Insights Into the Natural History of Recurrent Myocarditis, A Multicenter International Study (Re-Myo Study)

Background: Recurrence of acute myocarditis (AM) is challenging. The management and natural history of patients who experience a recurrence of AM (Re-AM) remain poorly characterized. The aim of this study is to investigate clinical characteristics and outcomes of patients with Re-AM. Methods: In this international multicenter study, 141 consecutive patients with biopsy-proven or cardiac magnetic resonance-proven Re-AM (35 [26-45] years, 77% male, median left ventricular ejection fraction 55%) were investigated and compared with 372 consecutive patients with single acute myocarditis (S-AM). The primary outcome was a composite of all-cause mortality, heart transplant and major ventricular arrhythmias. Results: Patients with Re-AM had more frequently a family history of cardiomyopathy (19% in Re-AM versus 2.8% in S-AM, P<0.001) and a diffuse late gadolinium enhancement compared with patients with S-AM (46% in Re-AM versus 34% in S-AM, P=0.019). The extent of late gadolinium enhancement also increased between the first and the second AM episode in patients with Re-AM (P=0.001). During a median follow-up of 33 months (interquartile range, 23-52) patients with Re-AM had a higher risk of primary outcome (P=0.001) compared with patients with S-AM, as well as a significantly elevated competing risk of major ventricular arrhythmias (P<0.001), which remained independently associated even after adjustment (hazard ratio, 2.15 [95% CI, 1.15-4.04], P=0.017). A family history of cardiomyopathy, autoimmune diseases, and ring-like late gadolinium enhancement was independently associated with a higher risk of recurrent AM. Conclusions: Re-AM is a distinct clinical subgroup of AM associated with generally worse prognosis and a specific increased arrhythmic risk compared with S-AM.