2024-无痛性心肌缺血-从病理生理到诊治

总biomedicines

ig,

Review

SilentMyocardialIschemia:FromPathophysiologytoDiagnosisandTreatment

PanagiotisTheofilis

1,Alexio

sS.Antonopoulos1,MariosSagris

1,AggelosPapanikolaou

1,

EvangelosOikonomou

2,KonstantinosTsioufis

1andDimitrisTousoulis1,*

11stDepartmentofCardiology,“Hippokration”GeneralHospital,NationalandKapodistrianUniversityofAthens,11527Athens,Greece;panos.theofilis@(P.T.);antonopoulosal@yahoo.gr(A.S.A.);

masagris1919@

(M.S.);

agepap25@otenet.gr

(A.P.);

ktsioufis@

(K.T.)

23rdDepartmentofCardiology,ThoracicDiseasesGeneralHospital“Sotiria”,NationalandKapodistrianUniversityofAthens,11527Athens,Greece;

boikono@

*Correspondence:

drtousoulis@

checkfor

updates

Citation:Theofilis,P.;

Antonopoulos,A.S.;Sagris,M.;

Papanikolaou,A.;Oikonomou,E.;Tsioufis,K.;Tousoulis,D.Silent

MyocardialIschemia:From

PathophysiologytoDiagnosisand

Treatment.Biomedicines2024,12,259.

/10.3390/

biomedicines12020259

AcademicEditor:ShakerA.Mousa

Received:3January2024

Revised:18January2024

Accepted:22January2024

Published:23January2024

Copyright:©2024bytheauthors.LicenseeMDPI,Basel,Switzerland.ThisarticleisanopenaccessarticledistributedunderthetermsandconditionsoftheCreativeCommonsAttribution(CCBY)license(

https://

/licenses/by/

4.0/).

Abstract:Silentmyocardialischemia(SMI),characterizedbyalackofovertsymptomsdespiteaninadequatebloodsupplytothemyocardium,remainsachallengingentityincardiovascularmedicine.Thepathogenesisinvolvesintricateinteractionsofvascular,neurohormonal,andmetabolicfactors,contributingtoperfusiondeficitswithoutthecharacteristicchestpain.Understandingthesemechanismsispivotalforrecognizingdiverseclinicalpresentationsanddesigningtargetedinterventions.DiagnosticstrategiesforSMIhaveevolvedfromtraditionalelectrocardiographytoadvancedimagingmodalities,includingstressechocardiography,single-photonemissioncomputedtomography(SPECT),positronemissiontomography(PET),andcardiacmagneticresonanceimaging(MRI).TreatingSMIisamatterofongoingdebate,astheavailableevidenceontheroleofinva-siveversusmedicalmanagementiscontroversial.Thiscomprehensivereviewsynthesizescurrentknowledgeofsilentmyocardialischemia,addressingitspathophysiology,diagnosticmodalities,andtherapeuticinterventions.

Keywords:silentischemia;coronaryarterydisease;pain

1.Introduction

Coronaryarterydisease(CAD)remainstheleadingcauseofmorbidityandmortalityworldwide[

1

],despitethetechnologicaladvancementsassistingdoctorsinitspromptrecognitionandmanagement.Itscardinalsymptomisanginapectoris,whichcanbetreatedpharmacologicallyorinvasively[

2

].AlthoughthemajorityofpatientssufferingfromCADreportanginaorequivalents,thereisasignificantproportionexhibitingischemiawithoutovertsymptomatology,alsoknownassilentmyocardialischemia(SMI).Thisconditionposesasignificantchallengeincontemporarycardiovascularmedicine.Thisischemicphenomenonoccurswhenthereisaninadequatesupplyofoxygen-richbloodtotheheart,usuallyduetonarrowedorblockedcoronaryarteries.Unliketypicalmyocardialischemia,whichpresentswithchestpain(angina)ordiscomfort,SMIdoesnotproducetheserecognizablewarningsigns,makingitsdiagnosisandmanagementcomplex[

3

].TheinsidiousprogressionofSMIposesasubstantialburdenonindividualsandhealthcaresystems,contributingtotheburdenofcardiovascularmorbidityandmortality.Itoftenremainsundetecteduntilmoreseverecomplications,suchasheartattacksorirreversibleheartdamage,occur.Consequently,addressingSMIinvolvesamultidimensionalapproachfocusingonearlydetection,riskfactormanagement,andpreventivestrategiestomitigateitsimpactoncardiovascularhealth.

ThisreviewendeavorstounravelthemultifacetedaspectsofSMI,spanningfromtheintricatepathophysiologicalunderpinningstotheevolvinglandscapeofdiagnosticmodalitiesandtherapeuticinterventions.

Biomedicines2024,12,259.

/10.3390/biomedicines12020259

/journal/biomedicines

Biomedicines2024,12,2592of14

2.MechanismsofIschemicCardiacPain

Visceralpainisorchestratedthroughtheautonomicnervoussystem,althoughinvesti-gatinghumanautonomicfunctionposeschallenges,oftennecessitatinginvasivemethods,therebyconstrainingourcomprehension.Theheartreceivesextensiveautonomicinnerva-tion,withwell-recognizedefferentstimulationeffects[

4

].Vagalstimulationdecreasesheartrateandhasanegativeinotropicimpact,whilesympatheticstimulationelicitsopposingresponses.Inthecontextofcardiacpain,itappearsthatafferentsympatheticnerveactivity,principallyinducedbyadenosine,ispivotalforconveyingpainsignalsfromthehearttothespinalcordandbrain(Figure

1

),overshadowingtheminorroleofthevagusnerveinafferentpaintransmission[

5

].

Figure1.Schematicrepresentationofthemechanismsofangina.A:adenosine;SC:spinalcord.

Afferentsympatheticneuronstraversefromthemyocardiumtothesuperiororin-feriorcardiacplexus,proceedingwithoutsynapsingthroughthesympatheticganglionchaintothedorsalhornofthespinalcord[

5

].Thisconnectivity,particularlytolaminaIneurons,suggestsaconvergencepointforsomaticandvisceralafferentpathways,possiblygivingrisetothereferredpaincharacteristicofanginapectoris.Theextensiveconnectionsbetweenthecardiacsympatheticplexi,thesympatheticganglionchain,andthespinalcordcontributetothepotentialexpressionofanginaacrossasignificantportionoftheupperbody.

Moreover,afferentneuronalconnectionsfromthetracheo-bronchialtree,lungs,esoph-agus,andstomachconvergewithcardiacafferentfibersatthesamesegmentallevelsofthespinalcord[

5

].Inthedorsalrootentryzone’slaminaI,afferentautonomicneuronsmayextendconnectingbranchesrostrallyandcaudally,potentiallysynapsingontoatransmittercellwhichreceivesinputsfromsensorynociceptiveneurons[

5

].ThisintricatenetworksuggestsacommonconnectioninlaminaIasthepointwhere‘angina’informationgainsaccesstorecognizedrostralpainpathways.However,theprecisemechanismsandpotentialcrosstalkremainspeculative.

Alterationsininhibitoryandexcitatoryneurotransmittersatthedorsalrootentryzonemayexplainalteredcutaneoussensitivitywithinthepatient’sdescribed“angina

Biomedicines2024,12,2593of14

territory”[

5

].Followingstimulationofneuronsinthelateralspinothalamictract,painprocessinginvolvesbrainareassuchastheperi-aqueductalgreymatter,nucleusraphemagnus,insula,thalamus,amygdalo-hippocampalapparatus,sensorycortex,andfrontalcortex,culminatingintheconsciousperceptionofpain.

Distinctivefeaturesofangina,sharedwithothervisceralpainsyndromes,differentiate itfromsomaticpain,primarilycharacterizedbyitspoorlylocalizednature[

5

].Theconver-genceofvisceralautonomicinputsontocommontransmittercells,sharedbybothvisceralandsomaticafferents,contributestothisphenomenon.Furthermore,individualvariations inthecharacter,intensity,andlocationofanginaperceptionariseduetothefailureof thesecommonspinalroutestocategorizeautonomicinformationasnociceptive.Patientsoftenrefrainfromcharacterizinganginaaspainful,optingfortermslike“discomfort”,“pressure”,or“heaviness”.

Traditionalfunctionalbrainareaclassificationsmayprovidelimitedassistanceinun-derstandingtheneurobiologyofangina,givenemergingevidenceofthemotorcortex’sroleinmaintainingchronicpainstates[

5

].Associationsbetweenanginapectorisandmyalgicpainincertainmusclegroupsunderscoretheintricaterelationshipbetweenvisceralandmusculoskeletalpain.Despitelimitedknowledgeofhigherbraincenters’processingofanginasignals,studiesonautonomicresponsestoesophagealpainofferparallels,suggest-inganeuroticism-dependentrangeofresponses.Thisnuancedinterplayunderscoresthecomplexityofanginaneurobiology,anarearipeforfurtherexplorationanddevelopment.

3.MechanismsofSilentMyocardialIschemia

SMIischaracterizedbyobjectiveevidenceofmyocardialischemiaintheabsenceofanginaoritsequivalents,suchasdyspnea,nausea,anddiaphoresis,inpatientswithCAD[

6

].Thisconditionresultsfromanimbalancebetweentheconsumptionandproduc-tionofadenosinetriphosphate(ATP),leadingtobiochemicaleventswithoutthemanifesta-tionoftypicalsymptoms.Notably,asubstantialpercentageoftransientischemicepisodes,rangingfrom50%to70%,donotpresentwithanginalchestpain[

7

].TheabsenceofpaininSMIcanleadtoincreasedmorbidityandmortalityduetothedelayedrecognitionofischemicevents.SMIiscategorizedintothreetypes[

8

],asshowninTable

1

.

Table1.Classificationofsilentmyocardialischemia[

8

].

Type

Definition

I

Occurringinpatientswithasymptomaticcoronaryarterydiseasewithoutcollateralanginalsymptoms.

II

Manifestinginpatientswithahistoryofmyocardialinfarction.

III

Observedinpatientswithconcurrentorcollateralmanifestationsofchronicstableangina,unstableangina,andvasospasticangina.

Mechanistically,SMIinvolvestheoccurrenceofmyocardialischemiawithoutanginaoritsequivalents.Spinalcardiacfiberstransmitanginalpainthroughafferentpathwaystothethalamusand,subsequently,tothecerebralcortex.Biochemicalsubstancesandreceptors,includingsubstanceP,glutamate,andtransientreceptorpotentialvanilloid-1(TRPV1)receptors,playcrucialrolesintheneurotransmissionofcardiacpain[

9

].Tumornecrosisfactorα(TNF-α)orInterleukin-1β(IL-1β)canenhancepaintransmissionsignalsbyloweringtheactivationthresholdofnociceptors[

9

].

VagalcardiacafferentfibersmaycontributetoSMIthroughthenucleusofthesolitarytractandtheC1–C2spinalsegments,mediatingbothtypicalandatypicalanginalpain[

9

].Sensoryinputfromothervisceralorganscanmimiccardiacpainduetoconvergencewithcardiacinputontospinothalamictractneurons,therebyreducingcardiacpain.Additionally,thepsychologicalstateofanindividualandthedescendingpathwaysfromthenucleusraphemagnusandtheponscanmodulatecardiacnociception.

Theischemicburden,reflectingthecombinedpresenceofovertandsilentischemia,correlateswiththemagnitude,duration,andseverityofischemicepisodes.Twocriti-

Biomedicines2024,12,2594of14

calparametersinSMIgenesisarethemagnitudeoftheischemicstimulusandthepainthreshold.Thepainthresholdmaybeelevated,leadingtoalackofpainsensation,asseeninconditionssuchascardiovascularautonomicneuropathy,particularlyindiabeticpatients[

10

].Studiesutilizingmeta-iodobenzylguanidinehavedemonstratedanotablydiminishedmyocardialsympatheticinnervationinindividualswithdiabetescomparedtothosewithoutdiabetes[

11

].Moreover,thereisevidenceofadiffuseabnormalityinmeta-iodobenzylguanidineuptakeamongdiabeticpatientswithsilentmyocardialischemia,indicativeofsympatheticdenervation.Autopsystudiesfurthersupportthesefindings,revealinginindividualswithdiabetesafragmentationofafferentsympatheticfibersinthemyocardium,areducednumberoffibers,andbeadedthickeningofnerves[

12

].Theseobservationsalignwithcharacteristicsofautonomicsensoryneuropathy,offeringapoten-tialexplanationfortheoccurrenceofsilentischemiaindiabetes.Insummary,theetiologyofsilentischemiainthecontextofdiabetesappearstoinvolveanatomicaldisruptionsincardiacsensorynervefibers.

4.EpidemiologyandPrognosisofSilentMyocardialIschemiaandInfarction

EstimatingtheprevalenceofSMIischallengingduetoitssilentnature,butitisbe-lievedtoaffect2–4%ofthegeneralpopulation,withhigherprevalenceincertainpatientgroups,suchasthosewithstableanginaordiabetes.WhenconsideringsilentMIpreva-lenceinthegeneralpopulation,itrangesfrom0.5%(inyoungerindividuals)to6.4%(intheelderly)[

13

].SMIexhibitsacircadianpattern,withahigherincidenceinthemorn-ing,possiblylinkedtophysiopathologicchangesduringthisperiod,includingincreasedheartrate,bloodpressure,andcatecholaminelevels,enhancedplateletaggregation,anddecreasedfibrinolyticactivity[

14

].TheratesofSMIaccordingtosexarecontradictoryacrosstheexistingstudies.Women,whooftenpresentatypicalsymptoms[

15

],werefoundtobeindependentlyassociatedwiththepresenceofSMIinonestudy[

16

].However,otherstudieshaveshownthatSMIprevalenceishigherinmalescomparedtofemales[

17

,

18

].Asfarasracialdisparitiesareconcerned,blackpatientshavebeenfoundtobenonsignificantlyrelatedtoahigherincidenceofSMIcomparedtowhitepatients[

18

].

Patientswithtype2diabetesareataheightenedriskofdevelopingSMI,contributingtoworselong-termoutcomesinfemalepatientsparticularly[

19

].InarecentanalysisoftheACCORD(ActiontoControlCardiovascularRiskinDiabetes)studyinvolvingindividualswithtype2diabetesmellitus,furtherevidencewasprovidedconcerningtheassociationofcardiacautonomicneuropathy(CAN)andSMI[

20

].Atthebaselinewithintheanalyzedcohort,theprevalenceofCANwas18.6%.Thosewithdiminishedheartratevariabilityexhibitedhighervaluesforbodymassindex,HbA1C,anddiabetesdurationandlowerhigh-densitylipoproteincholesterolandestimatedglomerularfiltrationrate.Additionally,thisgroupwasmorelikelytoincludecurrentsmokers,insulinusers,orindividualswithahistoryofretinopathy.Overamedianfollow-upperiodof4.9years,individualswithCANdemonstratedasilentmyocardialinfarction(MI)incidencerateexceeding1.5timesthatofthosewithoutCAN.Uponamultivariableadjustment,CANexhibitedasignificantassociationwithanelevatedriskofsilentmyocardialinfarction(HR1.91[95%CI1.14–3.18]).ThediagnosticperformancemetricsofCANforidentifyingsilentmyocardialinfarctionwereasfollows:sensitivity30.1%,specificity81.5%,positivepredictivevalue2.4%,andnegativepredictivevalue98.7%.Inthegroupofpatientswithdiabetesmellitus,thepresenceofchronickidneydisease(CKD)mightbeanotherfactorfavoringthedevelopmentofSMI.Hondaetal.conductedastudyof461patientswithdiabetesmellitus,freeofclinicalcardiovasculardisease,whosubsequentlyunderwentanergometerexercisetestfollowedbyinvasivecoronaryangiographyincaseofapositiveresultorfailuretoachieve90%ofthetargetedheartrate[

21

].TheprevalenceofSMIinthiscohortwasapproximately18%.SMIdemonstratedahigherprevalenceamongindividualswithCKD,anditsincidencecorrelatedwiththestageofCKDintheasymptomaticpatientswithdiabetesmellitus.Furthermore,thepatientswithbothCKDandSMIexperiencedunfavorableclinicaloutcomes.

Biomedicines2024,12,2595of14

PerioperativeSMIdeservesanhonorablementionasitisrelativelycommon.InthePe-rioperativeIschemicEvaluation(POISE)-1trial,5.0%ofpatientsexperiencedperioperativeMI,with65%oftheseindividualsnotpresentingischemicsymptoms[

22

].Thethirty-daymortalityrateswerecomparablebetweenthepatientswithperioperativeMI,whetheraccompaniedbyischemicsymptomsornot.Puelacheretal.conductedtroponinscreeninginaprospectivecohortof2018patientsundergoingnoncardiacsurgery,revealingthatonly6%ofthosewithperioperativeMIreportedtypicalchestpain[

23

].Theirfindingsindicatedsimilar30-daymortalityratesbetweenpatientswithperioperativeMIlackingotheris-chemicMIcriteriaandthoseexhibitingatleastoneischemicfeature.However,theissueofprognosticallysignificantmyocardialinjuryfollowingnoncardiacsurgeryextendsbeyondperioperativeMI.TheVascularEventsinNoncardiacSurgeryPatientsCohortEvaluationStudy(VISION)involvedarepresentativesampleofover40,000patientsaged45andolder.InVISION,5191patientsencounteredmyocardialinjuryafternoncardiacsurgery,charac-terizedbytroponinelevationattributabletoanischemiccause[

24

].ThestudyrevealedthatbothperioperativetroponinelevationwithoutmeetingtheuniversaldefinitionofMIandperioperativeMIfulfillingtheuniversaldefinitionwereassociatedwith30-daymor-talityafternoncardiacsurgery.Remarkably,93%ofpatientswithmyocardialinjuryafternoncardiacsurgeryinVISIONwereasymptomatic,and22%mettheuniversaldefinitionofMI.Finally,inthestudyofWilcoxetal.,theprevalenceofpostoperativeMIwas0.37%,withaffectedindividualsfacinganaugmentedshort-termriskofdeath[

25

].Amongtheidentifiedindependentriskfactorsweresmokingexposureanddiabetesmellitus.

Prognostically,asilentMImightalsosignifyanincreasedriskofsuddencardiacdeath(SCD),asreportedbyananalysisoftheARIC(AtherosclerosisRiskinCommunities)studyandtheCHS(CardiovascularHealthStudy)[

26

].Inparticular,thecombinedhazardratiosforsilentandclinicalMIinrelationtosuddencardiacdeath(SCD)were2.65(95%CI:2.18–3.23)and3.99(95%CI:3.34–4.77),respectively.TheriskofSCDassociatedwithsilentMIismorepronouncedinwhiteindividuals,males,andthoseofyoungerage.Thepopulation-attributablefractionofSCDattributedtosilentMIwas11.1%,andsilentMIwaslinkedtoanabsoluteriskincreaseof8.9suddencardiacdeathsper1000person-years.Additionally,theinclusionofsilentMIsignificantlyenhancedthepredictiveaccuracyforbothSCDandnon-SCD.

WhiletheevidencesurroundingtheprognosticimportanceofsilentMIismounting,arecentstudyhasquestionedthishypothesis.Basedonananalysisofthemulti-ethnicstudyofatherosclerosisinvolvingintermediate-riskparticipantsfreefromclinicalcardiovasculardisease,theinvestigatorsinitiallyfoundthatsilentMI(prevalence2.2%)wasassociatedwithagreaterincidenceofatheroscleroticcardiovasculardisease[

27

].However,whenthiswasaddedontopofthepooledcohortequationforincidentevents,therewasonlyamodest,nonsignificantimprovementindiscriminationandreclassification.

5.ScreeningandDiagnosisofSilentIschemia

Inthissection,wedescribethearrayofdiagnosticmethodsavailabletodetectSMI(Table

2

).AsthemajorityofindividualspresentingwithSMIareaffectedbyCANinthesettingofDM,moststudiesinvolveparticipantsfromthissubgroupofpatients.WhilescreeninganddiagnosingSMImightseemattractive,thelatestEuropeanSocietyofCardi-ology(ESC)guidelinesonchroniccoronarysyndromesadviseagainsttheuseoffunctionalimaginginthegeneralpopulationofasymptomaticsubjects,providingonlyaweakrecom-mendation(IIb-C)forthoseatthehighestrisk(presenceofDM,strongfamilyhistoryofCAD,veryhighriskofhavingCADbasedonothertests)[

28

].

Biomedicines2024,12,2596of14

Table2.Overviewofstudiesutilizingvariousmethodsofsilentmyocardialischemiaassessment.

Author

Year

Population(Number

ofParticipants)

Method

Findings

Laukkanenetal.[

29

]

2001

MenwithnopriorCAD(1769)

ETT

PrevalenceofSMIduringexercise:15.3%SMIduringexercise→1.7-foldriskofACSand3.5-foldriskofCADmortality

Albenqueetal.[

30

]

2022

Asymptomatic,withDMandhigh-risk

features(273)

TTE

OR1.39(95%CI1.14–1.70)perpercentageLVGLSincreaseforpredictivepositivestress

echocardiography

OR5.16(95%CI1.96–13.59)forLVGLSworsethan__18%forpredictivepositivestress

echocardiography

Sozzietal.[

31

]

2007

Asymptomatic,withDMandnoprior

CAD(161)

DSE

Ischemiaprevalence:28%

AdverseeventswerehigherinthepresenceofanabnormalDSE(24%vs.11%at5years)

Fateh-Moghadametal.[

32

]

2009

Asymptomatic,withtype2DM(211)

ESEorDSE

SMI:28.9%

PositiveSEassociatedwitha13.5-foldriskofMACCE.

Cortigianietal.[

33

]

2017

Asymptomatic,

high-riskpatientswithDM(230)

SE+LAD-CFVR

IschemiaorabnormalLAD-CFVRin23%andwaspredictiveofincidentMACE(HR6.12,

95%CI3.22–11.62)

Staceyetal.[

34

]

2018

Asymptomatic,

high-riskpatients(327)

DS-cardiacMRI

SMIwaspredictiveoffuturecardiovascularevents/survival(adjustedHR:4.07,95%CI1.95–8.73,p<0.001)

Pezeletal.[

35

]

2021

Asymptomatic,

high-riskpatients(903)

DipyridamolecardiacMRI

SMI:12.2%

SMIwasanindependentpredictorofincidentMACE(HR6.66,95%CI4.41–9.23)and

cardiovascularmortality(HR:6.21,95%CI3.89–9.48)

DIAD[

36

]

2004

Asymptomatic,withtype2DM(522)

Adenosine

Tc-99msestamibiSPECT

SMI:22%

Moderate/Largedefects:6%

Lacourciereetal.[

37

]

2006

Asymptomatic,withessential

hypertension(543)

Dipyridamole

Tc-99msestamibiSPECT

AbnormalSSS:28%

GreaterprevalenceandseverityofSMIincoexistingDM

Zellwegeretal.[

38

]

2009

Asymptomatic,withnopriorCAD(3664)

ExerciseTc-99msestamibiSPECT

SMI:21%

Patientswithhigh-riskischemiahadhighereventratesatfollow-upcomparedtolesserSMI(3.1%vs.0.4%,p=0.0001)

Yamasakietal.[

39

]

2010

Asymptomatic,withtype2DMand

high-riskfeatures(485)

Stress/RestTc-99m

tetrofosminSPECT

SSS≥9wasindependentlyassociatedwithahigherincidenceofMACE(HR3.39,95%

CI1.78–6.43,p=0.0002)

Xiao-Rongetal.[

40

]

2019

Asymptomatic,withtype2DM(614)

Adenosine

Tc-99msestamibiSPECT

SMI:21.3%

PredictorsofSMI:malesex,diabeticretinopathy,LDL-C

Pateletal.[

41

]

2023

DMwithoutknownCAD(2730)

Rb-82Rest/StressPET

SMI:30.5%(significantin12.5%)ReducedMBFRin62%of

asymptomaticpatients

CMDpresentinapproximately33%irrespectiveofsymptoms

ReducedMBFRandnotSMIorsymptomswerepredictiveofincidentdeath

CAD:coronaryarterydisease;ETT:exercisetreadmilltest;SMI:silentmyocardialischemia;ACS:acutecoronarysyndrome;DM:diabetesmellitus;TTE:transthoracicechocardiography;LVGLS:leftventriculargloballongi-tudinalstrain;OR:oddsratio;CI:confidenceinterval;DSE:dobutaminestressechocardiography;ESE:exercisestressechocardiography;MACCE:majoradversecardiacandcerebrovascularevents;LAD-CFVR:leftanteriordescendingarterycoronaryflowvelocityreserve;MACE:majoradversecardiovascularevents;HR:hazardratio;DS:dobutaminestress;MRI:magneticresonanceimaging;SPECT:single-photonemissioncomputedtomography;

SSS:summedstressscore;LDL-C:low-densitylipoproteincholesterol;PET:positronemissiontomography;MBFR:myocardialbloodflowreserve;CMD:coronarymicrovasculardysfunction.

Biomedicines2024,12,2597of14

5.1.ExerciseTreadmillTest

Anexercisetreadmilltest(ETT),alsoknownasastresstestortreadmillstresstest,isadiagnosticprocedureperformedtoassessthecardiovascularsystem’sresponsetophysicalexertion.ThistestiscommonlyusedtoevaluatethepresenceofCAD,determineexercisecapacity,andidentifyabnormalheartrhythms.FindingssuchasST-segmentchangesontheECGduringexerciseorahypotensiveresponseareconsideredabnormal.

AnETTmaysometimesbeorderedasthefirstnon-invasivemethodofischemiaassessmenteveninasymptomaticindividuals.Amongtheearlieststudiesusingthisapproachwas

theoneconductedbyLaukkanenetal.in1769middle-agedmaleindividuals

whowerefreefromcardiovasculardisease[

29

].SMIduringexercisewaspresentin10.7%oftheparticipants,amongwhom15.3%facedanacutecoronaryeventand7.9%diedfromcardiovascularcauses.Afteranadjustmentfortraditionalcardiovascularriskfactors,thepresenceofSMIduringexercisewasaccompaniedbya1.7-foldhigherriskofacutecoronaryeventsanda3.5-foldhigherriskofcardiovascularmortality,withthosefindingsbeingofgreatermagnitudeinindividualswithcoexistentsmoking,hyperlipidemia,orhypertension.Critically,thisstudyhighlightedthattheST-segmentchangesthatareprolongedordevelopafterexercisearealsopredictiveofadverseoutcomes.

5.2.Echocardiography

EchocardiographyplaysacrucialroleintheassessmentofSMIasitprovidesvaluableinformationaboutcardiacstructureandfunction,helpingcliniciansidentifyareasofcompromisedbloodflowandpotentialischemicdamage.TTEisthemostcommonlyusedechocardiographictechniqueforSMIassessment.Echocardiographicimagesarecarefullyanalyzedforregionalwallmotionabnormalitiesandchangesinejectionfraction.Strainimagingisatechniquethatassessesthedeformationofmyocardialtissueduringthecardiaccycle.Reducedstraininspecificregionsmayindicatecompromisedbloodflowandmyocardialischemia,evenintheabsenceofsymptoms.Re