Eosinophilic Myocarditis: Is Endomyocardial Biopsy Essential for Diagnosis in the Era of Advanced Cardiac Imaging?

A 60-year-old female presented with dyspnea and chest pressure. Clinical presentation, laboratory data, echocardiography, and cardiac magnetic resonance (CMR) imaging findings confirmed diagnosis of eosinophilic myocarditis and obviated unnecessary invasive endomyocardial biopsy. She was treated with oral steroid and oral anticoagulation. Follow-up CMR imaging showed resolution of the left ventricle thrombus with improvement in endomyocardial inflammation. Copyright:

INTRODUCTION

Idiopathic hypereosinophilic syndromes (HESs) are characterized by persistently elevated eosinophil count (>1500 eosinophils/mm3), the absence of a primary and secondary cause of eosinophilia, and evidence of eosinophil-mediated end-organ damage.[123456] Cardiac involvement in idiopathic HES, eosinophilic myocarditis (EM), occurs in roughly half of patients and is associated with high morbidity and mortality. [1234578910] Therefore, early diagnosis and treatment of EM is crucial. Advanced cardiac imaging tools, echocardiography and cardiac magnetic resonance (CMR), can detect EM accurately and timely.[7101112] We present a case of HES with heart and lung involvement, stressing the role of advanced cardiac imaging.

CASE REPORT

A 60-year-old female with a medical history of hypothyroidism and tobacco and methamphetamine use presented with 3 days of worsening dyspnea and chest pressure. After initial evaluation at an outside hospital, she was transferred to our facility for further management. On arrival, her temperature was 98 F, pulse was 104 beats/min, blood pressure was 100/60 mmHg, and arterial oxygen saturation was 94% on 2 L of oxygen. Physical examination revealed a regular tachycardia with a 3/6 systolic murmur over the apex and decreased bilateral basilar lung sounds. She quit smoking 1 year prior, and her last methamphetamine use was 2 years prior. Differential diagnoses included acute coronary syndrome, pulmonary embolism (PE), acute heart failure, acute myocarditis, pneumonia, endocarditis, and methamphetamine toxicity.

Electrocardiography demonstrated sinus tachycardia with T-wave inversions in V2 through V6. Initial laboratories showed an elevated troponin 0.21 ng/ml (reference range: 0.0–0.04) and D-dimer 0.73 mcg/ml (reference range: 0.0–0.4). White blood cell count was elevated to 13,000/μl with an elevated absolute eosinophil count of 1900/μl (14.6%). Basic metabolic panel was unremarkable, as was urine drug screen.

Computed tomography (CT) angiography of the chest showed bilateral PE. Two-dimensional transthoracic echocardiography (TTE) and contrast TTE revealed left ventricle (LV) EF of 55%, Grade 3 LV diastolic dysfunction, moderate mitral regurgitation, and LV regional wall motion abnormality with a large laminated obliterating LV mid and apical thrombus [Figure 1a–c and Videos 1 and 2]. Coronary angiogram was normal. CMR showed LV endomyocardial edema on T2-weighted images, endomyocardial fibrosis, and extensive LV mural thrombus with obliteration of the LV cavity [Figures 2a and 3a], normal right ventricular function, and normal pericardium. To check for myocardial edema, we used a triple inversion recovery sequence using a T2-weighted black-blood single-shot fast spin-echo technique. To check for fibrosis, we used a T1-weighted postcontrast phase-sensitive inversion recovery technique to look for late gadolinium enhancement.

Figure 1

(a) Apical four-chamber two-dimensional image at end-diastole showing thrombus obliterating apical left ventricular cavity (arrowed). (b) Modified apical four-chamber two-dimensional image at end-diastole showing thrombus obliterating apical left ventricular cavity, extending into the mid-anterolateral left ventricular wall (arrowed). (c) Pulsed wave Doppler image of left ventricular inflow velocity showing Grade 3 left diastolic dysfunction. Note E/A >2, deceleration time 110 ms. (d) Apical four-chamber color Doppler image with baseline shift of Doppler scale showing moderate mitral regurgitation (Proximal isovelocity surface area ( PISA) radius 0.89 cm, effective regurgitant orifice area 0.34 cm2). (e) Apical four-chamber two-dimensional image with echo contrast at end-diastole showing space-occupying lesion in left ventricular apex due to laminated thrombus

Figure 2

(a) Cardiac magnetic resonance imaging. Apical two-chamber, left ventricle endomyocardial edema on T2-weighted images (arrow) and extensive left ventricle mural thrombus with obliteration of the left ventricle cavity (star). (b) Six-month follow-up cardiac magnetic resonance imaging. Apical two-chamber showing resolution of left ventricle thrombus (star) and improvement in myocardial edema (arrow)

Figure 3

(a) Cardiac magnetic resonance imaging, apical four-chamber, postcontrast late gadolinium enhancement images showing extensive subendocardial fibrosis (arrow) and left ventricle mural thrombus (star). (b) Cardiac magnetic resonance imaging, apical four-chamber, follow-up postcontrast late gadolinium enhancement images showing significant improvement of subendocardial fibrosis (arrow) and resolution of left ventricle mural thrombus (star)

The patient's hypercoagulable evaluation was unremarkable. There was no etiology for a hypersensitivity reaction. Secondary causes of hypereosinophilia, including parasitic infection, allergic, and pulmonary, were all negative. A bone marrow biopsy showed 3% blasts and no evidence of primary eosinophilic bone marrow disease. C-reactive protein was elevated 1.2 mg/dl (reference range: 0.0–0.9). Anti-neutrophil cytoplasmic antibodies were negative.

Intravenous (IV) heparin was started for bilateral PE and LV thrombus. Prednisone 60 mg oral was started for EM. During hospitalization, she developed respiratory distress and was transferred to the intensive care unit. Chest X-ray showed increased interstitial infiltrates of both lungs. She was started on high-flow oxygen. Chest CT showed significant progression of pulmonary infiltrates. Respiratory decompensation was felt to be from eosinophilic pneumonia. She was started on IV pulse steroids, 1 g methylprednisolone, for 3 days. Her eosinophilia improved and she responded rapidly. Steroids were tapered and she was discharged home on oral steroids and oral anticoagulation.

During follow-up, eosinophil counts initially rebounded, necessitating prolonged maintenance of low-dose steroid therapy. Follow-up CMR after 6 months showed normal biventricular function with resolution of LV mural thrombus, decreased subendocardial fibrosis, and improved endomyocardial edema [Figures 2b and 3b]. While her LV thrombus resolved on the follow-up CMR, she remained on oral anticoagulation indefinitely for unprovoked PE.

DISCUSSION

EM is a rare form of myocardial inflammation secondary to eosinophilic infiltration of the myocardium. Eosinophils remain viable in cardiac tissue for weeks, eventually degranulating and releasing toxic substances. These toxins damage endothelial cells and myocytes, causing necrosis and thrombosis which ultimately can lead to endomyocardial fibrosis.[467] The clinical course of EM varies from asymptomatic to life-threatening cardiogenic shock.[13479] EM has around 17%–22.3% inhospital mortality rate in case series.[19]

Echocardiography is the first diagnostic imaging tool in patients with suspected EM.[16] As mural fibrosis develops, LV compliance decreases resulting in restrictive cardiomyopathy [Figure 1c].[812] Fibrosis also affects the papillary muscles and chordae tendineae, resulting in mitral regurgitation [Figure 1d].[1812] The most distinctive feature of EM on TTE is the obliteration of the apex in the left, right, or both ventricles by laminar thrombus [Videos 1 and 2].[12681213] Contrast echocardiography is invaluable for differentiating LV thrombus from other causes of LV apical obliteration, such as hypertrophic cardiomyopathy [Figure 1e and Video 2].[61012]

CMR is a newer imaging tool for the diagnosis of myocardial disease in a patient with HES.[381013] CMR can provide detailed information about staging of EM and prognosis.[139101314] CMR can aid in differentiating EM from other forms of myocarditis. EM mostly affects the endocardial and subendocardial myocardium while other forms of myocarditis affect the epicardium and mid-myocardial area, a difference which can be detected by CMR imaging.[379]

There was high clinical suspicion for EM in our patient based on presentation and laboratory results. Typical TTE findings and CMR provided complementary diagnostic and prognostic information. Historically, endomyocardial biopsy (EMB) has been the “gold standard” for diagnosis of EM.[614] EMB has an estimated sensitivity of only 50% and can miss the diagnosis if the area biopsied is not involved.[139131415] EMB is an invasive procedure and carries a risk for iatrogenic complications.[13414] Moreover, in the absence of right ventricular involvement in our patient per CMR, it is quite conceivable that right ventricular EMB would have exposed the patient to increased risk without diagnostic benefit. In patients with uncertain diagnosis of EM and nonpathognomonic CMR findings, it is reasonable to use CMR to guide EMB to decrease the risk of complication and increase sensitivity.[34689]

Early diagnosis and treatment is critical to reduce morbidity and mortality. Thrombosis is common in EM.[126] Embolic events originating from the intracardiac thrombus are seen in up to 25% of EM cases.[261012] Early detection of intracardiac thrombosis and initiation of anticoagulation can prevent embolic events. Secondary causes of HES and primary hematologic diseases should be treated accordingly.[37] Corticosteroids remain the cornerstone of treatment for the different types of HES.[789] In steroid-resistant cases, tyrosine kinase inhibitor imatinib has been shown to be effective.[137] Here, early initiation of high-dose steroids and anticoagulation controlled the progression of the disease, preserved cardiac function, and prevented embolic complications.

CONCLUSIONS

EM is rare, and in the past, definitive diagnosis has required EMB. In our patient, the diagnosis and decision to proceed with specific therapy were based on a high index of suspicion gleaned from clinical and echocardiographic data, supported by confirmatory CMR findings. EMB should be reserved for patients in whom the diagnosis remains uncertain after noninvasive imaging.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.