Abstract Body (Do not enter title and authors here): Background:
COVID-19 and, more rarely, its mRNA vaccination have been associated with myocarditis, often with greater incidence and severity in males. Long-term outcomes, such as recovery of left ventricular ejection fraction (LVEF), particularly in context of sex differences, remain poorly understood.
Hypothesis:
We hypothesized that sex-based differences exist in LVEF recovery following COVID-19-related myocarditis.
Methods:
We conducted a retrospective cohort study of 85,376 COVID-19 patients (January 2020–January 2024) in the Mass General Brigham system. 1,193 had undergone a CMR and 259 had a myocardial biopsy. We included patients with either biopsy or CMR-confirmed myocarditis based on Lake Louise criteria (for acute cases) or clinically suspicious late gadolinium enhancement (LGE) patterns (for delayed imaging), excluding alternative causes (e.g., other viral infections, immunotherapy) and patients with amyloidosis or sarcoidosis. A total of 51 patients met our criteria and were categorized into: COVID-19 infection (acute: <14 days, delayed: ≥14 days) or vaccination. Patients were followed up to May 2025.
Results:
Among 51 patients (mean age 47±15, 26 female), 44 had infection-related myocarditis (26 acute, 18 delayed), 4 were vaccine-related, and 3 had recurrent myocarditis with infection and vaccination. Cases were followed for a minimum of 2 years and median of 4 years. LVEF reduction was seen in 24 patients (10 females; none vaccine-related; mean EF 34% ± 12%) with 15 (63%) making full recovery to baseline or LVEF > 50% within a median of 3 months. Most recovered patients received guideline-directed therapy, though some improved without it. Out of 9 without recovery, 8 were males and 6 had acute infection. 90% of females vs 42% of males had LVEF recovery, p=0.03. CMR revealed LGE in 94%, mostly in basal inferolateral region; T2 elevation in 22% and T1 in 27%. One biopsy confirmed fulminant necrotizing myocarditis. No deaths or transplants occurred.
Conclusions:
This multi-center study presents one of the largest cohorts of CMR- or biopsy-confirmed myocarditis associated with COVID-19 and is the first to demonstrate sex differences in LVEF recovery. Half of our patients experienced reduced LVEF, with 18% failing to recover, most of whom were males. No vaccine-associated cases led to reduced LVEF. Our findings highlight the prognostic value of sex and importance of long-term follow-up. Prospective studies are needed to confirm predictors of recovery.