Cardiogenic shock treated with immunosuppression: a case presentation of acute fulminant eosinophilic myocarditis

Eosinophilic Myocarditis is a rapidly progressive form of myocarditis, associated with several underlying conditions including inammatory bowel disease. A 34-year old male with a history of Ulcerative Colitis on Iniximab presented with chest pain, dyspnoea and a recent febrile illness. Serum troponin levels were raised and ECG showed right bundle brunch block. Subsequent emergency coronary angiography showed unobstructed coronary arteries but echocardiography revealed severely impaired left ventricular function. He clinically deteriorated rapidly, developing atrio-ventricular block and cardiogenic shock requiring inotropic and mechanical circulatory support. Endomyocardial biopsy specimens showed diffuse eosinophilic inltration. Aggressive corticosteroid therapy was initiated and there was a gradual resolution of ventricular function. Peripheral eosinophil counts were within the normal range throughout the illness. Disease activity was monitored with multimodality imaging including PET-CT. Immunosuppression was maintained with Ciclosporin and Mycophenolate Mofetil, avoiding long-term steroid therapy.

unobstructed coronary arteries but echocardiography revealed severely impaired left ventricular function. He clinically deteriorated rapidly, developing atrio-ventricular block and cardiogenic shock requiring inotropic and mechanical circulatory support. Endomyocardial biopsy specimens showed diffuse eosinophilic in ltration. Aggressive corticosteroid therapy was initiated and there was a gradual resolution of ventricular function. Peripheral eosinophil counts were within the normal range throughout the illness. Disease activity was monitored with multimodality imaging including PET-CT.
Immunosuppression was maintained with Ciclosporin and Mycophenolate Mofetil, avoiding long-term steroid therapy.

Case Description
A 34-year old male presented with a 2 day history of intermittent chest pain and dyspnoea with generalised malaise and a febrile illness 5 days prior. He had a history of Ulcerative Colitis (UC) on In iximab, having previously developed pancreatitis secondary to Azathioprine. He had no risk factors for cardiovascular disease.
Emergency coronary angiography showed unobstructed coronary arteries and an initial attempt at right ventricular endomyocardial biopsy (EMB) was complicated by haemodynamically compromised complete heart block requiring temporary pacemaker insertion.
He was transferred to the intensive care unit (ICU) due to ongoing haemodynamic instability and a fever of 38.7, commenced on intravenous furosemide, milrinone and Co-Amoxiclav. The working diagnosis was of a fulminant myocarditis. Further deterioration evidenced by a cardiac index of 1.7l/min/m2, rising lactate and escalating inotropic requirements resulted in the insertion of an Impella CP® and a successful EMB. This showed orid myocarditis with diffuse in ltration of predominantly lymphocytes and eosinophils, con rming the diagnosis of Eosinophilic Myocarditis (EM). (See Figure 1).
He was commenced on 1g IV Methylprednisolone for 3 days followed by oral prednisolone (1mg/kg) but needed 3 further days of intravenous methylprednisolone 500mg due to a rising Troponin and lactate while switching to oral steroids. He was maintained on Hydrocortisone 80mg QDS and Mycophenolate The inotropes were successfully weaned and Impella explanted 7 days after insertion. A repeat TTE showed an improvement in LV function with an EF of 60%. Cardiac MRI showed global myocardial oedema and limited mid-wall brosis compatible with an acute myocarditis. The MMF dose was increased and His Hs-T began to persistently downtrend. He was discharged on Bisoprolol 1.25mg OD, Ramipril 5mg OD, MMF 1.5g BD, Spironolactone 25mg OD and Prednisolone 90mg OD to be reduced by 5mg per week.
An 18FDG PET-CT scan showed increased FDG uptake in the myocardium involving the septum, anterior and mainly lateral walls suggesting active in ammation (Figure 2a). Over the coming months, he was maintained on MMF 1.5mg BD with a tapering regime of prednisolone with the addition of Ciclosporin 100mg BD due to a mildly raised Troponin. After 5 months of treatment, a repeat 18FDG PET revealed the myocardial in ammation had completely resolved with no new areas of active in ammation (Figure 2b).
He remains stable on MMF and Ciclosporin.

Discussion
EM is a rare, rapidly progressing form of myocarditis characterised by marked eosinophilic in ltration and in ammation of the myocardium causing myocyte necrosis and endomyocardial brosis [1]. It may be associated with hypersensitivity reactions, intercurrent infection, malignancy or immune-mediated disorders, such as eosinophilic granulomatosis with polyangiitis (EGPA) or as part of a hypereosinophilic syndrome (HES) [2,3].
EM associated with Ulcerative Colitis (UC) has previously been described in the literature and is associated with more fulminant forms of myocarditis [4]. Myocarditis related to In iximab use has also been described, due to a hypersensitivity reaction, but this as the cause of myocarditis in this patient is unlikely given the absence of peripheral eosinophilia [5].
Though the vast majority (over 75%) of cases of EM have marked peripheral eosinophilia, particularly when associated with in ammatory bowel disease or hypersensitivity reactions, normal eosinophil counts in EM have rarely been described [6,7].
The clinical presentation and severity of EM can vary. According to a systematic review, patients with EM who develop arrythmias in the acute phase, tend to be ventricular tachycardia or brillation [8]. High grade atrio-ventricular block, as seen in this patient, has yet to be described and may be suggestive of advanced in ltration of the conduction pathways, re ective of the severity of his disease.
EM can rapidly cause cardiogenic shock and temporary mechanical support may be indicated in a minority of patients [8]. Despite advanced acute heart failure therapies and immunosuppression, the risk of in-hospital mortality remains high, thus prompt diagnosis and treatment are crucial to prevent adverse Currently, there is a lack of consensus regarding immunosuppression in these patients, particularly as maintenance therapy. There is evidence for the e cacy of corticosteroid therapy, and currently remain the basis of treatment for the majority of patients with EM. However, the duration of treatment and regimen for long-term immunosuppression remains controversial [10].
In this case, the patient had previously developed pancreatitis related to Azathioprine use. Therefore, the choice of long-term immunosuppression that would prevent relapse of UC and recurrence of EM, while avoiding the deleterious effects of long-term corticosteroid therapy, required careful consideration. Crucially, peripheral eosinophil count was not a reliable marker of adequate immunosuppression, having been within the normal range throughout his illness. This case highlights the role of using other tests such as circulating Troponin levels and evidence of myocardial in ammation on serial PET-CT imaging, as markers to re ect the degree of disease activity and thus adequacy of immunosuppressive therapy.
To our knowledge, this is the rst case reported in the literature of EM associated with UC in the absence of peripheral eosinophilia. This patient was maintained on long term immunosuppression with Ciclosporin and MMF, thereby avoiding long-term steroid use.
This case highlights the importance of prompt EMB in these patients to guide immunosuppression, the role of mechanical circulatory support to aid myocardial recovery, and the role of multi-modality imaging including TTE, CMR and PET-CT to assess for improvement in cardiac function and to monitor for response to treatment.
EM is a rare condition with potentially fatal consequences. The risk of EM recurrence, development of dilated cardiomyopathy or ventricular arrythmias is unknown. Given the lack of clinical trials for the treatment of EM, it is by encouraging the reporting and follow-up of cases of EM that a consensus can be made on the treatment and risk-strati cation of these patients.

Declarations
This study has been approved by local ethics committee and been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent for participation and publication
The patient involved in the case study has provided informed consent for their participation in the study and publication of the case report, including images of histology slides and PET-CT imaging.
Availability of data and material Not applicable

Code availability
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Authors' contributions
The listed authors (Dr. Chatrath and Dr.Dar) were both involved in the conception of the case report, acquisition of the data, drafted the work and revised it critically before approving the submitted version.  Figure 1 Eosinophilic in ltration in myocardium with myocyte necrosis (H&E stain x 200 and x400 magni cation). Figure 2 a -PET-CT images using 18F-FDG, showing increased FDG uptake (likely representing in ammation) mainly in the anterolateral wall of the myocardium and the anterolateral papillary muscle (arrows). b -PET-CT images using 18F-FDG showing almost complete resolution of FDG uptake along the anterolateral wall of the myocardium and with only FDG uptake persisting in the anterolateral papillary muscle (arrows).