Infective Endocarditis at Autopsy - Endocardites Aquitaine

13 Pages·2012·2.78 MB·English

Infective Endocarditis at Autopsy
A Review of Pathologic Manifestations and Clinical Correlates
Manuel L. Ferna´ndez Guerrero, MD, Beatriz A´lvarez, MD, Fe´lix Manzarbeitia, MD,
and Guadalupe Renedo, MD
hospitalacquiredin11(50%).Theabsenceoffever,cardiacmurmurs,
Abstract: The frequencyof autopsies appears to be declining, and
andmanyofthetypicalstigmataofendocarditismayhaveledtothe
the usefulness hasbeenchallenged.We reviewedcasesof autopsied
diagnosisbeingoverlookedclinically.
activeinfectiveendocarditis(IE)during2periodsbasedontheavail-
Brainbleeding,cardiacfailureandlessfrequentlyacutemyocardial
abilityofhigh-tech2-dimensionalechocardiograms:Period1(P1)in-
infarctwerethemostcommoncausesofdeath.
cluded40casesstudiedfrom1970to1985,andPeriod2(P2)included
IE continues to be missed frequently until autopsy. Postmortem
28casesseenfrom1986to2008Vthatis,beforeandaftertheintro-
examinationisanimportanttoolforevaluatingthequalityofcare,and
ductionofechocardiogramsinourinstitution.Weconductedthestudy
forguidingteachingandresearchrelatedtocardiovascularinfections.
toreassessthepathologyofIEandtodeterminehowfrequentlydiag-
nosisisnotmadeduringlife. (Medicine2012;91:152Y164)
Theageof patientsincreased10yearsonaveragebetweenthe 2
periods, and comorbidities were significantly more frequent in P2. Abbreviations: CT = computed tomography, IE = infective
Whilethefrequencyofrheumaticvalvediseaseandprostheticvalve endocarditis, MRI = magnetic resonance imaging, P1 = Period 1,
endocarditis (PVE) decreased, degenerative valve disease increased. P2=Period2,PVE=prostheticvalveendocarditis,TTE=transthoracic
IsolatedmitraloraorticvalveIEwasmostcommon.Right-sidedIEwas echocardiogram,TEE=transesophagealechocardiogram.
observed in patients with Staphylococcus aureus bacteremia from
infected venous lines. In most cases IE involved only the cusps of
cardiac valves. ‘‘Virulent’’ microorganisms caused ulcerations, rup-
ture,andperforationofthecuspsandnecrosisofchordaetendiniaeand INTRODUCTION
perivalvularapparatus.InPVEthelesionswerelocatedbehindthesite Inspiteoftheestablishedvalueandthecompellingscientific
ofattachment,andvegetationswereseenonthesewingringinboth evidence in favor of autopsy, its usefulness has been chal-
metallicandbiologicprostheses.Infectionspreadtoadjacentstructures lenged, and the frequencyof autopsies in general and in uni-
andmyocardiumwithringabscessobservedin88%ofcases.Prosthetic versityhospitalsappearstobe declining.31,61 Several reasons
detachmentcausingvalveregurgitationwasassociatedwithabscesses have been suggested to explain this trend: cost, reluctance to
in76%ofcases;thesepatientsdevelopedpersistentsepsisandsevere ask the familyfor permission to carryout the autopsy, doubt
cardiacfailure.ObstructionoccurredinpatientswithPVEofthemitral about the value of the procedure, and confidence in newer
valve. Acute purulent pericarditis was observed in 22% of cases, diagnostictechniques.
mainlyinpatientswithaorticvalveIEandmyocardialabscesses. Before the introduction of echocardiography as a diag-
Grossinfarctswereseenin63%ofcasesbutwereasymptomaticin nostic tool in infective endocarditis (IE), definitive diagnosis
mostinstances.Thespleen,kidneys,andmesenterywerethesitesmost restedonvisualizationofcardiacvegetationsduringsurgeryor
frequently involved. Myocardial infarctions were found in less than autopsy.79 Now the echocardiogram, particularly the transe-
10%ofcases.Abscesseswerealsofrequentlyfoundandwereacom- sophageal echocardiogram (TEE), allows identification of
monsourceofpersistentfeverandbacteremia.Glomerulonephritiswas valvevegetations,anddirectvisualizationisnolongerrequired
morecommoninthefirstperiod.Brainpathologyconsistedofischemic for definitive clinical diagnosis of IE.41 However, discrepan-
andhemorrhagicinfarctsandabscesses.Cerebralbleedingwasmore cies between clinical and autopsy diagnoses persist in spite of
frequentinpatientswithPVEonanticoagulanttherapy.Neutrophilic progressinmedicalskillsandtechnology.8,33
meningitiswasobservedinS.aureusIE. ThediagnosisofIEisnotaneasymatter.Manifestations
DiagnosisofIEwasnotmadeduringlifein14(35%)casesduring are not always typical, and many are nonspecific and similar
P1 and 12(42.8%) cases in P2.Overall,diagnosiswas missed until tothosefoundinmanyothersystemicdiseases.45,47,49 In ad-
autopsyin38.2%ofcases.IEwashospitalacquiredin28instances. dition, IE frequently occurs in elderly patients with comor-
Whileaclinicaldiagnosiswasmadeinallbut4casesofearly-onset bidities, and manifestations of endocarditis can be wrongly
PVE (23.5%), the diagnosis was not made during life in 22 of 51 attributedtotheunderlyingdisease.14,73,84Hence,thediagnosis
patients with native-valve IE (43.1%). Of these 22 patients, IE was ofIEisoftennotconsideredandmaybemisseduntilautopsy.At
thepresenttime,whenIEfrequentlyoccursasanosocomialin-
fectionduringadmissionforanothercondition,misseddiagnoses
FromtheDivisionofInfectiousDiseases(DepartmentofMedicine)andSur- maybeevenmorefrequent.10,22Y24,28Ofnote,ina2007seriesof
gical Pathology, Instituto de Investigaciones Sanitarias Fundacio´n Jime´nez autopsiesfromaspecializedcardiologyhospital,theclinicaldi-
D´ıaz,UniversidadAuto´nomadeMadrid,Madrid,Spain. agnosisofIEwasnotmadeduringlifein27%ofcases.64
Theauthorshavenofundingorconflictsofinteresttodisclose.
Since the publication of large autopsy seriesin the early
Allfigurescanbeviewedincoloronlineathttp://www.md-journal.com.
Reprints:ManuelL.Ferna´ndezGuerrero,MD,Fundacio´nJime´nezD´ıaz. antimicrobialera,15,21,34,53wehavewitnessedseveralchanges
Avda.ReyesCato´licos,2;28040Madrid,Spain intheepidemiology,microbiology,diagnostics,andtherapeu-
(e-mail:[email protected]). ticsofIE.6,10,14,30,45,47,49,70Fewrecentstudieshavefocusedon
Copyright*2012byLippincottWilliams&Wilkins
pathologic manifestations of endocarditis or have compared
ISSN:0025-7974
DOI:10.1097/MD.0b013e31825631ea clinical and autopsy diagnoses of IE in a general hospital.64
152 &
www.md-journal.com Medicine Volume91,Number3,May2012
&
Medicine Volume91,Number3,May2012 InfectiveEndocarditisatAutopsy
Minimallyinvasiveautopsy,acombinationofcomputedtomog- exact test when samples were small. Differences between
raphy(CT)withmagneticresonanceimaging(MRI)followedby groupswereconsideredsignificantatpvalueG0.05.
ultrasonography-guided biopsy that has been proposed as an
alternativetoautopsy,failedtodemonstrateIEin1study.85
Inthecurrentstudywereassessedtheroleofpostmortem RESULTS
examinationasasourceofknowledgeinIE,basedontheidea Wediscussheretheresultsofthestudy,andpresentper-
thatunderstandingthemorphologicchangescausedbythein- tinentcasereportstoillustratethefindings.
fection provides the basis for diagnosis and therapy. Specifi- The number of autopsies performed in our institution
cally we studied how frequently the diagnosis was not made showedacontinuousdeclinesincethe1990sdespiteasignifi-
during life, and how frequently autopsy showed unexpected cantincreaseinthenumberofadmissionstothehospital.The
findingscomparedtotheclinicaldiagnosisandclinicalcause autopsyratedeclinedfrom14.8%and14.6%ofalldeathsin1975
of death. We also provide here a review of the general mor- and 1985, respectively, to 5.73% in 1994, 4.9% in 2000, and
phologyofIEwithanupdateofclinicalcorrelates. 2.29%in2008.FrequencyofIEatautopsyrangedfrom0.5%in
1971to3.9%in1984(average,1.5%intheentireperiod).
InP1,January1970throughDecember2008,750patients
receivedadiagnosisofIEatFundacio´nJime´nezD´ıaz,Madrid.
METHODS
From1970to1985,227caseswereseen,ofwhom86(37.8%)
Weconductedaretrospectivereviewofpatientswithac- died. Postmortem examination was performed in 40 (46.5%)
tive IE in whom autopsy was performed in a tertiary care, ofthesedeceasedpatients.InP2,from1986to2008,523cases
university-affiliated hospital serving a population of 350,000 of IE were seen, of whom 116 (22.1%) died. Autopsy was
peopleindowntownMadrid,Spain. performedin28(24.1%)casesofIEduringthisperiod.Hence,
TheclinicaldiagnosisofIEwasmadefollowingthecri- 68autopsiedpatientswereassessedandcomposethebasisfor
teria proposed by von Reyn et al79 during the first period of thisstudy.
thestudyandtheDukemodifiedcriteria41afterthefirstperiod. Themeanageincreasedfrom46.6yearsinP1to57.6years
(Study periods are defined below.) Autopsy diagnosis was inP2.Nodifferenceswereobservedinthedistributionbysex.
made on the basis of macroscopic and microscopic examina- Oneormorecomorbidconditionwasfoundin11(27.5%)cases
tion. Specifically, pathologic diagnosis of IE required the studiedinP1.Incomparison,17(60.7%)casesinP2had1or
presenceofvegetationsincardiacvalvesormuralendocardium morecomorbidcondition(pG0.01).Solidneoplasms(n=4and
composed by fibrin, platelets, leukocytes, or histiocytes. Be- n=5inP1andP2,respectively),chronicrenalfailureonhe-
cause patients were commonly treated with antimicrobials, modialysis(n=2andn=5,respectively),cirrhosisoftheliver
thepresenceofmicroorganismsonGramstainofvegetations (n=2andn=6,respectively),andothermiscellaneousdiseases
was not required for inclusion. Only cases of active endo- suchasdiabetesmellitus,atherosclerosisanditscomplications,
carditisVdefined by positive blood cultures within 2 weeks systemic lupus erythematosus, rheumatic polymyalgia, or
before death, or microorganisms identified in Gram stain of polyneuropathywerethemostcommonunderlyingdisorders.
vegetations, or truly endocardial pathogens isolated in tissue Apredisposingvalvedisorderwasobservedin72.5%and
culturesVwereincludedinthe analysis. Because ofthe simi- 75%ofcasesinP1andP2,respectively.Whilethefrequency
larities with IE, 2 cases of infective aortitis of the ascending ofrheumaticvalvediseaseandPVEdecreasedfromP1toP2
thoracicaortawerealsoassessed. (10/25% vs. 4/14.2% and 12/30% vs. 5/17.8%, respectively),
Thecompleteautopsychartsandtheclinicalandlabora- thefrequencyofdegenerativevalvediseaseincreased(5/12.5%
tory recordswere reviewed by 2 clinicians and 1 pathologist. vs.9/32.1%; pG0.05).All casesofPVEdevelopedwithin1
Welookedattheclinicalmanifestations,methodsfordiagnosis, year after valve replacement and were considered early-onset
alternativediagnoses,causativeagents,complications,labora- PVE. Other less frequent underlying cardiac diseases were
tory findings, medical treatment, and pathologic findings. congenital cardiomyopathyand myxoid valve disease. A pre-
Postmortemexaminationwasperformedfollowingtherecom- existentcardiacconditioncouldnotbedeterminedin11/17.5%
mendationsoftheCollegeofAmericanPathologists.37 When and7/25%ofcasesofP1andP2,respectively(pnotsignificant).
permissionwasgranted,thebrainwasalsoexamined. IEwashospitalacquiredin28(41%)instances.Eighteen
Caseswereclassifiedinto2differentperiodsoftimebased cases occurred during P1 (12 early PVE, 5 associated with
on the availability of 2-dimensional echocardiograms in our infectedcentralvenouslines,and1inapatientonhemodial-
institution:Period1(P1)from1970to1985,beforetheintro- ysis),and10occurredduringP2(5earlyPVE,2inpatientson
ductionofhigh-tech2-dimensionalechocardiograms;andPe- hemodialysis, 2 due to infected central venous catheters, and
riod 2 (P2) from 1986 to 2008, when both transthoracic another1associatedwithurologicinstrumentation).
echocardiogram(TTE)andlaterTEEwereavailableandrou- The microorganisms isolated from blood cultures and/or
tinelyusedinthediagnosisofIEinourhospital. valvevegetationsareshowninTable1.Staphylococcusaureus,
Hospital-acquired IE was defined as endocarditis devel- coagulase-negative staphylococci, and enterococci were the
opingQ72hoursafteradmissioninassociationwithahospital- most common etiologic agents. As expected, less invasive
based procedure or during another hospitalization within the bacteria such as Streptococcus viridans were less frequently
preceding8weeks.22Prostheticvalveendocarditis(PVE)was foundinthisseriesofautopsies.Gram-negativebacilli,which
definedasearlyonsetwhenitdevelopedwithinthefirstyear intheearlydaysof cardiacsurgerywereimportant causes of
aftervalvereplacement.42,65 early-onsetPVEinourinstitution,werenotfoundinP2.
Isolated mitral or aortic valve and combined mitral and
StatisticalAnalysis aorticvalveswerethemostcommonsitesofIEwithintheheart
SPSS v. 11.0 (SPSS Inc., Chicago, IL) was used for the (Table2).In5autopsies,muralendocarditisoftherightatrium
statistical analysis. Continuous variables were expressed as andeustachianvalvewasobserved.Inaddition,isolatedleftatrial
mean (range). Discrete variables were expressed as percen- endocarditiswasnotedin1autopsiedpatient.Wenotethat the
tages.Associationsweretestedbychi-squaretestortheFisher clinicaldiagnosisofmostofthesecasesofmuralendocarditis
153
*2012LippincottWilliams&Wilkins www.md-journal.com
&
Ferna´ndezGuerreroetal Medicine Volume91,Number3,May2012
TABLE1. MicrobialEtiologyofInfectiousEndocarditisin
Autopsiesof68Patients
TimePeriodNo.(%)
Period1 Period2
(1970Y1985) (1986Y2008)
Etiology (n=40) (n=28)
Staphylococcusaureus 10(25) 9(32)
Coagulase-negative 4(10) 4(14)
staphylococci
Enterococci 6(15) 5(18)
Streptococcusviridans 3(7) 2(7)
OtherGram-positive 4(10) 4(14)
bacteria*
Gram-negativebacilli† 6(15) 0
Fungi‡ 1(2.5) 3(11)
Unknown 6(15) 1(3.5) FIGURE1. Case1.TricuspidvalveendocarditisduetoS.aureus.
Notevegetationsoncusps,thechordaetendiniaeandalarge
*Beta-hemolyticstreptococci. vegetativemassonthemuralatrialendocardiuminvolvingthe
†Pseudomonas aeruginosa, Serratia marcescens, Burkholderia eustachianvalve.EThisfigurecanbeviewedincoloronline
cepacia. athttp://www.md-journal.com.^
‡Candidaalbicans,Aspergillusfumigatus.
bialtherapywasreinitiated,butthepatientfollowedadownhill
course with gastric bleeding, shock, and respiratory failure.
wasnotmadeduringlife,andallcorrespondedtopatientswith Postmortemexaminationshowedextensiveendocarditisofthe
S.aureusbacteremiafromaninfectedcentralvenouscatheter. tricuspidvalve,eustachianvalve,andrightatrium(Figure1).
Thefollowinghistoryillustratesthecomplexityofclinical Pulmonaryemboliandlunginfarctswerealsoobserved.
diagnosisof1ofthesecases.
CardiacPathology
Case1 A summary of cardiac pathology is shown in Table 3.
A73-year-oldmanwithcoloncancerandmetastasestothe Cardiacweightrangedfrom363gto810g(mean,494g).In
liverwasadmittedbecauseofhematemesis.Acentralvenous most cases endocarditis involved only the cusps of cardiac
linewas inserted for administration of blood and fluids. Five valves.Vegetationsmeasuredfrom3mmto42mmingreater
dayslaterhedevelopedfever,andS.aureuswasisolatedfrom diameter and were always located on the atrial aspect of the
bloodcultures.Thecatheterwaswithdrawnandtreatmentwith mitral valve and on the ventricular aspect of the semilunar
intravenouscloxacillinwasstarted.Feverrapidlysubsided,and
antimicrobial therapy was discontinued after 12 days. Fever
and staphylococcal bacteremia relapsed. No murmurs were TABLE3. CardiacPathology
heard,andTTEdidnotshowvalveabnormalities.Antimicro-
TimePeriodNo.(%)
Period1 Period2
TABLE2. AnatomicSiteInvolvedinInfectiveEndocarditis (1970Y1985) (1986Y2008)
Involvement (n=40) (n=28)
TimePeriodNo.(%)
Onlycusps 17(42.5) 18(64.2)
Period1 Period2
Rupturedchords 2 3(10.7)
(1970Y1985) (1986Y2008)
McCallumpatches 1 4(9.5)
Site (n=40) (n=28)
Ringabscess 12(30) 8(28.5)
Singlevalve PVE 10 5
Mitral 13(32.5) 11(39) Aorticvalve 6 2
Aortic 10(25) 9(32) Mitralvalve 4 3
Tricuspid 2(5) Nativevalve 2 0
Multiplesites Aorticvalve 1 1
Mitral&aorticvalves 8(20) 5(18) Dehiscence(onlyPVE) 9(75) 4(80)
Mitral&tricuspidvalves 1 0 Valveobstruction 4(10) 1
Aortic&tricuspidvalves 1 1 PVE 3(75) 1(100)
Mitral&aortic&tricuspidvalves 1 0 Nativevalve 0 1
Mural 5(12.5)* 1 Pericarditis 6(15) 9(32)
Ascendingaorta 1 1 Focalmyocarditis 5(12.5) 3(10.7)
*Isolatedrightatriumorassociatedwithtricuspidvalveinvolvement Intracardiacfistulae 2 1
(n=4);isolatedleftatrium(n=1). Myocardialinfarction 4(10) 2(7.1)
154
www.md-journal.com *2012LippincottWilliams&Wilkins
&
Medicine Volume91,Number3,May2012 InfectiveEndocarditisatAutopsy
The shape of vegetationswas polypoid, cauliflower-like or ver-
rucous,andthesurfaceroughorgranular.
Generallyspeaking,smallvegetationsnotproducingsig-
nificant damage ofthe cuspswere not associatedwithsevere
hemodynamic disturbance (Figure 3A). On the other hand,
moreinvasiveinfectionscausingulcerations,ruptureandper-
foration of the cusps, and necrosis of chordae tendiniae and
perivalvular apparatus were generally associated with greater
degreesofheart failure(Figure3B). Rupturedchordae tendi-
niae were seen exclusively in cases of mitral endocarditis
caused by S. aureus. Extension of infection into the sur-
roundingmyocardiumwithabscessformationwasobservedin
5casesof aorticnative-valve endocarditis. Satelliteleft atrial
vegetations due to regurgitant, high-velocity jet stream
(McCallum patches) were observed in a few cases of mitral
endocarditis(Figure4).
FIGURE2. A.Vegetationmeasuring32(cid:1)41mmonthemitral PathologyofPVE
valve.B.Microscopicview(originalmagnification(cid:1)100). Seventeenprostheticvalveswereassessed:12duringP1
GramstainshowingabundantmicrocoloniesofGram-positive (8metallicand4porcinevalves)and5duringP2(allmetallic
bacteria.CulturesyieldedS.aureus.EThisfigurecanbeviewed valves).Rigid-frameprostheticvalves,suchastheBjo¨rk-Shiley,
incoloronlineathttp://www.md-journal.com.^ Medtronic-Hall, and Hall-Kaster and Hancock porcine biopros-
theticvalves,weremostfrequentlyusedinourinstitutionduring
bothperiods.
valves. The largest vegetations were observed in infections
Ineachcase,infection waslocatedbehindthesiteofat-
causedbyS.aureus(Figure2A).Whennottreatedwithanti-
tachment, and vegetationswere seen on the sewing ring both
microbials, vegetations were composed of a matrix of fibrin
inmetallicandinbiologicprostheses(Figure5A).Frequently,
and platelets with scarce macrophages and bacterial micro-
infection spread to adjacent structures and surrounding myo-
colonies, although in staphylococcal infections infiltrates by
cardium with abscess formation. Ring abscess was observed
polymorphonuclearcellswerecommonlyobserved(Figure2B).
in15of17(88%)cases,withoutdifferencesbetweenaorticand
mitral valve endocarditis or metallic and biologic prostheses.
Ringabscessinvolvedtheentireannulusin3andonlyaportion
oftheannulusinanother12(Figure 5B). Three patientswith
aortic valve endocarditis and myocardial abscess extending
intotheinterventricularseptumpresentedwithatrioventricular
conductiondisturbances.
FIGURE3. Differentseverityofvalvedamage.A.Small
vegetationslocatedonthelineofclosureoftheventricularsurface
ofthecuspsofaorticvalveinacaseofenterococcalendocarditis.
B.Severemitralvalvedamagewithhemorrhage,ulceration, FIGURE4. McCallumpatchesontheatrialsurfaceduetothe
andruptureofthecuspsandchordaetendiniaeinacase erosiveactionofhigh-velocityregurgitantflowinacaseofacute
ofendocarditiscausedbyS.aureus.EThisfigurecanbeviewed mitralinsufficiencyduetoS.aureusendocarditis.EThisfigurecan
incoloronlineathttp://www.md-journal.com.^ beviewedincoloronlineathttp://www.md-journal.com.^
155
*2012LippincottWilliams&Wilkins www.md-journal.com
&
Ferna´ndezGuerreroetal Medicine Volume91,Number3,May2012
in 76.4% of cases. Valve obstruction was found in 5 (7.3%)
casesinthisseries.Completeorpartialprostheticobstruction
byvegetativematerialoccurredin4of7patientswithPVEof
themitralvalve.
Case2
A 62-year-old man with mitral stenosis had a valve re-
placementwithametallicBjo¨rk-Shileyvalve.Twoweekslater
he was readmitted with fever and shortness of breath. No
murmurs were heard, and peripheral stigmata of IE were not
seen.Bloodcultureswerenegative,andhewasstartedonan-
timicrobial therapy with vancomycin and gentamicin. He
remainedfebrileand developedrefractory cardiacfailureand
shock, and died shortly after admission. At autopsy, mitral
endocarditis caused by coagulase-negative staphylococci was
found. The prosthesis was almost completely obstructed by
vegetativematerial(Figure7).
Acutepurulentpericarditiswasobservedin22%ofcases,
mainlyinpersonswithaorticvalveendocarditisandmyocardial
abscessescausedbyvirulentmicroorganismssuchasS.aureus
or Pseudomonas aeruginosa. Pericarditis was associated with
persistentfeverinmostpatients.Chestpainorothersymptoms
associatedwithpericarditiswerenotobserved.However,pericar-
dialeffusionwasobservedbyechocardiographywhenavailable.
Focalmyocarditiswasamicroscopicfindingin12.5%and
10.7% of cases in P1 and P2, respectively, but its frequency
wasprobablyunderestimatedbecausemultiplehistologicsec-
FIGURE5. A.Hancockporcinebioprosthesis.Notevegetations
tions were not routinely examined. The lesions consisted of
onthesewingring,whileporcinecupsappearfreeofinfection.
B.PVEoccurringonamitralmetallicvalve.Notetheinfective scattered infiltrates of mononuclear cells with focal and dis-
processsurroundingtheentiresewingringandannulus.EThisfigure cretenecrosisofmyocytes(Bracht-Wa¨chterbodies).Myocar-
canbeviewedincoloronlineathttp://www.md-journal.com.^ ditisdidnotseemtoresultincardiacfailureinpatientsinwhom
itwasfound.
Myocardial infarcts were observed in e10% of cases in
Intracardiac fistulae were observed in 2 cases of aortic bothperiods.Althoughnotcommonlyfound,acutemyocardial
PVEcausedbyS.aureusandStreptococcusviridans(Figure6). infarct was always symptomatic, and was the cause of death
Ringabscessesburrowed intoadjacent structuresthrough the inatleast1case.Myocardialinfarctscontributedtomortality
atrialseptumintotherightatriumorthroughtheinterventric- in another 5 patients by causing worsening cardiac failure or
ularseptum intotherightventricle.Thesepatientsdeveloped precludingcardiacsurgery.
persisting sepsis and severe cardiac failure and died despite
antimicrobialtherapy.
SystemicPathology
Prosthetic detachment causing severe regurgitation was
The systemic pathology consisted of visceral infarcts and
associatedwithabscessesofthesewingringandwasobserved
abscessesandwasparticularlycommonandfloridincasesofleft-
sidedendocarditis(Table4).Grossinfarctswereseen43(63.2%)
FIGURE6. IntracardiacfistulaeduetoaorticPVEdueto
Streptococcusmitior.Theringabscessburrowedintoadjacent FIGURE7. Case2.Mitralvalveobstructioncausedby
structuresthroughtheventricularseptumintotherightventricle, massivevegetationsinacaseofearly-onsetPVEcausedby
producingasinustractcoveredbyalargevegetativemass. coagulase-negativestaphylococci.Thepatientpresentedwith
Thepatientdevelopedunremittingfeverandrefractoryheart heartfailurewithoutcardiacmurmurs,andthediagnosiswas
failure.EThisfigurecanbeviewedincoloronlineat misseduntilautopsy.EThisfigurecanbeviewedincoloronline
http://www.md-journal.com.^ athttp://www.md-journal.com.^
156
www.md-journal.com *2012LippincottWilliams&Wilkins
&
Medicine Volume91,Number3,May2012 InfectiveEndocarditisatAutopsy
maturia.Finallyhedevelopedsevereaorticinsufficiencywith
TABLE4. SystemicPathology acuteheartfailureanddied.Atautopsy,aorticendocarditiswith
perforationandruptureofthecuspsandextensiveinfarctsinthe
TimePeriodNo.(%)
spleenandkidneyswereseen(Figure8).
Period1(1970Y1985) Period2(1986Y2008) Abscesseswerefrequentlyfoundinleft-sidedendocarditis
Feature (n=40) (n=28) and involved the kidneys, spleen, and liver. Lung abscesses
were observed in cases of both right-sided and left-sided en-
Infarcts
docarditis.Abscesseswereacommoncauseofpersistentfever
Spleen 14(39) 8(29)
andbacteremia.
Kidneys 11(30) 10(36)
Lungs 6(17)
Mesentery 3(7.5) 1(3.6) Case4
Abscess A71-year-oldwomanwithdiabetesmellituswasadmitted
Kidneys 7(19) 5(18) because of hyperglycemic hyperosmolar coma. A central ve-
Lungs 5(14) 2(7) nouslinewasinsertedandtherapywithinsulinandfluidswas
Spleen 2 3(11) immediately started. General and metabolic conditions im-
proved but she developed S. aureus bacteremia. The central
Liver 2 1(3.6)
venouslinewasremovedandtherapywithcefazolinwasgiven.
Septicspleen 12(30) 6(21.4)
Feverpersistedandinthefollowingdaysasystolicmurmurof
Arterialemboli 4(10) 2(7)
mitral insufficiency was noted. Bacteremia subsided but
Glomerulonephritis 6(15) 2(7)
spiking fever persisted despite antimicrobial therapy. On the
Mycoticaneurysms 3(7.5) 2(7) morningofthe19thhospitaldaythepatientfaintedandbecame
drowsy.Afacialandlefthemiparesiswasobserved.Shedied
48hourslater.Atautopsy,mitralendocarditisandalargeab-
autopsiedpatients.Thespleen,kidneys,andmesenterywerethe scessinthespleenwereobserved.
sites most frequently involved. Lung emboli and infarcts were Emboli of large arteries (iliac, subclavian, femoral) and
exclusivelyobservedincasesofright-sidedendocarditis. mycoticaneurysms(ascendingaorta,femoralandcerebralar-
Alarge,congestive,friable,septicspleenthatwaseasily teries)wereotherlessfrequentfindingsinthecurrentseries.
broken during extraction of the viscera was commonly ob- One patient with coarctation of the aorta had S. aureus
served.Theweightofthespleenrangedfrom50gto1050g. aortitis leading to aortic rupture and sudden death. The fol-
Whilemostsplenicandrenalinfarctswereclinicallysilent,on lowingcasereportfeaturesapatientwhodevelopedsuture-line
occasionpatientsdevelopedpainandhematuria. aortitisaftercardiacsurgery.
Case3 Case5
A 69-year-old man with cancer of the urinary bladder A63-year-olddiabeticmanwasadmittedbecauseoffever
developedfeverandEnterococcusfaecalisbacteremia.Adia- and chest pain. Five months before, coronary artery bypass
stolicaorticmurmurwasheard.Antimicrobialtreatmentwith graftinghadbeenperformedforsevere3-vesselatherosclerotic
ampicillin plus gentamicin was started. TTE showed aortic disease. On examination Janeway spots were observed in the
valvevegetationsmeasuring12mmindiameterandmildaortic padsofthefingersofthelefthand.Nomurmurswereheard,and
insufficiency.Fortyhoursafteradmissionhedevelopedpleu- bloodcultureswerenegative.TEEdidnotshowvalvevegeta-
riticpainintheleftflankthatradiatedtotheshoulder.ChestX-ray tions but did demonstrate widening of the ascending aorta.
filmsshowedamildpleuraleffusionintheleftlung.Cardiac ACTscanshowedamycoticaneurysmofascendingaortaand
surgerywasnotconsidered.Thepatient’sclinicalconditionwas aorticarch.Treatmentwithvancomycin,gentamicin,andampho-
deteriorating, and he had acute lumbar pain followed by he- tericinBwasstartedbutthepatientsuddenlydied.Atautopsy,a
FIGURE8. Case3.Thepatientdevelopedpleuriticpainintheleftflankduetoasplenicinfarctandlumbarpainwithhematuria.
A.Bilateralrenalinfarcts.Noteextensiveinfarctintheinferiorpoleoftheleftkidney.B.Splenicinfarcts.EThisfigurecanbeviewedin
coloronlineathttp://www.md-journal.com.^
157
*2012LippincottWilliams&Wilkins www.md-journal.com
&
Ferna´ndezGuerreroetal Medicine Volume91,Number3,May2012
FIGURE9. Case5.A.Aortitisafterbypassgrafting.Infectionoccurredonthesuturelineofpreviousaortotomy,andamycotic
aneurysmoftheascendingaortaandthoracicarchdeveloped(arrows).Thepatientpresentedwithfeverandperipheralstigmata
ofendocarditisanddiedduetoaorticrupture.AO=ascendingaorta,TA=thoracicaorta,RSA=rightsubclavianartery,RCA=right
carotidartery,LSA=leftsubclavianartery.B.Microscopicviewofaorticwall(Grocottstain;originalmagnification(cid:1)100).Typical
hyphaedividingatrightanglesareshown.CulturesyieldedAspergillusfumigatus.EThisfigurecanbeviewedincoloronlineat
http://www.md-journal.com.^
mycoticpseudoaneurysmoftheascendingaortasecondarytoin- Neutrophilicmeningitiswasfrequentlyobservedincases
fectiveaortitisatthelevelofthesuture-lineofpreviousaortot- ofendocarditiscausedbyS.aureus.Mostofthesepatientsalso
omy was found. The arterial wall showed a destructive and hadfocalembolicencephalitislocatedintheconvexityofthe
inflammatory process with abundant hyphae (Figure 9). Cul- brainandmicroabscesses.
turesofthearterialwallyieldedAspergillusfumigatus. The following case report illustrates the presentation of
Glomerulonephritis was more common during P1 than acuteendocarditismimickingacutebacterialmeningitis.
duringP2.Microscopically,mostcaseswerefocalglomerulo-
nephritis,withonly1caseseeninP1showingsignsofdiffuse
glomerulonephritisduetoimmunecomplexes.
Case6
An 84-year-old man was admitted because of fever,
BrainPathology
headache, and drowsiness. He had a previous diagnosis of
Thebrainwasexamined in20cases(Table 5). Ischemic
diabetes mellitus, hypertension, and chronic renal failure.
andhemorrhagicinfarctsandabscesseswerethemostcommon
Twenty-four hours before admission he suddenly developed
macroscopic findings. Infarcts predominated in the area sup-
spikingfever,chills,andsevereheadache.Onexaminationhe
pliedbythemiddlecerebralarteryandwerelocatedinfrontal
wasfebrile(39-C)andobtunded.Neckstiffnesswasnoted.No
andparietallobes(Figure10).Hemorrhagicinfarctsweremore
murmursorperipheralstigmatawereobserved.Cerebrospinal
frequentinpatientswithPVEonanticoagulanttherapy(80%).
fluid was mildly cloudy and contained 1500 polymorphonu-
Subduralhematomawasalsofoundin1patientwithPVEon
clear leukocytes, protein 135 mg/dL, and glucose 35 mg/dL.
dicumaroltherapy.
A Gram stain was negative. Treatment with cefotaxime and
Brainabscesseswereobservedin6(30%)casesandwere
vancomycin was started. The patient became comatose, renal
associatedwithinfectionscausedbyvirulentmicroorganismssuch
failureworsened,andhedied48hoursafteradmission.Blood
asS.aureus,P.aeruginosa,orSerratiamarcescens(Figure11).
culturesyieldedS.aureus.Atautopsy,aorticvalveendocarditis
wasfound.Multiplecorticalcerebralsepticemboliwithbrain
TABLE5. BrainPathology* abscessesandneutrophilicmeningitiswereobserved.
ThediagnosisofIEwasnotmadeduringlifein14(35%)
TimePeriodNo.(%) casesstudiedinP1andin12(42.8%)casesinP2.Overall,the
Period1(1970Y1985) Period2(1986Y2008) diagnosiswasmisseduntilautopsyin38.2%ofcases.Asmen-
Feature (n=12) (n=8) tioned above, IE was hospital acquired in 28 instances. While
a clinical diagnosis was made in all but 4 cases of early-onset
Infarcts 7(59) 5(62.5)
PVE (23.5%), the diagnosis was not made during life in 22 of
Bleeding 5(41.6) 5(62.5) 51patientswithnative-valveendocarditis(43.1%,p=0.19).Of
PVE 5 3 these22patientswithafaileddiagnosis,IEwashospitalacquired
Abscesses 4(33) 2(25) in11(50%).Theabsenceoffever,cardiacmurmurs,andmany
Subdural 0 1 ofthetypicalstigmataofendocarditismayhaveledtothediag-
hematoma nosis being overlooked clinically. Disseminated malignancies,
Subarachnoid 1 0 diabetesmellitus,chronicrenalfailure,hemodialysis,andcollagen
bleeding vasculardiseaseswerethemostcommoncomorbiditiesobserved
Mycotic 1 1 inthesecases.Metastaticdisease,systemiclupuserythematosus
aneurysms or lupus-like disease, bacterial pneumonia, catheter-associated
Meningitis 3(7.5) 2(25) bacteremia, Gram-negative sepsis, acute brain thrombosis and
acute bacterial meningitis were other diagnoses entertained in
*Twelveand8brainsexaminedinP1andP2,respectively.
patientswhosediagnosisofendocarditiswasnotmadeduringlife.
158
www.md-journal.com *2012LippincottWilliams&Wilkins
&
Medicine Volume91,Number3,May2012 InfectiveEndocarditisatAutopsy
FIGURE10. A.Frontoparietalinfarctinapatientwithnative-valveenterococcalendocarditis.B.Extensivebrainhemorrhageina
caseofPVEcausedbyS.aureus.Patientsonanticoagulanttherapymaydevelophemorrhagicinfarcts.EThisfigurecanbeviewedin
coloronlineathttp://www.md-journal.com.^
Right-sided and mural endocarditis were unexpected find- DISCUSSION
ingsatautopsy,andaclinicaldiagnosiswasnotmadeinanyof FewpostmortemstudiesofIEhavebeenpublishedinre-
thesecases.Negativebloodculturescontributedtoamisseddi- cent years, and most have dealt with particular aspects of in-
agnosisofIEinsomecasesduringtheearlyyearsofthisstudy. fection such as predisposing cardiac conditions or specific
Improvementinmicrobiologictechniquesmadeculture-negative lesions.5,76,77Hence,thefrequencywithwhichIEisfoundat
IEarareconditioninP2. autopsyatthepresenttimeisdifficulttoascertain.Inreports
Causesofdeathare showninTable 6. Brain emboli and publishedinthe1960sand1970s,thefrequencyrangedfrom
cerebralbleeding,andlessfrequentlymyocardialemboliwith 0.5%to1.5%ingeneralhospitals2butmayhavebeenlowerin
acutemyocardialinfarctionandacutepulmonaryemboliwere oncology hospitals or higher in specialized cardiovascular
the most common causes of death in patients with IE. Con- hospitals.59,61 In our institution, IE was observed in 1.3% of
gestiveheartfailurewasanimportantdeterminantofmortality autopsiedpatients.
in both periods. The primary cause of death was not defini- Asshowninthisandpreviousreports,theageofpatients
tively established in the postmortem study in a minority of withIEhasincreasedinthelast2decades,andconsequently
cases(4inP1and1inP2). comorbiditiesaresignificantlymorecommonnowthaninthe
past.14,43,73,84Solidneoplasms,chronicrenalfailure,cirrhosis
of the liver, and other chronic debilitating diseases such as
diabetes mellitus or collagenvascular diseases are frequently
observed in patients with IE.17,26,38,55,56 These comorbidities
increasethemortalityof infectionandmaybeanobstaclefor
accurateclinicaldiagnosisofIE.26,56
Althoughapreexistentcardiacdefectisnotalwayspresent,
IE generally occurs on a predisposing valve disorder.6,7,45,47
As shown by others, the frequency of rheumatic valve dis-
ease has been decreasing while the frequency of degenerative
valve disease has been increasing over the years.43,45Y47,73 It
is noteworthythat autopsies ofPVE decreased from P1 toP2,
TABLE6. CausesofDeath
TimePeriodNo.(%)
Period1(1970Y1985) Period2(1986Y2008)
Cause (n=40) (n=28)
Emboli 16(40) 14(50)
Cardiacfailure 10(25) 6(21.4)
Pulmonary 3 0
embolism
Bleeding 2 1
Septicshock 2 4(14.2)
Aorticrupture 1 1
FIGURE11. A.MultiplebrainabscessesVfrontalandtemporal Acuterenalfailure 1 0
lobesandthalamusVinacaseofPVEcausedbySerratia Acutemyocardial 1 1
marcescens.B.Samepatient,symmetricabscessesincerebellum. infarction
EThisfigurecanbeviewedincoloronlineat Undetermined 4 1
http://www.md-journal.com.^
159
*2012LippincottWilliams&Wilkins www.md-journal.com
&
Ferna´ndezGuerreroetal Medicine Volume91,Number3,May2012
probably due to the lower incidence of early PVE in our in- andHACEKgroupofmicroorganisms.6,9,11However,weob-
stitution,whichhasalsobeenobservedinother medicalcen- served the largest vegetations in cases of endocarditis caused
tersinthelast decades.32,42,56Inaddition, becauseprosthetic byS.aureus.25
heart valves are recognized as important predisposing factors ThelesionsofPVEhaddifferentcharacteristics.1,4,42,44,57,68
for endocarditis, the diagnosis is frequently considered, and First, infection occurring on both metallic and biologic pros-
patients areappropriatelytreated; evenifthey die, autopsyis thetic valves was always located in the sewing ring, and ex-
oftennotrequested. tension into the surrounding myocardium was commonly
IEismainlyaninfectionoftheleft-sideoftheheartinvolv- observed.1,4,68Abscessformationandoccasionalintracardiac
ing mitral or aortic valve or both simultaneously. Right-sided fistulae were severe consequences of annular infection.3,80
endocarditisisoftenaninfectionassociatedwithintravenousdrug Moreover,dehiscensewasobservedinthree-quartersofcases
usethatreachedepidemicproportionsinrecentdecades.16,25,52,58 astheresult ofloosening suturesininfectedandfriableperi-
However, tricuspidvalve endocarditis inintravenousdrug users valvular tissue, which dislodged the prosthesis from its an-
isgenerallyamorebenigninfectionwithlowmortalitywhose chorage.Cardiacfailurewastheinevitableconsequenceofthe
incidencehasdeclinedattheturnofthecentury.25Bacteremia ensuingvalveincompetence.
associated with central venous catheters, flow-directed pulmo- Remarkably,vegetativelesionsofthevalveleafletswere
nary artery catheterization, pacemakers, and other invasive in- notseeninanyofthe4autopsiedpatientswithPVEinvolving
strumentation of the heart, are important causes of right-sided porcine bioprostheses. Isolated involvement of the porcine
endocarditisatthepresenttime.7,18,23,30,54,62,81,82Wenotethat, cusps has been found with variable frequency, and is more
in6casesinthisseries,IEwaslocatedonthemuralendocar- common in cases of late-onset PVE. Generally, infections
diumoftherightatriumandeustachianvalvewithorwithout originatedfromextracardiacfocithatreachedthecuspsthrough
simultaneous tricuspid valve and in the left atrial appendage. thebloodstream.12Ontheotherhand,infectioninvolvingboth
Eustachianvalve endocarditis has been rarely reported in in- theringandtheleafletswasfrequent,andthelocationseemed
travenous drug users, but whether the disease is actually rare to be independent of the timing of acquisition.29 Our obser-
or whether it is missed because this valve is not routinely vations suggest that isolated annular involvement in cases of
studied byechocardiography isnot known.66 All casesin the PVE occurring on bioprostheses may result from direct con-
current series were associated with infected intracardiac ve- tamination of the sewing ring during the operation or in the
nous catheters and S. aureus bacteremia, and may be consid- immediatepostoperativeperiod.12,44
ered the human counterpart of the experimental endocarditis Ofparamountprognosticimportancewastheformationof
modelinanimals.54,75,81,82Cathetersinsidetheheartproduce intracardiac fistulae, an unusual but severe complication of
mechanical damage on the endocardium, which is character- PVEoftheaorticvalvecharacterizedbypersistentsepsis,heart
ized by hemorrhages and thrombus formation, the so-called block,andrefractorycardiacfailure.1,3,4,58,80Inaddition,direct
nonbacterial thrombotic endocarditis.45,62 Thrombus composed extension into the pericardial sac leading to acute purulent
ofplateletsandfibrincanbecolonizedifadherentmicroorgan- pericarditis was mainly found in cases of suppurative aortic
isms reach the bloodstream and then IE ensues.45 Due to the endocarditiscausedbyS.aureus.13
absenceofcardiacmurmursandthelackofsystemicemboli,the Obstructionseemedtooccurmostcommonlyincasesof
diagnosiswascommonlymisseduntilautopsy. PVEofthemitralvalve.1,4Apictureofseverecardiacfailure
The diagnostic usefulness of conventional echocardiog- refractorytomedicaltreatmentintheabsenceofnewcardiac
raphyislimitedinright-sidedmuralIE.52Ithasbeensuggested murmurswasthemainmanifestationinthesecases.
that multiplaneTEEmayimprovediagnosticaccuracy.51,52,65 AutopsyrevealedtheundisputednatureofIEasamulti-
We, and others, believe that a systematic examination of the system disease. Visceral infarcts and abscesses, along with
eustachianvalveshouldbeincludedintheechocardiographic renalandvasculardamage,werecommonlyseen,andinmany
survey of patients suspected of having right-sided endocar- instances were unexpected findings not recognized while the
ditis.66,67 ‘‘Breakthrough’’ or relapsing bacteremia after dis- patientwasalive.Thespleen,kidneys,mesentery,andthelung
continuation of therapy has been suggested as a major in cases of right-sided endocarditis, were the most common
diagnostic hallmark of this particular infection.23,25,83 Mural sites for emboli, infarcts, and abscesses. Persistent fever and
endocarditis of the left-side of the heart has been rarely ob- breakthroughandrelapsingbacteremiawerethemostcommon
served,andmostcasesoccurredonventricularaneurysmsand and typical manifestations.25,35,39,40,83 Although rare, acute
the appendage of the left atrium.27,78 In the current series, myocardial infarction was an important cause of mortality or
isolated left atrial endocarditis was seen in a patient with seemed to contribute to death in some patients. Myocarditis
chronic atrial fibrillation who developed catheter-associated andotheracutefocallesionshavebeenobservedinmanycases
S.aureusbacteremia.25 in whom numerous histologic sections of myocardium were
Becausemostcasesoccurredonregurgitantvalves,vegeta- examined.13 Because thiswas not routinelyperformed in our
tionswerelocatedonthelineofclosureoftheatrialsurfaceof cases,myocarditiswasrarelyfound.
the mitral valve or on the ventricular surface of the cusps of Glomerulonephritis is also an important complication of
aorticvalvedownstreamoftheregurgitantflow.13,45,59Inafew IE.50 However, in the current series glomerulonephritis was
cases of mitral insufficiency, McCallum patches were ob- not a prevalent finding, and, interestingly, we observed a de-
served. However, infections caused by invasive microorgan- crease in the number of cases in the second period of study.
isms such as S. aureus were not limited tovalve leaflets, but Focalorsegmentalproliferationofendothelialandmesangial
tended to produce a more severe infection characterized by cellswithneutrophilicinfiltrationandfibrinoidnecrosiswere
ulceration, rupture, and perforation of the cusps and necrosis thechangesmostfrequentlyobserved.Diffuse,immunecomplex
ofchordaetendiniaeandperivalvularapparatus.13,57,59Exten- glomerulonephritiswasrarelyseen.Observationsmadeinthe
sion of infection into the surrounding myocardium with ab- preantibiotic era suggested that infection with less virulent
scessformationwasseeninnative-valveendocarditisandeven microorganisms,byvirtueoftheirindolentsubacuteorchronic
morefrequentlyinPVE.Largevegetationshavebeenfoundin course, favored an antibody response predisposing to im-
IE caused by fungi, Granulicatella, and Abiotrophia species munecomplexglomerulonephritis.48Hence,itispossiblethat
160
www.md-journal.com *2012LippincottWilliams&Wilkins
&
Medicine Volume91,Number3,May2012 InfectiveEndocarditisatAutopsy
the predominance of cases of acute endocarditis and early was documented, it was considered to be associated with in-
treatment with antibiotics may have decreased the number of travenouscathetersorfocalbacterialinfections.
casesofglomerulonephritisatthepresenttime.48 Patients with hospital-acquired enterococcal bacteremia
Even more important, due to the greater severity of the havenotbeentraditionallyconsideredatriskofdevelopingIE,
lesions, was brain pathology. Symptomatic central nervous and an echocardiogram was not routinely performed in these
system complications have been found in 17%Y35% of cases individuals.24However,thereisasignificantriskofIEinthe
ofIE.36,46,69Using MRI and neurochemical markers of brain elderlywithdegenerativevalvediseaseinwhomthediagnosis
damage, brain emboli have been detected in 65%Y80% of of IE may be missed. We believe that an echocardiogram
cases.20,69Theincidenceofbrainemboliishigherinpatients shouldbeperformedinthissubsetofpatientswithnosocomial
with S. aureus endocarditis.20,25 As expected, infarcts pre- enterococcal bacteremia and in other people at risk, such as
dominated in the area supplied by the middle cerebral artery those with cardiac prostheses.23 Bacterial pneumonia, Gram-
andwerelocatedinthefrontalandparietallobes.Somecases negativesepsis,oracutebacterialmeningitiswereotherdiag-
developedneutrophilicmeningitisresultingfrommultiplepe- noses entertained in cases in which the diagnosis of IE was
ripheralemboliwithmicroabscessformationextendingtothe missed during life. Negative blood cultures contributed to
meninges and into subarachnoid space, a pathologic picture a missed diagnosis of endocarditis in some cases during the
resemblingfocalembolicsuppurativeencephalitis. earlyyearsofthisstudy.
Of catastrophic consequences was brain bleeding, seen Our observations reinforce the importance of autopsy in
mostly in patients with PVE on anticoagulant therapy,72,74 a providingdatafortheevaluationofthequalityofcare,andfor
major cause of death in the current series. Overall, brain teachingandresearchpurposes.Regularcomparisonsofclin-
damage due to ischemic infarcts and cerebral hemorrhage icalandautopsydiagnosesmayprovidepertinentinformation
was the main cause of death in this series. In comparison, toimprovethefuturemanagementofpatientswithIE.
cardiacfailurewasalessimportantcauseofmortality.Similar
observationshavebeenpreviouslyreported.13,59Thisisproba-
blyduetotheincreasinguseofcardiacsurgerytotreatcardiac REFERENCES
failure resultingfromvalveinsufficiency.6Uncontrolledinfec-
1. AndersonDJ,BulkleyBH,HutchinsGM.Aclinopathologic
tion, embolization to other vital organs such as myocardium, studyofprostheticvalveendocarditisin22patients:morphologic
and the associated chronic debilitating diseases were common basisfordiagnosisandtherapy.AmHeartJ.1977;94:
causes of death in patients with IE. Missed diagnoses also 325Y332.
contributedtomortalityinsomecases.
2. AngristA,OkaM,NakaoK.Preventionandcontrolofbacterial
Earlierpostmortemstudiesshowedthattheclinicaldiag- endocarditis.NYJMed.1968;32:922Y934.
nosisofIE isfrequentlynotmadeduringlife.Robinsonetal
3. AngueraI,MiroJM,SanRomanJA,deAlarconA,AnguitaM,
foundthatdiagnosiswasnotmadeclinicallyin43%ofcases,
aproportionthatwasgreaterinelderlypatients.59,71Buteven AlmiranteB,EvangelistaA,CabellCH,VilacostaI,RipollT,MunozP,
NavasE,Gonzalez-JuanateyC,SarriaC,Garcia-BolaoI,FarinasMC,
today,intheeraofmoderndiagnostictechnology,IEcontinues
RufiG,MirallesF,PareC,FowlerVGJr,MestresCA,deLazzariE,
to be a disease whose diagnosis is frequently not made until
GumaJR,delRioA,CoreyGR.Aorto-CavitaryFistulain
autopsy.Saadetal64reportedin2007thatdiagnosisofIEwas
EndocarditisWorkingGroup.Periannularcomplicationsininfective
missed until autopsy in 27% of cases seen in a specialized
endocarditisinvolvingprostheticaorticvalves.AmJCardiol.
cardiology hospital. The diagnosis of IE has frequently been 2006;98:1261Y1268.
missed clinically in patients admitted to intensive care units
4. ArnettEN,RobertsWC.Prostheticvalveendocarditis.
andinrecipientsofsolidorgantransplants.19,60,63
Clinicopathologicanalysisof22necropsypatientswithcomparison
In the present study, the clinical diagnosis was missed
ofobservationsin74necropsypatientswithactiveendocarditis
during life in 38% of cases. Surprisingly, we did not find a
involvingnaturalleft-sidedcardiacvalves.AmJMed.1976;38:
decreaseinthenumberofmisseddiagnosesinthesecondpe- 281Y292.
riodofstudy,whenbothTTEandTEEwerefullyavailablein
5. AtkinsonJB,VirmaniR.Infectiveendocarditis:changingtrends
our institution. In many of these cases, IE was a nosocomial
andgeneralapproachforexamination.HumPathol.1987;18:
infection presumably acquired during invasive diagnostic or 603Y608.
therapeuticproceduressuchascentralvenouscatheterization,
urologicinstrumentation,ormajorsurgery. 6. BaddourLM,WilsonWR,BayerAS,FowlerVGJr,BolgerAF,
LevisonME,FerrieriP,GerberMA,TaniLY,GewitzMH,TongDC,
Health care-associated endocarditis is increasing world-
SteckelbergJM,BaltimoreRS,ShulmanST,BurnsJC,FalaceDA,
wide and represents one of the major epidemiologic changes
NewburgerJW,PallaschTJ,TakahashiM,TaubertKA;Committeeon
ofIEinthelast2decades.10,14,23,28,30,70Asshownherein,the
RheumaticFever,Endocarditis,andKawasakiDisease;Councilon
diagnosis is difficult and the condition may go unrecognized
CardiovascularDiseaseintheYoung;CouncilsonClinical
untilautopsy.62Lackoffeverorcardiacmurmursandtheab-
Cardiology,Stroke,andCardiovascularSurgeryandAnesthesia;
sence of typical stigmata of endocarditis often made the di-
AmericanHeartAssociation;InfectiousDiseasesSocietyofAmerica.
agnosis difficult during life. Moreover, the diagnosis of IE
Infectiveendocarditis:diagnosis,antimicrobialtherapy,and
occurringonunusualsitessuchasthetricuspidvalveandinthe managementofcomplications:astatementforhealthcare
right atrium is far more difficult to make and often is not professionalsfromtheCommitteeonRheumaticFever,Endocarditis,
suspectedduring life.57,58 Thediagnostic usefulnessof echo- andKawasakiDisease,CouncilonCardiovascularDiseaseinthe
cardiography is limited in these cases.52 For these reasons it Young,andtheCouncilsonClinicalCardiology,Stroke,and
istemptingtosuggestthatnosocomialIErepresentsamedical CardiovascularSurgeryandAnesthesia,AmericanHeartAssociation:
problemofgreatermagnitudethanpreviouslyshown,andthat endorsedbytheInfectiousDiseasesSocietyofAmerica.Circulation.
casesmaybemisdiagnosed. 2005;111:e394Ye434.
Importantly, the nonspecific manifestations of IE were 7. BaddourLM,EpsteinAE,EricksonCC,KnightBP,LevisonME,
frequentlyattributedtotheunderlyingdisease.Inthesecases, LockhartPB,MasoudiFA,OkumEJ,WilsonWR,BeermanLB,Bolger
anechocardiogramwasoftennotperformed,andifbacteremia AF,EstesNAIII,GewitzM,NewburgerJW,SchronEB,TaubertKA;
161
*2012LippincottWilliams&Wilkins www.md-journal.com