Brown University, Providence, RI, USA
Clinical History
A 32-year-old woman with rheumatoid arthritis presented with worsening dyspnea on exertion, fatigue, and stable angina five weeks after initiation of abatacept therapy. At the time of admission her medications included leflunomide 10 mg PO daily, mesalamine 2400 mg PO BID, celecoxib 200 mg PO daily, divalproex sodium 500 mg PO daily, and warfarin 5 mg PO BID for a recently diagnosed right upper extremity deep venous thrombosis. Physical exam was notable for tachycardia and bilateral pitting lower extremity edema. Vital signs were otherwise within normal limits.
Electrocardiogram demonstrated sinus tachycardia and diffuse nonspecific T-wave inversions (Figure 1). Laboratory evaluation revealed a prothrombin time of 29.5 seconds (reference range 11.0-13.2 seconds) with an international normalized ratio of 3.2 (reference range 0.8-1.2). The complete blood count showed marked eosinophilia, with an absolute eosinophil count of 26,000 cells/uL, representing 79.5% of the differential (normal range, 0%–4%). Troponin I was within a normal range. A brain natriuretic peptide was elevated at 903 pg/mL (reference range 0-33 pg/mL). A transthoracic echocardiogram (TTE) revealed a mild reduction in biventricular systolic function with apical hypokinesis (Movie 1). A CT pulmonary angiogram showed no pulmonary embolism but did show focal patchy airspace disease and bronchial thickening consistent with inflammation.
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| Figure 1. A twelve lead electrocardiogram showing sinus tachycardia and non-specific T wave abnormalities. |
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| Movie 1. A TTE with apical 4 chamber (A), apical 2 chamber (B), and apical 3 chamber (C) views demonstrating mildly reduced left ventricular (LV) systolic dysfunction with apical akinesis. |
CMR Findings
Cardiac magnetic resonance (CMR) imaging was performed on a 1.5 Tesla Symphony scanner (Siemens Healthineers AG, Erlangen, Germany). CMR demonstrated mild biventricular systolic dysfunction with underfilled ventricular chambers, including a left ventricular end-diastolic volume (LVEDV) of 71 mL (indexed 43 mL/m²), left ventricular ejection fraction (LVEF) of 45%, and right ventricular ejection fraction (RVEF) of 47% (Movie 2). Biventricular apical intracavitary filling defects consistent with thrombi were identified, along with diffuse biventricular subendocardial late gadolinium enhancement (LGE), consistent with endocardial fibrosis (Figure 2).
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| Movie 2. Cine balanced steady state free precession (bSSFP) two chamber (A), three chamber (B), and four chamber (C) with mild biventricular systolic dysfunction and apical hypertrophy. |
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| Figure 2. Phase sensitive inversion recovery (PSIR) in a four chamber (A), two chamber (B), and apical short axis (C) views with subendocardial LGE in all apical segments and a small LV apical thrombus (orange arrow) and a small right ventricular apical thrombus (green arrow). |
Conclusion
The differential diagnosis included infectious etiologies, drug-induced myocardial injury, primary hypereosinophilic syndrome (HES), hypersensitivity reactions, rheumatologic disease, myeloproliferative disorders, and malignancy. An extensive diagnostic evaluation—including stool ova and parasite testing, infectious studies, tryptase, IgE levels, direct Coombs testing, and an acute hepatitis panel—was unrevealing. Antinuclear antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA) screens were positive; however, myeloperoxidase and proteinase-3 antibodies were negative. Based on the constellation of findings, the patient was diagnosed with drug-induced eosinophilic endocarditis (Löffler endocarditis), attributed to recent abatacept exposure. Abatacept was immediately discontinued, and immunosuppressive therapy was initiated with prednisone 60 mg orally once daily. Eosinophilia resolved within five days of treatment initiation.
The patient was treated with intravenous diuretics until euvolemic and was discharged on furosemide 20 mg orally once daily. Follow-up CMR performed four months later demonstrated resolution of both left and right ventricular thrombi and normalization of biventricular systolic function (LVEF 61%, RVEF 55%), with persistent diffuse biventricular subendocardial fibrosis (Figure 3). Warfarin was discontinued after six months of anticoagulation. No complications were noted during 10 months of follow-up.
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| Movie 3. Cine bSSFP two chamber (A), three chamber (B), and four chamber (C) showing normal biventricular systolic function. |
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| Figure 3. PSIR four chamber (A), two chamber (B), and three chamber (C) showing LGE in all apical segments and absence of apical thrombi. |
Perspective
Drug-induced eosinophilic endocarditis, or Löffler endocarditis, is a rare but potentially life-threatening manifestation of hypereosinophilic syndrome (HES), characterized by eosinophilic infiltration of the endocardium leading to inflammation, fibrosis, and myocardial dysfunction.[1,2] Clinical presentation is variable, ranging from asymptomatic disease to fulminant heart failure.[1,3] Ventricular thrombus formation may occur during the thrombotic stage of disease.[4,5]
In this case, CMR demonstrated classic features of eosinophilic endocarditis, including intracavitary thrombi and diffuse biventricular subendocardial LGE. When integrated with marked peripheral eosinophilia, a negative alternative diagnostic workup, and recent exposure to a novel immunomodulatory agent, these findings supported a diagnosis of abatacept-induced eosinophilic endocarditis.
Prompt discontinuation of the offending agent is central to management. Corticosteroid therapy may be used to suppress eosinophilic inflammation, while CMR plays a crucial role in diagnosis, assessment of disease severity, and longitudinal monitoring. Endomyocardial biopsy may be considered in select cases but is not routinely required.
Cardiac involvement is reported in up to 40–50% of patients with HES.[1,5] Early recognition and intervention are critical, as timely treatment may lead to clinical remission. This case underscores the value of follow-up CMR in assessing therapeutic response and excluding alternative etiologies of cardiomyopathy.
In conclusion, abatacept-associated eosinophilic endocarditis is a rare and poorly understood complication. Drug-induced eosinophilic endocarditis should be considered in patients who develop new-onset heart failure symptoms and marked eosinophilia following initiation of abatacept. Serial CMR provides a powerful tool for diagnosis and longitudinal assessment of treatment response.
References
- Polito MV, Hagendorff A, Citro R, Prota C, Silverio A, De Angelis E, Klingel K, Metze M, Stobe S, Hoffmann KT, Sabri O, Piscione F, Galasso G. Loeffler’s Endocarditis: An Integrated Multimodality Approach. J Am Soc Echocardiogr 2020;33(12):1427-1441.
- van Kessel DJ, Jerzewski A, Kardux JJ, Habets J. Loeffler’s endocarditis. Eur Heart J Cardiovasc Imaging 2015;16(3):343.
- Niemeijer ND, van Daele PL, Caliskan K, Oei FB, Loosveld OJ, van der Meer NJ. Loffler endocarditis: a rare cause of acute cardiac failure. J Cardiothorac Surg 2012;7:109
- Hagendorff A, Hümmelgen M, Omran H, Pizzulli L, Zirbes M, Bierhoff E, Sommer T, Pfeifer U, Kirchhoff PG, Nitsch J, Lüderitz B. Endokarditis fibroplastica Löffler im thrombotischen Stadium bei isolierter rechtsventrikulärer Gewebe-Eosinophilie [Löffler fibroblastic endocarditis in the thrombotic stages in isolated right ventricular tissue eosinophilia]. Z Kardiol. 1998 Apr;87(4):293-9.
- Brambatti M, Matassini MV, Adler ED, Klingel K, Camici PG, Ammirati E. Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes. J Am Coll Cardiol 2017;70(19):2363-2375.
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Case prepared by:
Pranav Bhagirath, MD, PhD
Editorial Team, Cases of SCMR
Department of Cardiology, Hospital Clínic Barcelona, Barcelona, Spain
