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CoronaryMicrovascularDisease:DoesItExist?
EAAmsterdam,MDDistinguishedProfessorCardiologyandInternalMedicineUCDavisSchoolofMedicineandMedicalCenterSacramento,CA
63yo womanwithchestpain• ExertionalCP3-4x/wk,+/- responsetomeds• NormalbaselineECG.Pos ETT,Neg ESE• SeveralvisitstoEDwithCP
– NonspecificST-TduringCP,negativetroponins
• 1Admission:Neg eval forACS– Coronaryangio:10-20%stenoses inLAD/RCA,LVEF60%……………………………………………………………………………….
• Onmultipleantianginalmeds,RFreduction• GI,pulmonary,musculoskeletalw/uNEG.Counselingforpsychosocialstress
CoronaryMicrocirculation
• Classification• Anatomy/Physiology• Clinical• Assessmentofcoronarymicrocirculation• Prognosis• Management
CoronaryMicrocirculation
• Classification• Anatomy/Physiology• Clinical• Assessmentofcoronarymicrocirculation• Prognosis• Management
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TermsAppliedtoSyndromeofChestPainwithoutObstructiveCAD
• CardiacsyndromeX• Coronarymicrovasculardysfunction(CMD)• Microvascularangina• Endothelialdysfunction• Impairedcoronaryvasodilatorcapacity• Impairedcoronaryflowreserve• ………………………………………………………………• Abnormalpainperception(“sensitiveheart”)• Somatoformdisorder
TR
Clinical Setting
ClassificationofCoronaryMicrovascularDysfunction
TYPE 1 absence of myocardial disease and obstructive CAD
Risk factors Microvascular angina
Endothelial dysfunction SMC dysfunction Vascular remodeling
PathogeneticMechanisms
Type 2 myocardial diseases HCM,DCM,amyloid
Stable CAD, ACSType 3 obstructive CAD
Type 4 iatrogenic PCI,CABG
Vascular remodelingEndothelial dysfunctionSmooth muscle dysfunctionAutonomic dysfunctionImpaired arteriolar function
TypeofMVD
F.Crea etal. EuropeanHeartJournal2014;35,1101–1111
TR
Clinical Setting
ClassificationofCoronaryMicrovascularDysfunction
TYPE 1 absence of myocardial disease and obstructive CAD
Risk factors Microvascular angina
• Endothelial dysfunction • SMC dysfunction • Vascular remodeling• Impaired arteriolar fxn
PathogeneticMechanisms
Type 2 myocardial diseases HCM,DCM,amyloid
Stable CAD, ACSType 3 obstructive CAD
Type 4 iatrogenic PCI,CABG
Vascular remodelingEndothelial dysfunctionSmooth muscle dysfunctionAutonomic dysfunctionImpaired arteriolar function
TypeofMVD
F.Crea etal. EuropeanHeartJournal2014;35,1101–1111
F.Crea etal. EuropeanHeartJournal2014;35,1101–1111
ClassificationofCoronaryMicrovascularDysfunction
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CoronaryMicrocirculation
• Classification• Anatomy/Physiology• Clinical• Assessmentofcoronarymicrocirculation• Prognosis• Management
CoronaryArteriesandArterioles
RCA
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RCA
BLUSH
CoronaryArterySizeandDistribution
CoronaryArteryPhysiology:Endothelium-Derived/OtherVasoactiveAgents
The coronary arterioles are normally in a relatively dilated state
Adenosine
VASCULARLUMEN
CoronaryArteryPhysiology:Endothelium-Derived/OtherVasoactiveAgents
The coronary arterioles are normally in a relatively dilated state
Adenosine
VASCULARLUMEN
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CoronaryMicrocirculation
• Classification• Anatomy/Physiology• Clinical• Assessmentofcoronarymicrocirculation• Prognosis• Management
CMD– Demographics
–20-30%ofpatientswithanginal-typeCPhavenoobstructiveCAD(normalor<50%stenosis)• Usuallyhaveobjectiveevidenceofischemia
–Women:~3-5Xmorefrequentthaninmen
–ExcludeotheretiologiesofCP• Coronaryspasm,myocardialbridging,pericarditis,GI/Pul/MS/Psychosocialstress…
ClinicalPresentation- CMD– Allpts
• CPandnonobstructive orNLcoronaryarteries• ButbroadcontinuumofSx,RFs,ischemiatestresults
– GroupA)Typicalangina,+RFs,ischemiaonnoninvasivetests• ETT,stressimaging,AmbulatoryECG
– GroupB) AtypicalCP,+/- RFs,+/- ischemiastresstests
– GroupC)VariabledatafromgroupsAandB• Sx,RFs,Tests
ExerciseTreadmill
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ExerciseTreadmill
7min
CoronaryMicrocirculation
• Classification• Anatomy/Physiology• Clinical• Assessmentofcoronarymicrocirculation• Prognosis• Management
ImpressionofCoronaryMicrocirculationbyMyocardialBlush
ImpressionofCoronaryMicrocirculationbyMyocardialBlush
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ThePhysiologic“Angiogram”
• IntracoronaryAcetylcholine– Testsintegrityofmicrovascularendothelium– Normal:increaseCBF>50%abovecontrol
• IntracoronaryAdenosine– Testsdirectresponseofmicrovasculardilatation– Normal:increaseinCBF≥2.5Xovercontrol
ImagingMethods
• PositronEmissionTomography(PET)Rubidium– Imagestransmyocardial distributionofCBF,detectsimpairedriseinsubendocardial CBFindicativeofCMD
• CardiacMRI– Detectsinadequatesubendocardial distributionofCBF,therebyidentifyingCMDbyinadequateincreaseinresponsetostress(adenosine)
Copyright ©2012 American College of Cardiology Foundation. Restrictions may apply.
Murthy, JACC 2012;59:E1373
Coronary Microvascular Function in Patients with Suspected CAD: Relation to Gender
307 women, 97 men
Frequency/magnitude of coronary microvascular dysfunction are similar in both genders
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Reducedsubendocardial perfusionprovidingevidenceforcoronaryMVD
CardiacSyndromeXNEJM2002;346:1948
STRESS-INDUCEDMICROVASCULARISCHEMIA
BermanetaL. JACC4/16
NormalstressperfusionMRI
Uniformcontrastenhancementoflvmyocardium
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41yo runnerwithchestpainandnormalcoronaryangio
ReducedsubendocardialenhancementduringGadoliniuminfusion(darkarea,arrow)
• StressperfusionMRIwithGadoliniunm
CoronaryMicrocirculation
• Classification• Anatomy/Physiology• Clinical• Assessmentofcoronarymicrocirculation• Prognosis• Management
Prognosis• Initiallyfelttoberelativelybenign• Recentfindings:CMDassociatedwithadverseclinicaloutcomes(Murthy,Circ 2014,129:2518)
• CFR<2.0,n=641pts,61yo,1.3yr interval– 8.6%MACE,5%mortality
• CMD:Prevalence/outcomessimilarinthesexes
CoronaryMicrocirculation
• Classification• Anatomy/Physiology• Clinical• Assessmentofcoronarymicrocirculation• Prognosis• Management
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Management• Antianginalmeds (incl.ranolazione),Riskfactormodification• Statins,ACEI/ARB
– Enhancedendothelialfunction
• CardiacRehab– Comprehensive,exercise-centered
• Hormonereplacementtherapy– Beneficialeffectonendothelium(?),giveforshortestpossibleinterval
..……………………………………………………………………………………………………………..
• Counseling– Psychosocialstressreduction,sx mayberelatedtosomatoformdisorder
• Imipramine– EffectiveinsomeptswithDx sensitiveheart
OurPatient
• MRI:Nostress-inducedsubendocardial ischemia• NoobstructiveCAD,negativestressimagingtests• ConsiderSomatoformDisorderorSensitiveHeart• Imipraminewasaddedtohertherapy.
Copyright ©2012 American College of Cardiology Foundation. Restrictions may apply.
Murthy, JACC 2012;59:E1373
Coronary Microvascular Function in Patients with Suspected CAD: Relation to Gender
307 women, 97 men
Summary• Coronarymicrovasculardisease:real,multipleetiologies,can
occurasisolatedabnormality• Dx requiresrigorousevaluation• MorewomenthanmenwithMVD(butratesimilarinW/M)• Adverseprognosticeffecthasbeendocumented• Diagnostic approach favors MRI or PET rubidium scan• ………………………………………………………………………………………..• Managementnotyetspecific,multipleapproaches• Considersomatoformdisorder,sensitiveheart