Elevated Sera sST2 Is Associated With Heart Failure in Men <= 50 Years Old With Myocarditis

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Authors	CORONADO Michael J. BRUNO Katelyn A. BLAUWET Lori A. TSCHOPE Carsten CUNNINGHAM Madeleine W. PANKUWEIT Sabine VAN LINTHOUT Sophie JEON Eun Seok MCNAMARA Dennis M. KREJČÍ Jan DOBROVOLNÁ Julie DOUGLASS Erika J. ABSTON Eric D. BUCEK Adriana FRISANCHO Augusto J. GREENAWAY Merci S. HILL Anneliese R. SCHULTHEISS Heinz P. COOPER Leslie T. FAIRWEATHER DeLisa
Year of publication	2019
Type	Article in Periodical
Magazine / Source	Journal of the American Heart Association
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://www.ahajournals.org/doi/10.1161/JAHA.118.008968
Doi	http://dx.doi.org/10.1161/JAHA.118.008968
Keywords	biomarkers; heart failure; myocarditis; sex differences; sST2
Description	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)ST2 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 sST2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST2 levels were higher in healthy men (P=8 x 10(-6)) and men with myocarditis (P=0.004) compared with women. sST2 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 sST2 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 sST2 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 sST2 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 sST2 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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