13_AcuteMyocardialInfarction_WillisGodinDOFall2012-kc13.pptx

8/9/2019 13_AcuteMyocardialInfarction_WillisGodinDOFall2012-kc13.pptx

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Acute Myocardial Infarction

Willis E. Godin, D.O.South Jersey Heart Group

Lourdes Cardiology Services


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Acute Coronary Syndrome

(ACS)Refers to the array of clinical signs and

symptoms produced by acutemyocardial ischemiaUnstable anginaNon-ST-segment-elevation MIST-segment-elevation MI

Each condition shares commonpathophysiologic origins related to theinstability and rupture of artheroscleroticvulnerable plaques


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Unstable angina and NSTEMI

ifferentiated one from the other byprimarily by their severity

!hether the ischemia is prolongedenough to lead to structural myocardialdamage and to the release ofdetectable mar"ers of myocardial in#ury Troponin I $TnI% Troponin T $TnT%&reatine "inase $&'%-M(


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Coronary heart disease

Ma#or cause of morbidity and death in theUnited States

)ffecting appro*imately +, million )mericansSomeone in the US e*periences a coronary

event every . seconds/ and someone diesfrom a coronary event every minute0

More than +01 million hospitali2ations for )&S

in the US each year irect and indirect costs of &3 areestimated to be more than 4+,. billion in556 alone


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Pathohysiology

Unstable angina and NSTEMI resultfrom a disparity bet7een myocardial

o*ygen delivery and demand/ 7hichusually presents as angina occurring7ith limited physical activity or at rest $acrescendo pattern%0


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!emand"and"deli#ery mismatch

)ssociated 7ith U)8NSTEMI&an occur because of dynamic obstruction

from9 Intense arterial spasm :rogressive/ severe/ flo7-limiting atherosclerosis

due to intimal hyperplasia or to lipid/ calcium/ andthrombus deposition/ or to fibrointimal hyperplasiaafter :&I

&oronary artery dissection &onditions that alter myocardial o*ygen demand

or supply/ such as intense emotion/ tachycardia/ oruncontrolled systemic hypertension $secondaryMI%


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Pathohysiology

The most frequent mechanism ofischemia during limited physical activity

or at rest is a primary reduction of themyocardial o*ygen supply due torupture or ulceration of a vulnerableatherosclerotic plaque

Results in endothelial in#ury andassociated thrombosis and dynamicvasoconstriction


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Pathohysiology

:laque fissure or rupture e*poses the highlythrombogenic subendothelium to circulatingplatelets and 7hite blood cells/ 7hich in turn

activates the coagulation cascadeThe resultant platelet adhesion and

aggregation at the site of plaque disruptionleads to transient thrombosis or subtotalcoronary artery occlusion 7ith dynamicvasoconstriction

)ctivated platelets release po7erfulpromoters of vasoconstriction and plateletaggregation/ including thrombo*ane )/

serotonin/ adenosine diphosphate/ andlatelet-activatin factor


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Pla$ue %uture

&an occur in mildly or severelystenosed coronary arteries

;ften occurs in arteries 7here theatherosclerotic lesions previously hadcaused only mild-to-moderateobstruction


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!uration of ischemia

The duration of ischemia caused by theplatelet-fibrin thrombi and severe dynamicvasoconstriction determines the overall

clinical picture0 If ischemia is neither severe nor prolonged

$usually


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Pathohysiology

:atients 7ith U)8NSTEMI remain at high ris"for a ne7 infarction and its sequelae/including sudden cardiac death/ until the

endothelial in#ury is repairedU)/ NSTEMI/ and STEMI represent a

pathophysiologic continuumThis concept has led to the development of

effective pharmacologic therapies that/ usedin con#unction 7ith careful and rapid ris"-assessment strategies and catheter-basedtherapies/ improve outcomes in U)8NSTEMIpatients0


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Atherosclerosis

:rogressive in nature&hronic inflammatory and multifocal disease

involving medium- and large-si2ed arteriesMay begin in the subendothelium as early as

in the +st decade of lifeUsually develops in lesion-prone vascular

areas that e*hibit underlying endothelialdysfunction as a response to chronic/multifactorial in#ury to the arterial 7all


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Endothelial in&ury

>lo7 shear stress3ypertension Immune-comple* deposition and complement

activationSmo"ingiabetes mellitus )gingSubstance abuse InfectionMechanical in#ury $coronary angioplasty/ stent

placement/ heart transplantation%


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Endothelial !ysfunction

) process regarded as a precursor tothe development of vascular disease

&haracteri2ed by disruption of vessel-7all homeostasis/ 7hich is signified bydecreased vasodilation/ increasedvasoconstriction/ increased o*idativestress and inflammation/ deregulation ofthrombosis and fibrinolysis/ abnormalsmooth-muscle-cell proliferation/ and adeficient repair mechanism0


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!iagnosis ' %is Stratification

Early ris" stratification is vital in thetimely diagnosis and treatment of )&S

)ssessment of patients 7ith suspected )&S should include9&linical history:hysical e*amination + lead E&?(iochemical mar"er measurementNoninvasive ris" stratification


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Clinical istory

) thorough clinical history is of utmostimportance in the initial evaluation andtreatment of patients 7ith suspected )&S

Typical symptoms of )&S include chest painor discomfort that may or may not radiate tothe arm/ bac"/ nec"/ #a7/ or epigastrium

!omen and elderly patients are more li"ely to

present 7ith atypical features/ such asshortness of breath/ 7ea"ness/ diaphoresis/nausea/ and lightheadness


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Physical E*amination

>indings of patients 7ith suspected )&S are often normal

)ttention must be paid to the presenceof complications of )&S9 )cute @A failure3ypotensionS= gallopNe7 or 7orsening mitral regurgitation:ulmonary edema


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Electrocardiograhy

:lays an important role in initialassessment/ emergency treatment/

prognostication/ and subsequentdecision-ma"ing regarding the definitivetreatment of patients 7ith suspected

)&S

3igh specificity for diagnosing STEMIRemains test of +st choice


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+iochemical marers

!hen ischemia is prolonged enough toproduce myocardial necrosis/ theintegrity of the myocytic membrane islost

&ardiac en2ymes and other substancesthen lea" into the peripheral blood/ and

their elevated levels in the bloodstreamare indicative of acute myocardialinfarction $)MI%


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+iochemical marers

&ardiac troponins9 gold standard ofbiomar"ers for establishing a diagnosisof )MI:reviously/ elevated levels of &' and its

cardiac-specific isoform &'-M( 7ere usedto ma"e a diagnosis of )MI

)ny elevation in the circulating levels ofthese biomar"ers may provide a clinicaldistinction bet7een U) and NSTEMI


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Cardiac Troonins

E*cellent independent mar"ers of short-term and long-term prognoses

Ris" of death 7ithin the first 1 days isdirectly proportional to cardiac troponinlevels/ and the prognostic information isindependent of other clinical and

electrocardiographic ris" factors


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Cardiac Troonins

etectable in the serum 1-+ hoursafter onset of myocardial necrosis

:ea" +-1D hours from symptom onsetSerial sampling/ including the

acquisition of a baseline sample and afollo7-up sample D-+ hours after

symptom onset/ is recommended


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%is Stratification

&linical features/ E&?/ and cardiactroponin levels are fairly insensitive forimmediately ruling out )&S

It is important to reliably stratify patients7ho are at high or lo7 ris" of an MI and7ho are li"ely to have adverse events inthe near future TIMI score

:URSUIT score?R)&E score


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TIMI ris score

TIMI II( trial:rimary endpoint 7as the composite of

all-cause death/ ne7 or recurrent MI/ orsevere recurrent ischemia that promptsurgent revasculari2ation by day +1

Simple -point score that can be

calculated easily at the bedside


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Treatment strategies

Initial treatment9 Invasive vs0&onservative

espite the debate/ it is no7 7idelyaccepted that the initial medical therapyfor patients 7ith suspected )&S shouldinclude relieving the ischemia and

preventing further myocardial damage


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Treatment strategies

3o7 clinicians go about this is largely dictatedby the initial ris" assessment and continuedpatient monitoring in a controlled environment

3emodynamically unstable patients 7ithrefractory ischemic pain are monitored in acritical care environment and are ta"en to thecardiac catheteri2ation laboratory as soon aspossible

Most patientsF conditions stabili2e after a briefperiod of medical therapy at 7hich time theycan be further triaged according to )&Sguidelines


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Nitrates

Endothelium-independent vasodilatory effectson the coronary and peripheral vascular beds

ilate venous capacitance vessels and

peripheral arteriolesecrease preload and afterload@ead to decrease in both myocardial 7all

stress and o*ygen demand

Relieve coronary spasm in atheroscleroticvessels and increase o*ygen delivery to thesubendocardial region that is supplied by theseverely narro7ed coronary artery


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Nitrates

ISIS-1 and ?ISSI-= studiesNo survival benefit or decrease in recurrent

myocardial infarction

Should be used in patients 7ho haverefractory ischemic discomfort

&ontraindicated9 :atients 7ho have ta"en sildenafil/ tadalafil/ or

vardenafil in the previous 1 hours Systemic hypotension Mar"ed tachycardia Severe aortic stenosis Right ventricular infarct


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+"Adrenergic +locers

ecrease sinus node rate andatrioventricular node conductionvelocity/ systolic blood pressure/ andcontractile responses at rest and duringe*ercise

ecrease myocardial o*ygen demand

and increase the length of diastole?ood anti-ischemic agents


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+"+locers

Recommended that )&S patients 7ithoutcontraindications should receive their initialdose of an oral (-bloc"er 7ithin the first 1

hours of medical therapy;vervie7 of literature $+6DD% sho7ed a +=C

relative reduction in the ris" of progressionfrom U) to an MI

:ooled analysis of . trials $55=% sho7ed a.5C reduction in mortality at =5 days and ,months


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Calcium channel blocers

Reduces myocardial contraction andrela*ation of vascular smooth muscle/ 7hichincreases coronary blood flo7

ecrease afterload and heart rate/ 7hilerela*ing the left ventricle and increasingarterial compliance

ma#or classes9 ihydropyridine

Nifedipine/ amlodipine Nondihydropyridine

Aerapamil/ diltia2em


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Calcium channel blocers

Not routinely given to )MI patients dueto lac" of convincing evidence that theyactually reduce death

&&(s can be used as =rd-line anti-ischemic agents $after nitrates and (-bloc"ers% in patients 7ho have elevatedblood pressure or angina at rest

Short acting nifedipine should beavoided due to increased adverseevents


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Antilatelet theray

)cetylsalicylic acid $)spirin%Thienopyridines

Ticlopidine&lopidogrel:rasugrel


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Asirin

&auses irreversible acetylation of serine.6 of cycloo*ygenase $&;G-+% inplatelets and the endothelium/ therebypreventing thrombo*ane ) $TG)%production and resultant plateletaggregation


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Asirin

Reduces the ris" of angina/ death/ or MIby appro*imately =5C in patients 7ith&)

+661 - the )ntiplatelet TrialistsF&ollaboration meta-analysis of +1trials $5/555 pts%

55 - meta-analysis of D studies$+=./555 pts%


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Thienoyridines

(loc" :H+ receptor signaling toprevent production of adenyl cyclase/thereby inhibiting platelet activationthrough adenosine diphosphate $):%

@imit ):-mediated conversion of?:IIb8IIIa to its active form

Mechanism of action is independent ofand complementary to that of aspirin


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Ticloidine

+st-generation thienopyridineIn combination 7ith )S)/ reduces rate

of vascular death and MI by 1,C inNSTEMI patientsUsed less frequently than the ne7er

thienopyridines because of its potential

for side effects9Rash/ nausea/ neutropenia/

thrombocytopenia


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Cloidogrel

nd-generation thienopyridineMost 7idely used and studied ):-

receptor-bloc"ing agent&):RIE study $+66,% 9 +6/+D. pts&URE trial $55+% 9 +/., pts&3)RISM) trial $55,%:&I-&URE trial $55+%


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Cloidogrel

6C relative ris" reduction in adversecardiovascular events $vascular death/MI/ or ischemic stro"e% 7hen compared

to aspirin - $&):RIE%5C reduction in the primary composite

endpoint $cardiovascular death/ MI/ orstro"e% up to + months of f8u - $&URE%

=+C reduction in cardiovascular deathor MI in patients undergoing :&I - $:&I-&URE%


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,lycorotein IIb-IIIa Inhibitors

:latelets are activated through multiplepath7ays/ ho7ever/ the final commonpath7ayJ of platelet activation andaggregation invloves a conformationalchange of the ?:IIb8IIIa receptors froma resting state to an active state


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)bci*imabTirofiban

eptifibatide


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E:I& trial $+661% - =.C reduction in primarycomposite endpoint $death/ MI/ recurrentischemia% in pts given abci*imab vs placebo

&):TURE trial $+66% - =5C relativereduction of death/ MI/ or recurrent ischemiain pts given abci*imab

:RISM study $+66D% - =C reduction indeath/ MI/ or recurrent ischemia in pts giventirofiban

:URSUIT trial $+66D% - +5C reduction in therelative ris" of death and MI in pts giveneptifibatide


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Anticoagulants

Unfractionated heparin@o7-molecular-7eight heparin

Eno*aparin dalteparin

>actor G inhibitors fondaparinu*


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earin (U. and /M0)

>RIS& trial $+66% - ,=C relative ris"reduction in death or MI in pts givendalteparin vs placebo

ESSEN&E trial $+66% - the ris" of death/ MI/or recurrent angina 7as significantly lo7er inpts given eno*aparin vs U>3 $+,0,C vs+60DC%

TIMI ++( trial $+666% - +10=C ris" reduction ofdeath/ MI/ or need of urgent revasculari2ationin pts given eno*aparin vs U>3


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Early"Conser#ati#e and Early"In#asi#e Strategies

&oronary angiography aids in definingthe e*tent and location of &) and indirecting the definitive care strategy:&I8stenting&)(?Medical management

)ngiography is an invasive procedureand there is a small ris" of seriouscomplications $K+ in +/555 cases%


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Early"Conser#ati#e and Early"In#asi#e Strategies

In the early-invasive strategy/ allpatients 7ithout contraindicationsundergo coronary angiography 7ith theintent to perform revasculari2ation7ithin 1 to 1 hours of hospitaladmission0

The early-conservative strategyconsists of aggressive medical therapyfor patients


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TIMI"III+ trial

&ompared an early-invasive strategy to anearly-conservative strategy in U)8NSTEMI pts$+661%

:rimary endpoint9 composite of death/ MI/ orabnormalities on a e*ercise stress test at ,7ee"s

No significant difference in the occurrence ofthe composite endpoint bet7een the groups0

3o7ever/ the average length of initialhospitali2ation/ the incidence ofrehospitali2ation 7ithin , 7ee"s/ and thenumber of days of rehospitali2ation all 7ere

significantly lo7er in the early-invasive group


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1AN2UIS trial

&ompared an early-conservativestrategy to an early-invasive strategy$+66D%

&ombined endpoint of death and non-fatal MI occurred in =0=C of pts in theearly-conservative group and 0C of

pts in the early-invasive group

$No benefit of early-invasive strategy%


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.%ISC"II trial

&ompared an early-conservative strategy toan early-invasive strategy $+666%

Incidence of the composite endpoint of death

or MI 7as 601C in the early-invasive groupand +0+C in the early-conservative group

>urthermore/ angina symptoms and hospitalreadmissions 7ere reduced by .5C 7ith the

use of the early-invasive strategy


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Conclusions

)&S is associated 7ith high rates ofadverse cardiovascular events/ despiterecent therapeutic advances

:laque composition and inflammationare more important in the pathogenesisof )&S than is the actual degree of

stenosis


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Conclusions

The cornerstone of contemporarytreatment remains early ris"stratification and aggressive medicaltherapy/ supplemented by coronaryangiography in appropriately selectedpatients


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Conclusions

)n early-invasive treatment strategy isof most benefit to high-ris" patients

)n early-conservative strategy isrecommended for lo7-ris" patients


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Conclusions

)d#unctive medical therapy 7ith )S)/clopidogrel/ ?:IIb8IIIa inhibitors/ and either@M!3 or U>3/ in the appropriate setting/

further reduces the ris" of ischemic eventssecondary to thrombosis )nticoagulation and short- and long-term

inhibition of platelet aggregation should beachieved by appropriately evaluating the ris"

of bleeding complications in each patientOur goal 9 enhance both short- and long-term

event-free survival

13_AcuteMyocardialInfarction_WillisGodinDOFall2012-kc13.pptx

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