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.

Keywords

Fulminant myocarditis / intravenous immunoglobulin / in-hospital mortality / ECMO / organ dysfunction

References

[1] Kociol RD,Fang JC.Recognition and initial management of fulminant myocarditis: a scientific statement from the american heart association.Circulation2020;141:e69-92

[2] Drazner MH,Cooper LT.2024 ACC expert consensus decision pathway on strategies and criteria for the diagnosis and management of myocarditis: a report of the American College of Cardiology Solution Set Oversight Committee.J Am Coll Cardiol2025;85:391-431

[3] Ammirati E,Adler ED.Management of acute myocarditis and chronic inflammatory cardiomyopathy: an expert consensus document.Circ Heart Fail2020;13:e007405 PMCID:PMC7673642

[4] Schulz-Menger J,Gröschel J.2025 ESC guidelines for the management of myocarditis and pericarditis.Eur Heart J2025;46:3952-4041

[5] Nunez JI,Reyes-Castro T.Outcomes with peripheral venoarterial extracorporeal membrane oxygenation for suspected acute myocarditis: 10-year experience from the extracorporeal life support organization registry.Circ Heart Fail2023;16:e010152

[6] Schmidt M,Huang F.Temporary mechanical support in fulminant myocarditis: prognostic factors and clinical implications from the FULLMOON study.Intensive Care Med2026;52:240-51

[7] Tschöpe C,Bozkurt B.Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.Nat Rev Cardiol2020;18:169-93 PMCID:PMC7548534

[8] Ammirati E,Varrenti M.Acute myocarditis: 2024 state of the art.Eu Heart J Suppl2025;27:i56-60 PMCID:PMC11836720

[9] Schwab I.Intravenous immunoglobulin therapy: how does IgG modulate the immune system?.Nat Rev Immunol2013;13:176-89

[10] Danieli MG,Gammeri L.Intravenous immunoglobulin as a therapy for autoimmune conditions.Autoimmun Rev2025;24:103710

[11] Robinson J,Vandermeer B,Klassen TP.Cochrane Heart GroupIntravenous immunoglobulin for presumed viral myocarditis in children and adults.Cochrane Database Syst Rev2020;8:CD004370 PMCID:PMC8210245

[12] Mcnamara DM,Starling RC.Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy.Circulation2001;103:2254-9

[13] Huang X,Su G,Shuai X.Intravenous immunoglobulin therapy for acute myocarditis in children and adults: a meta-analysis.Int Heart J2019;60:359-65

[14] Zhou N,Jiang J.Impact of mechanical circulatory support and immunomodulation therapy on outcome of patients with fulminant myocarditis: Chinese registry of fulminant myocarditis.Sig Transduct Target Ther2021;6:350 PMCID:PMC8492670

[15] Yu D,Ma G.Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: a retrospective study.Exp Ther Med2014;7:97-102 PMCID:PMC3861110

[16] Thai TBT,Nguyen HS.Effect of intravenous immunoglobulin and steroids in acute myocarditis in children: a systematic review and network meta-analysis.Pediatr Res2026;4655

[17] Nimmerjahn F.Anti-inflammatory actions of intravenous immunoglobulin.Annu Rev Immunol2008;26:513-33

[18] Shock A,Nimmerjahn F.Dissecting the mechanism of action of intravenous immunoglobulin in human autoimmune disease: lessons from therapeutic modalities targeting Fcγ receptors.J Allergy Clin Immunol2020;146:492-500

[19] Leuschner F,Dutta P.Silencing of CCR2 in myocarditis.Eur Heart J2015;36:1478-88 PMCID:PMC4465633

[20] Wang Y,Yu S.Neutrophil CAPNS1 regulates cardiac inflammation and injury by promoting NETosis in CVB3-induced myocarditis.Free Radic Biol Med2026;248:500-15

[21] Mantri M,Mckellar DW.Spatiotemporal transcriptomics reveals pathogenesis of viral myocarditis.Nat Cardiovasc Res2022;1:946-60 PMCID:PMC10035375

[22] Ueda T,Hatano M.Prognostic factors associated with early recovery from veno‐arterial extracorporeal membrane oxygenation support in patients with fulminant myocarditis.J Am Heart Assoc2025;14:e039673 PMCID:PMC12229129

[23] Hsu HR,Grover J.Predictors of successful weaning from veno-arterial extracorporeal membrane oxygenation (V-A ECMO): a systematic review and meta-analysis.PLoS ONE2025;20:e0310289 PMCID:PMC11922212

[24] Cooper LT,Feldman AM.The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology.Circulation2007;116:2216-33

[25] Baumeier C,Aleshcheva G,Escher F.Advancing precision medicine in myocarditis: current status and future perspectives in endomyocardial biopsy-based diagnostics and therapeutic approaches.J Clin Med2023;12:5050 PMCID:PMC10419903

[26] Ferreira VM,Holmvang G.Cardiovascular magnetic resonance in nonischemic myocardial inflammation.J Am Coll Cardiol2018;72:3158-76

[27] Caobelli F,Galea N.Cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) imaging in the diagnosis and follow-up of patients with acute myocarditis and chronic inflammatory cardiomyopathy: a review paper with practical recommendations on behalf of the European Society of Cardiovascular Radiology (ESCR).Int J Cardiovasc Imaging2023;39:2221-35 PMCID:PMC10674005

[28] Caforio ALP,Gimeno JR.Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.Eur Heart J2024;45:2548-69

[29] Thomas LE,Pencina MJ.Overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial.JAMA2020;323:2417

[30] Hernán MA,Hernández-Díaz S,Shrier I.Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses.J Clin Epidemiol2016;79:70-5 PMCID:PMC5124536

[31] Ammann EM,Fillman KM.Intravenous immune globulin and thromboembolic adverse events: a systematic review and meta‐analysis of RCTs.Am J Hematol2016;91:594-605

[32] Kobayashi RH.Immune globulin therapy and kidney disease: overview and screening, monitoring, and management recommendations.Am J Health Syst Pharm2022;79:1415-23 PMCID:PMC9389421