Hypereosinophilic syndrome: a rare cause of ST-elevation myocardial infarction and thrombus formation on the aortic valve

Abstract

We present a case of a man in his 30s presenting with ST-segment elevation myocardial infarction and eosinophilia. The patient underwent thrombus aspiration and initially echocardiographic evaluation was normal. The patient was discharged after 2 days, but was hospitalised again after 6 days. Echocardiographic evaluation now revealed a thrombus formation on the aortic valve. Laboratory data revealed increasing eosinophilia, and treatment with high-dosage corticosteroids and hydroxyurea was initiated as eosinophilic disease with organ manifestations could not be precluded. Eosinophils normalised and the patient was discharged again. The combination of hypereosinophilia and absence of infection, rheumatological disorders and malignancy, led to reactive or idiopathic hypereosinophilic syndrome being the most plausible diagnoses. The patient was closely monitored in the cardiology and haematology outpatient clinics. Echocardiographic evaluation, performed 6 weeks after the patient was discharged, showed significant regression in the size of the thrombus mass.

Background

Hypereosinophilic syndrome (HES) is defined as absolute eosinophil counts exceeding 1500 cells/mL in peripheral blood for more than 6 months, causing damage to one or more organs.¹ Cardiac involvement has been reported in up to 40–50% cases and is considered the most common cause of mortality due to HES.^{2 3} While mural thrombosis, ventricular dilation and mitral involvement are described as the most common cardiac manifestations, ST-segment elevation myocardial infarction (STEMI) and aortic valve involvement have rarely been reported.^{3 4} This case report describes an extremely rare case of HES presenting as STEMI and thrombus formation on the aortic valve.

Case presentation

A man in his 30s, treated for obesity with the GLP-1 analogue semaglutide but otherwise healthy, was admitted to the emergency department with acute onset of epigastric pain and chest pain radiating to the left arm. One week prior to hospitalisation, the patient had experienced symptoms of gastroenteritis, primarily vomiting and diarrhoea without contacting the health system. The ECG showed ST-segment elevations in leads II-III, aVF and precordial V5-V6, compatible with inferior STEMI. Subsequently, cardiac catheterisation revealed a thrombus in the proximal part of right coronary artery. The patient was treated with thrombectomy without implantation of any stents as complete revascularisation was achieved after aspiration of the thrombus and no residual stenosis was observed (figure 1) (video 1).

Figure 1.

Coronary angiography of the right coronary artery revealing embolisation.

Video 1. Coronary angiography of the right coronary artery revealing embolisation.

bcr-2023-259494supp001.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2023-259494.video01

On admission, laboratory data revealed leucocytosis (19.3×10⁹ /L) with eosinophilia (0.93×10⁹ /L), neutrophilia (13.0×10⁹ /L), elevated haemoglobin values (11.6 mmol/L) and C reactive protein (CRP) 12 mg/L (reference value <6.0). Polycythemia vera was considered a possible diagnosis, though dehydration due to gastroenteritis with secondary haemoconcentration was deemed more plausible, as haemoglobin normalised after fluid management.

The patient underwent a comprehensive evaluation to rule out potential sources of embolism and endocarditis, including transthoracic, and transoesophageal echocardiography (TEE) with the use of saline-contrast and full blood analysis including blood culture. We found no signs of atrial septal defect, patent foramen ovale, left atrial appendage or left ventricular thrombi and no valvular lesions.

Two days after hospitalisation, the patient was discharged with a planned subsequent evaluation in the haematology outpatient clinic. However, the patient was re-hospitalised 6 days after the first admission due to abdominal pain and discomfort. The new transthoracic echocardiographic evaluation was suggestive of a novel thickening of the aortic valves. The subsequent TEE revealed a new 2×2 cm size mass adhering to the non-coronary aortic cusp, but with otherwise no indication of valvular insufficiency, myocardial infiltrative disease or ventricular regional wall abnormalities (figures 2 and 3) (videos 2 and 3). Treatment with low-molecular weight heparin and antibiotics were initiated as thrombus or vegetation were interpreted the most likely causes. A cardiac MRI scan was performed with no signs of gadolinium uptake in the mass consistent with a thrombus adhering to the non-coronary aortic valve cusp. Furthermore, the MRI showed mild sequelae from an inferior infarction assessed by subendocardial late gadolinium enhancement and distal hypokinesia of the left ventricle. Left ventricular ejection fraction was 57% and described as discretely reduced.

Figure 2.

Transoesophageal echocardiography from second hospitalisation showing thrombus formation on the non-coronary aortic cusp. Short-axis view at aortic valve level.

Figure 3.

Transoesophageal echocardiography from second hospitalisation showing thrombus formation on the non-coronary aortic cusp. Long-axis view.

Video 2. Transoesophageal echocardiography from second hospitalisation showing thrombus formation on the non-coronary aortic cusp. Short-axis view at aortic valve level.

bcr-2023-259494supp002.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2023-259494.video02

Video 3. Transoesophageal echocardiography from second hospitalisation showing thrombus formation on the non-coronary aortic cusp. Long-axis view.

bcr-2023-259494supp003.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2023-259494.video03

Laboratory data again showed leucocytosis (11.9×10⁹ /L), but now with moderate eosinophilia (3.1×10⁹ /L) and CRP 28 mg/L. Blood cultures were negative. HES was suspected and semaglutide was discontinued to eliminate the possibility of it contributing to a reactive condition. 100 mg prednisone daily was ordinated. PET-CT, done to rule out malignancy, revealed heavy FDG-uptake in the pharyngeal tonsils. Tonsillectomy demonstrated eosinophilic infiltration, but with no signs of malignancy. Bone marrow biopsy showed normal cellularity with eosinophilia (8%) and no morphological signs of lymphoid or myeloid disease. No dysplasia was observed and blast counts were normal. Cytogenetics, PCR and myeloid oncomine next-generation sequencing panel were normal including negative KIT D816 and JAK-2 mutations and negative FIP1L1-PDGFRa and ETV6-PDGFRb gene fusions. Flow cytometry identified a small population of TRBC1-negative T-lymphocytes, but the immune profile did not match any classic cytokine-producing T-cell populations, and the clone was concluded to be reactive. Furthermore, ANCA titres were negative ruling out the diagnosis of ANCA associated vasculitis. Microscopic examination of faeces revealed no signs of parasites. Reactive or idiopathic HES was considered the most plausible diagnosis.

As eosinophilia persisted after 7 days of corticosteroid therapy, hydroxuyrea was initiated leading to normalisation of eosinophils (0.49×10⁹ /L) on the 12th day.

There was still no regression of the aortic valve mass; however, the patient was considered in stable condition and discharged from the hospital on prednisone, hydroxyurea and warfarin with a planned close follow-up at the cardiology and haematology outpatient clinics.

TEE performed in the outpatient clinic 6 weeks after the patient was discharged revealed significant regression in the thrombus mass, which now measured 1.0×0.7 cm. Reactive HES due to semaglutide was considered possible, and a gradual reduction in prednisone dose was initiated as eosinophils were normalised. Prednisone and hydroxyurea were discontinued 8 weeks after the patient was discharged. The patient is in good shape with no sequelae. Semaglutide has not been restarted.

Discussion

HES is a group of presumed underreported rare haematological disorders defined by eosinophilia exceeding 1500 cells/mL in peripheral blood persisting for over 6 months, resulting in damage to one or more organs due to eosinophilic inflammation.¹ Identifying a possible underlying secondary cause is vital for selecting the appropriate treatment of the condition.

Malignancies, infections, allergies, rheumatological disorders and drug reactions should all be explored. In the absence of a secondary cause and exclusion of primary haematological clonality, the condition can be termed idiopathic.⁵

Cardiac involvement is observed in up to 40–50% of cases of HES, and is the most frequent cause of HES-related mortality.^{2 3} Clinically, cardiac manifestations in HES often include formation of mural thrombosis in the apex of both left and right ventricles, endocardial thickening, dilation of the left ventricle and involvement of the posterior mitral leaflet leading to mitral regurgitation.^{3 4}

From a pathological standpoint, cardiac involvement in HES comprises three well-described stages. Initially, eosinophilic infiltration causes endocardial necrosis. This initial stage is followed by the formation of mural thrombosis at the inflammation site. Eventually, the thrombus is replaced by fibrosis, potentially leading to restrictive or dilated cardiomyopathy. This progression might also affect the heart valves, resulting in reduced mobility and valvular incompetence.⁶

To our knowledge, the uncommon presentation of HES with thrombosis formation at the aortic valve has only been reported once.⁷ Additionally, myocardial infarction is a rarely reported complication of HES, previously reported as caused by endomyocardial fibrosis and thrombus formation in the left ventricular outflow tract.^{8 9} The combination of HES presenting as myocardial infarction followed by thrombosis on the aortic valve, makes this case particularly unique.

In our case, the patient presented with STEMI likely caused by embolisation. Yet, the absence of ASD, PFO or signs of mural thrombosis in the initial TEE-examination suggests the emboli might have originated from a thrombus at the aortic valve. Multiple thrombus formations at the aortic valve are plausible, with a subsequent thrombus observed during the TEE in the patient’s second hospitalisation.

In this case, we based the diagnosis on peripheral eosinophilia and eosinophilic infiltration in the bone marrow and tonsils combined with clinical presentation as STEMI caused by embolisation. The time criteria for HES was not fulfilled, however eosinophil counts had not been measured within the last 10 years and treatment could not be delayed due to the life threatening symptoms. It is important to note that organ manifestations were already present at eosinophil counts below the diagnostic criteria for HES, which could question the diagnosis. Literature however suggests that there are no linear correlation between eosinophil counts and the severity of organ manifestations.¹⁰

The patient had begun treatment with semaglutide a few weeks before the incidence, and this drug was considered a possible cause as hypereosinophilia related to treatment with semaglutide has earlier been reported.¹¹ However, despite discontinuing semaglutide, eosinophil counts continued to rise despite treatment with high doses of prednisone, which raised doubts about semaglutide as the triggering factor of a reactive condition.

Replacement of the native aortic valve with a mechanical valve, was considered to minimise the risk of further embolisation. However, concerns of surgery related risks and prospective lifelong warfarin treatment in a young patient deemed a conservative approach to preserve the native aortic valve more favourable.

Learning points.

• Hypereosinophilic syndrome (HES) is a rare cause of cardiac mural and valvular thrombus formation.

• HES can rarely cause coronary embolisation and should be considered as differential diagnosis, especially in younger individuals presenting with symptoms of myocardial infarction and persistent unexplained eosinophilia.

• Treatment with prednisone, hydroxyurea and heparin or surgical replacement of the aortic valve should be considered in HES with aortic valve thrombosis, taking both the risk of further embolisation and surgery related risks into concern.

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