Table Of ContentAndersonetal.JournalofCardiothoracicSurgery2013,8:12
http://www.cardiothoracicsurgery.org/content/8/1/12
CASE REPORT Open Access
An unusual case of giant cell myocarditis missed
in a Heartmate-2 left ventricle apical-wedge
section: a case report and review of the literature
Kim Anderson1, Michel Carrier2, Philippe Romeo3, Guy B Pelletier1, Mark Liszkowski1, Normand Racine1,
Michel White1 and Anique Ducharme1*
Abstract
Herein we present a case offulminant myocarditis in a woman previously treated for B-cell lymphoma. While the
clinical context was suggestive of adriamycin-inducedcardiomyopathy, the initial pathologyof the Heartmate-2
apical core showed lymphocytic myocarditis. After 8months ofstability,the patient presented with progressive
heart failure and recurrent ventricular arrhythmias. Anendomyocardial biopsy revealed findings typical ofgiant cell
myocarditis (GCM); poor response to immunosuppressive therapyand marked hemodynamic instabilityled to
urgent transplantation. To our knowledge, this is the firstreported case of GCM following an acute lymphocytic
myocarditis and the second GCM case associated with B-cell lymphoma.
Keywords: Giant cell myocarditis, Lymphocytic myocarditis, Lymphoma, Immunosuppression, Hearttransplant,
Endomyocardialbiopsy, Left ventricular assist device
Background this life-threatening condition. In particular, this case
Giant cell myocarditis (GCM) is a rare form of fulminant raises many important issues, including 1) the potential
myocarditiswhichhasapooroutcomewithouthearttrans- relationshipbetweenGCMandlymphocyticmyocarditis;
plantation [1]. The involvement of T-lymphocytes may ex- 2) the possibility that the large LVapical specimen could
plain the common association with other autoimmune have missed GCM; and 3) the presence of atheroscler-
conditions and the potential role of immunosuppressive osis lesionsinthedonor heart.
therapyinGCM[1,2].Wedescribethe challengingcaseof
a woman previously treated for B-cell lymphoma who pre-
Case presentation
sented to the emergency department in cardiogenic shock.
A 41 years old woman was transferred to our hospital in
While the clinical context suggested adriamycin-induced
cardiogenic shock. Fourteen months earlier she has been
cardiomyopathy, the Heartmate-2 apical core pathology
treated for a cutaneous centro-follicular type-B lymphoma
showedlymphocyticmyocarditis.Afterinitialimprovement with R-CHOP (total adriamycin dose of 300 mg/m2) and
on mechanical support,she presented with recurrent heart
has well recovered since. Echocardiography at presentation
failuresymptoms 8months later; aRV endomyocardial bi-
showedadilatedleftventricle(LV),leftventricularejection
opsy was performed and revealed GCM. Immunosuppres-
fraction (LVEF) of 10%, and preserved right ventricle (RV)
sive therapy was initiated but persistent RV failure and
function; the coronary angiography was normal. She was
arrhythmicstormledtourgenttransplantation.
initially supported by an Impella-2.5L, followed by a
This clinical scenario illustrates the need for a better
Heartmate-IIfivedayslater.HistologyoftheLV-apicalcore
understanding of the pathophysiology of fulminant myo-
section showed multifocal interstitial inflammatory infil-
carditis, in order to improve diagnostic and treatment of
trates, predominantly lymphocytic, with edema and exten-
sive mycocytes destruction, without giant cell or extensive
*Correspondence:[email protected] necrosis (Figure 1). Immunohistochemistry revealed a
1DepartmentofMedicine,MontrealHeartInstitute,UniversityofMontreal,
T-cell phenotype, different from the previous lymphoma
5000,BelangerEast,Montreal,QCH1T1C8,Canada
Fulllistofauthorinformationisavailableattheendofthearticle and immunofluorescence was suggestive of acute
©2013Andersonetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.
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Figure1Leftventricularapicalcorespecimen.Interstitial Figure2Rightventriclularendomyocardialbiopsy.Mixed
inflammatoryinfiltraterichinlymphocytes(arrows)inanareaof inflammatoryinfiltratewithgiantcells(arrows)inabackgroundof
myocytelossassociatedwithperipheralmyocyteinjury(HPS,20X). severemyocytesdropoutandfeaturesofgranulationtissue(HPS,20X).
lymphocytic myocarditis. She received a defibrillator and however, there was evidence of sub-acute myocardial is-
was discharged on standard heart failure therapy. She chemia and severe three-vessel disease (Figure 4), in
improved on Heartmate-II support with minimal spite of a reported ‘normal’ coronary angiogram at the
symptoms. donor site.
Eight months later she was readmitted after two weeks
of congestive symptoms; NT-proBNP (3421 ng/L, from
1454 in June) and troponins T (0,58 mcg/L, normal Discussion
≤ 0.03 mcg/L) were increased and echocardiography The clinical presentation of GCM is usually dramatic,
showed a decline in LVEF (30% from 45% 2-months but some may present an indolent course with presence
prior), absence of aortic valve opening and a dilated and ofsymptomsfor months toyearsbeforetheproperdiag-
hypokinetic RV. An endomyocardial biopsy (EBM) nosis is made [3]. Ventricular arrhythmias are initially
revealed severe mycocytes’ dropout, associated primarily found in 14% of patients, but will develop in 50% of the
with granulation tissue, a mixed inflammatory infiltrate patients; fascicular and high degree atrioventricular
and the presence of multinucleated giant cell with a blocks are also frequently encountered [1]. The median
non-myogenic appearance (Figure 2), all suggestive of survival without heart transplantation is poor, between
GCM. Immunosuppressive therapy was initiated with 3.0 to 5.5 months from the onset of symptoms [1,3], and
high dose corticosteroids and cyclosporine [1]. Unfortu-
nately, she developed incessant ventricular tachycardia
and profound RV failure requiring amiodarone and mil-
rinone; she underwent urgent transplantation 16-days
later.
Histopathology of the explanted heart showed diffuse
and irregular interstitial fibrosis, without extensive ne-
crosis, associated with residual areas of granulation tis-
sue, mild to moderate lymphocytic infiltrates and mild
foci of myocytes damage (Figure 3). The post-operative
course was complicated by persistent shock, requiring
right side extracorporeal life support, an intra-aortic bal-
loon pump and continuous renal replacement therapy.
Immunosuppressive regimen comprised of rabbit antith-
ymocyte globulin (RATG) induction, corticosteroids,
mofetilmycophenolate, basiliximab and later tacrolimus.
Unfortunately, she died of multi-organ failure one Figure3Nativeheartexplants:Leftventricularsection.
Extensiveinterstitialfibrosiswithresidualareasofgranulationtissue
month after transplantation. At autopsy, no signs of
andmildlymphocyticinfiltrates(HPS,10X).
giant cell or hyperacute rejection could be found;
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anti-alphabeta[9]T-cellreceptorantibodies,supportingthe
roleofaT-cellmediatedautoimmuneprocessinGCM.
Clinically, immunosuppressive therapy might improve
survivalinGCM,incontrastwithothertypesofmyocar-
ditis [10]. In a retrospective study, GCM patients who
received immunosuppression (corticosteroids and cyclo-
sporine, with/without azathioprine) had an improved
survival without cardiac transplantation (12.3 versus 3.0
months (p=0.001)), while corticosteroids alone had no
effect [1]. An observational study of biopsy-proven
GCM patients (excluding those with fulminant presenta-
tion) and symptoms of heart failure or arrhythmia
reported that treatment with cyclosporine and corticos-
teroids for one year, with/without muromonad-CD3 pre-
treatment for ten days dramatically improved survival
Figure4Autopsyexplantsofthedonorheart,sectionofthe
(64%) without cardiactransplantation[2].
midleftanteriordescendingcoronaryartery.Severeconcentric
intimalatheroscleroticplaquewithsignificantluminalstenosis Whether there was a relationship with lymphocytic
(Movat,20X). myocarditis or if its presence could have been a contrib-
uting factor to GCM development in our patient
remains unclear. The reported sensitivity of RV-EMB in
relapse in the transplanted graft may occur in up to 25% adults is relatively low for a precise diagnosis of myocar-
ofthe cases[1-3]. ditis, from 10-67% [10], but seems better for GCM, up
Histopathology is characterized by the presence of to 80% [11], despite significant interobserver variability
multinucleated giant cells, with diffuse myocardial ne- [1]. Predictors of the absence of giant cell in the
crosis in the absence of granulomatous myocarditis; fi- explanted heart after a positive EMB include long delay
brosis maybeprominent.Theprecise pathophysiology is between the EMB performance and the explanted heart’s
unknown, but seems to involve a T-lymphocytes- pathologic analysis and symptoms duration [11]. The
mediated autoimmune process, which may explain the possibility that the large LV core specimen could have
common association (up to 20%) with other auto- missed GCM is unlikely but whether the lymphocytic
immune disorders, typically inflammatory boweldiseases infiltrates may have triggered an inflammatory response
and tumors, mostly thymoma [1,2]. Association with leading to development of giant cells infiltrates remains
lymphoma has been described twice in the literature. unanswered. Another diagnosis possibility included the
One patient presented in cardiogenic shock; multi-organ recurrence of lymphoma, but immunohistochemistry
infiltration (including the myocardium), with centrocytic depicted a different phenotype of T-cell infiltrate; also,
lymphoma cells, myocytolysis and extensive fibrosis while we cannot provide evidence that the granulomas
associated with a mixed cellular infiltrate including giant seen on the RV biopsy specimen were not secondary to
cells were seen at autopsy [4]. Another case occurred in an immune response to infection or inotropic drugs,this
the context of autologous bone marrow transplantation is highly improbable, given the fact that she was not on
with IL-2 activated stem cells. Autopsy revealed myocar- inotropes at the time of RV-EBM and that not infectious
dial infiltration withT-helper lymphocytes and apoptosis agents were found despite extensive workup. Lastly, dif-
ofmyocytes.Theauthors suggestedthatIL-2 might have ferentiating GCM from a granulomatous myocarditis
stimulated a preferential activation of T-helper lympho- can be difficult [12], but the fulminant presentation, the
cytes resulting in an autoimmune process manifested as absence of atrioventricular block and the poor outcome
GCM[5]. aremore typicalofGCM[13].
Kodamaandcolleaguesdevelopedanexperimentalmodel The last lesson learned from this case were the autopsy
of GCM using Lewis rats inoculated with human cardiac findings of severe coronary atherosclerosis in the trans-
myosin fragments and sacrificed at 14 and 84 days. They planted heart. As transplant cardiologist, we are often fa-
showed typical myocarditis with multinucleated giant cells cing critical decision making such as to reject/accept a
anddiffusefibrosisintheearlyphase,withdisappearanceof donorheartforourcriticallyillpatients.Unfortunately,we
the mononuclear infiltrates in the later phase suggestive of sometimes rely on incomplete or erroneous information,
healedmyocarditis.Anti-cardiacmyosinantibodiesweresig- as was the so-called “normal angiogram” report from the
nificantly higher in the groups sacrificed earlier, but all had referring center. Having known the real extent of CAD
higher titersthan controls [6].Thesefindings couldbepre- (revealed at autopsy) in this donor heart, we would have
vented by cyclosporine [7], FK-506 (Tacrolimus) [8] and gone without transplantion, significant donor coronary
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atherosclerosis being a major risk for early graft failure, Received:19September2012Accepted:11January2013
with reported 30-day mortality of 7.5% with single-vessel Published:17January2013
involvementand42.3%withmultiple-vesseldisease[14].
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doi:10.1186/1749-8090-8-12
Citethisarticleas:Andersonetal.:Anunusualcaseofgiantcell
Acknowledgements
myocarditismissedinaHeartmate-2leftventricleapical-wedgesection:
WeareespeciallygratefultotheMontrealHeartInstitute’stransplantation
acasereportandreviewoftheliterature.JournalofCardiothoracic
team.
Surgery20138:12.
Authors’financialsupportinformation
DrDucharmeissupportedbytheFonddeRechercheenSantéduQuébec
(FRSQ)andDrWhiteholdstheCarolynandRichardJ.RenaudResearchChair
inHeartFailure.
Authordetails
1DepartmentofMedicine,MontrealHeartInstitute,UniversityofMontreal,
5000,BelangerEast,Montreal,QCH1T1C8,Canada.2DepartmentofCardiac
Surgery,MontrealHeartInstitute,UniversityofMontreal,5000,BelangerEast,
Montreal,QCH1T1C8,Canada.3DepartmentofPathology,MontrealHeart
Institute,UniversityofMontreal,5000,BelangerEast,Montreal,QCH1T1C8,
Canada.
