Predictors of long-term myocardial fibrosis after an acute myocarditis

Abstract Background Myocardial fibrosis can occur following an acute myocarditis, despite clinical recovery and normalized left ventricular (LV) systolic function. The mechanisms and predictors underlying fibrosis burden are important to understand. Cardiac magnetic resonance (CMR) allows detailed assessment of inflammatory injury and subsequent myocardial scarring. Purpose To identify predictors of extensive myocardial fibrosis on follow-up CMR after an episode of acute myocarditis. Methods We included all patients hospitalized with acute myocarditis between 2015 and 2024 who underwent CMR during index hospitalization and at follow-up. Clinical characteristics, laboratory parameters, and CMR findings were collected. A multivariable logistic regression model was constructed to identify predictors of extensive myocardial fibrosis (involving >2 myocardial segments) at follow-up. Results 63 patients were included; 15.9% were female, with a median age of 33.4 years (IQR 22.6–45.6). The prevalence of hypertension, dyslipidaemia, diabetes mellitus, and active smoking was 7.9%, 9.5%, 1.6%, and 36.5%, respectively. Prior ischemic heart disease was present in 3.2% and known atrial fibrillation in 1.6%. On index CMR, mean LV end-diastolic volume was 87 ±14.6mL, mean LV ejection fraction (LVEF) was 56 ±8.2%, and mean right ventricular EF was 54 ±6.9%. Myocardial oedema was limited to ≤2 segments in 9.5% of patients, while the majority (90.5%) exhibited more extensive involvement (>2 segments), with a median of 6 (IQR 4–9) segments, corresponding to approximately 35% of myocardial involvement. Follow-up CMR was performed after a median of 308 days (IQR 178–490). LV volumes were similar to baseline, while significant improvement was observed in both LVEF (60%, p<0.001) and right ventricular EF (56%, p=0.009). Of the 63 patients, only 3 had complete resolution at follow-up. Residual myocardial oedema was present in 2 patients. 31.7% exhibited fibrosis involving ≤2 segments, whereas 63.5% had extensive fibrosis, with a median of 3 (IQR 2–6) myocardial segments involved. In univariable analysis, greater baseline oedema extent (OR 1.32, 95% CI 1.10–1.60) and higher troponin levels (OR 2.53, 95% CI 1.19–5.41) were associated with more extensive fibrosis at follow-up. In multivariable analysis, baseline myocardial oedema extent remained the only variable associated with more extensive fibrosis, showing a strong trend toward independent association (OR 1.21, 95% CI 0.997–1.47; p=0.053) (Table 1). Conclusions Approximately two-thirds of patients develop myocardial fibrosis involving more than two segments following an acute myocarditis. The extent of myocardial oedema on index CMR emerged as the strongest determinant of subsequent fibrosis burden, underscoring the central role of acute inflammatory injury in long-term myocardial remodelling.Predictors of extensive fibrosisFor image description, please refer to the figure legend and surrounding text.