非抗心律失常药物的抗房

非抗心律失常药物的抗房颤作用心房颤动特点临床上最常见的需药物与非药物治疗的心律失常并非是一种良性心律失常慢性房颤多发生于器质性心脏病患者，少数患者无心脏病证据发生率随年龄增加而增高缺血性脑卒中的主要原因之一快速心室率未能控制者，可发生心动过速性心肌病心房颤动的流行病学

累积发生率男性为2.2%、女性为

1.7%70％左右的房颤发生在器质性心脏病大约30％的房颤无任何可发现的病因病死的最主要原因是缺血性脑卒中，其发生率随年龄增加明显升高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心房颤动的病理生理和电生理机制

房颤常发生于三种不同的临床情况无心脏病证据患者，称原发性房颤虽无心脏病证据，但有诱发房颤发生的非心脏性疾病(甲亢等)，为继发性房颤发生于器质性心脏病者的继发性房颤

心房颤动的病理生理和电生理机制

心房颤动的病理组织学心房扩张和不均匀分布的纤维化(窦房结)

见于器质性心脏病非特异的散在纤维化

继发于全身性疾病心房肌细胞离子通道的功能异常或未识别的非病理性结构异常

发生于健康人的阵发性房颤(孤立性房颤)心房颤动的病理生理和电生理机制心房颤动的电生理机制异位局灶自律性增强学说(Scherf

等，1953)多个子波折返激动学说(Moe等，1959)触发因素：房早、房扑、房速、AVNRT、AVRT、交感或迷走神经活性改变等心房颤动的病理生理和电生理机制局灶性房颤的起源部位肺静脉(90%以上尤其为左、右上肺静脉)其他部位包括：界嵴、上、下腔静脉、冠状静脉窦、房室交界区、房间隔、

Marshall

韧带、心房游离壁起源于肺静脉、腔静脉、冠状静脉窦的房颤可能与肌袖(muscularsleeve)有关?心房颤动的分类阵发性房颤：发作持续<7d，大多可自行转复，并可反复发作持续性房颤：发作48小时以上未能自行转复而需要药物或非药物干预永久性房颤：发作持续几天（≥7d）或几年心房颤动的治疗原则控制心室率预防栓塞性事件转复心房颤动为窦性心律直流电转复心律药物复律及维持窦性心律非药物预防房颤复发心脏起搏预防心房颤动(?)TreatmentstrategiesforAFAtrialfibrillationAntiarrhythmicdrugsPreventivePacingAlateandbpaceHybridtherapyAtrialDefibrillatorMAZE-surgeryCatheterablationACE-I、ARB、Statin、DiureticEffectivenessofrhythmcontrolinAF

withOAPandAADafterlinearRACAHybridtherapyutilizingcathterRAmazeprocedureswithOAPandAADcanbeperformedsafelyandcanreestablishrhythmcontrolinselectedpatientswithrefractorypersistentorpermanentAFOAP:overdriveatrialpacingAAD:

antiarrhythmic

durg具有抗心律失常作用的

非抗心律失常药物Angiotensinconvertingenzymeinhibitors(ACE-I)AngiotensinreceptorBlocker(ARB)StatinDiuretics非抗心律失常药物

抗心律失常作用的可能机理

ACE-I和ARB抗心律失常作用的可能机理包括：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在房颤节律控制中的作用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应用ACE-I和ARB预防房颤

(a

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

JAmColl

Cardiol,2005Jun7;45(11):1832-9应用ACE-I和ARB预防房颤

(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%应用ACE-I和ARB预防房颤

(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结果：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