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=8×10-6) 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.

• Keywords
• biomarkers, heart failure, myocarditis, sST2, sex differences,
• MeSH
• Biomarkers blood   MeSH
• Biopsy MeSH
• Adult MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Interleukin-1 Receptor-Like 1 Protein blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Myocardium pathology   MeSH
• Myocarditis blood   complications   diagnosis   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Follow-Up Studies MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Sex Factors MeSH
• Heart Failure blood   diagnosis   etiology   MeSH
• Age Factors MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Comparative Study MeSH
• Names of Substances
• Biomarkers MeSH
• IL1RL1 protein, human MeSH Browser
• Interleukin-1 Receptor-Like 1 Protein MeSH