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

<jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> 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) <jats:styled-content style="fixed-case">ST</jats:styled-content> 2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> 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 <jats:styled-content style="fixed-case">sST</jats:styled-content> 2 levels were examined by <jats:styled-content style="fixed-case">ELISA</jats:styled-content> in humans and mice and correlated with heart function according to sex and age. Sera <jats:styled-content style="fixed-case">sST</jats:styled-content> 2 levels were higher in healthy men ( <jats:italic>P</jats:italic> =8×10 <jats:sup>−6</jats:sup> ) and men with myocarditis ( <jats:italic>P</jats:italic> =0.004) compared with women. <jats:styled-content style="fixed-case">sST</jats:styled-content> 2 levels were elevated in patients with myocarditis and New York Heart Association class <jats:styled-content style="fixed-case">III</jats:styled-content> ‐ <jats:styled-content style="fixed-case">IV</jats:styled-content> heart failure ( <jats:italic>P</jats:italic> =0.002), predominantly in men ( <jats:italic>P</jats:italic> =0.0003). Sera <jats:styled-content style="fixed-case">sST</jats:styled-content> 2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( <jats:italic>r</jats:italic> =0.231, <jats:italic>P</jats:italic> =0.0006), but not in women ( <jats:italic>r</jats:italic> =0.172, <jats:italic>P</jats:italic> =0.57). Sera <jats:styled-content style="fixed-case">sST</jats:styled-content> 2 levels were also significantly higher in male mice with myocarditis ( <jats:italic>P</jats:italic> =0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( <jats:italic>P</jats:italic> <0.001), but not estradiol ( <jats:italic>P</jats:italic> =0.32), increased sera <jats:styled-content style="fixed-case">sST</jats:styled-content> 2 levels in male mice with myocarditis. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> We show in a well‐characterized subset of heart failure patients with clinically suspected and biopsy‐confirmed myocarditis that elevated sera <jats:styled-content style="fixed-case">sST</jats:styled-content> 2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old. </jats:p> </jats:sec>