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T H E C C B Y - N C - N D L I C E N S E ( h t t p : / / c r e a t i v e c o mm o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 / ) .

CASE REPORT

CLINICAL CASE

Multimodal Imaging for the Diagnosis ofIsolated Cardiac Sarcoidosis

David W. Louis, MD,a Alexa Papaila, MD, MPH,a Wasiq Sheikh, MD,a Michael K. Atalay, MD, PHD,b

Brian G. Abbott, MDa

ABSTRACT

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We report a case of isolated cardiac sarcoidosis (CS) diagnosed using a multimodality imaging approach. A patient pre-

sented after an out-of-hospital, ventricular fibrillation–mediated cardiac arrest. The use of echocardiography, cardiac

magnetic resonance, and fluorodeoxyglucose-positron emission tomography enabled the diagnosis of isolated CS.

(Level of Difficulty: Beginner.) (J Am Coll Cardiol Case Rep 2020;2:1074–8) © 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/).

HISTORY OF PRESENTATION

A 72-year-old Caucasian woman with a history ofadvanced atrioventricular (AV) block with AV disso-ciation presented after an out-of-hospital, ventricularfibrillation–mediated cardiac arrest. Physical exami-nation was notable for elevated jugular venous pres-sure, bibasilar crackles, and cool extremities withoutedema. Limited bedside echocardiogram revealedsevere left ventricular (LV) dysfunction and regionalwall motion abnormalities (RWMAs). Emergency

EARNING OBJECTIVES

CS should be suspected in patients withnonischemic cardiomyopathy, cardiac con-duction disease, and ventricular arrhythmias.A multimodality imaging approach should beutilized when diagnosing CS.Updated guidelines now allow for a clinicaldiagnosis of CS without endomyocardialbiopsy.

N 2666-0849

m aThe Lifespan Cardiovascular Institute, Warren Alpert Medical SchoolbDepartment of Diagnostic Imaging, Warren Alpert Medical School of B

rs have reported that they have no relationships relevant to the content

e authors attest they are in compliance with human studies committees

tutions and Food and Drug Administration guidelines, including patient co

JACC: Case Reports author instructions page.

nuscript received February 14, 2020; revised manuscript received April 2

coronary angiography revealed nonobstructive coro-nary artery disease.

PAST MEDICAL HISTORY

The patient’s medical history included hypothyroid-ism and asymptomatic advanced AV block of un-known duration for which she had refused permanentpacemaker placement.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis for nonischemic cardio-myopathy (NICM) includes infiltrative disease(sarcoidosis and amyloidosis), acute myocarditis(idiopathic giant cell myocarditis, necrotizing eosin-ophilic myocarditis, and lymphocytic myocarditis),stress-induced cardiomyopathy, left ventricularnoncompaction cardiomyopathy, and hypertrophiccardiomyopathy, as well as cardiotoxic drugs (che-motherapeutics), thyroid disease, and illicit sub-stances (cocaine, amphetamines).

https://doi.org/10.1016/j.jaccas.2020.05.021

of Brown University, Providence, Rhode Island; and

rown University, Providence, Rhode Island. The au-

s of this paper to disclose.

and animal welfare regulations of the authors’ in-

nsent where appropriate. For more information, visit

5, 2020, accepted May 6, 2020.

AB BR E V I A T I O N S

AND ACRONYM S

CMR = cardiac magnetic

resonance

CS = cardiac sarcoidosis

FDG = fluorodeoxyglucose

PET = positron emission

tomography

J A C C : C A S E R E P O R T S , V O L . 2 , N O . 7 , 2 0 2 0 Louis et al.J U N E 1 7 , 2 0 2 0 : 1 0 7 4 – 8 Multimodal Imaging for the Diagnosis of Isolated Cardiac Sarcoidosis

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INVESTIGATIONS

Notable laboratory findings on arrival included a peaktroponin-I of 0.028 ng/ml, brain-type natriureticpeptide of 585 pg/ml, whole blood lactate of3.7 mmol/l, and serum creatinine 1.18 mg/dl. Com-plete blood count, basic metabolic panel, thyroidfunction tests, and liver function tests were otherwisewithin normal limits. Admission 12-lead electrocar-diogram (Figure 1) revealed varying PR conduction,trigeminy, right bundle branch block, left anteriorfascicular block, and ST-segment depressions in V2 toV6. Transthoracic echocardiogram revealed an LVejection fraction of 15% to 20% and a tricuspidannular plane systolic excursion of 10 mm. ExtensiveRWMAs were noted with diffuse akinesis of theinferoseptal, inferior, inferolateral, anterolateral, andanterior wall segments, and hypokinesis of the basaland mid-anteroseptal walls. Grade III diastolicdysfunction was noted. Strain imaging was notperformed.

Cardiac magnetic resonance (CMR) was performedrevealing global hypokinesis of the LV with severelyreduced systolic function and extensive areas of bothtransmural and subepicardial late gadoliniumenhancement (LGE) throughout most basal segments,

FIGURE 1 Initial Electrocardiogram

Electrocardiography post-cardiac arrest: varying PR conduction, trigemin

T-wave inversions in V2 to V6.

as well as patchy subepicardial LGE in themid-ventricular and apical segments(Figure 2). No hilar adenopathy was noted.Given our high index of suspicion for isolatedcardiac sarcoidosis (CS), fluorodeoxyglucose(FDG) positron emission tomography (PET)with computed tomography (CT) imaging wasperformed, which demonstrated increasedFDG uptake in the septal, distal anterior, and

mid-to-basal inferior walls of the LV and apicalanterior wall of the right ventricle (Figures 3A to 3C,Figure 4). Single-photon emission CT (SPECT) perfu-sion abnormalities were seen on the accompanyingresting myocardial single-photon emission CT perfu-sion images, most prominently involving the septum(Figures 3D to 3F). Areas of FDG uptake on PET/CTcorrelated to areas of LGE on CMR.

MANAGEMENT

A diagnosis of isolated CS was established. The pa-tient was initiated on oral prednisone along withlisinopril and spironolactone. Beta blockade was nottolerated. Amiodarone was given to decrease furtherrisk of ventricular arrhythmias. An implantablecardioverter-defibrillator was placed.

y, right bundle branch block, left anterior fascicular block, and deep

FIGURE 2 Cardiac Magnetic Resonance Imaging

Late gadolinium enhancement (acquired using inversion-recovery with spoiled gradient echo readout) short-axis (A to C) and long-axis

(D to E) images showing a nonischemic hyperenhancement pattern (arrows). T2-weighted midventricular short-axis image (F) acquired using

short-tau inversion recovery with fast spin echo readout and 51 ms echo time demonstrating heterogenous high signal (arrows) consistent

with edema in the septal and anterior segments.

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DISCUSSION

Sarcoidosis is a multisystem disease propagatedlargely by overactivation of tissue macrophagesleading to variable combinations of bilateral hilarlymphadenopathy, pulmonary, cardiac, neurologic,bone, ophthalmic, or dermatologic involvement. CSappears to be underdiagnosed by clinicians, as au-topsy records have documented cardiac involvementin upwards of 25% of patients with known sarcoid-osis. Epidemiological studies have found significantlyhigher rates of CS in Japanese women over the age of50 years and African Americans (1).

Signs and symptoms of CS are vague and mayinclude palpitations, pre-syncope, ectopy, ventriculararrhythmias, AV block, bundle branch blocks, andsudden death. Distinguishing CS from acute myocar-ditis (idiopathic giant cell myocarditis, necrotizingeosinophilic myocarditis, and lymphocytic myocar-ditis) can be challenging. Symptom onset to time ofpresentation is more rapid in idiopathic giant cellmyocarditis and eosinophilic myocarditis compared

with CS (2). Similarly, symptomatic heart failure ismore common with myocarditis (2). Elevated eosin-ophil counts may be suggestive of eosinophilicmyocarditis.

Cardiac imaging plays an integral role in the diag-nosis of CS (Table 1). Common transthoracic echo-cardiogram findings include LV systolic dysfunction,RWMA in a noncoronary distribution, interventricularseptal thinning, and abnormal strain rates (1,3). CMRis suggestive of CS when LGE is seen in a patchy andmultifocal distribution, usually involving the basalseptum and basal lateral walls, mid-myocardium, andepicardium of the myocardium (1,3). FDG-PET typi-cally shows focal FDG uptake with or without restingperfusion defects and wall motion abnormalities (1,3).FDG-PET uptake patterns may help differentiate CSfrom other nonischemic processes including acutemyocarditis. In CS, regions of fibrosis along the basalor midventricular septum may be seen, comparedwith myocarditis, which commonly follows specificvascular territories in the inferior and inferolateralmyocardial segments (4). Endomyocardial biopsy can

FIGURE 3 FDG-PET and Technetium Tc-99m Tetrofosmin SPECT Imaging

Fluorodeoxyglucose (FDG) positron emission tomography (PET) images (A to C) showing increased FDG uptake in the septal, distal anterior,

and mid-to-basal inferior walls of the left ventricle and apical anterior wall of the right ventricle (arrows). Resting myocardial single photon

emission computed tomography (SPECT) perfusion images (D to F) showing abnormalities most prominently involving the interventricular

septum (arrows).

J A C C : C A S E R E P O R T S , V O L . 2 , N O . 7 , 2 0 2 0 Louis et al.J U N E 1 7 , 2 0 2 0 : 1 0 7 4 – 8 Multimodal Imaging for the Diagnosis of Isolated Cardiac Sarcoidosis

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be pursued if histological examination is warranted(5); however, the patchy distribution of fibrosiscommonly leads to false negative samples, with sen-sitivities as low as 20% (6).

Guidelines for the diagnosis of CS have recentlybeen updated to reflect advancements in multi-modality cardiac imaging. The 2016 Japanese Cir-culation Society Guideline on Diagnosis andTreatment of Cardiac Sarcoidosis now separatespatients into either a “clinical diagnosis group” or“histological diagnosis group” based on whether ornot endomyocardial biopsy has been performed,and provides additional guidelines on diagnosingisolated CS. These guidelines differ from other so-cietal guidelines (7–10), which all require endo-myocardial biopsy for diagnostic confirmation. Amultimodality imaging approach without endo-myocardial biopsy may allow for a more rapid

initiation of immunosuppressive therapy andimproved outcomes.

FOLLOW-UP

Repeat FDG-PET 6 months later revealed improve-ment in LV ejection fraction from 20% to 58% withoutsignificant interval changes in perfusion abnormal-ities or intense regional FDG uptake. Outpatient PPMinterrogation revealed underlying sinus rhythmwithout further ventricular arrhythmias. Overall,these findings suggest persistent myocardial inflam-mation despite clinical recovery, possibly indicativeof premature follow-up imaging.

CONCLUSIONS

Isolated CS should be suspected in patientswith an unexplained nonischemic cardiomyopathy,

FIGURE 4 Fluorodeoxyglucose Positron Emission

Tomography With Computed Tomography

Fluorodeoxyglucose positron emission tomography with

computed tomography imaging of the heart showing increased

activity in the interventricular septum (arrow), distal anterior,

and mid to basal inferior walls. In the correct clinical context,

these findings are consistent with a pro-inflammatory state

such as sarcoidosis.

TABLE 1 Multimodal Imaging Findings in Cardiac Sarcoidosis

Echocardiogram � LV dysfunction� RWMA not explained by coronary artery dis-

ease or in a noncoronary artery distribution� Basal thinning of the ventricular septum� Abnormal ventricular wall anatomy (ventricu-

lar aneurysm, regional ventricular wallthickening)

� Abnormal strain imaging

CMR � 1 or more patchy regions of late gadoliniumenhancement atypical for myocardial infarction(i.e., sparing the endocardial border and not inthe distribution of prior myocardial infarction)

FDG-PET � CS most commonly associated with focal FDGuptake in isolation or on background of milddiffuse uptake with or without resting perfu-sion defects and wall motion abnormalities

� PET perfusion tracers can help excludeobstructive coronary artery disease

� Identification of ongoing active inflammation

CS ¼ cardiac sarcoidosis; FDG ¼ fluorodeoxyglucose; LV ¼ left ventricular;PET ¼ positron emission tomography; RWMA ¼ regional wall motionabnormalities.

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conduction abnormalities, and/or life-threateningarrhythmias. A multimodality imagingapproach should be considered in cases of sus-pected CS. Recent guideline updates now allow

for the diagnosis of CS without endomyocardialbiopsy.

ADDRESS FOR CORRESPONDENCE: Dr. Brian G.Abbott, The Lifespan Cardiovascular Institute, War-ren Alpert Medical School of Brown University, 593Eddy Street, RIH APC 814, Providence, Rhode Island02903. E-mail: BAbbott@lifespan.org.

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2. Okura Y, Dec GW, Hare JM, et al. A clinical andhistopathologic comparison of cardiac sarcoidosisand idiopathic giant cell myocarditis. J Am CollCardiol 2003;41:322–9.

3. Slart R, Glaudemans A, Lancellotti P, et al.A joint procedural position statement on imagingin cardiac sarcoidosis: from the Cardiovascular andInflammation & Infection Committees of the Eu-ropean Association of Nuclear Medicine, the Eu-ropean Association of Cardiovascular Imaging, andthe American Society of Nuclear Cardiology. J NuclCardiol 2018;25:298–319.

4. James OG, Christensen JD, Wong TZ, Borges-Neto S, Koweek LM. Utility of FDG PET/CT in in-flammatory cardiovascular disease. Radiographics2011;31:1271–86.

5. Cooper LT, Baughman KL, Feldman AM, et al. Therole of endomyocardial biopsy in the managementof cardiovascular disease: a scientific statementfrom the American Heart Association, the AmericanCollege of Cardiology, and the European Society ofCardiology. Circulation 2007;116:2216–33.

6. Uemura A, Morimoto S, Hiramitsu S, Kato Y,Ito T, Hishida H. Histologic diagnostic rate ofcardiac sarcoidosis: evaluation of endomyocardialbiopsies. Am Heart J 1999;138:299–302.

7. Judson MA, Baughman RP, Teirstein AS,Terrin ML, Yeager H Jr. for the ACCESS ResearchGroup. Defining organ involvement in sarcoidosis:the ACCESS proposed instrument. A case controletiologic study of sarcoidosis. Sarcoidosis VascDiffuse Lung Dis 1999;16:75–86.

8. Birnie DH, Sauer WH, Bogun F, et al. HRS expertconsensus statement on the diagnosis and

management of arrhythmias associated with car-diac sarcoidosis. Heart Rhythm 2014;11:1305–23.

9. Hunninghake GW, Costabel U, Ando M, et al.ATS/ERS/WASOG statement on sarcoidosis.American Thoracic Society/European RespiratorySociety/World Association of Sarcoidosis and otherGranulomatous Disorders. Sarcoidosis Vasc DiffuseLung Dis 1999;16:149–73.

10. Terasaki F, Azuma A, Anzai T, et al. JCS 2016guideline on diagnosis and treatment of cardiacsarcoidosis- digest version. Circ J 2019;83:2329–88.

KEY WORDS cardiac magnetic resonance,cardiomyopathy, heart failure,positron-emission tomography, ventricularfibrillation