老年性瓣膜性心臟病

---主動(dòng)脈瓣狹窄衛(wèi)生部北京醫(yī)院何青內(nèi)容老齡和瓣膜病老年AS的臨床特點(diǎn)老年AS的治療策略內(nèi)容老齡和瓣膜病老年AS的臨床特點(diǎn)老年AS的治療策略1854WilliamStokes

在他的教科書

“Thediseasesoftheheartandtheaorta”中描述鈣化性主動(dòng)脈瓣病的特征為：

(1)permanentpatencyofthevalveinwhichthediametermaybeincreasedordiminished; (2)anextremeossificgrowthalongthevalvesurroundingtheventricle,atwhichthevalvesareoftendestroyed; (3)anatheromatousdepositontheventricularsurfaceofthevalvewhichisoftenseeninthecontextoffattydegenerationoftheheart.1904年Monchkebery首先發(fā)現(xiàn)人在自然衰老過程中會(huì)出現(xiàn)退行性變，引起主動(dòng)脈瓣的鈣化、狹窄。1910年Dewisky首先描述了二尖瓣環(huán)的鈣化。

NaliniMRajamannanetal,Heart2003;89:801–8051997年美國B.FENDLEYSTEWART等人報(bào)道了5201例≥65歲老年人的心血管健康研究，提示經(jīng)心臟超聲檢查，主動(dòng)脈瓣硬化發(fā)生率是26%，主動(dòng)脈狹窄為2%。在≥75歲的人群中，硬化發(fā)生率是37%，狹窄為2.6%。與退行性瓣膜病相關(guān)的獨(dú)立危險(xiǎn)因子包括年齡（年齡每增長十年危險(xiǎn)增長2倍）、性別（男性為女性兩倍）、吸煙（仍然吸煙者增加危險(xiǎn)35%）和高血壓（有高血壓病史者危險(xiǎn)增加20%）。其他明確的危險(xiǎn)因子有LP（a）和LDL-C的水平。作者認(rèn)為與主動(dòng)脈瓣硬化和狹窄相關(guān)的臨床因素明確，且類似于動(dòng)脈粥樣硬化的危險(xiǎn)因素。STEWARTETAL.AORTICSTENOSISRISKFACTORSJAmCollCardiol1997;29:630–4正常主動(dòng)脈瓣膜Thenormalaorticvalvecomprises3layers.Theventricularis,ontheventricularsideoftheleaflet,iscomposedofelastinrichfibersthatarealignedinaradialdirection,perpendiculartotheleafletmargin.Thefibrosa,ontheaorticsideoftheleaflet,comprisesprimarilyfibroblastsandcollagenfibersarrangedcircumferentially,paralleltotheleafletmargin.Thespongiosaisalayeroflooseconnectivetissueatthebaseoftheleaflet,betweenthefibrosaandventricularis,composedoffibroblasts,mesenchymalcells,andamucopolysaccharide-richmatrix.Theselayersworkinconcerttoprovidetensilestrengthandpliabilityfordecadesofrepetitivemotion.

FreemanandOttoCalcificAorticValveDiseaseCirculationJune21,2005早期病變：瓣膜主動(dòng)脈側(cè)內(nèi)皮下細(xì)胞、脂質(zhì)和細(xì)胞外基質(zhì)的積聚，伴內(nèi)皮下彈力層的移位。晚期病變：更加明顯的脂質(zhì)、細(xì)胞、細(xì)胞外基質(zhì)的聚集，彈力層移位、斷裂。鈣化性主動(dòng)脈瓣疾病組織學(xué)改變Potentialpathwaysdepictingcalcificaorticvalvedisease.Tlymphocytesandmacrophagesinfiltrateendotheliumandreleasecytokinesthatactonvalvularfibroblaststopromotecellularproliferationandextracellularmatrixremodeling.Asubsetofvalvularfibroblastswithinfibrosalayerdifferentiateintomyofibroblaststhatpossesscharacteristicsofsmoothmusclecells.LDLthatistakenintothesubendotheliallayerisoxidativelymodifiedandtakenupbymacrophagestobecomefoamcells.ACEiscolocalizedwithapolipoproteinB(ApoB)andfacilitatesconversionofangiotensinII(AngII),whichactsonangiotensin1receptors(AT-1R),expressedonvalvularmyofibroblasts.Asubsetofvalvularmyofibroblastsdifferentiateintoosteoblastphenotypethatiscapableofpromotingcalciumnoduleandboneformation.ILindicatesinterleukin;TGF,transforminggrowthfactor;andMMP,matrixmetalloproteinases.FreemanandOttoCalcificAorticValveDiseaseCirculationJune21,2005

病變早期：內(nèi)皮損傷機(jī)械作用細(xì)胞外脂質(zhì)聚集炎癥反應(yīng)細(xì)胞外液和ACE作用

病變晚期：

隨著病變的進(jìn)展，纖維膜層的纖維母細(xì)胞分化成具有平滑肌特點(diǎn)的成肌纖維細(xì)胞，瓣膜硬化。后者具有成骨作用，在炎癥因子等的共同刺激下，鈣鹽沉積，瓣膜上進(jìn)一步形成鈣化結(jié)節(jié)。 瓣膜的骨化，可能和鈣鹽的代謝有關(guān)，有研究認(rèn)為鈣鹽沉積是一個(gè)主動(dòng)的過程，也可能和遺傳有一定的關(guān)系。病理機(jī)制脂蛋白聚集細(xì)胞滲出細(xì)胞外基質(zhì)形成瓣膜增厚、硬化、鈣化瓣葉活動(dòng)受限流出道受阻左室肥厚、左室舒張功能、收縮功能受損、充血性心衰、心絞痛、心律失常、暈厥FreemanandOttoCalcificAorticValveDisease3317導(dǎo)致AS的主要原因：正常三葉瓣的鈣化和退行性變，隨年齡而增加和冠心病相關(guān)的多種危險(xiǎn)因子常于AS相伴先天性主動(dòng)脈瓣畸形，二葉瓣、單葉瓣風(fēng)濕先天性主動(dòng)脈二瓣畸形致狹窄風(fēng)濕性主動(dòng)脈瓣狹窄鈣化的退行性主動(dòng)脈瓣狹窄內(nèi)容老齡和瓣膜病老年AS的臨床特點(diǎn)老年AS的治療策略FreemanandOttoCalcificAorticValveDiseaseCirculationJune21,2005瓣膜的鈣化病變和形成動(dòng)脈粥樣硬化的臨床因素類似大部分主動(dòng)脈瓣硬化的病人臨床沒有癥狀，或其心血管病危險(xiǎn)因素已得到控制，但臨床事件的發(fā)生率仍然是高的。有16%診斷為主動(dòng)脈瓣硬化的病人在8年內(nèi)進(jìn)展為嚴(yán)重的主動(dòng)脈瓣狹窄。老年人主動(dòng)脈瓣硬化和心血管發(fā)病率和死亡率的相關(guān)性

ASSOCIATIONOFAORTIC-VALVESCLEROSISWITHCARDIOVASCULARMORTALITYANDMORBIDITYINTHEELDERLY

CATHERINEM.OTTOetal.NEnglJMed1999;341:142-7N=5621，年齡>65歲，前瞻性研究，超聲心動(dòng)圖檢查，平均隨訪5年Conclusions: Aorticsclerosisiscommonintheelderlyandisassociatedwithanincreaseofapproximately50%intheriskofdeathfromcardiovascularcausesandtheriskofmyocardialinfarction,evenintheabsenceofhemodynamicallysignificantobstructionofleftventricularoutflow.

CATHERINEM.OTTOetal.NEnglJMed1999;341:142-7伴有“良性”主動(dòng)脈瓣增厚病人發(fā)生主動(dòng)脈瓣狹窄的危險(xiǎn)性

TheRiskoftheDevelopmentofAorticStenosisinPatientsWith“Benign”AorticValveThickening

JohnE.Cosmi,etal,ArchInternMed.2002;162:2345-2347N=2131，回顧性研究，心臟超聲診斷，15.9%伴有“良性”主動(dòng)脈瓣增厚病人發(fā)生主動(dòng)脈瓣狹窄的危險(xiǎn)性

TheRiskoftheDevelopmentofAorticStenosisinPatientsWith“Benign”AorticValveThickening

JohnE.Cosmi,etal,ArchInternMed.2002;162:2345-2347Conclusions:

Aorticvalvethickeningwithoutstenosisiscommon,anditmayprogresstosignificantAS.ItispossiblethatthisdevelopmentofASmayberesponsibleforsomeoftheincreasedmorbidityandmortalityinpatientswithAVT. 1973年《中華醫(yī)學(xué)雜志》“老年人冠狀動(dòng)脈粥樣硬化性心臟病臨床與病理的對(duì)照分析”一文報(bào)道一例明顯鈣化性主動(dòng)脈瓣狹窄的老年病人尸檢提示多處不同發(fā)展階段內(nèi)膜下心梗，但沒有明顯的冠脈狹窄病變，認(rèn)為AS可以引起MI，而且這種梗塞是反復(fù)發(fā)生的和范圍較小的。國內(nèi)北京醫(yī)院報(bào)道6例臨床追隨30年以上，又進(jìn)行了尸解證實(shí)為嚴(yán)重鈣化性主動(dòng)脈瓣狹窄的老年病例，生前的臨床特點(diǎn)均為逐漸出現(xiàn)并加重的心底部收縮期雜音，均有心電圖的缺血改變和心臟超聲的左室肥厚、瓣膜鈣化表現(xiàn)，6例中5例生前有心肌梗死病史。尸檢的病理特點(diǎn)是反復(fù)發(fā)生，不同時(shí)間，分散和灶性的非透壁性心梗，冠脈病變可以較輕甚至無明顯病變。6例中5例為猝死，其原因考慮與主動(dòng)脈瓣狹窄患者的血液動(dòng)力學(xué)障礙有關(guān)仍可有心梗的發(fā)生。齊欣、王瑞萍、錢貽簡等中華內(nèi)科雜志2000年2月第39卷第2期內(nèi)容老齡和瓣膜病老年AS的臨床特點(diǎn)老年AS的治療策略JointRecommendationsofAmericanHeartAssociationandAmericanCollegeofCardiologyforaorticvalvereplacementinpatientswithaorticstenosisAorticvalvereplacementindicated

Inpatientswithsevereaorticstenosiswithitsclassic“SAD”symptoms(syncope,angina,and/ordyspnoea

Inpatientswithsevereaorticstenosiswhoarehavingcoronaryarterybypassgrafting

Inpatientswithsevereaorticstenosishavingsurgeryontheaortaorotherheartvalves

Inpatientswithsevereaorticstenosiswithleftventricularsystolicdysfunction(ejectionfraction<50%)Aorticvalvereplacementpossiblyindicated

Inpatientswithmoderateaorticstenosishavingcoronaryarterybypassgraftingorsurgeryontheaortaorotherheartvalves

Inpatientswithasymptomaticsevereaorticstenosiswithabnormalresponsetoexercise(suchasdevelopmentofsymptomsorasymptomatichypotension)

Inpatientswithasymptomaticsevereaorticstenosisifthereislikelihoodofrapidprogression(age,calcification,andcoronaryarterydisease)orifsurgerymightbedelayedatthetimeofsymptomonset

Inpatientswithmildaorticstenosishavingcoronaryarterybypassgraftingwhenthereisevidenceofmoderatetoseverecalcification,suggestingthatprogres