老年性瓣膜性心脏病-主动脉瓣狭窄

老年性瓣膜性心脏病

---主动脉瓣狭窄卫生部北京医院何青内容老龄和瓣膜病老年AS的临床特点老年AS的治疗策略内容老龄和瓣膜病老年AS的临床特点老年AS的治疗策略1854WilliamStokes

在他的教科书

“Thediseasesoftheheartandtheaorta”中描述钙化性主动脉瓣病的特征为：

(1)permanentpatencyofthevalveinwhichthediametermaybeincreasedordiminished; (2)anextremeossificgrowthalongthevalvesurroundingtheventricle,atwhichthevalvesareoftendestroyed; (3)anatheromatousdepositontheventricularsurfaceofthevalvewhichisoftenseeninthecontextoffattydegenerationoftheheart.1904年Monchkebery首先发现人在自然衰老过程中会出现退行性变，引起主动脉瓣的钙化、狭窄。1910年Dewisky首先描述了二尖瓣环的钙化。

NaliniMRajamannanetal,Heart2003;89:801–8051997年美国B.FENDLEYSTEWART等人报道了5201例≥65岁老年人的心血管健康研究，提示经心脏超声检查，主动脉瓣硬化发生率是26%，主动脉狭窄为2%。在≥75岁的人群中，硬化发生率是37%，狭窄为2.6%。与退行性瓣膜病相关的独立危险因子包括年龄（年龄每增长十年危险增长2倍）、性别（男性为女性两倍）、吸烟（仍然吸烟者增加危险35%）和高血压（有高血压病史者危险增加20%）。其他明确的危险因子有LP（a）和LDL-C的水平。作者认为与主动脉瓣硬化和狭窄相关的临床因素明确，且类似于动脉粥样硬化的危险因素。STEWARTETAL.AORTICSTENOSISRISKFACTORSJAmCollCardiol1997;29:630–4正常主动脉瓣膜Thenormalaorticvalvecomprises3layers.Theventricularis,ontheventricularsideoftheleaflet,iscomposedofelastinrichfibersthatarealignedinaradialdirection,perpendiculartotheleafletmargin.Thefibrosa,ontheaorticsideoftheleaflet,comprisesprimarilyfibroblastsandcollagenfibersarrangedcircumferentially,paralleltotheleafletmargin.Thespongiosaisalayeroflooseconnectivetissueatthebaseoftheleaflet,betweenthefibrosaandventricularis,composedoffibroblasts,mesenchymalcells,andamucopolysaccharide-richmatrix.Theselayersworkinconcerttoprovidetensilestrengthandpliabilityfordecadesofrepetitivemotion.

FreemanandOttoCalcificAorticValveDiseaseCirculationJune21,2005早期病变：瓣膜主动脉侧内皮下细胞、脂质和细胞外基质的积聚，伴内皮下弹力层的移位。晚期病变：更加明显的脂质、细胞、细胞外基质的聚集，弹力层移位、断裂。钙化性主动脉瓣疾病组织学改变Potentialpathwaysdepictingcalcificaorticvalvedisease.Tlymphocytesandmacrophagesinfiltrateendotheliumandreleasecytokinesthatactonvalvularfibroblaststopromotecellularproliferationandextracellularmatrixremodeling.Asubsetofvalvularfibroblastswithinfibrosalayerdifferentiateintomyofibroblaststhatpossesscharacteristicsofsmoothmusclecells.LDLthatistakenintothesubendotheliallayerisoxidativelymodifiedandtakenupbymacrophagestobecomefoamcells.ACEiscolocalizedwithapolipoproteinB(ApoB)andfacilitatesconversionofangiotensinII(AngII),whichactsonangiotensin1receptors(AT-1R),expressedonvalvularmyofibroblasts.Asubsetofvalvularmyofibroblastsdifferentiateintoosteoblastphenotypethatiscapableofpromotingcalciumnoduleandboneformation.ILindicatesinterleukin;TGF,transforminggrowthfactor;andMMP,matrixmetalloproteinases.FreemanandOttoCalcificAorticValveDiseaseCirculationJune21,2005

病变早期：内皮损伤机械作用细胞外脂质聚集炎症反应细胞外液和ACE作用

病变晚期：

随着病变的进展，纤维膜层的纤维母细胞分化成具有平滑肌特点的成肌纤维细胞，瓣膜硬化。后者具有成骨作用，在炎症因子等的共同刺激下，钙盐沉积，瓣膜上进一步形成钙化结节。 瓣膜的骨化，可能和钙盐的代谢有关，有研究认为钙盐沉积是一个主动的过程，也可能和遗传有一定的关系。病理机制脂蛋白聚集细胞渗出细胞外基质形成瓣膜增厚、硬化、钙化瓣叶活动受限流出道受阻左室肥厚、左室舒张功能、收缩功能受损、充血性心衰、心绞痛、心律失常、晕厥FreemanandOttoCalcificAorticValveDisease3317导致AS的主要原因：正常三叶瓣的钙化和退行性变，随年龄而增加和冠心病相关的多种危险因子常于AS相伴先天性主动脉瓣畸形，二叶瓣、单叶瓣风湿先天性主动脉二瓣畸形致狭窄风湿性主动脉瓣狭窄钙化的退行性主动脉瓣狭窄内容老龄和瓣膜病老年AS的临床特点老年AS的治疗策略FreemanandOttoCalcificAorticValveDiseaseCirculationJune21,2005瓣膜的钙化病变和形成动脉粥样硬化的临床因素类似大部分主动脉瓣硬化的病人临床没有症状，或其心血管病危险因素已得到控制，但临床事件的发生率仍然是高的。有16%诊断为主动脉瓣硬化的病人在8年内进展为严重的主动脉瓣狭窄。老年人主动脉瓣硬化和心血管发病率和死亡率的相关性

ASSOCIATIONOFAORTIC-VALVESCLEROSISWITHCARDIOVASCULARMORTALITYANDMORBIDITYINTHEELDERLY

CATHERINEM.OTTOetal.NEnglJMed1999;341:142-7N=5621，年龄>65岁，前瞻性研究，超声心动图检查，平均随访5年Conclusions: Aorticsclerosisiscommonintheelderlyandisassociatedwithanincreaseofapproximately50%intheriskofdeathfromcardiovascularcausesandtheriskofmyocardialinfarction,evenintheabsenceofhemodynamicallysignificantobstructionofleftventricularoutflow.

CATHERINEM.OTTOetal.NEnglJMed1999;341:142-7伴有“良性”主动脉瓣增厚病人发生主动脉瓣狭窄的危险性

TheRiskoftheDevelopmentofAorticStenosisinPatientsWith“Benign”AorticValveThickening

JohnE.Cosmi,etal,ArchInternMed.2002;162:2345-2347N=2131，回顾性研究，心脏超声诊断，15.9%伴有“良性”主动脉瓣增厚病人发生主动脉瓣狭窄的危险性

TheRiskoftheDevelopmentofAorticStenosisinPatientsWith“Benign”AorticValveThickening

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

Aorticvalvethickeningwithoutstenosisiscommon,anditmayprogresstosignificantAS.ItispossiblethatthisdevelopmentofASmayberesponsibleforsomeoftheincreasedmorbidityandmortalityinpatientswithAVT. 1973年《中华医学杂志》“老年人冠状动脉粥样硬化性心脏病临床与病理的对照分析”一文报道一例明显钙化性主动脉瓣狭窄的老年病人尸检提示多处不同发展阶段内膜下心梗，但没有明显的冠脉狭窄病变，认为AS可以引起MI，而且这种梗塞是反复发生的和范围较小的。国内北京医院报道6例临床追随30年以上，又进行了尸解证实为严重钙化性主动脉瓣狭窄的老年病例，生前的临床特点均为逐渐出现并加重的心底部收缩期杂音，均有心电图的缺血改变和心脏超声的左室肥厚、瓣膜钙化表现，6例中5例生前有心肌梗死病史。尸检的病理特点是反复发生，不同时间，分散和灶性的非透壁性心梗，冠脉病变可以较轻甚至无明显病变。6例中5例为猝死，其原因考虑与主动脉瓣狭窄患者的血液动力学障碍有关仍可有心梗的发生。齐欣、王瑞萍、钱贻简等中华内科杂志2000年2月第39卷第2期内容老龄和瓣膜病老年AS的临床特点老年AS的治疗策略JointRecommendationsofAmericanHeartAssociationandAmericanCollegeofCardiologyforaorticvalvereplacementinpatientswithaorticstenosisAorticvalvereplacementindicated

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

Inpatientswithsevereaorticstenosiswhoarehavingcoronaryarterybypassgrafting

Inpatientswithsevereaorticstenosishavingsurgeryontheaortaorotherheartvalves

Inpatientswithsevereaorticstenosiswithleftventricularsystolicdysfunction(ejectionfraction<50%)Aorticvalvereplacementpossiblyindicated

Inpatientswithmoderateaorticstenosishavingcoronaryarterybypassgraftingorsurgeryontheaortaorotherheartvalves

Inpatientswithasymptomaticsevereaorticstenosiswithabnormalresponsetoexercise(suchasdevelopmentofsymptomsorasymptomatichypotension)

Inpatientswithasymptomaticsevereaorticstenosisifthereislikelihoodofrapidprogression(age,calcification,andcoronaryarterydisease)orifsurgerymightbedelayedatthetimeofsymptomonset

Inpatientswithmildaorticstenosishavingcoronaryarterybypassgraftingwhenthereisevidenceofmoderatetoseverecalcification,suggestingthatprogres