Hong Yang,1,2 Wuyun Qidamugai,1,2 Luyun Wang,1,2 FuYang Liu,1 Yi He,1,2 Zheng Xu,3 Li Zhang,4 Fan Li,1,2 Hong Wang,1,2,* Jiangang Jiang1,2,* 

1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China; 3Division of Cardiology, Shanxi Bethune Hospital, Taiyuan, 030032, People’s Republic of China; 4Division of Cardiology, Minda Hospital of Hubei Minzu University, Enshi, 445099, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiangang Jiang, Division of Cardiology, Department of Internal Medicine Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email jiangjg618@126.com Hong Wang, Division of Cardiology, Department of Internal Medicine Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email hong_wang1988@126.com

Background: Although temporary mechanical circulatory supports (tMCS) combined with immunoregulatory therapy (IT) can reduce the mortality of patients with fulminant myocarditis (FM), a considerable proportion still progress to chronic persistent cardiac dysfunction. It is unclear if angiotensin-converting enzyme (ACE) inhibitors can further prevent such dysfunction under tMCS combined with IT.
Methods: This multicenter, retrospective, observational study included 124 FM patients with a left ventricular ejection fraction (LVEF) ≤ 40%. Among them, 90 (72.58%) received ACE inhibitors and 34 (27.42%) did not. Patients had echocardiography during follow-up. Logistic regression analysis, subgroup analysis, and restricted cubic spline modeling were used to identify clinical variables associated with the primary outcome.
Results: The primary outcome was defined as an LVEF < 55% at the last follow-up. The median follow-up was 12 (6, 18) months. 46 patients (37.1%) had an LVEF < 55% at the last follow-up. Among them, 25 (27.78%) received ACE inhibitors and 21 (61.76%) did not. In the non-ACE inhibitors group, LVEF declined from baseline over 24 months. Among the 49 patients (39.52%) with a left ventricular end-diastolic dimension (LVEDD) ≥ 5cm at admission, 29 (59.18%) had an LVEF < 55% at the last follow-up. 15 patients (51.72%) took ACE inhibitors and 14 (48.28%) did not. Multivariate logistic regression analysis revealed that ACE inhibitors (HR = 0.19, 95% CI: 0.04– 0.96, P = 0.045) and LVEDD (HR = 9.18, 95% CI: 2.73– 30.83, P < 0.001) were independently associated with an LVEF < 55% at the last follow-up, and the risk increased linearly with LVEDD (P for nonlinear > 0.05).
Conclusion: ACE inhibitors may improve left ventricular (LV) function and prevent chronic persistent cardiac dysfunction in FM patients. Although they can partially reverse LV remodeling, increased LVEDD during long-term follow-up may reduce their therapeutic benefits.

Keywords: fulminant myocarditis, chronic persistent cardiac dysfunction, angiotensin-converting enzyme inhibitors, left ventricular ejection fraction