Successful early steroid and anticoagulant treatment for Loeffler’s endocarditis related to eosinophilic granulomatosis with polyangiitis

Abstract

Loeffler’s endocarditis is cardiac damage mediated by hypereosinophilia with a poor prognosis. A 45-year-old woman with Loeffler’s endocarditis caused by eosinophilic granulomatosis with polyangiitis had hypereosinophilia (blood eosinophil count 32.4 × 10⁹/L) and left ventricular systolic and diastolic dysfunction (left ventricular ejection fraction 45%, e’ 5.1 cm/s). Echocardiography showed a left ventricular apical thrombus (32 × 30 mm). The cardiac magnetic resonance imaging scan showed a subacute thrombus (an iso-intensity area on T1-weighted images and a high-intensity area on T2-weighted images). We administered prednisolone and anticoagulant immediately. The eosinophil count rapidly decreased. After 8 weeks, the thrombus gradually decreased in size (28 × 17 mm) and cardiac function improved (left ventricular ejection fraction 58%, e’ 8 cm/s). On the follow-up cardiac magnetic resonance imaging scan, the thrombus gradually became organized (the high-intensity area on T2-weighted images became iso-intense). The subendocardial late gadolinium enhancement showed fibrosis only in a small part of the anterior left ventricular wall. Early steroids and optimal anticoagulant therapy may improve cardiac function and prognosis. Additionally, cardiac magnetic resonance imaging may be an important modality for diagnosis and follow-up.

<Learning objective: In patients with Loeffler’s endocarditis, early steroid treatment inhibits progression to the fibrotic stage and improves cardiac function. Anticoagulants decrease the size of the thrombus and also lead to improvement in left ventricular function. Cardiac magnetic resonance imaging can detect the phase of Loeffler’s endocarditis by identifying fibrosis and characteristics of the thrombus. Therefore, cardiac magnetic resonance imaging may be an important modality for diagnosis and follow-up.>

Introduction

Loeffler’s endocarditis is cardiac damage meditated by eosinophilic infiltration on the endocardium. Loeffler’s endocarditis related to eosinophilic granulomatosis with polyangiitis has rarely been reported previously [1]. Cardiac involvement is one of the important causes of death in eosinophilic granulomatosis with polyangiitis [2]. Patients with cardiac involvement have a poor prognosis and need immunosuppressive treatment as soon as possible [2], [3].

Case report

A 45-year-old woman complained of sensory loss in the left heel five months prior to presentation, but it disappeared by itself after one month. A visual field disorder in the right eye appeared three months prior to presentation, which improved after several days. She was admitted to our hospital because of numbness and pain in the back of the left lower leg and plantar foot, which had persisted for two months, and she also complained of dyspnea. She had a previous history of sinusitis and bronchial asthma (one year previously).

On admission, her blood pressure was 117/92 mmHg, pulse rate was 111 beats per minute, and body temperature was 38.0 °C. Cardiac murmur and breath sound abnormalities were not heard, and swelling was not revealed. However, the left toe muscles were weakened, and the Achilles tendon reflex in the left leg had disappeared. Both lower legs exhibited purpura. The physical findings suggested mononeuropathy and livedo reticularis.

Laboratory data on admission were as follows. The white blood cell count was 48.3 × 10⁹/L and eosinophil count was markedly increased (32.4 × 10⁹/L; 67%). The renal function was worsening (creatinine 1.23 mg/dL), and the serum C-reactive protein was 16.4 mg/dL. The antinuclear antibody titre was ×40, and antineutrophilic cytoplasmic antibody was negative. Troponin-I and N-terminal fragment pro-brain type natriuretic peptide were elevated (2.4 ng/mL and 19 × 10⁴ pg/mL). The nerve conduction test revealed that the left tibial nerve, left peroneal nerve, and both sural nerves were disordered, which was thought to be multiple mononeuropathy. The chest X-ray revealed heart enlargement, and electrocardiography showed negative T-waves in leads II, III, aVF, and V1-6 (Fig. 1A, B). The left ventricular ejection fraction was decreased to 45%, and a mass-like thrombus (32 × 30 mm) was observed in the left ventricular apex by transthoracic echocardiography (Fig. 2A-D). Mitral inflow velocity and mitral annular velocity showed diastolic dysfunction (e’ 5.1 cm/sec, E/e’ 14.1). Mitral regurgitation was mild, and pericardial effusion was revealed (Fig. 2A–D). There was no right ventricular involvement or right ventricular apical thrombus.

Fig. 1.

Chest X-ray showed enlargement of the cardiac silhouette (cardiac-to-thoracic width ratio: 58%) and no pleural effusions (A). Electrocardiography showed negative T-waves in leads II, III, aVF, and V1-6 and ST depression in lead V4-6 (B).

Fig. 2.

Transthoracic echocardiography on admission revealed pericardial effusion (arrows) and thrombus (32 × 30 mm) in the left ventricular apex (arrows) (A: parasternal long axis; B: mid-left ventricular parasternal short axis; C: apical left ventricular parasternal short axis and D; apical four-chamber).The thrombus in the left ventricular apex (arrows) gradually reduced in size; 31 × 16 mm after 4 weeks (E) and 28 × 17 mm after 8 weeks (F).

These examination findings indicated Loeffler’s endocarditis with hypereosinophilia, but cardiac biopsy was not performed. The etiology of the hypereosinophilia was determined to be eosinophilic granulomatosis with polyangiitis by the diagnostic criteria of the American College of Rheumatology (1. history of bronchial asthma, 2. eosinophilia, 3. multiple mononeuropathy, and 4. history of paranasal sinus abnormality) [4]. Early treatment was needed because of the cardiac involvement, and prednisolone 60 mg per day was administered orally beginning on day one. Anticoagulant therapy with intravenous heparin and enalapril was also administered.

Additional examinations were performed as follows. The bone marrow examination was undertaken on the next day. The bone marrow cells were negative for FIP1L1-PDGFRA fusion, and neoplastic disorder was unlikely. On brain magnetic resonance imaging, multiple cerebral infarctions were identified in the border zone (watershed) regions between the major cerebral supply arteries. The multiple cerebral infarctions were thought to be caused by micro-vascular injuries by eosinophilia or embolism by cardiac thrombus. Cardiac magnetic resonance imaging revealed a subacute thrombus in the left ventricular apex (which showed iso-intensity on T1-weighted images and high intensity on T2-weighted images) (Fig. 3A, B). Late gadolinium enhancement could not be performed because of renal dysfunction.

Fig. 3.

Cardiac magnetic resonance images on admission (A, B) and after 10 weeks (C, D, E, F). On admission, the thrombus in the left ventricular apex showed iso-intensity on T1-weighted images (A) and high intensity on T2-weighted images (B). After 10 weeks, the thrombus in the left ventricular apex reduced. The iso-intensity on T1-weighted images did not change (C) and the high intensity on T2-weighted images gradually became iso-intensity (D). Additionally, subendocardial late gadolinium enhancement was revealed in small part of the anterior left ventricular wall (arrows) in a two-chamber view (E) and a short axis view (F).

After 9 days, methylprednisolone 1000 mg per day intravenously was added to prednisolone orally for 3 days in order to reduce the dose of oral prednisolone. The eosinophil count and the serum C-reactive protein rapidly decreased and became normal on day 12. The pericardial effusion disappeared, and the enlargement of the cardiac silhouette was improved (cardiac-to-thoracic width ratio: 50% and 46% after 2 and 5 weeks, respectively). Additionally, brain natriuretic peptide concentration rapidly decreased (951 pg/mL on day 3, 124 pg/mL after 2 weeks, and 68 pg/mL after 5 weeks). The thrombus in the left ventricular apex gradually decreased in size (31 × 16 mm after 4 weeks, 28 × 17 mm after 8 weeks) on echocardiography (Fig. 2E and F). Left ventricular systolic and diastolic function also improved (left ventricular ejection fraction 56%, e’ 6.3 cm/s, E/e’ 10.8 after 4 weeks, and left ventricular ejection fraction 58%, e’ 8 cm/s, E/e’ 10 after 8 weeks). Furthermore, the neurological abnormalities and multiple cerebral infarctions on brain magnetic resonance imaging did not get worse. The prednisolone was gradually reduced, and heparin was changed to warfarin orally. After 10 weeks, follow-up cardiac magnetic resonance imaging was performed. The thrombus in the left ventricular apex reduced and high intensity on T2-weighted images gradually became iso-intensity (Fig. 3C, D). Additionally, cardiac magnetic resonance imaging revealed subendocardial late gadolinium enhancement in a small part of the anterior left ventricular wall (Fig. 3E, F).

The multiple cerebral infarctions did not expand, and no associated hemorrhages were observed on the follow-up brain magnetic resonance imaging (MRI) scan. Furthermore, the patient’s neurological abnormalities gradually improved with medical treatment and rehabilitation. Her condition did not worsen after reducing the dose of prednisolone, and she was discharged on prednisolone (15 mg per day) after 3 months.

Discussion

We diagnosed the patient with Loeffler’s endocarditis related to eosinophilic granulomatosis with polyangiitis, because she had hypereosinophilia and cardiac involvement (thrombus in the left ventricular apex) was detected by transthoracic echocardiography. We administered early treatment with steroids and anticoagulant. Hypereosinophilia and inflammation quickly improved, and the thrombus gradually diminished. In addition, cardiac systolic and diastolic function improved, and this contributed to a good clinical prognosis.

Loeffler’s endocarditis proceeds through three stages as follows: 1) an acute necrotic stage, 2) a thrombotic stage, and 3) a fibrotic stage [1], [5]. These stages could overlap and may not be clearly distinguished. First, eosinophils and lymphocytes infiltrate the endomyocardium, and degranulated eosinophil cationic protein induces endomyocardial necrosis and apoptosis (acute necrotic stage) [1], [5], [6]. Consecutively, a thrombus forms along the damaged myocardium [5]. Thrombi typically develop at the left and right ventricular apices (thrombotic stage) [1], [5]. These thrombi could be the cause of emboli such as cerebral infarctions [7]. Finally, the thrombi are replaced by fibrosis and scarring (fibrotic stage) [5]. Fibro-inflammatory remodelling of the valvular structures results in regurgitation of the mitral and tricuspid valves [1], [5]. In addition, endomyocardial fibrosis leads to diastolic dysfunction and restrictive cardiomyopathy [1], [5]. The valve disease and restrictive abnormality induce heart failure and worsen the prognosis. Cardiac magnetic resonance imaging can detect the phase of Loeffler’s endocarditis by identifying fibrosis and characteristics of the thrombus. In our patient, the follow-up cardiac magnetic resonance imaging scan showed that the thrombus gradually became organized (the high-intensity area on T2-weighted images became iso-intense). Additionally, the subendocardial late gadolinium enhancement showed fibrosis only in a small part of the anterior left ventricular wall. Therefore, cardiac magnetic resonance imaging may be an important modality for diagnosis and follow-up.

For the management of Loeffler’s endocarditis, control of blood eosinophil count is most important [6]. Early steroid treatment decreases eosinophilic infiltration and cationic protein [6]. This prevents the progression of cardiac damage in the endomyocardium and inhibits formation of thrombus and fibrosis. In some cases, steroids improve systolic function (left ventricular ejection fraction) and diastolic function (Doppler mitral inflow velocity) [1], [8]. Steroids may halt the progression of disease and improve survival [8]. In our case, we took a few days to diagnose eosinophilic granulomatosis with polyangiitis; however, we started to administer steroids on admission day because her condition was clearly associated with Loeffler’s endocarditis. Early steroid treatment inhibited progression to the fibrotic stage and improved the cardiac function (left ventricular ejection fraction and E/e’). Cardiac magnetic resonance imaging 10 weeks after admission showed small late gadolinium enhancement in a limited region of the left ventricular anterior wall. Late gadolinium enhancement can identify myocardial fibrosis in patients with Loeffler’s endocarditis [9]. In our patient, small late gadolinium enhancement meant that early steroid treatment could have prevented fibrosis. Early steroid treatment is considered to be one of the key drugs in patients with Loeffler’s endocarditis.

Anticoagulant therapy is reasonable if thrombi are indicated. Some case reports indicate that anticoagulant decreases the size of the thrombus [1], [8], [10]. The resolution of apical obliteration is associated with enlargement of the effective left ventricular cavity and consequent reduction of the ventricular filling pressure [10]. It also leads to improvement of left ventricular ejection fraction and diastolic function. In our patient, anticoagulant played effective roles in preventing worsening cerebral infarction and good positive remodelling of left ventricular function by apposition of the thrombus in the left ventricular apex. Cardiac magnetic resonance imaging can detect a ventricular thrombus with a higher degree of sensitivity and specificity than echocardiography [5]. Then physicians can decide how to use anticoagulant treatment effectively.

In conclusion, early diagnosis and treatment of Loeffler’s endocarditis is important. Early steroid treatment and optimal anticoagulant therapy may improve the cardiac function and prognosis.

Conflict of interest

The authors declare that there is no conflict of interest.