Kuliah CAD

5/98 MedSlides.com 1

Coronary Artery Disease

Pendrik TandeanCardiology and Internal Medicine

Deparment, Medical Faculty Hasanuddin University Makassar


Coronary Artery Disease Coronary Artery Disease

Partial Partial Total Total

≥ 1 coronary artery and branches

Blood flow Blood flow

• Occluded of the coronary arteryOccluded of the coronary artery

Kuliah PJK, 2004Kuliah PJK, 200411



Left Coronary Artery


Right Coronary Artery


Global Burden of Cardiovascular Disease

• In 2002 : CVD contributed to approximately a third of all global deaths (17 million). 80% of burden is in low and middle income countries.

• By 2020 : CHD and Stroke will become the leading cause of death and disability worldwide. Mortality for CVD will increase to 20 million.


Worldwide Statistics

Each year:• > 4 million patients are admitted with

unstable angina and acute MI • > 900,000 patients undergo PTCA

with or without stent


Risk Factors for cardiovascular disease

• Modifiable :• - Smoking• - Dyslipidemia (Raised LDL-C, Low

HDL-C, Raised triglycerides)• - Raised Blood pressure• - Diabetes melitus• - Obesity


Risk factors for cardiovascular disease

• Non-Modifiable :• - Personal History of CVD• - Family History of CVD• - Age• - Gender


Summary of risk factors for coronary

heart disease

Shaper et al (1982); Staper et al (1985)Shaper et al (1982); Staper et al (1985)

Major factorsMajor factors HypertensionHypertensionElevated serum cholesterolElevated serum cholesterolCigarette smokingCigarette smokingMale genderMale genderIncreasing ageIncreasing agePrevious history of coronary heart Previous history of coronary heart

diseasedisease

Secondary factorsSecondary factors Glucose intoleranceGlucose intoleranceLeft ventricular hypertrophyLeft ventricular hypertrophyFamily history of coronary heart Family history of coronary heart

diseasediseaseLack of exerciseLack of exerciseExcessive alcohol consumptionExcessive alcohol consumptionObesityObesity

Other factorsOther factors Contraceptive pillContraceptive pillStressStressPersonalityPersonality


Family History

“Premature CHD”

Men (first degree) < 55 years. Women (first degree) <65 years.


VesselVessel

KidneyKidney

HypertensionHypertensionLeft Ventricular Left Ventricular HypertrophyHypertrophy

Chronic Heart FailureChronic Heart Failure

Myocardial InfarctionMyocardial Infarction

Congestive Heart Congestive Heart DiseaseDisease

ArrhythmiaArrhythmiaArteriosclerosisArteriosclerosis

Peripheral Vascular DiseasePeripheral Vascular Disease

Coronary Heart Disease Coronary Heart Disease

Renal InsufficiencyRenal Insufficiency

HeartHeart BrainBrain

StrokeStroke


Pathophysiology of HT Induced CVDPathophysiology of HT Induced CVD

Unstable Plague

Central Nervous System

Sympathetic Activity RAAS Kidney

Vasc Resistance CO ( HR + Force )

HypertensionHypertension

Endothelial Dysfunction

Acute Coronary Syndrome

Shear ForceShear ForceTachyarrhythmia

LVHInsulin Resistant

Disturb MicrocirculationPlatelets Aggregation

Na+/H2OReabsorbsion

RO S Macrophage & Inflammatory Cells

Immunologic Cells ( T – Cells ) MMP, NO

Acceleration Of Atherosclerosis

Plague

Metabolic diseases

Cerebralinsufficiency


SHEAR FORCESHEAR FORCE

Decreased driving pressure to a.coronaria

Platelets Activation

Plaques rupture


NO synthesis

ROS

ACE activityACE activity

Angiotensin II Bradikinin

Diabetes

Viral Infection Hypertension/ shear Force

Oxidized Lipids / Free Radicals

Dyslipidemia

NF-kB TGF- MCP-1 PAI-1 IL- 6

ROS

Inflammation-thrombosis-fibrosis-plaque disruption


VesselLumen

Endothelial cells

Intima

Media

CytokinesandGrowth factors

Monocyte

Monocyte

MCP-1

Adhesion moleculesLDL

Macrophage foam cell Macrophage

Colonystimulating factors

Tissuefactors

Mildly Oxidized LDLLDL

Smooth muscle cell

ExtensivelyOxidized

LDL

Lipid removal

Lipid uptake

Oxidation

SMCProliferation

Ca++

Ca++

Ca++

Ca++Ca++

Ca++Ca++

Ca++

Current Concepts of Atherogenesis:Ca++ as Second Messenger in Atherogenic Processes

Adapted from Khramsch & Sharma, 1997

Ca++


INSULININSULINRESISTANCERESISTANCE

decreasedecrease Uptake of glucose fromUptake of glucose fromblood into cellsblood into cells

Blood insulin Blood insulin levelslevels

Blood glucose Blood glucose levelslevels

Hypertrophy ofHypertrophy ofvascular smoothvascular smoothmuscle and leftmuscle and leftventricleventricle

Blood LDL-cholesterolBlood LDL-cholesteroland VLDL-cholesteroland VLDL-cholesterollevelslevels

Blood HDL-Blood HDL-cholesterolcholesterollevelslevels

Blood pressureBlood pressureAtherosclerosisAtherosclerosisand risk of coronary and risk of coronary heart diseaseheart disease

Insulin resistance, dyslipidemia and cardiovascular disease

increaseincrease increaseincrease

DeFronzo & Ferrannini (1991)DeFronzo & Ferrannini (1991)

increaseincreaseincreaseincrease

increaseincreaseincreaseincrease

increaseincrease

decreasedecrease


0

200

400

600

800

No riskfactors

+Highcholesterol

+Glucoseintolerance

+Smoking +LVH

Systolic blood pressure (105 mmHg)Systolic blood pressure (195 mmHg)

Probability (per 1000)Probability (per 1000)

Risk factorsRisk factors

8-year probability of developing coronary heart disease in

hypertensives

Castelli (1984)Castelli (1984)


Serum lipids and lipoproteins: risk factors for coronary heart

disease

Lipid/Lipoprotein Effect on coronary heart disease

risk if level is:Decreased Increased

Total cholesterol LDL-cholesterol HDL-cholesterol Triglycerides

LDL= low-density lipoprotein; HDL=high-density lipoprotein

Shaper et al (1985)


CORONARY ARTERY DISEASE

• 1. Stable angina pectoris• 2. Acute Coronary Syndrome A. Unstable angina pectoris B. Q wave acute myocardial infarction : -NSTEMI -STEMI C. Non Q wave AMI : -NSTEMI -STEMI


STABLE ANGINA PECTORIS

• Stable angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back or arms, typically elicited by exertion or emotional stress and relieved by rest or nitroglycerin. Less typically, discomfort may occur in the epigastric area.


Diagnosis of stable angina

• Clinical assesment• Laboratory test• Specific cardiac investigations


History

• Features of the history important in risk stratification include current smoking, increasing age, prior MI, symptoms of heart failure, and the pattern of occurance(recent onset or progressive), and severity of angina, particularly if unresponsive to therapy.


Physical examination

• Patient with (suspected) angina pectoris should be focused on identification or exclusion of causal or associated conditions or precipitating factors and on risk stratification.


LABORATORY TEST

• Fasting plasma glucose and lipid profile (TC,HDL,LDL,TG) should be evaluated in all patients with stable angina, to establish the patient’s risk profile and ascertain the need for treatment. A full blood count and serum creatinine are also indicated in all patients.


LABORATORY TEST

• Futher laboratory testing, including OGTT, cholesterol subfractions (ApoA, ApoB), hemocysteine, Lpa, NT-BNP, haemostatic abnormalities and markers of inflammation such as hsCRP, may a role in selected patients.


LABORATORY TEST

• Measurement of markers of myocardial damage such as troponin, should be measured if evaluation suggests clinical instability or acute coronary syndrome.

• Thyroid function should be tested if dysfunction suspected clinically.


Chest X-ray

• Should be requesed only in patients with suspected heart failue, valvular disease or pulmonary disease.

• The presence of cardiomegaly, pulmonary congestion, atrial enlargement and cardiac calcifications have been related to prognosis.


ECG

• All patient with suspected angina pectoris based upon symptoms should have a resting 12 lead ECG

• Resting ECG abnormalities, ST depression, Q waves, left anterior hemiblock and left bundle-branch block, are associated with an adverse prognosis in stable angina.


Time (ms)Time (ms)

SS

TT

200200 400400 600600

-0.5-0.5

00

0.50.5

QQ

PP

1.01.0

Voltage (mV)Voltage (mV)

RR

Normal conduction wave from an electrocardiogram


Ischemia & Infarction• Types of ST-segment depression

UPSLOPING – very nonspecific for the diagnosis of ischemia. Associated with a lot of false positive exercise tests.

HORIZONTAL – likely associated with ischemia.

DOWNSLOPING – almost certainly associated with an ischemic myocardium


ECG STRESS TESTING

• In the majority of patients the exercise ECG is the initial test of choice to diagnosis coronary disease and risk stratify.


ECG STRESS TESTING

• DIAGNOSIS OF CAD. ST segment depression during exercise is used to define a positive test.

• Sensitivity and spesificity are 68% and 77% respectively.

• Exercise ECG testing is not of diagnosis value in presence of LBBB, paced rhythm and WPW syndrome.


ECG STRESS TESTING

• Result are less reliable in patients with an abnormal resting ECG in the presence of LVH, electrolyte imbalance, intraventricular conduction abnormalities and during use of digitalis.

• Exercise ECG testing is also less sensitive and specific in women.


STRESS TESTING IN COMBINATION WITH IMAGING

• Exercise testing with echocardiograpy

• Single Photon Emission Computed Tomography (SPECT)

• Stress Cardiac magnetic Resonance (CMR)


OTHER INVESTIGATIONS

• ECHOCARDIOGRAPHY AT REST• ELECTRON BEAM CT and MULTI-

SLICE CT.• MAGNETIC RESONANCE (MR)

ARTERIOGRAPHY• CORONARY ANGIOGRAPHY.


CORONARY ARTERIOGRAPHY

• Providing reliable anaomical information to identify the presence or absence of coronary lumen stenosis, define therapeutic options (suitability of medical treatment or myocardial revascularization) and determine prognosis.


TREATMENT

• Aims of treatment. A. Improve prognosis by preventing

myocardial infarction and death B. Minimize or abolish symptoms.


Non-pharmacological

• Advice should be given for the management of an acute attack, i.e. to rest, at least briefly, from the activity that provoked the angina and the use of sublingual nitrate for acute relief of symptoms.

• Need to seek medical advice if angina persist >10-20 minutes after rest and/or is not relieved by sublingual nitrates.


Non-Pharmalogical

• Stop cigarette smoking• Mediterranean diet, with vegetables,

fruit, fish and poultry being the mainstays.

• Weight reduction diet --- Overweight• Alcohol in moderation may be

beneficial, but excessive consumption is harmful


Non-Pharmacological• Fish oil rich in omega-3 fatty acids (n-3

polyunsaturated fatty acids) are recommended at least once weekly

• Physical activity within the patients limitation should be encouraged.

• Concomitant disorders such as diabetes and hypertension should be managed appropriately.

• Sexual intercouse may trigger angina. Nitroglycerine prior to intercourse may be helpful.


Pharmacological therapy

• Antitrombotic drugs. Antiplatelet therapy to prevent coronary trombosis is indicated. Low dose aspirin (75-100 mg) is the drug of choise in most cases.

• Aspirin allergic --- clopidogrel• Aspirin + clopidogrel --- post stenting or

after ACS• History of GI bleeding --- aspirin + proton

pum inhibitor



• Anticoagulant drugs (warfarin or thrombin inhibitors), which are combined with aspirin in certain high risk patients, such as post MI, are not indicated in the general stable angina pectoris without a separate indication such as atrial fibrillation for example.



• Lipid lowering drugs• ACE inhibitors• Beta-blockers• Antianginal drugs : beta-blockers,

calcium antagonist and organic nitrates


Coronary artery bypass surgery

• Two main indications --- prognostic and symptomatic

• Prognostic benefit : reduction in cardiac mortality

• CABG has also been shown to effectively reduce symptoms of angina and ischemia in patients with coronary disease.


Better Prognosis with Coronary artery bypass surgery

• Significant stenosis of the left main stem• Significant proximal stenosis of the three

major coronary arteries• Significant stenosis of two major coronary

arteries, including high grade stenosis of the proximal left anterior descending coronary artery

• Three vessel disease with impaired ventricular function.


Percutaneous coronary intervention (PCI)

• PCI may be considered an alternative to CABG for relief of symptoms in almost all cases

• On available evidence, PCI compared to medical therapy does not provide survival benefit in stable angina, but PCI is more often effective than medical treatment in reducing events that impair quality of life



5/98 MedSlides.com 49Unstable PlaqueUnstable Plaque Occlusive ThrombusOcclusive Thrombus

Fixed Coronary ObstructionFixed Coronary Obstruction(Chronic Ischemic Heart Disease)(Chronic Ischemic Heart Disease)

PATOGENESIS PATOGENESIS

Kuliah PJK, 2004Kuliah PJK, 200477


Acute Coronary SyndromeIschemic DiscomfortUnstable Symptoms

No ST-segmentelevation

ST-segmentelevation

Unstable Non-Q Q-Waveangina AMI AMI

ECG

AcuteReperfusion

HistoryPhysical Exam


Acute Coronary Syndrome• The spectrum of clinical conditions

ranging from:– unstable angina– non-Q wave MI– Q-wave MI

• characterized by the common pathophysiology of a disrupted atheroslerotic plaque


Unstable Angina - Definition• angina at rest (> 20 minutes)• new-onset (< 2 months) exertional

angina (at least CCSC III in severity)• recent (< 2 months) acceleration of

angina (increase in severity of at least one CCSC class to at least CCSC class III)

Agency for Health Care Policy Research - 1994Canadian Cardiovascular Society Classification


CANADIAN CARDIOVASCULAR SOCIETY FUNCTIONAL

CLASSIFICATION• CLASS I No angina with ordinary

activity. Angina with strenuous, rapid or prolonged exertion.

• CLASS II Slight limitation of ordinary activity ; angina when walking up stairs briskly, or walking on a cold or windy day.

• CLASS III Marked limitation ; angina when walking at normal pace up flight of stairs, or walking 1-2 blocks distance.

• CLASS IV Angina on minimal exertion or at rest.


Unstable AnginaLikelihood of CAD

• Previous history of CAD• presence of risk factors• older age• ST-T wave ischemic ECG changes

Agency for Health Care Policy Research - 1994


Unstable Anginaprecipitating factors

• Inappropriate tachycardia– anemia, fever, hypoxia, tachyarrhythmias,

thyrotoxicosis• High afterload

– aortic valve stenosis, LVH• High preload

– high cardiac output, chamber dilatation• Inotropic state

– sympathomimetic drugs, cocaine intoxication


Unstable Anginaprognostic indicators

• Presence of ST-T-wave changes with pain• Hemodynamic deterioration

– pulmonary edema, new mitral regurgitation,– 3rd heart sound, hypotension

• Other predictors– left ventricular dysfunction, extensive CAD,

age, comorbid conditions (diabetes mellitus, obstructive pulmonary disease, renal failure, malignancy)


Unstable Anginapathogenesis

• Plaque disruption• Acute thrombosis• Vasoconstriction



• Plaque disruption– Passive plaque disruption

soft plaque with high concentration of cholesteryl esters and a thin fibrous cap

– Active plaque disruptionmacrophage-rich area with enzymes that may degrade and weaken the fibrous cap; predisposing it to rupture



• Acute Thrombosis– Vulnerable plaque

• disrupted plaque with ulceration• occurring in 2/3 of unstable patients• the exposed lipid-rich core abundant in

cholesteryl ester is highly thrombogenic– Systemic Hypercoagulable State

• disrupted plaque with erosion• occurring in 1/3 of unstable patients



• Vasoconstriction– the culprit lesion in response to deep

arterial damage or plaque disruption– area of dysfunctional endothelium near

the culprit lesion– platelet-dependent and thrombin-

dependent vasoconstriction, mediated by serotonin and thromboxane A2



• Process of resolution– spontaneous thrombolysis– vasoconstriction resolution– presence of collateral circulation

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


Non-Q-Wave MIclues to diagnosis

• Prolonged chest pain• Associated symptoms from the

autonomic nervous system– nausea, vomiting, diaphoresis

• Persistent ST-segment depression after resolution of chest pain


Prinzmetal’s Anginaclues to diagnosis

• Transient ST-segment elevation during chest pain

• Intermittent chest pain– often repetitive– usually at rest– typically in the early morning hours– rapidly relieved by nitroglycerine

• Syncope (rare), Raynaud’s, migraine


Unstable AnginaRisk Stratification

Low Risk• new-onset exertional angina• minor chest pain during exercise• pain relieved promptly by nitroglycerineManagement• can be managed safely as an outpatient

(assuming close follow-up and rapid investigation)



Intermediate Risk• prolonged chest pain• diagnosis of rule-out MIManagement• observe in the ER or Chest Pain Unit• monitor clinical status and ECG• obtain cardiac enzymes (troponin T or I)

every 8 to 12 hours



High Risk• recurrent chest pain• ST-segment change• hemodynamic compromise• elevation in cardiac enzymesManagement• monitor in the Coronary Care Unit


Risk Stratification by ECG

The risk of death or MI at 30 days is strongly related to the ECG at the time of chest pain.

• ST depression 10%• T-wave inversion 5%• No ECG changes 1-2%


Unstable AnginaTherapeutic Goals

Therapeutic Goals• Reduce myocardial ischemia • Control of symptoms • Prevention of MI and deathMedical Management• Anti-ischemic therapy• Anti-thrombotic therapy


Unstable AnginaMedical Therapy

• Anti-ischemic therapy– nitrates, beta blockers, calcium antagonists

• Anti-thrombotic therapy– Anti-platelet therapy

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

– Anti-coagulant therapy • heparin, low molecular weight heparin

(LMWH), warfarin, hirudin, hirulog


Unstable AnginaAnti-ischemic Therapy

• restrict activities• morphine• oxygen• nitroglycerine

– pain relief, prevent silent ischemia, control hypertension, improve ventricular dysfunction

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


Unstable AnginaAnti-ischemic Therapy

• beta-blockers– lowering angina threshold– prevent ischemia and death after MI– particularly useful during high sympathetic tone

• calcium antagonists– particularly the rate-limiting agents– nifedipine is not recommended without

concomitant ß-blockade


Unstable AnginaAnti-thrombotic Therapy

• Thrombolytics are not indicated• “lytic agents may stimulate the

thrombogenic process and result in paradoxical aggravation of ischemia and myocardial infarction”

TIMI IIIB InvestigatorsCirculation 1994; 89:1545-1556


Platelets in Acute Coronary Syndromes

• Platelets play a key role in ACS• Sources of platelet activation (triggers)

– thromboxane A2 (TXA2)– ADP– epinephrine– collagen– thrombin


Unstable AnginaAnti-platelet Therapy

• aspirin is the “gold standard”– irreversible inhibition of the cyclooxygenase

pathway in platelets, blocking formation of thromboxane A2, and platelet aggregation

– in AMI, ASA reduced the risk of death by 20-25%– in UA, ASA reduced the risk of fatal or nonfatal MI

by 71% during the acute phase, 60% at 3 months, and 52% at 2 years

– bolus dose of 160-325 mg, followed by maintenance dose of 80-160 mg/d


Thrombus formation and the actions of antithrombotic

agents

Cross-section of blood vessel


Overview of antiplatelet agentsDrug Brand name Mechanism of action Dosing

Low-dose acetylsalicylic acid (LD-ASA)

Aspirin® Irreversibly modifies COX and inhibits TXA2

Oral: 50–325mg once daily

ADP-receptor antagonists

Clopidogrel Plavix®/Iscover®

Irreversibly inhibits ADP-mediated platelet activation

Oral: 75mg once daily (300mg loading dose in ACS)

Ticlopidine Ticlid® Oral: 250mg twice dailyPhosphodiesterase inhibitors

Dipyridamole Persantin Retard®

Inhibits phosphodiesterase, enhances PGI2 production and reduces platelet aggregation

Oral: 75–100mg four times daily

Dipyridamole with LD-ASA

Aggrenox® Oral: dipyridamole 200mg + LD-ASA 25mg, twice daily

Glycoprotein IIb/IIIa-receptor antagonists

AbciximabEptifibatideTirofiban

ReoPro®

Integrilin®

Aggrastat®

Inhibits platelet aggregation by blocking glycoprotein IIb/IIIa receptors on platelets

IV infusion under specialist medical care. Dosages vary between drugs and for different indications. Administered with heparin and LD-ASA

ACS, acute coronary syndrome; ADP, adenosine diphosphate; COX, cyclooxygenase; IV, intravenous; PGI2, prostaglandin I2; TXA2, thromboxane A2.


GP IIb/IIIa ReceptorFinal Pathway to Platelet Aggregation

• Platelet activation and aggregation are early events in the development of coronary thrombosis

• GP IIb/IIIa receptors on activated platelets undergo a conformational change allowing recognition and binding of fibrinogen

• Fibrinogen “acts like glue”, bridging GP IIb/IIIa receptors on adjacent platelets, leading to platelet aggregation


GP IIb/IIIa ReceptorKVGFFGR

• There are approximately 50,000 GP IIb/IIIa receptors on each platelet

• KVGFFGR is a specific region within GP IIb/IIIa receptor that is thought to be involved in platelet activation


Incidence of Ischemic Events

0

2

4

6

8

10

12

14

16

No aspirin(early 1980s)

Aspirin Aspirin + Heparin

16%

12%

9%

Incidence of death and MI



• Thienopyridines– ticlopidine (Ticlid)– clopidogrel (Plavix)

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



• Ticlopidine– in an open-label, randomized study in patients

with unstable angina– ticlopidine 250 mg bid vs. placebo reduced the

risk of fatal or nonfatal MI by 46% at 6 months– benefit not seen at 7 days, but became apparent

after 10 days of therapy (the time required for full antiplatelet activity)

– an alternative for patient with aspirin intolerance

Circulation 1990;82:17-26



• Clopidogrel– CAPRIE (Clopidogrel versus Aspirin in Patients at

Risk of Ischemic Events)– 19,000 patients randomly assigned to clopidogrel

(75 mg/d) or to aspirin (325 mg/d)– there was an 8.7% reduction in the combined

incidence of stroke, MI, or death (P=.043)– patients with MI did better with aspirin– patients with PVD or stroke did better with

clopidogrelLancet 1996;348:1329-1339

Circulation 1998;97:1107



• GP IIb/IIIa inhibitors– abciximab (monoclonal antibody)– eptifibatide (peptidic inhibitor)– lamifiban and tirofiban (non-peptides)

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


Unstable AnginaAnti-coagulant Therapy

• Heparin– recommendation is based on documented

efficacy in many trials of moderate size– meta-analyses (1,2) of six trials showed a

33% risk reduction in MI and death, but with a two fold increase in major bleeding

– titrate PTT to 2x the upper limits of normal

1. Circulation 1994;89:81-882. JAMA 1996;276:811-815


Unstable AnginaAnti-coagulant Therapy

• Low-molecular-weight heparinadvantages over heparin:– better bio-availability– higher ratio (3:1) of anti-Xa to anti-IIa activity– longer anti-Xa activity, avoid rebound– induces less platelet activation– ease of use (subcutaneous - qd or bid)– no need for monitoring


Unstable Angina Anti-coagulant Therapy

• Low-molecular-weight heparin– ESSENCE Trial (Efficacy and Safety of

Subcutaneous Enoxaparin in non-Q-Wave Coronary Events Study)

– at 30days, there was a relative risk reduction of 15% -16% in the rate of death, MI, or refractory ischemia as compared to standard heparin

N Eng J Med 1997;337:447-452


ESSENCE Trialincidence of death, MI, or recurrent angina

N Eng J Med 1997;337:447-452

0

5

10

15

20

25

0

5

10

15

20

25

heparin Lovenox heparin Lovenox

n=1564 n=1607 n=1564 n=1607

19.8%16.6%

P=0.019

23.3%

19.8%P=0.016

Day 14 Day 30


Unstable Angina Coronary Interventions

• TIMI 3B – early intervention vs conservative strategy

(coronary angiography within 24-48 hrs, followed by angioplasty or bypass surgery)

– 1473 patients with UA or non-Q-wave MI were randomized, there were no difference between the groups in the rates of death or MI at 1 year

Circulation 1994;89:1545-1556


Acute Myocardial Infarction

Myocardial Infarction if the rapid development of myocardial necrosis by a critical imbalance between oxygen supply and demand to the myocardium


Classification• Acute coronary syndromes include ST-elevation MI (STEMI) Non ST-elevation MI ( NSTEMI) Unstable Angina• Cardiac markers in circulation

indicates myocardial infarction and help categorize MI and is a useful adjunct to diagnosis


History• Chest Pain- anterior precordium

tightness• Pain may radiate to jaw, neck and

epigastrium• Dyspnea- angina equivalent, poor LV

function• Nausea/abdominal pain with

posterior MI• Anxiety


History

• Nausea with and without vomiting• Diaphoresis or sweating• Syncope or near syncope• Elderly present with MS changes,

fatigue, syncope or weakness• As many as half of MI are clinically

silent


Physical

• The physical exam can often be unremarkable

• Hypertension• Hypotension• Acute valvular dysfunction may be

present• Rales• Neck vein distention


Physical

• Third heart sound may be present• A fourth heart sound poor LV

compliance• Dysrhythmias• Low grade fever


Causes

• Most frequent cause is rupture of an atherosclerotic lesion within coronary wall with subsequent spasm and thrombus formation

• Coronary artery vasospasm• Ventricular hypertrophy• Hypoxia• Coronary artery emboli


Causes

• Cocaine• Arteries• Coronary anomalies• Aortic dissection• Pediatrics Kawasaki disease, Takayasu

arteritis• Increased afterload which increases

myocardial demand


Risk factors for atherosclerosis

• Age• Male gender• Smoking• Hypercholesterolemia and triglyceridemia• Diabetes Mellitus• Poorly controlled hypertension• Type A personality


Risk factors for atherosclerosis

• Family History• Sedentary lifestyle


Differentials

• Acute coronary syndrome• Anxiety• Aortic stenosis• Asthma• Cholecystitis and biliary colic• Cholethiasis• COPD

5/98 MedSlides.com100

Differentials

• Aortic Dissection• Endocarditis• Esophagitis• Shock• Myocarditis• Pericarditis• Pulmonary embolism


Mechanisms of Myocardial damage

The severity of an MI is dependent of three factors

• The level of the occlusion in the coronary

• The length of time of the occlusion• The presence or absence of

collateral circulation


Cardiac Biomarkers

• Cardiac biomarkers are protein molecules released into the blood stream from damaged heart muscle

• Since ECG can be inconclusive , biomarkers are frequently used to evaluate for myocardial injury

• These biomarkers have a characteristic rise and fall pattern


Troponin T and I

• These isoforms are very specific for cardiac injury

• Preferred markers for detecting myocardial cell injury

• Rise 2-6 hours after injury Peak in 12-16 hours Stay elevated for 5-14 days


Creatinine Kinase ( CK-MB)

• Creatinine Kinase is found in heart muscle (MB), skeletal muscle (MM), and brain (BB)

• Increased in over 90% of myocardial infraction

• However, it can be increased in muscle trauma, physical exertion, post-op, convulsions, and other conditions


Creatine Kinase (MB)

• Time sequence after myocardial infarction Begins to rise 4-6 hours Peaks 24 hours returns to normal in 2 days• MB2 released from heart muscle and

converted to MB1.• A level of MB2 > or = 1 and a ratio of

MB2/MB1 > 1.5 indicates myocardial injury


Myoglobin• Damage to skeletal or cardiac muscle

release myoglobin into circulation• Time sequence after infarction Rises fast 2hours Peaks at 6-8 hours Returns to normal in 20-36 hours• Have false positives with skeletal

muscle injury and renal failure


Renal Failure and Renal Transplantation

• Diagnostic accuracy of serum markers of cardiac injury are altered in patients with renal failure

• Cardiac troponins decreased diagnostic sensitivity and specificity in patients receiving renal replacement therapy

• Current data show levels of troponin I are unaltered while levels of troponin T may be elevated


CBC

• CBC is indicated if anemia is suspected as precipitant

• Leukocytosis may be observed within several hours after myocardial injury and returns returns to levels within the reference range within one week


Chemistry Profile

• Potassium and magnesium levels should be monitored and corrected

• Creatinine levels must be considered before using contrast dye for coronary angiography and percutanous revascularization


C-reactive Protein (CRP)

• C- reactive protein is a marker of acute inflammation

• Patients without evidence of myocardial necrosis but with elevated CRP are at increased risk of an event


Chest X-Ray

• Chest radiography may provide clues to an alternative diagnosis ( aortic dissection or pneumothorax)

• Chest radiography also reveals complications of myocardial infarction such as heart failure


Echocardiography

• Use 2-dimentional and M mode echocardiography when evaluating overall ventricular function and wall motion abnormalities

• Echocardiography can also identify complications of MI ( eg. Valvular or pericardial effusion, VSD)


Electrocardiogram

• A normal ECG does not exclude ACS• High probability include ST segment

elevation in two contiguous leads or presence of q waves

• Intermediate probability ST depression

• T wave inversions are less specific


Localization of MI

• ST elevation only• Inferior wall- II, III, aVF• Lateral wall_ I, aVL, V4-V6• Anteroseptal- V1-V3• Anterolateral- V1-V6• Right ventricular- RV4, RV5• Posterior- R/S ratio >1 in V1 and T

wave inversion


Ischemia & Infarction• Indications of an acute infarction

• Usually no ECG changes are seen in the first few minutes after occlusion• Appearance of tall narrow T-waves or ST-segment elevation

• 5 to 30 minutes post occlusion• A few hours later, the T-waves invert (ischemia)

• in an MI, the T-wave inversion is symmetrical an may persist for years• inverted T-waves without other indications are not diagnostic of an MI

• ST-segment elevation – indication of injury (although it may be reversible)• ST-elevation may also indicate transmural ischemia• usually the first definite sign of an infarction• may or may not be accompanied by T-wave inversion• 1mm or more in limb leads or 2mm or more in precordial leads

• differentiate between early repolarization or “J-point elevation”• the larger the ischemic area, the greater the ST displacement• ST elevation persisting for more than a few hours may indicate ventricular aneurysm• ST depression may be seen in reciprocal leads.


Ischemia & InfarctionAcute anteriolateral MI


Ischemia & Infarction• Biomarkers in an MI:

Days after MI Onset

Mul

tiple

s of

the

AM

I cut

off L

imit

0 1 2 3 4 5 6 7 8

Myoglobin

Cardiac Troponin

CK-MB

Cardiac Troponin after unstable angina

0

1

2

5

10

20

50

AMI decision limit

Upper normal limit


Ischemia & Infarction• Indications of an old or “resolved” infarction

• Significant Q-waves where they don’t belong • (nonsignificant Q’s may be found in V1 alone, III alone, and AVR)

• These Q’s represent necrotic tissue r main vector directed away from that lead• In general, for Q’s to be significant:

• must be at least .03 - .04 seconds wide• must be at least 1/3rd of the height of the R-wave in the QRS complex• must be “new” (not seen in a previous tracing)• in most cases, they must be in more than one lead

• Speculating as to the location of the infarct:• Significant Q’s in II, III, AVF – old inferior infarction• Significant Q’s in I, V1, V2, V3 – old anterior infarction• Significant Q’s in V4, V5, V6 – old lateral infarction

• Infaract criteria (as well as all other voltage related diagnosis) may be invalid in the presence of BBB


Old Inferior MI

Ischemia & Infarction


Therapy

The goals of therapy in AMI are the expedient restoration of normal coronary flow and the maximum salvage of functional myocardium


Antiplatelet Agents• Aspirin at lease 160mg immediately • Interferes with function of

cyclooxygenase and inhibits the formation of thromboxane

• ASA alone has one of the greatest impact on the reduction of MI mortality.

• Clopidogrel, ticlopidine, have not been shown in any large scal trail to be superior to Aspirin in acute MI


Supplemental Oxygen

• Because MI impairs the circulatory function of the heart, oxygen extraction by the heart and other tissues may be diminished

• Supplemental oxygen should be administered to patient with symptoms and or signs of pulmonary edema or pulse oximetry readings less than 90%.


Nitrates• IV nitrates to all patients with MI and

congestive heart failure, persistent ischemia, hypertension, or large anterior wall MI

• Primary benefit vasodilator effect• Metabolized to nitric oxide in the

vascular endothelium, relaxes endothelium

• Vasodilatation reduces myocardial oxygen demand and preload and afterload


Beta-blockers

• Recommended within 12 hours of MI symptoms and continued indefinitely

• Reduces Myocardial mortality by decreasing arrythmogenic death

• Decrease the rate and force of myocardial contraction and decreases overall oxygen demand


Unfractionated heparin

• Forms a chemical complex with antithrombin III inactivates both free thrombin and factor Xa

• Recommended in patients with MI who undergo PTCA or fibrinolytic therapy with alteplase


Low-molecular weight heparin• Direct activity against factors Xa and

IIa• Proven to be effective in treating ACS

that are characterized by unstable angina or non ST- elevation MI

• Their fixed doses are easy to administer and laboratory testing to measure their therapeutic effect is not necessary makes them attractive alternative of un-fractionated heparin


Thrombolytics• Indicated with MI and ST segment

elevation greater than 0.1mV in 2 contiguous ECG leads, or new onset LBBB, who present less than 12 hours but not more than 24 hours after symptom onset

• The most critical variable in achieving successful fibrinolysis is time form symptom onset to drug administration


Thrombolytics• As a class the plasminogen activators

have been shown to restore coronary blood flow in 50-80% of patients

• Contraindication active intracranial bleeding, CVA 2months, CNS neoplasm, HTN, coagulopathy

• Retaplase slightly higher angiographic patency but did not translate into survival benefit

• Intracranial bleed risk major drawback


Glycoprotein IIb/IIIa Antagonists

• Potent inhibitors of platelet aggregation

• Use during PCI and in patients with high risk features ACS have been shown to reduce the composite end points of death, reinfraction and the need for target lesion


Surgical Revascularization• Emergent or surgical

revascularization in setting of failed PTCA in patients with hemodynamic instability and coronary anatomy amendable to surgical grafting

• Also indicated of mechanical complications of MI including VSD, free wall rupture, or acute MR

• Carries a higher risk of perioperative mortality than elective CABG


Lipid Management• All post MI patients should be on

AMA step II diet ( < 7% of calories from saturated fats)

• Post MI patients with LDL > 100 mg/dl are recommended to be on drug therapy to try to lower levels to <100 mg/dl

• Recent data indicate that all MI patients should be on statin therapy, regardless of lipid levels or diet


Long term Medications

• Most oral medications instituted in the hospital at the time of MI are continued long term

• Aspirin, beta blockers and statin are continued indefinitely

• ACEI indefinitely in patients with CHF, ejection fraction <.40, hypertension, or diabetes


T H A N K Y O UT H A N K Y O U


References• Acute Coronary Syndromes: Unstable angina and Non-Q-wave MI.

Pierre Theroux and Valentin Fuster. Circulation 1998:97:1195-1206• Aspirin, heparin, or both to treat acute unstable angina.

TherouxP, et al. N Eng J Med. 1988;319:1105-1111.• Risk of myocardial infarction and death during treatment with low dose

aspirin and intravenous heparin in men with unstable coronary disease. The RISC Group. Lancet 1990;336:827-830.

• Protective effects of aspirin against myocardial infarction and death in men with unstable angina.Lewis HD, et al. N Eng J Med. 1983;309:396-403.

• Aspirin, sulfinpyrazone, or both in unstable angina.Cairns JA, et al. N Eng J Med. 1985;313:1369-1375.


References• Antiplatelet treatment with ticlopidine in unstable angina: a controlled

multicenter clinical trial. Balsano F, et al. Circulation 1990;82:17-26.

• A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events.CAPRIE Steering Committee. Lancet 1996;348:1329-1339.

• Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users.Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation 1994;89;81-88

• Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patient s with unstable angina.Oler S, et al. JAMA 1996;276:811-815


References• Low molecular weight heparin versus unfractionated heparin for

unstable angina and non-Q wave myocardial infarction. Efficacy and Safety of Subcutaneous Enoxaparin in non-Q-Wave Coronary Events Study Group. N Engl J Med 1997;337:447-452.

• A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. PRISM - The Platelet Receptor Inhibition in Ischemic Syndrome Management Study Invistigators N Engl J Med 1998;338:1498-505

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