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Usefulness of Pericardial Effusion as New Diagnostic Criterion forNoninvasive Detection of Myocarditis

Peter Ong, MDa,*, Anastasios Athansiadis, MDa, Stephan Hill, MDa, Eva-Maria Kisperta,Gabor Borgulya, MD, MScb, Karin Klingel, MDc, Reinhard Kandolf, MDc, Udo Sechtem, MDa, and

Heiko Mahrholdt, MDa

Cardiovascular magnetic resonance (CMR) imaging holds promise for diagnosing myocar-ditis in vivo. The CMR diagnosis of myocarditis is determined by the ventricular morphol-ogy/function, late gadolinium enhancement, and T2-weighted imaging for myocardialedema. However, in routine clinical practice, we encounter patients with suspected myo-carditis in the absence of left ventricular dysfunction, myocardial edema, or late gadolin-ium enhancement. In the present study, we sought to determine whether the presence ofpericardial effusion could serve as a new diagnostic criterion and improve the sensitivity ofCMR imaging to detect myocarditis. A total of 35 consecutive patients with biopsy provenvirus-associated myocarditis, onset of clinical symptoms within the past 3 months, andnormal left ventricular function were enrolled in the present study. All patients underwentechocardiography, CMR imaging, and endomyocardial biopsy for workup of myocarditis.Late gadolinium enhancement was present in 16 patients (46%). Myocardial edema onT2-weighted imaging was present in 4 patients, but in just 1, it was the only abnormalfinding. Pericardial effusion was present in 14 patients (40%). In 7 patients with myocar-ditis (20%), pericardial effusion was the only abnormal finding. Pericardial effusion, usedas an additional diagnostic criterion, improved the sensitivity of CMR imaging for myo-carditis from 46% to 66% (p � 0.023). In conclusion, pericardial effusion detected by CMRimaging might serve as a new diagnostic criterion for the noninvasive diagnosis of myo-carditis in patients with recent onset of clinical symptoms and normal left ventricular
function. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:445–452)
Myocarditis is an important cardiac disease that can leadto persistent left ventricular dysfunction1 and life-threaten-ing arrhythmias.2 Several working groups have reported thatcardiac magnetic resonance (CMR) imaging holds promisefor diagnosing and monitoring myocarditis in vivo.3,4 Ac-cording to the current standardized Society for CardiovascularMagnetic Resonance (SCMR) and European CardiovascularMagnetic Resonance (EuroCMR) imaging protocols,5 CMRmaging evaluation of myocarditis is mostly determined byhe ventricular morphology and function, late gadoliniumnhancement (LGE), and the finding of myocardial edeman T2-weighted imaging in some cases. The primary aim ofhe present study was to determine whether the presence ofericardial effusion, as detected using CMR imaging, coulderve as a new diagnostic criterion and improve the sensi-ivity of CMR imaging compared to the current protocolsecommended by SCMR and EuroCMR.5 In addition, we

aDepartment of Cardiology, Robert-Bosch-Krankenhaus, Stuttgart,Germany; bClinical Trials Unit, St. George’s University of London, Lon-don, United Kingdom; and cDepartment of Molecular Pathology, Univer-sity of Tübingen, Tübingen, Germany. Manuscript received February 9,2011; manuscript received and accepted March 20, 2011.

This study was supported in part by grants SFB-TR 19 German Re-search Foundation, Bonn, Germany and BMBF 01EZ0817, Bonn, Ger-many to Drs. Kandolf and Klingel.

*Corresponding author: Tel: (�49) 711-8101-3456; fax: (�49) 711-8101-3795.

E-mail address: [email protected] (P. Ong).

0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved.doi:10.1016/j.amjcard.2011.03.068

sought to demonstrate that CMR imaging is capable ofdetecting pericardial effusion missed using standard routineechocardiography.

Methods

A total of 35 consecutive patients with biopsy provenviral myocarditis (inflammation and presence of viral ge-nomes) were included in this study. These patients had onsetof clinical symptoms within the previous 3 months (e.g.chest pain, dyspnea or palpitations, associated with recentgastrointestinal or respiratory infection and/or elevation ofinflammatory/cardiac markers) (Table 1) and normal leftventricular function (ejection fraction �60%) without anyfocal wall motion abnormalities. Workup for myocarditis atour institution comprised initial echocardiography, CMRimaging, and endomyocardial biopsy (EMB). Coronary ar-tery disease was ruled out by invasive angiography. Themean age of our population was 49 years (range 38 to 61),and 21 patients were men (60%). The patients with a typicalpresentation of pericarditis (i.e., acute onset of chest pain,ST-segment elevation in �1 coronary territory on the 12-lead electrocardiogram and angiographic exclusion of cor-onary artery disease) were excluded. The study compliedwith the Declaration of Helsinki, and all patients gave writ-ten informed consent for the procedures mentioned.

Electrocardiographic-gated CMR imaging was per-formed in breath-hold using a 1.5-T Magnetom Sonata
(Siemens Medical Systems, Erlangen, Germany). Accord-
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446 The American Journal of Cardiology (www.ajconline.org)

ing to the actual SCMR and EuroCMR recommendations,5

our CMR imaging protocol for the evaluation of myocardi-tis included cine, T2-weighted spin echo, and LGE CMRimaging.4 Both cine and contrast-enhanced long-axis im-ages (2-, 3-, and 4-chamber views) were acquired. Simi-larly, short-axis images were prescribed every 10 mm(6-mm slice thickness) from the base to apex.6 The in-planeesolution was typically 1.2 � 1.8 mm. Cine CMR imagingas performed using a steady-state free-precession se-uence. For assessment of myocardial edema, we applied areath-hold, black-blood, T2-weighted, triple inversion re-overy sequence (repetition time 2 � RR, excitation time 65s, inversion time 140 ms) in 3 (basal, midventricular, and

pical) short-axis slices (slice thickness 15 mm, gap 5 mm,

Table 1Clinical and imaging characteristics of all patients

Pt. No. Age (y) Gender SymptomOnset (d)

ChestPain

Dyspnea

1 19 Male 8 Yes No2 25 Male 6 Yes No3 26 Male 1 Yes No4 27 Male 42 No No5 28 Female 0 Yes Yes6 34 Female 90 Yes Yes7 37 Male 30 Yes No8 38 Male 0 Yes No9 38 Male 30 Yes Yes

10 39 Male 0 Yes No11 39 Male 14 Yes No12 40 Female 0 Yes No13 40 Male 0 Yes Yes14 42 Female 0 Yes No15 44 Male 0 Yes No16 46 Male 7 Yes No17 47 Female 21 Yes Yes18 48 Female 5 Yes No19 52 Male 45 Yes No20 52 Male 14 Yes No21 52 Male 60 Yes No22 56 Male 90 Yes Yes23 56 Male 90 No Yes24 57 Female 0 Yes No25 58 Female 30 Yes Yes26 59 Male 90 Yes Yes27 61 Male 0 Yes Yes28 63 Male 28 No No29 64 Female 2 Yes Yes30 64 Female 3 Yes No31 65 Female 28 Yes No32 66 Male 14 No Yes33 66 Female 14 Yes Yes34 72 Female 42 Yes No35 78 Female 10 Yes Yes

CRP � C-reactive protein (normal �5 mg/L); ECG � electrocardiographiciopsy; HHV-6 � human herpesvirus type 6; LGE � late gadolinium enhanjection fraction; NA � not available; ND � not diagnostic; PE � pericardi

* Troponin I, normal �0.16 �g/L.† 1 � ST-segment elevation; 2 � ST-segment depression; 3 � T inversion; 4‡ Gastrointestinal or respiratory.

eld of vision 340 to 380 mm, matrix 256 � 256).7 s

Contrast CMR images were acquired an average of 5 to10 minutes after contrast injection (power injector) using asegmented inversion recovery fast gradient echocardio-graphic technique, constantly adjusting the inversion time tothe null normal myocardium, as described previously.8 Foreach slice, a breath-hold of �15 seconds (depending on theRR interval) was necessary. Therefore, the total acquisitiontime was 20 to 30 minutes for all cine and contrast-en-hanced images. All patients were able to tolerate lying flatin the magnet until the examination was completed. Thecontrast dose (Magnevist [gadoteridol], Bayer Schering AG,Berlin, Germany) was 0.15 mmol/kg. If contrast enhance-ment was located in the epicardial quartile of the ventricularwall, T -weighted half Fourier acquisition single-shot turbo

alpitations TroponinI*

CRP ECGFindings†

Infection‡ WithinPast 3 mo?

No 15.40 33.0 1 NoNo 9.29 24.0 3 YesNo 44.00 39.0 1 YesYes 0.02 3.0 2 NoYes 0.38 3.0 4 YesNo 0.02 16.0 2 NoNo 0.36 3.0 4 NoNo 0.02 11.0 3 NoNo 0.02 3.0 3 YesNo 1.14 27.0 1 NoNo 0.02 3.0 1 NoNo 0.02 9.0 3 NoNo 0.02 86.0 1 NoNo 10.00 5.0 4 NoNo 0.02 3.0 2 NoNo 4.19 22.0 4 YesYes 0.02 3.0 4 YesNo 0.02 3.0 3 NoNo NA 5.0 4 YesNo 0.02 20.0 4 YesNo NA 3.0 3 NoYes NA 4.0 4 NoNo NA 11.0 4 NoYes 0.02 3.0 4 NoYes 0.02 3.0 3 NoNo NA 3.0 4 YesNo NA 40.0 1 NoNo 0.02 6.0 4 NoYes 0.02 3.0 2 NoYes 0.02 3.0 4 NoNo NA 38.0 4 NoNo NA 3.0 3 YesNo 0.02 7.0 3 YesNo 5.91 39.0 4 YesYes 0.04 8.0 4 No

end-diastolic volume; EBV � Epstein-Barr virus; EMB � endomyocardialLVEDD � left ventricular end-diastolic diameter; LVEF � left ventricular

on; PVB19 � parvovirus B19; T2 � T2-weighted images.

levant changes; 5 � sinus tachycardia; and 6 � left bundle branch block.

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447Cardiomyopathy/New Diagnostic Criterion for Myocarditis

among the contrast enhancement, epicardial fat, and peri-cardial effusion.

For easy visual CMR detection of pericardial fluid, weapplied a single shot inversion recovery steady-state free-precession sequence technique, such as is usually used forLGE imaging9 and obtained 2 separate images after a single80° inversion as displayed in Figure 1. The first image wascquired in the cardiac cycle in which the inversion pulseas applied, adjusting the triggering and inversion time toull normal myocardium identical to LGE. The secondmage was obtained 1 cardiac cycle later to allow recoveryf magnetization of the pericardial effusion, with settingsnd inversion time identical to those for the first image. Thisechnique resulted in 2 images: 1 with the pericardial effu-ion bright and another one with the pericardial effusion

Table 1(continued)

CMR Parameter

LVEF(%)

EDV(ml)

LVEDD(mm)

T2-WeightedImaging

LGE P

71 135 53 ND Yes Y60 183 56 Positive Yes N60 183 54 Positive Yes Y67 175 57 Normal No N67 85 45 NA No Y62 119 52 ND No N64 124 55 Normal No N70 128 39 Normal No N64 115 45 Normal Yes N67 131 52 Inconclusive No Y71 155 NA ND Yes Y65 137 51 Normal No N71 150 44 ND No Y76 104 44 Normal Yes N63 129 56 Normal Yes Y60 161 57 Normal Yes N65 100 44 Inconclusive Yes N82 87 38 Positive Yes Y61 160 43 ND Yes N78 186 57 ND Yes N72 152 51 Positive No N69 158 54 Inconclusive No Y62 191 62 ND No N65 111 NA ND Yes N64 100 46 NA No Y75 93 43 Inconclusive No N69 101 43 Normal No N60 151 55 NA No N71 108 49 NA No Y60 120 47 NA No Y82 94 41 NA No N73 97 43 NA Yes Y76 118 48 ND No N79 70 34 ND Yes N70 95 41 NA Yes Y

ark (nulled), allowing easy visual detection of the pericar- w

ial effusion when played as a cine loop by just looking forblinking” areas (Figure 1).

The cine and contrast images were evaluated separatelyy 2 blinded observers. The endocardial and epicardialorders were outlined on the short-axis cine images. Theolume and ejection fraction were derived by summation ofisks. For the quantitative analysis of the T2-weighted im-ges, regions of interest were drawn covering the completeeft ventricular myocardium and within a skeletal muscle inhe same slice. The myocardial signal intensity was relatedo that of the skeletal muscle: relative myocardial T2-eighted signal intensity � signal intensity of myocardium/

ignal intensity of skeletal muscle. A ratio of �2.0 wasonsidered abnormal according to volunteer data and pre-ious studies.7 Moreover, the diagnosis of abnormal T -

EchocardiographicParameter

PE

Biopsy Results

EMB Viral Genome Type

No Myocarditis PVB19No Myocarditis PVB19No Myocarditis PVB19No Myocarditis PVB19No Myocarditis PVB19No Myocarditis PVB19 � HHV6No Myocarditis PVB19 � HHV6No Myocarditis HHV6No Myocarditis PVB19 � HHV6No Myocarditis PVB19No Myocarditis PVB19No Myocarditis PVB19Yes Myocarditis HHV6No Myocarditis PVB19 � HHV6Yes Myocarditis PVB19 � HHV6 � EBVNo Myocarditis PVB19No Myocarditis HHV6No Myocarditis HHV6No Myocarditis PVB19No Myocarditis PVB19No Myocarditis PVB19Yes Myocarditis PVB19 � HHV6No Myocarditis HHV6No Myocarditis PVB19No Myocarditis HHV6No Myocarditis PVB19 � HHV6No Myocarditis EnterovirusNo Myocarditis PVB19No Myocarditis HHV6No Myocarditis PVB19No Myocarditis PVB19No Myocarditis PVB19 � HHV6No Myocarditis EBVNo Myocarditis HHV6Yes Myocarditis PVB19

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focal areas of high T2-weighted signal intensity (those witha signal intensity greater than the normal myocardium plus2 SDs) after the endocardial and epicardial contours weredrawn manually (Argus Software, Siemens Medical Sys-tems, Erlangen, Germany). The extent of LGE was planim-etered on the short-axis contrast images using an imageintensity level of �2 SDs greater than the mean of theremote myocardium to define contrast enhancement.10

Quantification of the pericardial fluid was derived by sum-mation of the disks on short-axis cine images from basal toapical. Pericardial fluid was considered abnormal pericar-dial effusion if the amount of pericardial fluid exceeded atotal volume of 15 ml according to the Horowitz type Cdefinition.11 All patients underwent a clinical routine echo-cardiographic study using a Vivid Seven digital ultrasoundscanner (General Electric, Horton, Norway). The protocolincluded 2-dimensional, M-mode, and color Doppler im-ages using a transthoracic approach to assess the size andfunction of the atria, ventricles, and valves, as well as thepresence of pericardial effusion from different angles.EMBs were preferentially taken from the ventricle demon-strating LGE. Those patients demonstrating LGE exclu-sively in the left ventricular free lateral wall underwentselective left ventricular biopsies, and those patients dem-onstrating LGE in the septal wall or having no LGE at allunderwent either biventricular or selective right ventricularbiopsies, if possible. Viral myocarditis was defined as myo-cardial inflammation as visualized by histologic/immunohisto-logic examination and by the detection of viral genomes bypolymerase chain reaction, as described previously.12 Endo-myocardial biopsies were stained with Masson’s trichromeand Giemsa stain and examined by light microscopy. Forimmunohistologic examination, the tissue sections weretreated with an avidin-biotin immunoperoxidase method(Vectastain Elite ABC Kit, Vector, Burlingame, California),applying the following monoclonal antibodies: CD3 (Tcells, Novocastra Laboratories, Newcastle, United King-dom), CD68 (macrophages, Dako, Hamburg, Germany),and HLA-DR-� (Dako, Hamburg, Germany) as describedreviously.12 The detection of �14 infiltrating leukocytes/m2 (CD3� T lymphocytes and/or CD68� macrophages)

n the presence of myocyte damage and/or fibrosis, in ad-ition to enhanced HLA class II expression in professional

Figure 1. Scheme of special “blinking” sequence for detection of pericardsequence technique). See text for further details.

ntigen-presenting immune cells, was used for the diagnosis

f myocarditis.12 DNA and RNA were extracted using pro-einase-K digestion followed by extraction with phenol/hloroform. Nested polymerase chain reaction/reverse tran-criptase-polymerase chain reaction was performed for theetection of enteroviruses (including coxsackieviruses ofroup B, various coxsackieviruses of group A, and echovi-uses), parvovirus B19, adenoviruses, human cytomegalo-irus, Epstein-Barr virus, and human herpesvirus type 6. Ascontrol for successful extraction of DNA and RNA, oli-

onucleotide sequences were chosen from the glyceralde-yde-3-phosphate-dehydrogenase gene. The specificity ofll viral amplification products was confirmed by automaticNA sequencing.10,12

Statistical analysis was done using the Statistical Pack-age for Social Sciences, version 14.0 (SPSS, Chicago, Illi-nois). The results are expressed as the mean � SD. The ttest was used to compare continuous variables. For valueswithout a normal distribution, the median and interquartileranges are stated, and the Mann-Whitney U test was used.The chi-square test was used for categorical variables. Thesensitivity for the different diagnostic approaches was cal-culated, and the McNemar test was used to show whetherthe reclassification of the different diagnostic approachesand increase in sensitivity were significant. A 2-tailed pvalue of �0.05 was considered significant.

Results

The clinical and imaging characteristics for all the patients

sion (modified single-shot inversion recovery steady-state free-precession

Table 2Comparison of sensitivity of different approaches

Protocol for Diagnostic Approach Sensitivity (%)

LGE � T2 49%LGE � PE 66%LGE � T2 � PE 69%Echocardiography vs CMR

Sensitivity for echocardiography to detect PE 29%Specificity for echocardiography to detect PE 100%

LGE � T1-weighted images with late gadolinium contrast enhancement;PE � pericardial effusion; T2 � T2-weighted images for detection of myo-ardial edema (abnormal by either visual assessment or ratio calculation).

PE � pericardial effusion.

ial effu

are listed in Table 1. The primary reason to seek medical

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attention was chest pain (n � 17) followed by dyspnea (n � 2),and palpitations (n � 1). The remaining patients had acombination of these presentations. Nine patients had ele-vated troponin I on presentation, and 17 patients presentedwith elevated C-reactive protein. The initial echocardio-gram was performed after a mean of 2.3 � 3.3 days. CMRimaging was performed after a mean of 2.1 � 1.7 days, and theEMB was performed a mean of 3.6 � 3.5 days after admis-sion. The patients with a history of respiratory or gastroin-testinal infection within the past 3 months more often hadpositive LGE compared to the patients without LGE (p �0.03).

We did not find any subendocardial ischemic LGE pat-tern. However, LGE in a nonischemic pattern was present in16 of the 35 patients, yielding a sensitivity of this diagnostic“LGE only” approach of 46% (Table 2). T2-weighted im-aging was available for 27 patients. In the other patients,T2-weighted imaging could not be obtained owing to gatingor breath hold problems. Four patients had an abnormalT2-weighted signal. The T2-weighted signal was consideredbnormal if either visual or quantitative analysis revealed anncreased T2-weighted signal intensity, as defined in the

“Methods” section. However, an abnormal T2-weighted sig-nal was generally present with LGE (n � 3), except in 1patient (patient 21, Table 1), in whom T2-weighted signallevation was the only abnormal CMR finding. In 14 of the7 patients, T2-weighted imaging was not diagnostic or was

inconclusive because of poor image quality and artifacts. IfLGE and T2-weighted findings were used as diagnosticriteria for myocarditis, the sensitivity of this approach,

Figure 2. CMR images of a 39-year-old man (patient 10) admitted for suddleft ventricular function, without focal wall motion abnormalities. (Third ro

2-weighted imaging for detection of myocardial edema was inconclumyocarditis. (Top 2 rows) Only pathologic finding was pericardial effusio

LGE � T2,” increased slightly to 49%, because 1 patient r

ith biopsy proven myocarditis had abnormal T2-weightedndings in the absence of LGE (Table 2).

Pericardial effusion was present in 14 patients (40%) andas the only pathologic finding (no LGE and normal T2-

weighted findings) in 7 (Figures 2 and 3). When the pres-ence of pericardial effusion was added as a diagnostic cri-terion, the sensitivity increased to 66% for “LGE pluspericardial effusion” and 69% for LGE plus T2 plus peri-cardial effusion (Table 2). The increase in sensitivity from49% (LGE plus T2) to 69% (LGE plus T2 plus pericardialffusion) was statistically significant with the McNemareclassification test (p � 0.023) and a Greenwood 95%onfidence interval of 10% to 39%. When comparing theesults of the new “blinking pericardial effusion” pulseequence (Figure 4) to the conventional CMR approach toetect pericardial effusion, all patients with pericardial ef-usion were correctly identified with the new technique.

Although pericardial effusion was diagnosed in 14 pa-ients by CMR imaging, it could be detected by echocardi-graphy in 4 only patients (29%). In the group of patientsithout any LGE or elevated T2-weighted signal (n � 18),ericardial effusion was detected by CMR imaging in 7atients but documented by echocardiography in 2 patients29%, Figure 5). The detection rate of pericardial effusionsing echocardiography was not influenced by the localizationf the pericardial effusion. Assuming that CMR imaging is theeference standard for in vivo detection of pericardial effusion,e calculated the sensitivity and specificity of echocardiogra-hy for the detection of pericardial effusion at 29% and 100%,

t of chest pain. (Top rows) Cine images (diastole, systole) revealed normaltrast images (LGE) showed no late gadolinium enhancement. (Bottom row)ut visually negative. Endomyocardial biopsy revealed parvovirus B19e arrows).

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(Left) and PE white (Right image, white arrows) for easy visual detection.


Discussion

The present data are unique in that we demonstrated thatthe presence of pericardial effusion used as an additionaldiagnostic criterion could significantly enhance the sensi-tivity of CMR imaging to detect myocarditis from 49% to69% compared to the SCMR and EuroCMR recommendedstandard approach,5 using endomyocardial biopsy as thereference standard. In addition, our data have demonstratedthat CMR imaging can often detect pericardial effusionmissed using routine transthoracic echocardiography.

In our cohort of patients with biopsy proven virus-asso-ciated myocarditis, the primary reason to seek medical at-tention was chest pain followed by dyspnea. This finding isin line with our previous results.12 Only 49% of patients hadabnormal C-reactive protein levels, and 46% had normalechocardiographic findings at rest on presentation. Elevatedtroponin was present in 26% of patients only. These findingshighlight the difficulties of diagnosing myocarditis on thebasis of conventional criteria.

Using the presence of LGE as the only diagnostic crite-rion in our population, the sensitivity was 46%, lower thanthat described in previous reports from our group10,12 butwithin the range of the findings from other groups.3 Thisiscrepancy with our previous data, however, is most likelyxplained by the very different inclusion criteria of theresent study compared to our older studies.

When using LGE plus T2-weighted imaging, the sensi-tivity of this CMR approach increased form 46% to 49%(Table 2), because all patients with an abnormal T2-weighted signal also had LGE, except for 1, in whom theelevated T2-weighted signal was the only abnormal CMR

nding. Thus, in our patients with biopsy proven myocar-itis and normal left ventricular function, T -weighted im-

V) function (cine), no LGE, negative or nondiagnostic (n/d) T2-weightedrrows). All patients had EMB findings with proof of viral myocarditis.

Figure 3. Three patients (patients 13, 22, and 28) with normal left ventricular (L

Figure 4. Example of special “blinking” sequence for detection of pericar-dial effusion (PE) in 3 patients (# patients 5, 25, and 29) showing PE dark

2ging added only minimal value with regard to the diagnos-

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tic performance of CMR imaging. This contradicts thefindings of others,7,13 who used the clinical criteria as ref-rence standard for myocarditis but is in line with thendings from De Cobelli et al,14 who found no elevated2-weighted signal in 78% of patients with histologically

proven active inflammation. In addition, in the presentstudy, T2-weighted images of diagnostic quality could onlybe obtained in 13 patients, reflecting the typical problems ofT2-weighted spin echo imaging caused by in-plane motion,signal loss resulting from RR variability, and other commonT2-weighted spin echo-related artifacts. Thus, technical im-provements and additional data validating the T2 findingsgainst the histopathologic findings are needed to determinehe future role of T2-weighted imaging for the evaluation of

yocarditis.When LGE plus the presence of pericardial effusion was

sed, the sensitivity of this approach increased from 46% to6% and increased to 69% when the T2-weighted data werelso included. Statistical analysis suggested a significantncrease in sensitivity of �10% (lower Greenwood 95%onfidence interval). This finding suggests that the presencef pericardial effusion might be an important diagnosticriterion for myocarditis, and is underscored by the findinghat other investigators have described pericardial effusionn �57% of patients with myocarditis.15,16 We, therefore,elieve that pericardial effusion should be considered aiagnostic criterion in those patients with clinically sus-ected myocarditis but no other abnormal findings on CMRmages obtained according to the standardized SCMR anduroCMR recommended protocols5 (Figures 2 and 3).

Echocardiography is the well-established first-linemethod for the detection of pericardial effusion in routineclinical practice17 owing to its ease and availability. Nev-

Figure 5. Three additional patients (patients 3, 11, and 32) with normal leftpericardial effusion (PE) sequence (white arrows). Pericardial effusion wa

rtheless, in the present study, clinical routine echocardiog-

aphy for the evaluation of myocarditis was capable ofetecting pericardial effusion in 4 of 14 patients only, usingMR imaging as the reference standard, regardless ofhether the standard CMR approach (cine, T2-weighted,

LGE) or the new pulse sequence for the detection of peri-cardial effusion we have described was used. However, thenew pericardial effusion sequence facilitated visual detec-tion of even small amounts of pericardial fluid (i.e., �30 ml)ecause of its “blinking” apparition (Figure 4).

Our results were based on a small and highly selected,ut excellently characterized, patient population. Further-ore, we did not implement the “early enhancement tech-

iques” as recently suggested by Friedrich et al,3 becausethis technique is currently not recommended by SCMR andEuroCMR.5 However, this is not very likely to affect ouresults, because our primary aim was to evaluate whetherhe presence of pericardial effusion could be an additionaliagnostic criterion in patients with biopsy-proven myocar-itis, not to evaluate the general diagnostic performance ofMR imaging in the setting of suspected myocarditis.

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usefulness of pericardial effusion as new diagnostic criterion for noninvasive detection of...

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