AU - Coronado, Michael J.

AU - Bruno, Katelyn A.

AU - Blauwet, Lori A.

AU - Tschöpe, Carsten

AU - Cunningham, Madeleine W.

AU - Pankuweit, Sabine

AU - van Linthout, Sophie

AU - Jeon, Eun Seok

AU - McNamara, Dennis M.

AU - Krejčí, Jan

AU - Bienertová-Vašků, Julie

AU - Douglass, Erika J.

AU - Abston, Eric D.

AU - Bucek, Adriana

AU - Frisancho, J. Augusto

AU - Greenaway, Merci S.

AU - Hill, Anneliese R.

AU - Schultheiss, Heinz Peter

AU - Cooper, Leslie T Jr.

AU - Fairweather, DeLisa

PY - 2019/1/22

Y1 - 2019/1/22

N2 - Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST 2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78% male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST 2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST 2 levels were higher in healthy men ( P=8×10-6) and men with myocarditis ( P=0.004) compared with women. sST 2 levels were elevated in patients with myocarditis and New York Heart Association class III - IV heart failure ( P=0.002), predominantly in men ( P=0.0003). Sera sST 2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( r=0.231, P=0.0006), but not in women ( r=0.172, P=0.57). Sera sST 2 levels were also significantly higher in male mice with myocarditis ( P=0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( P<0.001), but not estradiol ( P=0.32), increased sera sST 2 levels in male mice with myocarditis. Conclusions We show in a well-characterized subset of heart failure patients with clinically suspected and biopsy-confirmed myocarditis that elevated sera sST 2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old.

AB - Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST 2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78% male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST 2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST 2 levels were higher in healthy men ( P=8×10-6) and men with myocarditis ( P=0.004) compared with women. sST 2 levels were elevated in patients with myocarditis and New York Heart Association class III - IV heart failure ( P=0.002), predominantly in men ( P=0.0003). Sera sST 2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( r=0.231, P=0.0006), but not in women ( r=0.172, P=0.57). Sera sST 2 levels were also significantly higher in male mice with myocarditis ( P=0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( P<0.001), but not estradiol ( P=0.32), increased sera sST 2 levels in male mice with myocarditis. Conclusions We show in a well-characterized subset of heart failure patients with clinically suspected and biopsy-confirmed myocarditis that elevated sera sST 2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old.

KW - biomarkers

KW - heart failure

KW - myocarditis

KW - sex differences

KW - sST2

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