DefinitionandClinicalFeatures

慢性心力衰竭(充血性心力衰竭)心臟在正常充盈壓時無法提供有效的前向射血，心臟收縮功能下降，同時心室舒張末壓增加，心腔殘余血液增加，導致肺循環(huán)和體循環(huán)淤血Congestiveheartfailure(chronicheartfailure,CHF)isacomplexofsymptoms--shortnessofbreath,tachycardia,fatigue,andcongestion--thatarerelatedtotheinadequateperfusionoftissueduringexertionandtotheretentionoffluid.

慢性心衰的呼吸困難、心率增加、乏力、淤血等緣于組織灌注不足及體液潴留DefinitionandClinicalFeatures

慢性心力衰竭(充血性心力衰竭)Congestiveheartfailure

(chronicheartfailure,CHF)isthepathophysiologicstateinwhichtheheartisunabletopumpbloodataratecommensuratewith相稱thetissuerequirements,orcandosoonlyfromanelevatedfillingpressure.心輸出量不能滿足組織代謝需求,或需通過升高充盈壓代償Itsprimarycauseisthattheheartfailstoprovideadequateoutputatnormalfillingpressures,whichisassociatedwithasyndromeofreducedcontractioncapacityaswellaspulmonaryandsystemicvenouscongestion.主要原因是心臟在正常充盈壓時無法提供有效的前向射血，導致心臟收縮功能功能下降以及肺循環(huán)和體循環(huán)淤血SystemicandPulmonaryCirculationWhenleftventriclefailsLeftventricularend-diastolicpressure左室舒張末壓↑LAP左房壓↑Pulmonarycapwedgepressure肺毛細血管鍥壓↑Leftventriclecontraction↓左室射血↓ThickeningoftherespiratorymembranereducesO2exchangeEnlargedheart(Contraction↓LVEDP↑)andpulmonarycongestion(O2Exchange↓)ClinicalFeatures—Orthopnea特征與鑒別Exertionaldyspnea,nocturnalparoxysmaldyspneaandorthopnea—pulmonarycongestion早期運動性呼吸困難、夜間陣發(fā)性呼吸困難，急性加重呈端坐呼吸--肺淤血為左心衰特征Hypertension,MyocardialHypertrophyandDiastoleDysfunction心肌肥厚與舒張功能障礙NormalHypertensionDiastolicandSystolicHeartFailure

舒張性心衰與收縮性心衰均表現(xiàn)為呼吸困難(肺淤血)78yoWomanRecurrentPulEdema50yoManHCM頸靜脈怒張肝脾腫大下肢浮腫肺淤血運動性及夜間陣發(fā)性呼吸困難肺水腫端坐呼吸心源性哮喘心肌收縮力下降心腔殘余血增加左室舒張末壓增高腎灌注下降尿量減少

水鈉潴留頭昏、乏力、運動耐力下降反射性SNS及RAAS興奮，血管痙攣、心率加快、回心血量↑Whentheheartfails,arterialpressurereduceswhichcausesthebaroreceptorresponseandexcitationofsympatheticnervoussystem(SNS)andrenin-angiotensin-aldosteronesystem(RAAS).心輸出量下降導致反射性交感神經(jīng)系統(tǒng)及腎素血管緊張素醛固酮系統(tǒng)興奮Compensationmechanismsduringchronicheartfailure心衰代償機制及其作用AT1Renin-Angiotensin-AldosteroneSystemCompensationmechanismsduringchronicheartfailure心衰代償機制的不利影響Theepinephrine/norepinephrine(SNS)andangiotensin/aldosterone(RAAS)enhanceheartperformanceandcontractperipheralvesselwithwater/sodiumretentiontocompensateforreducedcardiacoutputandredistributionofbloodtoimportantorganssuchastheCNS.腎上腺素、去甲腎上腺素、血管緊張素使心肌收縮增強、心率加快、外周血管收縮、水鈉潴留，血流重新分配以保證重要臟器血流Inaddition,thevasoconstrictiveeffectorsoftheSNSandRAASleadtoanincreaseinsystemicvascularresistance,whichcontributestoanincreasedimpedance阻抗toleftventricularejection(increasedafterload)andthereforemyocardialoxygenconsumption.交感神經(jīng)及腎素血管緊張素醛固酮系統(tǒng)興奮增加外周阻力，進而導致心臟后負荷增加，心肌耗氧增加頸靜脈怒張

肝脾腫大下肢浮腫肺淤血運動性及夜間陣發(fā)性呼吸困難肺水腫端坐呼吸心源性哮喘心肌收縮力下降左室舒張末壓增高腎灌注下降尿量減少

水鈉潴留頭昏、乏力、運動耐力下降反射性SNS及RAAS興奮，血管痙攣、心率加快、回心血量↑強心Digitalis洋地黃類降低心臟負荷與氧耗β-blockerACEI降低前后負荷Vasodilator擴血管藥利尿Diuretics減輕水鈉潴留Diuretics利尿劑減輕肺淤血利用哪些途徑和藥物治療慢性心力衰竭？PharmacotherapyofCHF

治療慢性心衰的藥物Positiveinotropicagents正性肌力藥Digitalis洋地黃Diuretics利尿藥氫氯噻嗪呋塞米Vasodilators擴血管藥酚妥拉明β-adrenergicreceptorblockersβ腎上腺素能受體阻斷藥InhibitorsofRenin-AngiotensinSystem腎素血管緊張素系統(tǒng)抑制藥TherapeuticAimsofCHFCHFisamajorcontributortomorbidityandmortalityworldwide.Mortalityinpatientswithadvancedheartfailureexceeds50%at1year.現(xiàn)代社會中慢性心衰高發(fā)病率和高死亡率Whilepalliationofsymptoms緩解癥狀andimprovementinthequalityoflife

改善生活質量remainimportantgoals,itispossibletoapproachtherapywiththeexpectationthatdiseaseprogressioncanbeattenuated,減緩病情進展and,inmanyinstances,survivalprolonged.延長生存期

治療目標：緩解癥狀、降低死亡率，緩解病情進展、改善生存質量ClinicalconditionsthatprecipitatedeteriorationofCHFElevatedbloodpressure血壓升高Arrhythmia心律失常Myocardialischemia心肌缺血Mentalandphysicalstress心理與軀體應激Valvelesionandregurgitation先心或瓣膜病變所致的分流與反流Infection,esp.lunginfection各類感染尤其是肺部感染Highsaltintake高鹽飲食……慢性心衰治療同時糾正誘因同樣重要PharmacotherapyofCHF

治療慢性心衰的藥物Positiveinotropicagents正性肌力藥Diuretics利尿藥Vasodilators擴血管藥β-adrenergicreceptorblockersβ腎上腺素能受體阻斷藥InhibitorsofRenin-AngiotensinSystem腎素血管緊張素系統(tǒng)抑制藥化學結構基本骨架WilliamWithering1741－1799Positiveinotropicagents正性肌力藥

Cardiacglycosides強心苷Digitalis洋地黃類abstractsfromplantdigitalisDigoxin地高辛

cidellannid西地蘭Positiveinotropicagents正性肌力藥

Cardiacglycosides強心苷Digoxin地高辛po

cidellannid西地蘭ivActionsandusagesThecardiaceffectsare:increasingforceofcontraction增強心肌收縮力positiveinotropicaction

正性肌力作用cardiacslowing(negativechronotropicaction)負性頻率作用andreducedrateofconductionthroughtheAVnode負性傳導作用disturbancesofrhythm,對心肌電生理的影響especially

-blockofAVconduction抑制房室傳導-increasedectopicpacemakeractivity尤其是蒲氏纖維UsedinchronicheartfailureandforcontrollingventricularrateinatrialfibrillationMechanism

Cardiacglycosides強心苷MechanismsofpositiveinotropicactionInhibitionofNa+,K+-ATPase.CardiacglycosidesarepotentandhighlyselectiveinhibitorsoftheactivetransportofNa+&K+acrosscardiaccellmembranes.TheybindstoasubunitofNa+,K+-ATPase,increasingcytosolicNa+,whichinturnthroughNa+-Ca2+exchangeincreasesthelevelofcytosolicCa2+availabletointeractwiththecontractileproteins,therebyincreasingtheforceofcontraction.

抑制鈉鉀ATP酶，增加細胞內(nèi)游離鈣水平洋地黃體內(nèi)過程與給藥特點地高辛口服生物利用度60%-80%，但個體差異及不同廠家產(chǎn)品生物利用度差異很大地高辛以原型主要經(jīng)腎臟排泄，易蓄積中毒，應隨時根據(jù)患者尿量調(diào)整藥物劑量地高辛小劑量口服，西地蘭靜脈給藥起效快奎尼丁、胺碘酮、維拉帕米等均可升高地高辛血藥濃度利尿藥療效顯著時可能導致患者血容量不足、血液濃縮使地高辛血藥濃度升高AdverseEffectsof

Cardiacglycosides強心苷的不良反應Positiveinotropicagents正性肌力藥

Cardiacglycosides強心苷洋地黃降低心衰時的代償性交感興奮地高辛的應用與血藥濃度監(jiān)測UseofDigoxininClinicalPracticeandMonitoringofSerumLevels.Itisrecommendedthatdigoxinbereservedforpatientswithheartfailurewithatrialfibrillation,orforpatientsinsinusrhythmwhoremainsymptomaticdespitemaximaltherapywithACEinhibitorsandβantagonists.Digoxinmaybeuniqueamonginotropicdrugsbyvirtueofitsneurohumoraleffects,includingattenuationofsympatheticactivationandreninrelease.Moststudiessuggestthatthemaximalincreaseincontractilityisapparentatserumlevelsofdigoxinaround1.4to1.8nmol.Theneurohormonalbenefitsofdigoxinmayoccuratlowerserumlevelsof0.5-1ng/ml;higherconcentrationsarenotassociatedwithfurtherclinicalbenefit.UseofSympathomimeticsinCHF

交感激動藥在慢性心衰中的應用與爭議擬交感強心藥治療急性心功能障礙效果尚好，但治療慢性心衰僅暫時緩解緩解癥狀仍增加其死亡率Diuretics利尿劑Diureticsretainacentralroleinthepharmacologicalmanagementofthe“congestive”symptomsinpatientswithheartfailure.慢性心衰通常伴有水鈉潴留，肺淤血與外周循環(huán)受阻，利尿藥始終是治療心衰最重要的藥物之一。Diureticsreducebloodvolumethroughdiuresis利尿,leadingtoloweredpreloadandbloodpressure.利尿劑通過利尿作用降低血容量，亦可降低血壓，同時降低心臟前后負荷。Theyareusefulinrelievingthepulmonaryandperipheraledemaaswellashypertension.利尿劑對肺水腫及外周水腫緩解作用顯著，同時也能有效地治療高血壓。

急性左心衰發(fā)生肺水腫用藥舉例Diuretics利尿劑利尿劑通常分為強效、中效和弱效三類，常用的強效利尿藥為呋塞米又稱袢利尿劑(loopdiuretics)，中效為氫氯噻嗪，弱效利尿劑也為保鉀(K+-Sparing)利尿劑，如螺內(nèi)酯，可根據(jù)病情選用或聯(lián)合應用Usage:Furosemideisinjectedtorelievethepulmonaryedemaquicklyandefficiently,whilehydrochlorothiazideisthemostchoicesfororaladministration.呋塞米為強效利尿劑，可靜脈給藥有效緩解水腫包括肺水腫，口服通常選用氫氯噻嗪Adverseeffects:DiureticscouldcausedepletionofbloodvolumeandreflexSNSactivation,lowserumpotassium,whicharedetrimentaltoheartfailureandmayleadtoseverearrhythmias.過度利尿可導致水電解質平衡紊亂，低血容量可致反射性交感興奮，低血鉀、低血鎂等易致心律失常，應注意避免過度利尿，及時補充鉀，或與保鉀利尿藥合用。Vasodilators擴血管藥α-adrenergicblocker酚妥拉明（α受體阻斷藥）sodiumnitroprusside硝普鈉(NOdonor)Usage:usedforshort-termreleaseofsymptoms,byreducingpreloadandafterload

酚妥拉明用藥舉例Adverseeffects:tachycardia(reflexSNSactivation),avoidlong-termandlargedosesuse

硝普鈉須避光使用，過量可致氰化物中毒Useofβ-blockerinCHF

β受體阻斷藥在慢性心衰中的應用Heartfailureischaracterizedbysympathetichyperactivation,aneurohumoralstatethatreflectsbiologicalresponsesthatcanbebothcompensatoryandmaladaptive.既是代償又有適應不良增加心肌耗氧WhilemanyofsympathomimeticsincreasedmortalityinCHFpatients,anunexpectedmortalitybenefitwasseenwiththeadministrationofβadrenergicblockingdrugs.βadrenergicblockersreducetheheartworkloadandcatecholamines’myocardialtoxicity,producinglong-termbenefitsinpatientswithCHF.Startβblockeratlosedoseandwithdigitalisordiuretics.

小劑量開始啟用逐漸增加至最大耐受劑量，常常需合用強心苷和/或利尿劑Heartfunctionchangeswiththeuseofβ-blockerinCHFThedirecthemodynamiceffectofaβantagonistinpatientswithheartfailureistodepresscontractilefunction.Anincreaseinleftventricularsystolicfunctionbetween2and4monthsafterinitiationoftherapyisseenconsistently.InhibitorsofRenin-AngiotensinSystem抑制腎素血管緊張素系統(tǒng)的藥物Angiotensinconvertingenzyme(ACE)Inhibitors:ACEinhibitorssuppressAngIIandaldosteroneproduction,decreasesympatheticnervoussystemactivity,andpotentiatetheeffectsofdiureticsinheartfailure.However,AngIIlevelsfrequentlyreturntobaselinevaluesfollowingchronictreatmentwithACEinhibitors,dueinparttoproductionofAngIIthroughACE-independentenzymessuchaschymase,atissueprotease.PharmacotherapyofCHF

治療慢性心衰的藥物Positiveinotropicagents正性肌力藥Digitalis洋地黃類:Digoxin地高辛β-adrenergicagonists:dopamine多巴胺dobutamine多巴酚丁胺Diuretics利尿藥Loopdiuretics袢利尿藥強效利尿藥：furosemide呋塞米Thiazidediuretics中效利尿藥：

hydrochlorothiazide氫氯噻嗪Vasodilators擴血管藥α-adrenergicblocker酚妥拉明sodiumnitroprusside硝普鈉β-adrenergicreceptorblockersβ腎上腺素能受體阻斷藥Carvedilol卡維地洛(兼有α受體阻斷作用)

bisoprolol比索洛爾ACEIsandARB

血管緊張素轉化酶抑制劑及AT1受體阻斷劑Captopril卡托普利,losartan洛沙坦PharmacotherapyofCHF

治療慢性心衰的藥物Positiveinotropicagents正性肌力藥Cardiacglycosides(強心苷類,digitalis洋地黃類):Digoxin地高辛PhosphodiesteraseIII(PDE)inhibitors磷酸二酯酶峰抑制劑and

β-adrenergicagonists：dopamine多巴胺dobutamine多巴酚丁胺Diuretics利尿藥LoopDiuretics袢利尿藥，強效利尿藥furosemide呋塞米ThiazideDiuretics噻嗪類利尿藥，中效利尿藥：

hydrochlorothiazideK+-Sparingdiureticsandaldosteroneantagonists保鉀利尿藥及醛固酮拮抗劑，弱效利尿Vasodilators擴血管藥α-adrenergicblockers酚妥拉明,sodiumnitroprusside硝普鈉(Mixed)β-adrenergicreceptorblockersβ腎上腺素能受體阻斷藥、Carvedilol卡維地洛bisoprolol比索洛爾InhibitorsofRenin-AngiotensinSystem:ACEInhibitorsandAT1ReceptorAntagonists

血管緊張素轉化酶抑制劑及AT1受體阻斷劑Captopril卡托普利,losartan洛沙坦(沙坦類)USguidelinesforadultCHF

美國成人慢性心力衰竭治療指南解讀

NYHA心功能分類方法傳統(tǒng)

1級日常活動無明顯受限，心功能代償期

2級日?；顒铀綍r出現(xiàn)心衰癥狀

3級稍活動出現(xiàn)心衰癥狀

4級靜息狀態(tài)下有心衰癥狀

心力衰竭新的分類方法：一個對疾病過程進行客觀評價的分期系統(tǒng)對NYHA功能分級的補充A期心衰高危但沒有器質性心臟病或心力衰竭癥狀

B期器質性心臟病但沒有心衰癥狀

C期器質性心臟病并且既往或目前有心衰癥狀

D期需要特殊干預治療的難治性心力衰竭USguidelinesforadultCHF

美國成人慢性心力衰竭治療指南解讀

心力衰竭新的分類方法圖示TrymildexercisetherapyforyourCHFpatientsaftersymptomreliefPlantsinmyhometownNanping,FujianProvince補充幻燈CecilMedicine24thedition

開篇第一段Medicineisaprofessionthatincorporatesscienceandthescientificmethodswiththeartofbeingaphysician.Theartofattendingtothesickisasoldashumanityitself.Eveninthemoderntimes,theartof