Sex and autoimmunity in acute myocarditis: time for a refresh

Abstract

This article refers to 'Predictors of relapse, death or heart transplantation in myocarditis before the introduction of immunosuppression: negative prognostic impact of female gender, fulminant onset, lower ejection fraction and serum autoantibodies' by A. Baritussio et al., published in this issue on pages 1033-1044.The best management and long-term impact of myocarditis remain controversial partly because of the breadth of aetiologies and outcomes reported from relatively small clinical studies. Prospectively gathered, large and well-characterized myocarditis case series are needed to fill the gaps in this knowledge base and inform treatment strategies. In this context, the study by Baritussio et al. 1 in this issue of the Journal provides new and valuable insights into the mechanisms, risk of recurrence and management of acute myocarditis.Their series gathered 466 acute myocarditis patients with an average duration of symptoms of less than 1 day from a large academic referral centre. The diagnosis relied on standardized histological examination of heart tissue and validated imaging findings on cardiac magnetic resonance (CMR) in combination with clinical symptoms. The strengths of their study design include blinding of CMR readers to clinical data, prospective blood and tissue collection, and standardized outcome assessment methods. Their most impactful observations include the association of female sex, heart failure requiring inotropic or mechanical circulatory support, and higher autoantibodies titres with a greater risk of death or heart transplantation. Myocarditis recurrence, a rarely measured outcome, occurred in 18% of subjects and was associated with previous myocarditis and younger age.The higher risk of death or heart transplant in women deserves comment. This finding seems counter-intuitive because men are generally at higher risk of myocarditis (in this series 68% of subjects were male) and have greater area of delayed enhancement on CMR. 2 Decades of experimental studies document a protective effect of oestrogen and detrimental effect of testosterone in enteroviral myocarditis. 3 However, worse survival in women was also seen in epidemiological studies from the US and Poland. 4,5