非抗心律失常藥物的抗房

非抗心律失常藥物的抗房顫作用心房顫動特點臨床上最常見的需藥物與非藥物治療的心律失常并非是一種良性心律失常慢性房顫多發(fā)生于器質(zhì)性心臟病患者，少數(shù)患者無心臟病證據(jù)發(fā)生率隨年齡增加而增高缺血性腦卒中的主要原因之一快速心室率未能控制者，可發(fā)生心動過速性心肌病心房顫動的流行病學

累積發(fā)生率男性為2.2%、女性為

1.7%70％左右的房顫發(fā)生在器質(zhì)性心臟病大約30％的房顫無任何可發(fā)現(xiàn)的病因病死的最主要原因是缺血性腦卒中，其發(fā)生率隨年齡增加明顯升高Atrialfibrillationaccountsfor1/3ofallpatientdischarges

witharrhythmiaas

principaldiagnosis.

2%VF Datasource:BailyD.JAmColl

Cardiol.1992;19(3):41A.34%

Atrial

Fibrillation18%

Unspecified6%

PSVT6%

PVCs4%AFL9%SSS8%

Conduction

Disease3%SCD10%VTArrhythmiaasprincipaldiagnosisMortalityFramighamStudyBenjaminEJetal,FramighamHeartStudy,Circulation98;98:946-95255-74years75–94y心房顫動的病理生理和電生理機制

房顫常發(fā)生于三種不同的臨床情況無心臟病證據(jù)患者，稱原發(fā)性房顫雖無心臟病證據(jù)，但有誘發(fā)房顫發(fā)生的非心臟性疾病(甲亢等)，為繼發(fā)性房顫發(fā)生于器質(zhì)性心臟病者的繼發(fā)性房顫

心房顫動的病理生理和電生理機制

心房顫動的病理組織學心房擴張和不均勻分布的纖維化(竇房結)

見于器質(zhì)性心臟病非特異的散在纖維化

繼發(fā)于全身性疾病心房肌細胞離子通道的功能異?；蛭醋R別的非病理性結構異常

發(fā)生于健康人的陣發(fā)性房顫(孤立性房顫)心房顫動的病理生理和電生理機制心房顫動的電生理機制異位局灶自律性增強學說(Scherf

等，1953)多個子波折返激動學說(Moe等，1959)觸發(fā)因素：房早、房撲、房速、AVNRT、AVRT、交感或迷走神經(jīng)活性改變等心房顫動的病理生理和電生理機制局灶性房顫的起源部位肺靜脈(90%以上尤其為左、右上肺靜脈)其他部位包括：界嵴、上、下腔靜脈、冠狀靜脈竇、房室交界區(qū)、房間隔、

Marshall

韌帶、心房游離壁起源于肺靜脈、腔靜脈、冠狀靜脈竇的房顫可能與肌袖(muscularsleeve)有關?心房顫動的分類陣發(fā)性房顫：發(fā)作持續(xù)<7d，大多可自行轉(zhuǎn)復，并可反復發(fā)作持續(xù)性房顫：發(fā)作48小時以上未能自行轉(zhuǎn)復而需要藥物或非藥物干預永久性房顫：發(fā)作持續(xù)幾天（≥7d）或幾年心房顫動的治療原則控制心室率預防栓塞性事件轉(zhuǎn)復心房顫動為竇性心律直流電轉(zhuǎn)復心律藥物復律及維持竇性心律非藥物預防房顫復發(fā)心臟起搏預防心房顫動(?)TreatmentstrategiesforAFAtrialfibrillationAntiarrhythmicdrugsPreventivePacingAlateandbpaceHybridtherapyAtrialDefibrillatorMAZE-surgeryCatheterablationACE-I、ARB、Statin、DiureticEffectivenessofrhythmcontrolinAF

withOAPandAADafterlinearRACAHybridtherapyutilizingcathterRAmazeprocedureswithOAPandAADcanbeperformedsafelyandcanreestablishrhythmcontrolinselectedpatientswithrefractorypersistentorpermanentAFOAP:overdriveatrialpacingAAD:

antiarrhythmic

durg具有抗心律失常作用的

非抗心律失常藥物Angiotensinconvertingenzymeinhibitors(ACE-I)AngiotensinreceptorBlocker(ARB)StatinDiuretics非抗心律失常藥物

抗心律失常作用的可能機理

ACE-I和ARB抗心律失常作用的可能機理包括：DecreaseofwallstressandloweringofbloodpressureModulationofrefractorinessInterferencewithioncurrentsModificationofsympathetictoneandstabilizationofelectrolyteconcentrationInteractionbetweenARBandpotassiumchannelblockerontransmembraneactionpotentialsandcurrentsARBmodifiedthecardiacdelayedretifierhKv1.5.HEKGandKscurrentsAngiotensinogenAngiotensinIAngiotensinIIAT1AT2ReninACENon-ACEAT1Blockers

VasoconstrictionNeurohumoralretentionHydro-salineretentionCellgrowthVasodilation

GrowthInhibitionApoptosisEffectsofAT1receptorblockersonangiotensinIIandbradikininsynthesisandinactivationGeneticFactorsandModifiersandEnrivironmentalStressDeterminantLong-termCatecholamines

StructuralFreeRadicals

Modulators

Andacute

TriggersACEAngiotensinIIAldosterone

Cytokines

NitricOxideStructuralandElectricalRemodelingGeneStructureFibrosisIonchannerls

ExtracellularMatrixAotonomics

FiberorientationGapjunctionsCalciumhandlingRate

Activation

sequenceEnhancementofArrhythmia

HeterogencityFacilitatorsArrhythmiaArrhythmiaTriggersSubstratePhenotypicExpressionNewapproachestoantiarrhythmictherapy.EurHeartJ,2001EnalaprildecreasetheincidenceofatrialfibrillationinpatientswithleftventriculardysfunctionInsightFromtheStudiesOfLeftVentricularDysfunction(SOLVD)TrialBackgroundAFoccurringinthecourseofexperimentalHFinducedbyrapidventricularpacingisaccompaniedbyatrialelectricalandstructuralremodeling,includingatrialdilation,contractiledysfunction,andfibrosis.ACEIhavebeendemanstratedaroleforACEIinthepreventionofthisatrialstructureremodeling

SOLVDTrial

MethodsandResults391Pts374Pts17Pts186Pts/ACEI55Pts10Pts45PtsP<0001188Pts/plac.InsightFromtheStudiesOfLeftVentricularDysfunction(SOLVD)TrialConclusionTreatmentwiththeACE-IenalaprilmarkedlyreducestheriskofdevelopmentofAFinpatientswithleftven-triculardysfunction

Circulation,2003;107:2926-2931EnalaprildecreasetheincidenceofatrialfibrillationinpatientswithleftventriculardysfunctionTrandolaprilreducestheincidenceofAFafterAMIinptswithleft

ventriculardysfunctionTRACESTUDYBackground:ACE-IhaveanantiarrhythmiceffectonventriculararrhythmiasHaveACE-IaneffectonAF?Metholdsandresults:TrandoaprilontheincidenceofAFPtswithAMIandreducedleftventricularfunctionArandomizeddouble-blindplacebo-controlledstudyPedersenetal.Circulation,1999;100:376-380TrandolaprilreducestheincidenceofAFafterAMIinptswithleft

ventriculardysfunctionTRACESTUDY1577/1749ptsinsinusrhythm790pts-ACEI787pts-placeboN=22(2.8%)N=42(5.3%)AF

AF

F/u2-4years

P<0.05

TrandolaprilreducestheincidenceofAFafterAMIinptswithleft

ventriculardysfunctionTRACESTUDYConclusionTheresultsfromthepresentstudydemonstratethattrandolapriltreatmentreducestheincidenceofatrialfibrillationinpatientswithleftventriculardysfunctionafteracutemyocardialinfarctionPedersenetal.Circulation,1999;100:376-380ARB在房顫節(jié)律控制中的作用ARBasadjunctivetherapyforrhythmcontrolinatrialfibrillation:

ResultsoftheIrbesartan-Amiodaronetrial

MadridAH,etal.CardiacElectrophysiologyReview2003,7GroupIAmioGroupII

Amio+ARB

154/186ptsafterCV84.7963.1655.9179.52recurrentAF

freeofAF2mon.ofFU254dofFU(p=0.007)ARBtherapyforrhythmcontrolinAFTheresultsofthisprospectiveandrandomizedshowthatARBirbesartan,combinedwithAmio.ismoreeffectivethanAmio.aloneinthemaintenanceofsinusrhythminptswithpersistentAFaftercadioversionMostofthebenefitofirbesartan

occurrredduringthefirst2monthsaftercardioversionIrbesartanreducedtheimmediaterecurrenceofAFandthesocalled

subacuterecurrencesduringthefirstweeksMadridAH,etal.CardiacElectrophysiologyReview2003,7ARBtherapyforrhythmcontrolinAFARBtherapyforrhythmcontrolinAFConclusionsIrbesartanmayhaveantifibroticeffectsduenotonlytotheabilitytodiminishthesynthesisofcollagentypeImoleculesbutalsotoitscapacitytostimulatethedegradationofcollagentypeIfiberToreducethestructuralchangesthatoccurduringAFmaybemoreusefulinpreventingrecurrencesthaneffortsdesignedtominimizetheelectricalchangesaloneMadridAH,etal.CardiacElectrophysiologyReview2003,7ThepreventiveeffectofACEI、ARBandDiureticsto

AFafterRFCAofAFLBackground:ACEexpressionisincreasedinatrialbiopsiesofPtswithAFandAngIIconcentrationsareincreasedinanimalmodelsofAFACEIdiminishtheincidenceofAFafterMIandinthesettingofheartfailureARBreducetherecurrenceofAFaftercardioversionforpersist.AFMethods:196PtsreceivedRFCAAFoccurrence,echocardiographic,proceduralfactorsperiproceduraldrugusewasanalysedretrospectivelybyaCoxproportionalhazardmethodHeart,2004,90:1025-1030Results:Followup2.2y,114(58%)developed1episodeofAFAssociatedfactors:PresenceofpreproceduralAFHistoryofcardioversionThenumberofantiarrhythmicdrugsusedbeforetheprocedureUseofACEI,ARB,anddiureticswassignificantlyassociatedbyunivariateandmultivariateanalyseswithlessdevelopmentofAFHeart,2004,90:1025-1030ThepreventiveeffectofACEI、ARBandDiureticsto

AFafterRFCAofAFLConclusions:AhighproportionofPtsdevelopAFafterAFLablationTheincidenceofAFisrelatedtopre-ablationAFLanditspersistenceACEI,ARBanddiureticsseemtoprotectagainstAF

Heart,2004,90:1025-1030ThepreventiveeffectofACEI、ARBandDiureticsto

AFafterRFCAofAFLReductionintheoccurrenceofAF

inhypertensivePtswithACEItherapyBackground:

AFAngIIHypertensionCCBACEITheoccurrenceofAF?Methods:

Retrospective,longitudinalcohortstudyTimeforinvestigation:1995Jan-1999JuneprescriptionforeitheranACEIoraCCB8millionPtsAge18yFinalcohorts:2002Survivalanalysis:ComparetheincidenceofAFbetweengroupsJACC2004,44:159-164

ReductionintheoccurrenceofAF

inhypertensivePtswithACEItherapyResults:

Subjects:10926ptsMeanage:65yNew-onsetAF:ACEIvsCCB(0.85,95%CI:0.74-0.97)Hospitalization:ACEIvsCCB(0.74,95%CI:0.62-0.89)

JACC2004,44:159-164

ReductionintheoccurrenceofAF

inhypertensivePtswithACEItherapyConclusions:

ACEIwasassociatedwithareducedincidenceofAFforptswithhypertensioninausualcaresettingTheseresultsneedtobeconfirmedinalarge-scalerandomizedclinicaltrialJACC2004,44:159-164

ReductionintheoccurrenceofAF

inhypertensivePtswithACEItherapy應用ACE-I和ARB預防房顫

(a

meta-analysis)Objective:Toidentifyallrandomizedclinicaltrialdataevalua-tingACE-IorARBforthepreventionofAFMetholds:AsystematicrewiewoftheliteratureaboutallreportsoftheeffectofACEIsorARBsonthedevelopmentofAF

JAmColl

Cardiol,2005Jun7;45(11):1832-9應用ACE-I和ARB預防房顫

(a

meta-analysis)RESULTS11studiesN=563084inHF3inH-BP2F/uCV2F/uMI

ACE-Is/ARBsreducedRRRofAF28%:ACE-I:28%,p=0.01;ARB:29%,p=0.00002;HF:44%,p=0.007;Hypertensiononly12%,p=0.4andinpatientsfollowingCV48%應用ACE-I和ARB預防房顫

(a

meta-analysis)Conclusion:BothACE-IsandARBsappeartobeeffectiveinthepreventionofAF.Thisbenefitappearstobelimitedtoptswithsystolicleftventricu-lardysfunctionorLVhypertrophy

JAmColl

Cardiol,2005Jun7;45(11):1832-9RelationbetweenACEIIgenotypeandAFBackground:TheoccurrenceofAFinHCMis20%AFthromboembolismAFRASMethods:GenotypedtheI/DpolymorphismoftheACEgene(DDIDII)138pts(26AF&112Sinus)

JHumGenet,2002,47:184-189RelationbetweenACEIIgenotypeandAFResults:genotypeDDIDIIdistribution

15%46%38%occurrence3p7p16p(p<0.03vssinus)Conclusion:IIphenotypeisasignificantriskfactorforAFinHCM

JHumGenet,2002,47:184-189UsefulnessofStatindrugsinprotectingagainstAFinptswithCAD目的：ToexaminetheassociationbetweenStatinuseandincidenceofAFinptswhohadchronicstableCADbutwithoutpreviousAF結果：Studypopulation:449pts(agesof40-87years)Statinusers:263pts;Statinnonusers:186ptsStatinusers:9%(24/263pts);Statinnonusers:15%(28/186)ptsAmJCardiol2003;92:1379-1383UsefulnessofStatindrugsinprotectingagainstAFinptswithCADUsefulnessofStatindrugsinprotectingagainstAFinptswithCADConclusionUseofstatinsinpatients

withchronicstableCADappearstobeprotectiveagainstAFTheunderlyingmechanismforthiseffectisunknownbutappearstobeindependentofthereductioninserumcholesterollevelsAmJCardiol2003;92:1379-1383HMG-CoA

reductaseinhibitorAtorvastatinpreventsAFbyinhibitinginflammationinacaninesterilepericarditi