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MINI-FOCUS ISSUE: MYOCARDIAL AND PERICARDIAL INFLAMMATION

CASE REPORT: CLINICAL CASE

Left Ventricular Cavity ObliterationFrom Eosinophilic Myocarditis in a PatientWith Classic Hodgkin Lymphoma

Michael I. Brener, MD, Stefano Ravalli, MD

ABSTRACT

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A 43-year-old female with a history of hypereosinophilia developed acutely decompensated heart failure. Prototypical

features of eosinophilic myocarditis, including a distinctive left ventricular mass and severe mitral regurgitation,

were identified on a transthoracic echocardiogram. The patient’s eosinophilia was subsequently attributed to

Hodgkin lymphoma, and chemotherapy resolved her heart failure symptoms. (Level of Difficulty: Intermediate.)

(J Am Coll Cardiol Case Rep 2020;2:210–5) © 2020 The Authors. Published by Elsevier on behalf of the

American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license

(http://creativecommons.org/licenses/by-nc-nd/4.0/).

PRESENTATION

A 43-year-old female patient presented with short-ness of breath, hypotension, and tachycardia. Shedescribed progressive fatigue in the week leading upto admission and was referred to the emergencydepartment from an outpatient clinic for evaluationof resting hypoxia. The hemodynamics at admissionwere heart rate 104 beats/min, blood pressure88/45 mm Hg, respiratory rate 20, and SpO2 86% onroom air (100% when placed on noninvasive pressureventilation). On examination, the patient had dis-tended neck veins, a fourth heart sound, and mild

EARNING OBJECTIVES

Develop a differential diagnosis for intra-cardiac masses, particularly, left ventricularmasses.Appreciate the cardiac manifestations of a sys-temic condition such as hypereosinophilia.

N 2666-0849

m the Department of Medicine, Division of Cardiology, New York Presbyte

w York. Both authors have reported that they have no relationships rele

off, MD, MPH, served Guest Associate Editor for this paper.

ormed consent was obtained for this case.

nuscript received September 17, 2019; revised manuscript received Octob

pitting edema. Chest radiography revealed bilateralpleural effusions, pulmonary edema, and fluid in theminor fissure (Figure 1). Notable laboratory studiesfrom admission included an N-terminal pro–B-typenatriuretic peptide concentration of 3,771 pg/ml (up-per reference limit, 178 pg/ml) and elevated serumlactate concentration of 1.8 mmol/l (upper referencelimit, 1.6 mmol/l). An electrocardiogram showed nosigns of acute ischemia, and a computed tomography(CT) pulmonary angiogram showed no evidence of apulmonary embolus.

The history, examination, and laboratory data allpointed to a diagnosis of heart failure, prompting anurgent transthoracic echocardiogram (characteristicimages are highlighted in Figures 2 and 3; see alsoVideos 1, 2, 3, 4, 5, and 6). The echocardiogramrevealed an intracardiac mass within the left ven-tricular cavity, adjacent to the inferior and infero-lateral walls, with extension into the posterior mitralvalve leaflet. The left ventricular end-diastolicdimension was normal, but the mass obliterated the

https://doi.org/10.1016/j.jaccas.2019.10.046

rian-Columbia University Medical Center, New York,

vant to the contents of this paper to disclose. Adhir

er 17, 2019, accepted October 18, 2019.

FIGURE 1 PA Chest Radiograph

Posteroanterior (PA) chest radiograph demonstrates bilateral pleural effusions and pul-

monary vascular congestion.

AB BR E V I A T I O N S

AND ACRONYM S

CT = computed tomography

EM = eosinophilic myocarditis

WBC = white blood cell

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ventricular cavity during systole. In addition, therewas moderate left atrial enlargement and severemitral regurgitation (Figure 4). An echocardiogramperformed 6 months earlier showed none of theaforementioned findings were present (Figure 5).

MEDICAL HISTORY. Two years prior to the patient’spresentation, she underwent routine testing by herprimary care doctor and a complete blood count iden-tified marked hypereosinophilia (9.36 k WBC/mm3

with 45% eosinophils; upper reference limit, 4.9%).This finding prompted a number of subsequent testswhich revealed no evidence of an underlying ma-lignancy or myeloproliferative disorder, so her con-dition was diagnosed as primary eosinophilia andmanaged conservatively.

Three months prior to presentation, the pa-tient’s leukocytosis and eosinophilia progressed(20.06 WBC/mm3 with 73% eosinophils). She wasreferred to a hematologist and was started on imati-nib, 400 mg daily. However, she developed profounddiarrhea and treatment was stopped within 1 week.Shortly thereafter, the patient developed the symp-toms which brought her urgently to the authors’hospital.

DIFFERENTIAL DIAGNOSIS. This report presents thecase of a middle-aged female with symptoms of acuteleft heart failure and evidence of an intracardiac masson transthoracic echocardiography. The differentialdiagnosis for intracardiac masses is highlighted inTable 1. The differential of consequence can be nar-rowed based on the location of the intracardiac mass.In a seminal study by Dujardin et al. (1), among 75patients undergoing cardiac surgery for mass exci-sion, 8% had a mass located in the left ventricle.Mural thrombus accounted for one-half of all leftventricular masses, whereas lipomas and metastaticdisease were the next most common causes.

INVESTIGATIONS. The patient’s marked hyper-eosinophilia and echocardiogram led to a diagnosis ofeosinophilic myocarditis (EM). The echocardiogramfeatured many of the classic features of the throm-botic stage of the disease, including substantial muralthrombus, which was most pronounced in the inferiorand inferolateral walls, adjacent to the mitral valveand papillary muscle apparatus. The heart di-mensions were also inverted, with a small left ven-tricular cavity and a large left atrium. Furthermore,the condition often leads to mitral regurgitation,which was observed in this patient (Figure 4) as aconsequence of thrombus and, eventually, fibrosisdistorting the chordae tendinea, the mitral valveapparatus, and the leaflets themselves (2). The other

echocardiographic hallmarks of EM were notappreciated, including the “Merlon sign,”defined by basal hypercontractility andapical hypokinesis, and the “square-rootsign,” which describes septal and posteriorwall motion patterns on M-mode slices

through the mid-ventricle (3).

In light of these characteristic findings, advancedimaging such as cardiac magnetic resonance andcardiac biopsy were deferred. The patient ultimatelyunderwent a biopsy of a mediastinal mass, which wasdetected by cross-sectional imaging on presentationand classic Hodgkin lymphoma (nodular-sclerosingtype) was diagnosed. Further evaluation revealedthat her disease was restricted to lymph nodes abovethe diaphragm (Stage II) and that there were no otheradditional high-risk features.

MANAGEMENT. The patient presented originally inclinical heart failure and required hemodynamicoptimization prior to treatment of the underlyinglymphoid malignancy. Accordingly, diuresis andanticoagulation were commenced. Once her respira-tory status stabilized, chemotherapy with doxoru-bicin, vinblastine, and dacarbazine (AVD) wasadministered.

FIGURE 3 Images From Admission Transthoracic Echocardiography

Representative images from admission transthoracic echocardiography: (A) PLAX view in diastole. (B) PLAX view in systole. (C) PSAX view in diastole. (D) PSAX view in

systole. Abbreviations as in Figures 1 and 2.

FIGURE 2 PLAX View Illustrating a Large Mass

Parasternal long-axis (PLAX) view illustrates a large mass within the left ventricle emanating from the inferolateral wall.

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FIGURE 4 Color Doppler Images Illustrating Severe Eccentric Mitral Regurgitation

(A) Apical 4-chamber (A4C) view. (B) Color Doppler images illustrate severe, eccentric mitral regurgitation. (C) Apical 3-chamber (A3C) view. (D) Color Doppler images

demonstrate flow acceleration and nearly complete obstruction of the left ventricular outflow tract.

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DISCUSSION

Hypereosinophilia is defined by an absolute eosinophilcount in the peripheral blood>500 cells/mm3 andmayarise in the absence of an underlying cause (i.e., idio-pathic hypereosinophilic syndrome) or as a secondaryconsequence of many different conditions. Parasiticinfections, medication side effects (e.g., from antimi-crobials, antiretrovirals, medications with sulfa moi-eties, and non-steroidal anti-inflammatory drugs),autoimmune disorders, and hematologic malig-nancies, including classical Hodgkin lymphoma, arethe most common culprits of secondary hyper-eosinophilia (4). Eosinophilic tissue infiltration pro-duces the end-organ dysfunction associated with thecondition, and cardiac involvement occurs in mostcases. Pathophysiology is mediated by degranulationand release of eosinophils’ cardiotoxic cellular

contents, which activate intracardiac mast cells andlead to inflammation and fibrosis (5).

EM broadly characterizes the multiple cardiacmanifestations of hypereosinophilia, which rangefrom endomyocardial fibrosis resulting in a restrictivecardiomyopathy to valvular dysfunction related toLoeffler endocarditis to an eosinophilic coronaryarteritis. The condition has 3 distinct phases: 1) anacute inflammatory phase characterized by eosino-philic infiltration; 2) a thrombotic phase whereinflammation produces ventricular mural thrombi;and 3) a fibrotic phase where long-standing inflam-mation leads to a restrictive cardiomyopathy (5). Pa-tients progress through each of these phases atvariable paces. Symptoms and clinical presentationsdepend on the stage of EM. In the acute inflammatoryphase, patients develop heart failure symptoms andchest discomfort, which may mimic an acute coronary

FIGURE 5 Representative Images From Transthoracic Echocardiography Performed 6 Months Prior to Admission

(A) PLAX; (B) PSAX; (C) A4C; (D) apical 2-chamber view. Abbreviations as in Figures 1, 2, and 4.

TABLE 1

Neoplasm

Primary

Seconda

Non-neop

Benign

Miscella

Adapted fro

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syndrome. In the thrombotic phase, embolic compli-cations predominate. The fibrotic stage is typified byrestrictive heart failure physiology and prominentright heart dysfunction.

Differential Diagnosis of Intracardiac Masses

Common Rare

AngiosarcomaLeiomyosarcoma

LymphomaFibrous histiosarcoma

ry BreastLungRenalMelanoma

ThyroidHepaticAdrenalGenitourinary

lasms

masses MyxomaPrimary fibroelastomaHamartoma

LipomaRhabdomyomaFibroma

neous ThrombusVegetationCarcinoid

Calcified amorphous tumorInfiltrative disordersEndocardial disease

m Bruce (3).

Management hinges on prompt recognition of EMprior to the onset of irreversible fibrosis. Until tar-geted therapies for the underlying condition canbe initiated, patients should be treated withguideline-directed treatments for heart failure.Cardiogenic shock may complicate EM, and case re-ports describe the use of inotropes and mechanicalcirculatory support (6). Bradyarrhythmias from vary-ing degrees of atrioventricular block and tachyar-rhythmias such as ventricular tachycardia have alsobeen described in the context of EM (7). Anti-coagulation for mural thrombi is indicated as well.Once the patient is stabilized hemodynamically,therapy should be targeted at the underlying cause ofhypereosinophilia.

FOLLOW-UP. The present patient completed 1 cycleof chemotherapy without incident. Her peripheralblood eosinophil counts normalized immediately(4.20 WBC/mm3 with 1.4% eosinophils), and a repeatCT scan of her chest showed substantial reduction in

FIGURE 6 Representative PLAX Image From Echocardiography Performed

Approximately 2 Months Into Treatment

Note the regression of the mural thrombi compared with those in Figures 2 and 3.

PLAX ¼ parasternal long axis.

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tumor burden. She described no symptoms of heartfailure and no longer required diuretics. An echocar-diogram repeated 2 months into therapy demon-strated partial regression of the mural thrombus(Figure 6, Video 7).

CONCLUSIONS

This report describes a unique case of EM and Loefflersyndrome producing cavity-obliterating left ventric-ular thrombi and severe mitral regurgitation. Thepatient’s eosinophilia originated from Hodgkin lym-phoma, which was promptly treated with chemo-therapy, resulting in rapid resolution of her heartfailure symptoms.

ADDRESS FOR CORRESPONDENCE: Dr. MichaelBrener, New York Presbyterian-Columbia UniversityMedical Center, Department of Medicine, Division ofCardiology, 630 West 168th Street, PH 10-203, Box 93,New York, New York 10032. E-mail: mib2102@cumc.columbia.edu. Twitter: @MickeyBrener.

RE F E RENCE S

1. Dujardin KS, Click RL, Oh JK. The role of intra-operative transesophageal echocardiography inpatients undergoing cardiac mass removal. J AmSoc Echocardiogr 2000;13:1080–3.

2. Xie M, Cheng TO, Fei H, et al. The diagnosticvalue of transthoracic echocardiography foreosinophilic myocarditis: a single center experi-ence from China. Int J Cardiol 2015;201:353–7.

3. Bruce CJ. Cardiac tumors. In: Otto CM, editor.Textbook of Clinical Echocardiography. 6th edi-tion. Philadelphia: Elsevier, 2019:837–58.

4. Curtis C, Ogbogu P. Hypereosinophilic syn-drome. Clin Rev Allergy Immunol 2016;50:240–51.

5. Cheung CC, Constantine M, Ahmadi A, Shiau C,Chen LYC. Eosinophilic myocarditis. Am J Med Sci2017;354:486–92.

6. Howell E, Paivanas N, Stern J, Vidula H. Treat-ment of acute necrotizing eosinophilic myocarditiswith immunosuppression and mechanical circula-tory support. Circ Heart Fail 2016;9:e003665.

7. Wang TK, Watson T, Pemberton J, et al. Eosin-ophilic myocarditis: characteristics, diagnostics

and outcomes of a rare condition. Intern Med J2016;46:1104–7.

KEY WORDS diastolic heart failure,restrictive cardiomyopathy, ventricularthrombus

APPENDIX For supplemental videos,please see the online version of this paper.