Intravenous immunoglobulin use and in-hospital outcomes in adult fulminant myocarditis: a two-center retrospective cohort study

Abstract

Aim: To examine the association between intravenous immunoglobulin (IVIG) use and in-hospital outcomes in adults with fulminant myocarditis (FM). Methods: This two-center retrospective cohort study included 316 adults hospitalized with FM between January 2020 and January 2025; 184 received IVIG, and 132 did not. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were a composite of acute liver injury (ALI) or Kidney Disease: Improving Global Outcomes-defined acute kidney injury (AKI) and successful extracorporeal membrane oxygenation (ECMO) weaning with survival to discharge. We evaluated associations using multivariable and time-dependent Cox models, an analysis restricted to methylprednisolone-treated patients, propensity-score overlap weighting, Aalen-Johansen cumulative-incidence analyses, and Fine-Gray competing-risk models. Dose- and timing-related analyses were exploratory. Results: In-hospital death occurred in 17 of 184 IVIG-treated patients (9.2%) and 51 of 132 non-IVIG-treated patients (38.6%). IVIG use was associated with lower mortality across multiple models, including the multivariable Cox model (hazard ratio [HR], 0.23; 95% confidence interval [95%CI]: 0.14-0.40; P < 0.001), the time-dependent model (HR, 0.15; 95%CI: 0.08-0.29), the methylprednisolone-treated cohort (HR, 0.15; 95%CI: 0.08-0.27), and the overlap-weighted analysis (HR, 0.24; 95%CI: 0.07-0.87). ALI/AKI occurred in 53 of 184 IVIG-treated patients (28.8%) and 72 of 132 non-IVIG-treated patients (54.5%; adjusted HR, 0.43; 95%CI: 0.30-0.61; P < 0.001). Among ECMO-supported patients, successful weaning with survival to discharge occurred in 50 of 61 IVIG-treated patients and 6 of 18 non-IVIG-treated patients (subdistribution HR, 5.89; 95%CI: 2.96-11.73; P < 0.001). Exploratory dose- and timing-related estimates did not establish an optimal IVIG regimen. Conclusions: In this two-center retrospective cohort, IVIG use within a corticosteroid-containing care pathway was associated with lower in-hospital mortality, less ALI/AKI, and a greater likelihood of successful ECMO weaning with survival. Residual and unmeasured confounding preclude causal inference; prospective multicenter validation is required.