Andersons pediatric cardiology 1657
Bạn đang xem bản rút gọn của tài liệu. Xem và tải ngay bản đầy đủ của tài liệu tại đây (62.42 KB, 3 trang )
Study;however,therewereonlyeightpatientswithRCMinthiscohort,making
itdifficulttoextrapolatethedataonalargerscale.232
Etiology
SarcomericMutations
Mutationsinanumberofsarcomeric,cytoskeletal,andZ-bandproteinshave
beenassociatedwithRCM(seeTable61.1).AsinthecaseofHCMandDCM,
theadventoflow-costgeneticscreeninghasrevealedthatwhatwaspreviously
calledidiopathicRCMisinfactgeneticallydriven.Mutationsindesminare
associatedwithRCM,atrioventricularblock,andskeletalmyopathy.351Thisis
typicallyinheritedinanautosomaldominantpattern;however,recessive
inheritancehasalsobeendescribed.352Mutationsinmyosin-bindingproteinC,
β-myosinheavychain,troponinI,troponinT,filaminC,myopalladin,and
cardiacα-actinhavealsobeenlinkedtoRCM.70,353–355Giventheaffected
genes,itisnosurprisethatthereisoftenanoverlappingspectrumofdisease
withHCM.Next-generationsequencinghasalsoidentifiedanumberof
mutationsinnumeroussarcomeric,cytoskeletal,andZ-bandproteinsthatare
possiblypathogenic;however,furtherphenotypicevaluationsareneededto
confirmtheearlyfindings.356
EndomyocardialFibrosisandEosinophilic
Cardiomyopathy(LoefflerSyndrome)
EndomyocardialfibrosisisadiseaseoftropicalAfrica,Asia,andSouthAmerica
thatmayleadtorestrictivephysiology.Ithasabimodaldistributionwitha
notablepeakintheteenageyearsandagainaroundage30years.357Theoutcome
istypicallyverypoorandmanagementreliesonsymptomaticreliefand
anticoagulationowingtotheriskofthromboembolicdisease.358Thecause
remainsunclearbut—giventheindividualfactorsdonotadequatelyexplainthe
geographicandclinicalcharacteristicsofdisease—likelyinvolvesacombination
ofenvironmental,infectious,andgeneticriskfactors.359Restrictivephysiology
mayalsodevelopinthechronicphaseofhypereosinophilicdisease(Loeffler
syndromeorendocarditis).360
InfiltrativeDisease
CardiacsarcoidosisisararecauseofRCMinchildren.Thediseasetypically
manifestsassystolicdysfunctionwithorwithoutheartblockinyoungand
middle-agedadults.361,362Clinicalstudiesusingabroaderscreeningprotocol
suggestthatsubclinicalcardiacmanifestationsofdiseasemaybeevidentby
CMR.362,363Mutationsintransthyretinleadtoinheritedamyloidosis,whichmay
manifestasRCM;however,thisisagainamorenotablecauseofdiseasein
adultsthaninchildren.364Restrictivephysiologymayalsobeseeninthe
spectrumofdiseaseinpatientswithlysosomalstoragedisease,althoughthese
diseasesaretypicallyassociatedwithanHCMphenotype.
Pathology
Macroscopically,RCMischaracterizedbybiatrialdilationwithasmallor
normal-sizedleftventricularcavitywithoutthepresenceofventricular
hypertrophy.ThereisaspectrumofdiseasethatextendsintoHCM,so-called
HCMwithrestrictivephysiology.350Theatrialenlargementmaypredispose
patientstothedevelopmentofatrialthrombus.Microscopically,RCMis
characterizedpatchyatrialandventricularfibrosiswithvariablemyocyte
hypertrophy.344Fibrosismaybepresentinthesinuatrialandatrioventricular
nodesandcontributestotheriskofbradyarrhythmicdeath.365,366
Pathophysiology
RCMischaracterizedbyreducedventricularcompliance,leadingtoelevated
ventricularfillingpressuresandimpairedcardiacoutput.Chronicallyelevated
leftatrialpressuresmayleadtotherapidandunpredictabledevelopmentof
pulmonaryvasculardisease.346Arrhythmias—includinghigh-gradeheartblock,
atrialtachycardia,atrialfibrillation,ventriculartachycardia,andventricular
fibrillation—haveallbeenreportedandcontributetotheriskofdeath,both
suddenandduetothromboembolicdisease.346,350,366
ClinicalFeatures
Symptoms
Infantsandtoddlersmaypresentwithrespiratorydistress,tachypnea,andfailure
tothrive.Olderchildrenandadolescentspresentwithsimilarsymptomsaswell
aschestpain,nearsyncope,syncope,orpalpitations.Thevenouscongestion
associatedwithRCMmayalsoproducesignificantedemaandascites.
PhysicalExamination
Thephysicalexamfindingsareconsistentwiththoseexpectedforelevatedright
andleftventricularfillingpressures.Jugularvenousdistention,hepatomegaly,
ascites,andperipheraledemamaybepresent.Theapicalimpulseistypically
unremarkable.Thepulmonarycomponentofthesecondheartsoundisoften
accentuated,giventheelevatedpulmonaryarterypressures.Agallopis
frequentlyheard.
ElectrocardiographyandAmbulatory
ElectrocardiographicMonitoring
TheECGfindingsofRCMareoftenpathognomonic,withgiantsignificant
biatrialenlargement(Fig.61.11).Sinusnodebradycardia,atrialarrhythmias,
varyinggradesofatrioventricularblock,andQRSprolongationmaybe
present.366NonspecificST-andT-waveabnormalitiesarealsocommonly
present.
