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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2804_Библиотеки_им_академика_М_И_Перельмана

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EtiologyandPathophysiology
Myocardial ischemia resultsfrom decreased myocardial oxygen supply and/or increased demand. In themajorityofcases,NSTEMIisduetoasuddendecreaseinbloodsupplyviapartialocclusionofthe affectedvessel.In somecases, markedlyincreasedmyocardialoxygendemandmay leadtoNSTEMI (demandischemia),asseeninsevereanemia,hypertensivecrisis,acutedecompensatedHF,surgery,or anyothersignificantphysiologicstressor. Plaquerupturemaybetriggeredbylocaland/orsystemicinflammationaswellasshearstress.Rupture allows exposure of lipid-rich subendothelial components to circulating platelets and inflammatory cells,servingasapotentsubstrateforthrombusformation.Athinfibrouscap(thin-capfibroatheroma) isfelttobemorevulnerabletoruptureandismostfrequentlyrepresentedasonlymoderatestenosison angiography. Lesscommoncausesincludedynamicobstructionofthecoronaryarteryduetovasospasm(Prinzmetal angina, cocaineuse), coronaryarterydissection(morecommoninwomen),coronary vasculitis, and embolus.
ClinicalPresentation
HISTORY
The three principal presentations for UA are rest angina (angina occurring at rest and prolonged, usually>20 minutes), new-onset angina,andprogressive angina (previously diagnosed anginathat has become more frequent, lasts longer, or occurs with less exertion). New-onset and progressive anginashouldoccurwithatleastmildtomoderateactivity,CCSclassIIIseverity.
Female sex, diabetes, HF, end-stage kidney disease, and older age are traits that have been associated with a greater likelihood of atypical ACS symptoms. However, the most common presentationinthesepopulationsisstilltypicalanginalchestpain. Jaw,neck,arm,back,orepigastricpainand/ordyspneacanbeanginalequivalents. Pleuriticpain,painthatradiatesdownthelegsororiginatesinthemid/lowerabdomen,painthatcan be reproduced by extremity movement or palpation, and pain that lasts seconds in duration are unlikelytoberelatedtoACS.
PHYSICALEXAMINATION
Physicalexaminationshouldbedirectedatidentifyinghemodynamicinstability,pulmonarycongestion, andothercausesofacutechestdiscomfort. Objective evidence of HF, including peripheral hypoperfusion, heart murmur (particularly mitral regurgitation [MR] murmur), elevated jugular venous pulsation, pulmonary edema, hypotension, and peripheraledemaworsentheprognosis. Killip classification can be useful to risk stratify and identify patients with features of cardiogenic shock(Table4-10).
TABLE4-10
KILLIPCLASSIFICATION
33
Class Definition Mortality
a
(%)
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I Nosignsorsymptomsofheartfailure 6
II Heartfailure:S3gallop,rales,orJVD 17
III Severeheartfailure:pulmonaryedema 38
IV Cardiogenicshock:SBP<90mmHgandsignsofhypoperfusionand/or
signsofsevereheartfailure
81
JVD,jugularvenousdistention;SBP,systolicbloodpressure.
a
In-hospitalmortalityofpatientsin1965–1967withnoreperfusiontherapy(n=250).
33
Examinationmayalsogivecluestoothercausesofischemiasuchasthyrotoxicosisoraorticdissection (seeTable4-4).
DiagnosticTesting
ELECTROCARDIOGRAPHY
Priortoorimmediatelyonarrivaltotheemergencydepartment,abaselineECGshouldbeobtainedin allpatientswithsuspectedACS.Anormaltracingdoesnotexcludethepresenceofdisease. ThepresenceofQwaves,ST-segmentchanges,orT-waveinversionsissuggestiveofCAD. IsolatedQwavesinleadIIIonlyareanormalfinding. SerialECGsshouldbeobtainedtoassessfordynamicischemicchanges. ComparisontopriorECGsisimportantwhenevaluatinganECGfordynamicchanges. The posterior circulation (i.e., circumflex coronary artery distribution) is poorly assessed with standard ECGleadplacementandshould alwaysbeconsidered when evaluating patientswithACS. Posteriorleadsorurgentechocardiographymaymoreaccuratelyassessthepresenceofischemiawhen thesuspicionishigh. Approximately 50% of patients with UA/NSTEMI have significant ECG abnormalities, including transientST-segmentelevations,STdepressions,andT-waveinversions.
32,34
ST-segment depression in two contiguous leads is a sensitive indicator of myocardial ischemia, especiallyifdynamicandassociatedwithsymptoms.
ThresholdvalueforabnormalJ-pointdepressionshouldbe0.5mminleadsV2andV3and1mm
inallotherleads.
ST-segment depressionin multiple leads plus ST-segmentelevation inaVR and/or V1 suggests
ischemiaduetomultivesselorleftmaindisease. BiphasicordeeplyinvertedTwaves(>5mm)withQTprolongationinleadsV2toV4inthesetting
of stuttering chest pain within the past 24 hours suggests a critical lesion in the LAD artery distribution(Wellenssyndrome).
34
NonspecificST-segmentchangesorT-waveinversions(thosethatdonotmeetvoltagecriteria)are nondiagnosticandunhelpfulinmanagementofacuteischemia butareassociatedwitha higherrisk forfuturecardiacevents.
LABORATORIES
Acompletebloodcount,basicmetabolicpanel,fastingglucose,andlipidprofileshouldbeobtainedin allpatientswithsuspectedCAD.Otherconditionsmaybefoundtobe contributingtoischemia(e.g., anemia) or mimicking ischemia (e.g., hyperkalemia-related ECG changes) or mayalter management (e.g.,severethrombocytopenia).
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Troponinistherecommendedbiomarkerforassessmentofmyocardialnecrosis.
Troponin T andIassaysare highlyspecific and sensitive markers ofmyocardial necrosis. Serum troponin levels are usually undetectable in normal individuals, and any elevation is considered abnormal. Inpatientswithtroponinbelowthedetectablelimitoftheassaywithin6hoursoftheonsetofpain,a secondsampleshouldbedrawn8–12hoursaftersymptomonset. MIsizeandprognosisaredirectlyproportionaltomagnitudeofincreaseintroponin.
34
Creatinekinase(CK)-MBisnolongerarecommendedmarkerfortheinitialdiagnosisofNSTEMI.It lacksspecificitybecauseitispresentinbothskeletalandcardiacmusclecells.
CK-MBmaybeausefulassayfordetectingpostinfarctischemiabecauseafallandsubsequentrise in enzyme levels suggests reinfarction if accompanied by recurrent ischemic symptoms or ECG changes.
Brainnatriureticpeptide(BNP)canbeausefulbiomarkerofmyocardialstressinpatientswithACS, andelevationsareassociatedwithworseoutcomes.35SevereelevationsofBNPinthesettingofACS inpatientswithoutknownHFshouldraiseconcernforalargeinfarctionandurgentangiography.
TREATMENT
AcutetreatmentaimstoreducethesymptomsofchestpainandriskofrecurrentMIordeath. Riskstratificationcanbehelpful indeterminingtheappropriatetesting,pharmacologicinterventions, andtimingorneedforcoronaryangiography.
Risk of death or MI progression is elevated with the following high-risk ACS characteristics, whichshouldprompturgentcoronaryangiography(<2hours)withintenttorevascularize:
Recurrent/acceleratinganginadespiteadequatemedicaltherapy
SignsorsymptomsofnewHF,pulmonaryedema,orshock(highKillipClassification)
NeworworseningMR
NewLBBB
VT Severalclinicaltoolscanestimateapatient’sriskofrecurrentMIandcardiacmortality,suchasthe Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE)riskscores.TheTIMIriskscorecanbeusedtodeterminetheriskofdeathornonfatalMI upto1yearafteranACSevent(Figure4-2).
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Figure4-2 Fourteen-dayratesofdeath,MI,orurgentrevascularizationfromtheTIMI11BandESSENCEtrialsbased
on increasing TIMI risk score.Coronary artery disease (CAD) risk factors include family history of CAD, diabetes,
hypertension, hyperlipidemia, and tobacco use. ASA, aspirin; LMWH, low–molecular-weight heparin; MI, myocardial
infarction;TIMI,ThrombolysisinMyocardialInfarction;UFH,unfractionatedheparin.
36
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In the stabilized patient, two treatment strategies are available: the ischemia-driven approach (formerlytermedconservative)versustheroutineinvasiveapproach(earlydefinedas<24hoursof presentationordelayed>24hours).
The planned approach should always be individualized to the patient (Figure 4-3). All patients should receive aggressive antithrombotic,antiplatelet,andischemic medical therapynomatterthe finalrevascularizationstrategy.Table4-11summarizestheselectionapproach.
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Figure4-3 Diagnostic andtherapeutic approachtopatientspresentingwithacutecoronarysyndrome(ACS)focusing
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onantiplateletandantithrombotictherapy.*BivalirudinisanappropriatealternativetoUFHandLMWH,orattimeofPCI,
patients on UFH may be switched to bivalirudin. †Choose either clopidogrel, ticagrelor, or prasugrel as the second
antiplateletagent.#Indicators of recurrentischemia include worsening chest pain, increasing cardiac biomarkers, heart
failuresigns/symptoms,arrhythmia(VT/VF),anddynamicECGchanges.1UFHfor48hoursorLMWHuntildischargeor
up to 8 days and clopidogrel or ticagrelor for 1 year. ASA, aspirin; CABG, coronary artery bypass grafting; CAD,
coronary artery disease; EF, ejection fraction; LMWH, low–molecular-weight heparin; NSTEMI, non–ST-segment
elevation myocardialinfarction; PCI, percutaneous coronary intervention;Rx,treatment;STEMI, ST-segmentelevation
myocardial infarction; UA, unstable angina; UFH, unfractionated heparin; VT/VF, ventricular tachycardia/ventricular
fibrillation;WMA,wallmotionabnormality.
31,37
TABLE4-11
APPROPRIATE SELECTION OF ROUTINE INVASIVE VERSUS ISCHEMIA-DRIVEN REVASCULARIZATIONSTRATEGYINPATIENTSWITHNSTEMI/UA
Immediate/urgent invasive(within2h)
RefractoryAngina Worsening Signs or Symptoms of heart failure or Mitral
regurgitation HemodynamicinstabilityorShock SustainedVTorVF
Ischemia-driven
Low-riskscore(TIMI≤1orGRACE<109) Low-riskbiomarker-negativefemalepatients Patientorclinicianpreferenceintheabsenceofhigh-risk
features
Earlyinvasive(within24 h)
None of the above but a high-risk score (TIMI ≥ 3 or GRACE>140)
Rapidrateofriseinbiomarkers NeworpresumablynewSTdepressions
Delayedinvasive(24–72 h)
Noneoftheabovebutpresenceofdiabetes Renalinsufficiency(GFR<60) LVejectionfraction<40% Earlypostinfarctionangina PriorPCIwithin6months PriorCABG TIMI score ≥2 or GRACE score 109–140 and no
indicationforearlyinvasivestrategy
CABG,coronaryarterybypassgraft;GFR,glomerularfiltrationrate;GRACE,GlobalRegistryofAcuteCoronaryEvents;LV, leftventricular;NSTEMI,non–ST-segmentelevationmyocardialinfarction;PCI,percutaneouscoronaryintervention;TIMI, ThrombolysisinMyocardialInfarction;UA,unstableangina;VF,ventricularfibrillation;VT,ventriculartachycardia.
InACS,asopposedtostableIHD,aroutineinvasiveapproachwithpossiblePCIhasbeenshownto reducetheincidenceofrecurrentMI,hospitalizations,anddeath.Ingeneral,patientswithACS
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should undergo a routine invasive strategy unless it is clear that the risk outweighs the possible benefitinagivenpatient. Intheischemia-drivenapproach,ifthepatientdoesnotdevelophigh-riskACSfeatures,hasnormal subsequentcardiac biomarkers,hasnodynamicECGchanges,andrespondstomedical therapy, a noninvasivestresstestshouldbeobtainedforfurtherriskstratification.
Patientsshouldbeanginafreeforatleast12hourspriortostresstesting.
Ifapatientwithpositivecardiacbiomarkersisselectedfornoninvasivetesting,asubmaximalor
pharmacologicstresstest72hoursafterthepeakvaluemaybeperformed.
Coronaryangiographyisreservedforpatientswhodevelophigh-riskACSfeatures,haveahigh-
riskstresstest,developanginaatlowlevelsofstress,orarenotedtohaveanLVEF<40%. In theroutine invasive strategy, the patientis planned for a coronary angiography withintentto revascularize. An early (<24 hours from presentation) invasive approach is recommended for patientswithhigh-riskscoresorotherhigh-riskfeatures(seeTable4-11).
Note: Refractory chest pain, hemodynamic instability, or serious ventricular arrhythmias are
indicationsforanurgent/emergentinvasivestrategysimilartoSTEMI;thisisnottobeconfused
witharoutineinvasivestrategy. Anearlyinvasivestrategyisalsowarrantedinlow-orintermediate-riskpatientswithrepeatedACS presentationsdespiteappropriatetherapy. Aroutineinvasivestrategyisnotrecommendedforthefollowing:
Patientswithseverecomorbidillnessessuchasadvancedchronickidneydisease,end-stageliver
orlungdisease,ormetastatic/uncontrolledcancerwherebythebenefitsoftheprocedurearelikely
outweighedbytheriskfromtheroutineinvasiveprocedure
AcutechestpainwithalowlikelihoodofACSandnegativebiomarkers,especiallyinwomen
Medications
Patients presenting with UA/NSTEMI should receive medications that reduce myocardial ischemia throughreductioninmyocardialoxygendemand,improvementincoronaryperfusion,andpreventionof furtherthrombusformation. Thisapproachshouldincludeantiplatelet,anticoagulant,andantianginalmedications. Supplementaloxygenshouldbeprovidedifthepatientishypoxemic(<SpO290%)orhavingdifficulty
breathing.Routineuseofoxygenisnotneededandpossiblyharmful.
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Antiplatelettherapy
Table4-12summarizesavailableagentsanddosingrecommendationsforuseinACS.
TABLE4-12
ANTIPLATELETAGENTSINUA/NSTEMI
Medication Dosage Comments
Aspirin (ASA)
162–325 mginitial, then75– 100mg daily
Inpatientstakingticagrelor,themaintenancedoseofASA shouldnotexceed100mg.
Clopidogrel 300–600 IncombinationwithASA,clopidogrel(300–600mgloadingdose,
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mgloading dose,75 mgdaily
then75mg/d)decreasedthecompositeendpointof cardiovasculardeath,MI,orstrokeby18%–30%inpatientswith UA/NSTEMI.
39-41
Ticagrelor 180mg
loading dose,then 90mgbid
Ticagrelorreducedincidenceofvasculardeath,MI,orCVA (9.8%vs.11.0%)butwithhighermajorbleedingnotrelatedto CABG(4.5%vs.3.8%)ascomparedtoclopidogrel.
42,43
Prasugrel 60mg
loading dose,then 10mgdaily
Prasugrelhasincreasedantiplateletpotencycomparedto clopidogrel. Prasugrelreducedtheincidenceofcardiovasculardeath,MI,and stroke(9.9%vs.12.1%)attheexpenseofincreasedmajor (2.4%vs.1.1%)andfatalbleeding(0.4%vs.0.1%),compared toclopidogrel.
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Cangrelor 30µg/kgIV
bolus,then 4µg/kg/min
CurrentlyFDAapprovedonlyforpatientsundergoingPCI. Expenseandmodestevidenceofbenefitcomparedtoother P2Y12inhibitorslimituse.
Eptifibatide 180µg/kg
IVbolus, then2 µg/kg/min
a
EptifibatidereducestheriskofdeathorMIinpatientswithACS undergoingeitherinvasiveornoninvasivetherapyincombination withASAandheparin.
45,46
 Comparedtoabciximabandtirofiban,eptifibatidehasthemost consistenteffectsonplateletinhibitionwithshorteston-timeand drughalf-life.
47
Tirofiban 0.4µg/kg
IVbolus, then0.1 µg/kg/min
a
TirofibanreducestheriskofdeathorMIinpatientswithACS undergoingeitherinvasiveornoninvasivetherapyincombination withASAandheparin.
48-50
Abciximab 0.25mg/kg
IVbolus, then10 µg/min
b
AbciximabreducestheriskofdeathorMIinpatientswithACS undergoingcoronaryintervention.
51-53
Itshouldnotbeusedin patientsinwhompercutaneousinterventionisnotplanned.54 Plateletinhibitionmaybereversedbyplatelettransfusion.
ACS,acutecoronarysyndrome;CABG,coronaryarterybypassgrafting;CVA,cerebrovascularaccident; ESRD,end-stage renaldisease;GFR,glomerularfiltrationrate;HD,hemodialysis;MI,myocardialinfarction;NSTEMI,non–ST-segmentelevation myocardialinfarction;UA,unstableangina.
a
Infusiondosesshouldbedecreasedby50%inpatientswithaGFR<30mL/minandavoidedinpatientsonHD.
b
AbciximabmaybeusedinpatientswithESRDbecauseitisnotclearedbythekidney.
Earlydualantiplatelettherapy(DAPT)withaspirinplusaP2Y12inhibitorisstronglyrecommended forpatientswithNSTEMI/UAwithoutacontraindication(e.g.,uncontrolledseverebleeding,recent
neuraxialsurgeryortrauma,recenthemorrhagicstroke,orintra-cranialorspinalmetastases). DAPTshouldideallybecontinuedfor12monthsfromthe indexACSevent,regardlessofwhether revascularization is performed or not. See the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease for specific recommendationstailoredtostenttype,bleedingrisk,andotherconsiderations. Aspirinblocksplateletaggregationwithinminutes.
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Achewable162-to325-mgdoseofASAshouldbeadministeredimmediatelyatsymptomonset oratfirstmedicalcontactunlessacontraindicationexists.ThisshouldbefollowedbyASA81mg dailyindefinitely. IfanASAallergyispresent,clopidogrelmaybeasubstitution.Anallergyconsultationshouldbe obtainedforpossibledesensitization,preferablypriortotheneedforacoronarystent. AfterPCI,ASA81mgisthecurrentrecommendeddoseinthesettingofDAPT.
ClopidogrelisaprodrugwhosemetaboliteblockstheP2Y12receptorandinhibitsplateletactivation andaggregationbyblockingtheadenosinediphosphatereceptorsiteonplatelets.
The addition of clopidogrel to ASA reduced cardiovascular mortality and recurrent MI both acutelyandat11monthsoffollow-up.
39
Aloadingdoseof600mgshouldalwaysbegiveninnaïvepatients. In patients unable to take oral medications or unable to absorb oral medications due to ileus, rectal administration is unproven but has been reported. Alternatively, parenteral agents (e.g., cangrelororeptifibatide)maybeconsidered. Canbeusedaspartoftheprotocolinboththeischemia-drivenandroutinelyinvasivestrategies.
Prasugrelisalsoa prodrug thatblocks theP2Y12adenosinereceptor;itsconversionto itsactive metaboliteoccursfasterandtoagreaterextentthanclopidogrel.
Results in faster, greater, and more uniform platelet inhibition compared to clopidogrel at the expenseofhigherriskofbleeding.
55
ItdecreasesriskofCVDdeath,MI,CVA,andacutestentthrombosisascomparedtoclopidogrel inACSpatients,includingSTEMIpatients. Itshouldbeusedwithcautionoravoidedinpatientsolderthan75yearsandwhoweighlessthan 60kg.Itiscontraindicatedinthosewithpriorstrokeortransientischemicattack(TIA). UsedonlyintheinvasiveapproachofACSandonlyaftercoronaryanatomyisknownandPCIis planned.ThereisnobenefitoverclopidogrelwhentestedbeforeinitiationofPCI. PrasugrelmaybesuperiortoticagrelorwithregardstothecompositeofMI,stroke,anddeath.
56
TicagrelorisnotaprodrugandblockstheP2Y12adenosinereceptordirectly.
Reduces the risk of death,MI, CVA, and stent thrombosis as compared to clopidogrel inACS patients,includingSTEMIpatients.
42
AftertheloadingdoseofASA,themaintenancedoseofASAmustbe<100mg. Canbeusedaspartoftheprotocolinboththeischemia-drivenandearlyinvasivestrategies. Barring any contraindication, ticagrelor is the preferred P2Y12 inhibitor of choice due to the
mortalityadvantageoverothermedicationsinthisclass.
43
Relative contraindications include baseline bradycardia, severe reactive airways disease, and priorhemorrhagicstroke.
Cangrelorisaparenteral,direct,andreversibleinhibitoroftheP2Y12adenosinereceptor.
Ithasauniquelyrapidonset(<2minutes),potency(>90%plateletinhibition),andshortduration ofactionaftercessation(normalplateletfunctionafter1hour). Reduces the risk of death, MI, urgent revascularization, or stent thrombosis among patients undergoingPCI.
57
FDAapprovedonlyforpatientsundergoingPCI,andcurrentlyveryexpensive.Thus,itisnotyet recommendedforroutineuseineitherischemia-guidedorinvasivestrategy.Thus,werecommend consultingacardiologistbeforetheuseofcangrelor. Sometimes usedasa bridgingstrategyinpatientswhohavehadrecentPCIandrequire surgery whereDAPTisprohibited.Thisapproachisofunprovenbenefit.
Glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists (abciximab, eptifibatide, or tirofiban) block the
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