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.