الرحيم الرحمن اللله بسم

ACUTE CORONARY SYNDROME SIMPLE NOTES

Draz MY , Egypt 2008

Mb. Bch (Tanta), D. Sc (Al azhar) .,M. Sc (Cairo) ,M. Sc (Ain shams).

Surgeon ,Internist, Emergency Registrar.mahmood_yasin37@yahoo.com

AtherosclerosisAtherosclerosis

One of the most common diseases in U.S.AOne of the most common diseases in U.S.A..

50%50% of U.S. Deaths are attributed to MIof U.S. Deaths are attributed to MI

Atherosclerosis is the Principal cause of Atherosclerosis is the Principal cause of Death in Western World (Braunwald)Death in Western World (Braunwald)

Atherosclerosis begins in childhood and Atherosclerosis begins in childhood and advances throughout lifeadvances throughout life

RISK FACTORS AND PATHOGENESIS OF ATHEROMATOUS LESIONS OF ARTERIES.

CORONARY HEART DISEASE : CLINICAL CORONARY HEART DISEASE : CLINICAL MANIFESTATIONS AND PROBLEMSMANIFESTATIONS AND PROBLEMS

STABLE ANGINASTABLE ANGINAFIXED CORONARY FIXED CORONARY ATHEROMATOUS LESIONATHEROMATOUS LESION

UNSTABLE UNSTABLE ANGINA ANGINA

DYNAMIC CORONARY DYNAMIC CORONARY OBSTRUCTIONOBSTRUCTION

MIMIMYONECROSIS DUE TO ACUTE MYONECROSIS DUE TO ACUTE ISCH.ISCH.

HEART FAILUREHEART FAILUREMYOCARDIAL DYSFUNCTIONDUE MYOCARDIAL DYSFUNCTIONDUE TO INFARCTION OR ISCH.TO INFARCTION OR ISCH.

ARRYTHMIAARRYTHMIAALTERED CONDUCTION DUE TO ALTERED CONDUCTION DUE TO ISCH.OR INFARCTIONISCH.OR INFARCTION

SUDDEN DEATHSUDDEN DEATHV.TACH.,ASYSTOLE,MASSIVE MIV.TACH.,ASYSTOLE,MASSIVE MI

Myocardial IschemiaMyocardial Ischemia

•Spectrum of presentation•silent ischemia•exertion-induced angina•unstable angina•acute myocardial infarction

ACC/AHA 2002 GUIDLINESACC/AHA 2002 GUIDLINES

ACC/AHA 2002 GUIDLINESACC/AHA 2002 GUIDLINES

ACC/AHA 2002 GUIDLINESACC/AHA 2002 GUIDLINES

UNSTABLE ANGINA

Acute Coronary SyndromeAcute Coronary Syndrome

Ischemic DiscomfortUnstable Symptoms

No ST-segmentelevation

ST-segmentelevation

Unstable Non-Q Q-Waveangina AMI AMI

ECG

AcuteReperfusion

HistoryPhysical Exam

THROMBOSIS IN MYOCARDIAL THROMBOSIS IN MYOCARDIAL INFARCTION SCORE FOR UNSTABLE INFARCTION SCORE FOR UNSTABLE

AND NSTSMIAND NSTSMI

Unstable AnginaUnstable Anginaprecipitating factorsprecipitating factors

Inappropriate tachycardiaInappropriate tachycardia

anemia, fever, hypoxia, tachyarrhythmias, anemia, fever, hypoxia, tachyarrhythmias, thyrotoxicosisthyrotoxicosis

High afterloadHigh afterload

aortic valve stenosis, LVHaortic valve stenosis, LVH

High preloadHigh preload

high cardiac output, chamber dilatationhigh cardiac output, chamber dilatation

Inotropic stateInotropic state

sympathomimetic drugs, cocaine intoxicationsympathomimetic drugs, cocaine intoxication

Acute Coronary SyndromeAcute Coronary Syndrome

**Process of resolutionProcess of resolutionspontaneous thrombolysisspontaneous thrombolysis

vasoconstriction resolutionvasoconstriction resolution

presence of collateral circulationpresence of collateral circulation

**Delayed or absence of resolution may Delayed or absence of resolution may lead to non-Q-wave or Q-wave lead to non-Q-wave or Q-wave myocardial infarctionmyocardial infarction

Unstable AnginaUnstable AnginaTherapeutic GoalsTherapeutic Goals

**Therapeutic GoalsTherapeutic Goals

Reduce myocardial ischemiaReduce myocardial ischemia

Control of symptomsControl of symptoms

Prevention of MI and deathPrevention of MI and death

**Medical ManagementMedical Management

Anti-ischemic therapyAnti-ischemic therapy

Anti-thrombotic therapyAnti-thrombotic therapy

Unstable AnginaUnstable AnginaMedical TherapyMedical Therapy

Anti-ischemic therapyAnti-ischemic therapynitrates, beta blockers, calcium antagonistsnitrates, beta blockers, calcium antagonists

Anti-thrombotic therapyAnti-thrombotic therapyAnti-platelet therapyAnti-platelet therapy

aspirin, ticlopidine, clopidogrel, aspirin, ticlopidine, clopidogrel, GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitors

Anti-coagulant therapyAnti-coagulant therapy

heparin, low molecular weight heparin heparin, low molecular weight heparin (LMWH), warfarin, hirudin, hirulog(LMWH), warfarin, hirudin, hirulog

Unstable AnginaUnstable AnginaAnti-ischemic TherapyAnti-ischemic Therapy

restrict activitiesrestrict activities

morphinemorphine

oxygenoxygen

nitroglycerinenitroglycerinepain relief, prevent silent ischemia, control pain relief, prevent silent ischemia, control hypertension, improve ventricular dysfunctionhypertension, improve ventricular dysfunction

nitrate free period recommended after the first nitrate free period recommended after the first 24-48 hours24-48 hours

Unstable AnginaUnstable AnginaAnti-ischemic TherapyAnti-ischemic Therapy

beta-blockersbeta-blockerslowering angina thresholdlowering angina threshold

prevent ischemia and death after MIprevent ischemia and death after MI

particularly useful during high sympathetic toneparticularly useful during high sympathetic tone

calcium antagonistscalcium antagonistsparticularly the rate-limiting agentsparticularly the rate-limiting agents

nifedipine is not recommended without nifedipine is not recommended without concomitant ß-blockadeconcomitant ß-blockade

Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy

•ThienopyridinesThienopyridines–ticlopidine ticlopidine (Ticlid; Hoffmann-La Roche)(Ticlid; Hoffmann-La Roche)

–clopidogrel clopidogrel (Plavix; Bristol-Myers (Plavix; Bristol-Myers Squibb)Squibb)

•block platelet aggregation induced by block platelet aggregation induced by ADP and the transformation of GP ADP and the transformation of GP IIb/IIIa into its high affinity stateIIb/IIIa into its high affinity state

Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy

ClopidogrelClopidogrelCAPRIE CAPRIE (Clopidogrel versus Aspirin in Patients at Risk (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events)of Ischemic Events)

19,00019,000 patients randomly assigned to clopidogrel (75 patients randomly assigned to clopidogrel (75 mg/d) or to aspirin (325 mg/d)mg/d) or to aspirin (325 mg/d)

there was an there was an 8.7%8.7% reduction in the combined reduction in the combined incidence of stroke, MI, or death (P=.043)incidence of stroke, MI, or death (P=.043)

patients with MI did better with aspirinpatients with MI did better with aspirin

patients with PVD or stroke did better with patients with PVD or stroke did better with clopidogrelclopidogrel

Lancet 1996;348:1329-1339Circulation 1998;97:1107

Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy

GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitorsabciximab (monoclonal antibody)abciximab (monoclonal antibody)

eptifibatide (peptidic inhibitor)eptifibatide (peptidic inhibitor)

lamifiban and tirofiban (non-peptides)lamifiban and tirofiban (non-peptides)

direct occupancy of the GP IIb/IIIa receptor by a direct occupancy of the GP IIb/IIIa receptor by a monoclonal antibody or by synthetic monoclonal antibody or by synthetic compounds mimicking the RGDcompounds mimicking the RGD sequence for sequence for fibrinogen binding prevents platelet fibrinogen binding prevents platelet aggregationaggregation

Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy

Tirofiban Tirofiban (Aggrastat; Merk & Co.)(Aggrastat; Merk & Co.)PRISMPRISM (Platelet Receptor Inhibition for (Platelet Receptor Inhibition for Ischemic Syndrome Management)Ischemic Syndrome Management)

3,2003,200 patients with unstable angina were patients with unstable angina were treated with either heparin or tirofibantreated with either heparin or tirofiban

At 48 hours, there was significant risk At 48 hours, there was significant risk reduction (5.9% to 3.6%) in the rate of reduction (5.9% to 3.6%) in the rate of death, MI, or refractory ischemia. The death, MI, or refractory ischemia. The benefit was lost at 30 daysbenefit was lost at 30 days..

N Engl J Med 1998;338:1498-505

Unstable AnginaUnstable AnginaAnti-coagulant TherapyAnti-coagulant Therapy

Low-molecular-weight heparinLow-molecular-weight heparinadvantages over heparinadvantages over heparin::better bio-availabilitybetter bio-availability

higher ratio (3:1) of anti-Xa to anti-IIa higher ratio (3:1) of anti-Xa to anti-IIa activityactivity

longer anti-Xa activity, avoid reboundlonger anti-Xa activity, avoid rebound

induces less platelet activationinduces less platelet activation

ease of use (subcutaneous - qd or bid)ease of use (subcutaneous - qd or bid)

no need for monitoringno need for monitoring

NSTSMI

MYOCARDIAL PROTEINSMYOCARDIAL PROTEINS

Myoglobin

Actin,Myosin

Troponin

LDH

CK, AST

MYOFIBER STRUCTUREMYOFIBER STRUCTURE

TnI

ActinTropomyosin

TnC TnT

•

•

0 6 12 18 24 2 3 4 5 6 7 8 9 10

RE

LATI

VE

CO

NC

EN

TRAT

ION

DaysHours

TIME AFTER INFARCT

Normal

TroponinMyoglobin

CK, ASTLDH

STSEMI

In-stent Restenosis in small In-stent Restenosis in small vessels treated with vessels treated with rotational atherectomyrotational atherectomy

StentsStents

Coronary stents haveCoronary stents have

revolutionized the fieldrevolutionized the field

of coronary angioplastyof coronary angioplasty

due to their ability todue to their ability to

prevent abrupt closure ofprevent abrupt closure of

the artery afterthe artery after

angioplasty and also byangioplasty and also by

reducing restenosisreducing restenosis

Late LossLate Loss

• In- stent restenosis is a In- stent restenosis is a proliferative disease disorderproliferative disease disorder

• Late loss of between 0.8–1.0mm Late loss of between 0.8–1.0mm occurs in bare stentsoccurs in bare stents

• Lumen area reduction Lumen area reduction

Definite ACSDefinite ACSPossible ACSPossible ACS

(–) ECG;Normal biomarkers

(–) ECG;Normal biomarkers

Observe; repeat ECG, markers at 4-8 hrs

Observe; repeat ECG, markers at 4-8 hrs

No recurrent pain;(–) follow-up studiesNo recurrent pain;

(–) follow-up studiesRecurrent pain;

(+) follow-up studiesRecurrent pain;

(+) follow-up studies

Stress test; LVfunction if ischemia

Stress test; LVfunction if ischemia

(–) test: outpt follow-up(–) test: outpt follow-up

(+) test(+) test

Admit, Use AcuteIschemia PathwayAdmit, Use AcuteIschemia Pathway

ST ST

Use MI Guidelines

Use MI Guidelines

No ST No ST

ST-T ’s,chest pain, markers

ST-T ’s,chest pain, markers

Symptoms Suggestive of ACSSymptoms Suggestive of ACS

Emergency Room Triage of Patients with Acute Chest Pain by Means of Rapid Testing for Cardiac Troponin T or Troponin IChristian W. Hamm, M.D., Britta U. Goldmann, M.D., Christopher Heeschen, M.D., Georg Kreymann, M.D., Jürgen Berger, Ph.D., and Thomas Meinertz, M.D.

NEJM,Volume 337:1648-1653, Number 23December 4, 1997773 consecutive patients who had had acute chest

pain for less than 12 hours without ST-segment elevation on their electrocardiograms, troponin T and troponin I status (positive or negative) was determined at least twice by sensitive, qualitative

bedside tests based on the use of specific monoclonal antibodies.

TOTAL TOTAL PATIENTSPATIENTS

MI.PATIENTSMI.PATIENTSUNSTABLE UNSTABLE ANGINAANGINA

NONO..7737734747315315

Tn.I +VETn.I +VE171171= = 22%22% 4747==100%100%114114= = 3636% %

Tn.T +VETn.T +VE123123= = 1616 %%4444= = 9494% % 7070= = 2222% %

ConclusionsConclusions Bedside tests for cardiac-specific Bedside tests for cardiac-specific troponins aretroponins are highly sensitive for the early detection highly sensitive for the early detection of myocardial-cellof myocardial-cell injury in acute coronary injury in acute coronary syndromes. Negative test results aresyndromes. Negative test results are associated with associated with low risk and allow rapid and safe dischargelow risk and allow rapid and safe discharge of of patients with an episode of acute chest pain from the patients with an episode of acute chest pain from the emergencyemergency roomroom..

Missed Diagnoses of Acute Cardiac Ischemia in the Emergency Department.Pope ET AL.

Volume 342:1163-1170, Number 16, NEJM

April 20, 2000

Missed Diagnoses of Acute Cardiac Ischemia in the Emergency Department. Pope ET AL. Volume 342:1163-1170, Number 16, NEJM April 20, 2000

TOTAL NO.=10,689TOTAL NO.=10,689 % %FROM TOTALFROM TOTAL

ACUTE CARDIAC ISCHACUTE CARDIAC ISCH..1717

MIMI88

UNSTABLE ANGINAUNSTABLE ANGINA99

STABLE ANGINASTABLE ANGINA66

NON ISCH.CARDIACNON ISCH.CARDIAC2121

NON CARDIACNON CARDIAC5555

NO.NO.DISCHARGE DISCHARGE FROM EDFROM ED

% OF TOTAL% OF TOTAL

ACUTE MIACUTE MI88988919192.1%2.1%

UNSTABLE ANGINAUNSTABLE ANGINA96696622222.3%2.3%

It appears that the incidence of missed diagnoses of acute cardiac ischemia in the emergency department may be reduced by:

1 -Interpreting the electrocardiogram more accurately.

2 -Addressing clinical factors or preconceptions that obscure the recognition of acute myocardial infarction and unstable angina in women and nonwhite patients.

3 -Considering the possibility that acute cardiac ischemia may be present in patients with chief symptoms other than chest pain.

4 -Assessing recent changes in the clinical course of

angina more carefully.

العالمين رب لله الحمد