Abstract Body (Do not enter title and authors here): Introduction: The outcomes of acute myocarditis are heterogeneous and can lead to clinically significant consequences. However, the patient characteristics associated with adverse outcomes at presentation are not fully understood.

Objection: To investigate the association between the presence or absence of prodromal symptoms and in-hospital mortality in patients admitted with acute myocarditis.

Methods: We analyzed multicenter data registry (Tokyo CCU Network Database, comprising 76 institutions in the Tokyo metropolitan area). The study included 261 cases with acute myocarditis from January 2017 to December 2020, among which 260 required hospitalization from the emergency department. Patients were grouped based on the presence or absence of prodromal symptoms prior to hospitalization. Prodromal symptoms include the following: (a) chest pain; (b) dyspnea; (c) fever; (d) ful-like symptoms; and (e) others.The primary outcome was in-hospital death.

Results: Among the 261 patients with acute myocarditis, 187 patients (71.6%) exhibited prodromal symptoms, and 74 patients (28.3%) did not. The primary outcome occurred in 19 patients (25.6%) without prodromal symptoms and in 20 patients (10.6%) with prodromal symptoms (hazard ratio, 2.87; 95% CI, 1.34 to 6.13; P=0.004, Figure 1A). A multivariable-adjusted Cox regression analysis confirmed that the absence of prodromal symptoms was an independent predictor of poor prognosis, even after adjusting for age, sex and the history of diabetes and hypertension. Notably, this trend was pronounced among patients with Killip classes 2-4, revealing higher in-hospital mortality rate in the patients without prodromal symptoms compared to those with prodromal symptoms (48.6% vs 11.7%; P < 0.001, Figure 1B).

Conclusions: This study demonstrates that the absence of prodromal symptoms in patients with acute myocarditis is an independent predictor of poor prognosis, especially for patients presented with Killip classes 2-4.