Atherosclerosis, Coronary Heart Disease, Acute Coronary Syndrome and MI 11-11-11 Dr.

Divinigracia
Sources include lecture notes and 2012 trans. Please supplement this trans with Harrisons because this trans is following the lecture of Dr. Divinigracia and the book organizes this subject differently. OBJECTIVES: 1. Understand the importance of Coronary Artery Disease (CAD) 2. Understand the concepts behind the development of atherosclerosis, arteriosclerosis, and atherthrombosis 3. Understand the pathophysiology of atherosclerotic CAD 4. Know the risk factors leading to the development of CA 5. Know the clinical presentation and available treatments of CAD THE IMPORTANCE of CORONARY ARTERY DISEASE (CAD) CAD is the Most common cause of heart disease worldwide, in developed and developing countries. In a statistic taken from a study in 2004, Heart Disease and Diseases of the Vascular System comprise 30% of the causes of mortality in the Philippines from 1999-2004, making it the most common cause of death in country. This number continues to rise every year. WHO statistic (2012) rates ischemic heart disease (due to arteriolosclerosis) as the #1 and #2 causes of death worldwide. DEFINITIONS and TERMS 1.ATHEROSCLEROSISIt is a generalized and a progressive process, and can describe the hardening of any artery in the body (not just confined to the heart)

3.ATHEROTHROMBOSIS Atherothrombosis Formation of a clot or thormbus. If an atheroma ruptures, the contents can come in contact with the circulatiog blood and may form a thrombus. Combination of atherosclerosis & thrombosis. Usually gives rise to an acute coronary syndrome or attack. 4.ISCHEMIC VASCULAR DISEASES Results from ischemia due to arteriosclerosis. The most common forms are Myocardial Infarction (heart attacks ) or Cerebral infarctions (strokes/brain attack). Less common forms include peripheral vascular disease, PVD or PAD or PAO. Involves the peripheral vascular tree of the legs and arms. Results in ischemic symptoms (claudification). Chronic Ischemic Heart Disease- may involve the smaller vessels and microcirculation, gives rise to progressive myocardial disease or ischemic cardio myopathies. PATHOGENESIS of ATHEROSCLEROSIS 3 important elements that give rise to Atherosclerosis 1.Lipids 2.Inflammation 3.Thrombosis **Subendothelial layer is the sight of the atheroma formation **Fatty streak- This is the initial lesion of atherosclerosis; Arise from focal increases in the content of lipoprotein within regions of the intima. Very little lipid accumulation, mostly accumulation of platelets and smooth muscle. Different theories of atherosclerosis (AT) *Common to both theories is that an insult to to the endothelium wall triggers the formation of the atheroma. The theories differ in how the atheroma is formed. 1.Insudation hypothesis/Lipid Theory/Response to Injury theory Insudation The accumulation of substances derived from the blood. Normally the vessel endothelium is impenetrable. But when an insult occurs to the endothelium, the endothelium becomes dysfunctional and it releases substances that attracts cellular elements and an atheroma is formed. AT is a form of cellular proliferation of the intimal cells resulting from increased imbibing of lipids from the blood. 2.Encrustation hypothesis/thrombogenic theory

Athere means gruel Skleros means hard

A vascular form of dse. affecting primarily the intima of the large and medium sized muscular arteries (Aorta, carotid, femoral, iliac, and abdominal arteries).
Refers to the hardening of arteries due to deposition of gruel like substance mixed with other cellular elements from the blood vessel wall resulting in ischemia. The lesion is usually called an

artheroma (looks like a hump). The atheroma is characterized as a fibrofatty lesion and is made up of 2 elements, the soft lipid layer and a fibromuscular layer (made up of connective tissue and cellular elements). A vessel affected by atherosclerosis looks like a vessel with humps and bumps.

Atherosclerosis is often used interchangeably with arteriosclerosis, but when referring to hardening of the arteries due to specifically an atheroma, the term Atherosclerosis is more specific and should be used.

2.ARTERIOSCLEROSIS

intima of smaller muscular arteries and arterioles (almost at a microscopic level).

Arteria meaning artery A vascular form of dse. affecting the

It is a broader term that refers to the hardening of the arteries due to ANY insult such as lipid deposition, fibrosis or inflammatory disease.

1 of 11 Page

Atheroma is formed by of encrustation of the arterial wall from the components of the blood forming thrombi composed of platelets, fibrin and leukocytes. Again the common denominator is that something happens to the endothelial wall which leads to the formation of the thrombi, which leads to encrustation of the arterial wall and ultimately an atheroma formation.

Types of Plaques/Atheroma 1.Vulnerable Plaque A thin fibrous cap, infiltrates of Inflammatory cells, and lipid rich core make this plaque vulnerable to rupture and cause a thormbosis. Associated with sudden death. 2.Stable Plaque A Thick fibrous cap, less inflammation, and a small lipid core make this plaque less vulnerable to rupture. Associated with a slower progression. Patient has time to seek consult and begin a treatment plan. Types of Thrombi (after the atheroma ruptures and causes a clot and occlusion) 1.NON-OCCLUSIVE THROMBUS (does not occlude lumen of vessel) Can be termed as Unstable angina Non-Q-wave MI, depending on amount of plaque deposited which depends on the fibrinolytic system Factors limiting thrombosis Minor plaque disruption High flow Low thrombotic tendency (DM px have high thrombotic tendency) 2.OCCLUSIVE THROMBUS Q-wave MI Sudden death Factors favoring thrombosis Major plaque disruption Low flow or vasospasm Thrombotic tendency

***From 2012 Trans**** Endothelial released substances that contribute to the formation of the atheroma include

1.ENDOTHELIAL DERIVED GROWTH FACTOR: regulates proliferation of muscle cells and endothelial cells; overproduction results to overgrowth and narrowing of blood vessel; contributes to ATHEROMA formation which narrows the lumen. 2.VASOACTIVE SUBSTANCES: a)Vasoconstrictors: ENDOTHELIN & ANGIOTENSIN II: Constrict blood vessels that may produce hypertension; b)Vasodilators: NITRIC OXIDE (NO): Causes dilatation and balances the action of endothelin, both contributing to the normal vasculature tone. Need for increased blood flow sensed by endothelium more NO production dilatation inc. blood flow inc. nutrition to cells. If there is Endothelial dysfunction then less NO is produced, more endothelin & angiotensin II is released and this leads to vasoconstriction.

CLINICAL MANIFESTATIONS OF ATHEROCLEROSIS The disease may manifest as different ischemic vascular diseases: 1.Coronary Heart Disease
Stable Angina Acute MI Sudden death Unstable angina 2.Cerebrovascular disease Stroke Transient Ischemic Attacks 3.Peripheral arterial disease Intermittent claudication Increased risk of death from heart attack and stroke THE RISK FACTORS in DEVELOPING CAH/CAD/ARTERIOSCLEROSIS **Coronary Heart Disease: A mostly symptomless disease continuum beginning in childhood until its late Some of the common RISK FACTORS for heart disease Smoking High blood pressure o Hypertension doubles the risk of cardiovascular diseases High cholesterol o Abnormalities in plasma lipoproteins and derangements in lipid metabolism Diabetes o LDL particles of diabetics tend to be smaller and denser, and therefore more atherogenic Family history of heart disease 2 of 11 |Page

Once and atheroma is formed it has the potential to rupture and cause a thrombus which could obstruct the vessel and cause an acute coronary syndrome. Growth of an atheroma is based on the accumlation of lipid material. Time Sequence of an Atheroma From the 3rd decade on more fibrous tissue is formed on the vessel wall, 4th decade on more lipid is deposited and the atheroma may become more of a concern. It can become a complicated lesion and cause obstruction to the vessel. Patients only become symptomatic when the atheroma or thrombus occludes 75% of the vessel lumen.

 Peripheral artery disease Obesity LIFESTYLE risk factors Lack of exercise High-fat diet Emotional stress Type A personality (aggressive, impatient, competitive) MODIFIABLE risk factors Dyslipidemia o Raised LDL o Low HDL o Raised TGs Smoking HPN DM Obesity Dietary mellitus Obesity Dietary factors Thrombogenic factors (prone to develop clots) Sedentary lifestyle NON-MODIFIABLE risk factors Age Sex o There is excess coronary risk in men compared with premenopausal women. After menopause, however, coronary risk accelerates in women. estrogen plays a role Family history of premature CHD MAJOR RISK FACTORS for HEART ATTACK *Those that can be controlled, treated or modified Tobacco smoke High blood pressure High blood cholesterol levels Physical inactivity Obesity and overweight DM ****from 2012 Trans***** Atherosclerotic Risk Factors can be grouped into 2 categories: 1.modifiable (by lifestyle changes) 2.pharmacotherapy) or nonmodifiable (family history, age and gender) Risk Factors 1.Lipid disorders *The ATP III (National Cholesterol Education Project Adult Treatment Panel III) recommends lipid screening in all adults >20 y.o every five years *To achieve LDL goal, therapeutic lifestyle changes (TLC) are done (diet, exercise) *A >30 mg/dL excess from an age group's goal LDL level merits consideration for drug therapy 2.DM, Insulin Resistance, Metabolic Syndrome *Most patients with DM die of atherosclerosis and its complications *DM accelerates atherosclerosis and is a coronary heart disease equivalent, meaning if you have DM, you are considered to have arteriosclerosis until proven otherwise. *Diabetic dyslipidemia increases CV risk

*LDL particles in DM patients tend to be smaller and denser and more atherogenic, even if LDL levels are normal. 3. X Male Gender / Women in Postmenopausal State *Men are more at risk of having CVD than premenopausal women *Coronary risk accelerates after menopause *In premenopausal women, HDL levels are relatively higher than in men. Estrogen therapy lowers LDL cholesterol and raises HDL cholesterol. Theoretically this should lower risk in postmenopausal women but studies have shown that there was an increased incidence of thromboembolism. 4.Dysregulated Coagulation or Fibrinolysis *Related to formation of thrombosis, which causes the gravest complication of atherosclerosis *Imbalanced coagulation or fibrinolysis may cause instability of an arterial thrombusembolism 5.Homocysteine * Hyperhomocysteinemia may be related to coronary events 6.Inflammation *Increased c-reactive protein (CRP) predicts risk of MI and outcomes of ACS patients *Elevated fibrinogen and CRP reflects overall atherosclerotic burden MAJOR CHD RISK FACTORS other than LDL-C according to NCEP ATP-III POSITIVE risk factors (promote arteriosclerosis) Age Male >45 Female >55 Family Hx of CHD o 1st-degree relative with MI or sudden cardiac death o Male relative <age 55 o Female relative <age 65 Current cigarette smoking Hypertension: BP140/90 mmHg or an antihypertensive meds Low HDL-C: <40 mg/dL Diabetes is a CHD equivalent identifying patient as high risk NEGATIVE risk factors (prevents the development of arteriosclerosis) High HDL-C: if HDL is > or = 60 mg/dL, one risk factor can be eliminated CHD RISK EQUIVALENTS When the risk for a major coronary event equals an established CHD. So even if you don't have a sx, you could have a risk equivalent which would be equal to having a CHD. o Using the Framingham Scoring system, if you have a 10-year risk for hard CHD (MI or coronary death) that is >20%, then you have a CHD equivalent. This means that even if you don't have the overt dse, you are at risk of developing CHD.

3 of 11 |Page

**Hard CHD = myocardial infarction or coronary death ***Framingham Scoring System: Determining 10-year (short term) risk for developing CHD is carried out using Framingham risk scoring. The risk factors included in the Framingham calculation are age, total cholesterol, HDL cholesterol, systolic blood pressure, treatment for hypertension, and cigarette smoking. Because of a larger database, Framingham estimates are more robust for total cholesterol than for LDL cholesterol. Note, however, that LDL cholesterol remains the primary target of therapy. The Framingham risk score gives estimates for hard CHD which includes myocardial infarction and coronary death. DIABETES AS A CHD RISK EQUIVALENT 10-year risk for CHD = 20% High mortality with established CHD o High mortality with acute MI o High mortality post acute MI

The table above shows a schematic diagram of the risk factors of atherosclerosis and the other contributors to the development of atherosclerosis (Oxidative stress, endothelial dysfunction, inflammation,Thrombosis, and activation of the RAAS (vasconstriction)). INFLAMMATION as a risk factor for developing ATHEROSCLEROSIS Inflammation may determine plaque stability. It may lead to an unstable plaque which has increased leukocytic infiltrates and is more prone to rupturing .T cells, macrophages predominate at rupture sites. Cytokines and metalloproteinases influence both stability and degradation of the fibrous cap. Markers of inflammation like CRP correlate with coronary risk. The higher the level of CRP, the higher the coronary risk Lipid lowering may reduce plaque inflammation Lipid-lowering therapy (e.g. statins) reduces coronary events in part by mutating the inflammatory aspects of the pathogenesis of atherosclerosis. Effects of lipid therapy include: Decreases macrophage number Decreases expression of collagenolytic enzymes (MMP-1) Increases interstitial collagen Decreases expression of E-selectin Reduces calcium deposition By modulating lipid formation, the stability of a plaque can be maintained thus reducing the risk of coronary dse. C-Reactive Protein and h-CRP as a predictor of cardiovascular inflammation events CRP is an acute-phase protein produced by the liver in response to cytokine production (IL-6, IL-1, tumor necrosis factor) during tissue injury, inflammation or infection. It is a marker of inflammation High-sensitivity CRP (h-CRP) is at the lower spectrum of CRP, and their levels are more specific for cardiovascular inflammation events and can assess the risk of cardiovascular events. Potential Mechanisms Linking h-CRP to Atherothrombosis Cigarette smoking o Smokers have higher hs-CRP because smoking causes inflammation to the vascular wall. 4 of 11 |Page

The table Type 2 DM and CHD: 7-year incidence of fatal and non-fatal MI shows that a patient who is diabetic with no previous history of MI has the same risk of having an MI as a non-diabetic patient with history of MI (about 20%) . A diabetic patient with previous MI has a 45% chance of developing a repeat MI within 7 years.

The table Risk Factors and Association with AMI shows that Dyslipedemia has the most influence on the risk of developing AMI. Thus therapy is geared towards lowering LDL, TGs, and increasing HDLs. Eating fruits and vegetables, exercise, and moderate alcohol intake have a negative effect on developing AMI.

It is a possible Innocent bystander o Just an acute phase response marker It could be a Cytokine surrogate o IL-6, TNF-a, IL-1B Direct effect of CRP include o Innate immunity o Complement activation o CAM induction It could be a marker for prior infection o Chlamydia, H. pylori, CMV (one theory is that an infectious dse which is initiated by inflammation could lead to the initiation of atherosclerosis. The theory was studied testing the influence of chlamydia and pneumonia on atherosclerosis and results were negative. These infxns do not lead to artherosclerosis)

The graph below shows the total cholesterol distribution of ppl w/ or w/o CHD. 35% of CHD occurs in ppl with TC <200

The above table hs-CRP and risk of future stroke in apparently healthy men shows that the higher your hs-CRP level, the higher your risk for Stroke.

The above graph of The Framingham Heart Study, shows the association that lower cholesterol levels are associated with lower CHD risk and that higher total cholesterol levels are associated with higher risks of CHD.

In the above graph, Clinical Application of hsCRP for CV risk prediction shows that a patient with hs-CRP between 3mg/l and 10mg/l has a high risk for a cardiovascular event. A hs-CRP level above 10mg/L is due to an acute phase response to infection, arthritis, etc. A value of 10mg/Lshould be ignored and the test repeated in 3 weeks. LDL Cholesterol as a Risk Factor for CHD LDL levels are strongly associated with atherosclerosis and CHD events 10% increase results in a 20% increase in CHD risk Most patients with elevated LDL are untreated Only 4.5 million out of 28.4 million treated But 35% of CHD occurs in ppl with TC<200, so remember to always look at other risk factors

The above graph of The MRFIT study, shows the same association as The Framingham Study that lower cholesterol levels are associated with lower CHD risk and that higher total cholesterol levels are associated with higher risks of CHD. Effects of HDL Cholesterol on Total Cholesterol levels and CHD Risk HDL, the good cholesterol reverses cholesterol transport and provides an independent pathway for lipid removal from an atheroma, allowing hepatocytes to metabolize the sterol to bile acids that can be excreted. Low HDL cholesterol is a strong independent predictor of CHD The lower the HDL cholesterol level the higher the risk for atherosclerosis and CHD Low HDL is defined categorically as a level <40 mg/dL (a change from < 35 mg/dL in ATP II) 5 of 11 |Page

Target HDL level is >60mg/dl and o alcohol raises HDL Levels

HDL cholesterol tends to be low when triglycerides are high Triglycerides as a risk factor for CHD Recent data suggest that elevated triglycerides are an independent risk factor for CHD Normal triglyceride levels: <150 mg/dL Borderline-high triglycerides: 150 to 199 mg/dL High triglycerides: 200 to 499 mg/dL Very High: > or = 500 mg/dL o But having a high TG level (>500), the bigger concern is a risk of pancreatitis and not CHD. Non-HDL Cholesterol as a risk factor Non-HDL Cholesterol = TC HDL Cholesterol Non-HDL-C includes all atherogenic lipoprotein particles including LDL-C, Lp(a), IDL-C, and VLDL-C, and can be a better predictor of CHD vs. LDL levels Non-HDL Cholesterol is a good secondary target of therapy when serum TG > or = 200 mg/dL New non-HDL-C goal for patients with elevated TG is LDL-C goal +30 mg/dL NEW CONCEPTS FOR ATP (Adult Treatment Panel for Cholesterol) III The Inclusion of more patients in the high-risk categories (a greater focus on diabetes, non-coronary atherosclerosis, multiple risk factors) improves the ability to identify those at risk for developing CHD Incorporating global risk assessments in the guidelines helps improve identifying those at risk Checking the complete fasting lipoprotein profile is recommended (fasting for at least 10-12 hours to get a more accurate basal level) Definition of low HDL-C is now < 40 mg/dL for males and female Triglyceride cut point lowered from 200 mg/dL to 150 mg/dL Modified Treatment Guidelines Optimal Goal for ppl with high risk: o LDL-C < 100 mg/dL o before it was <130mg/dl but with the advent of more potent lipid lower drugs and increased risk, it has been recommended to be at 100mg/dl Goal for ppl with CHD and those with a CHD risk equivalent: o LDL-C <100 mg/dL

CHD Risk Equivalent s (10-year risk > 20%) 2 + Risk Factors (10-year risk < or = 20%) 0 1 Risk Factor

129: drug optional)

<130

>=130

<160

>=160

10-year risk 10-20%: >=130 10-year risk <10%: >=160 >=190 (160189: LDL-Clowering drug optional)

-> The above grapgh Possible Relationship between LDL-C levels and CHD Risk shows that the benefit of lowering LDL-C is a curvillinear line. This means that more benefit from lowering LDLC is seen with higher LDL-C levels versus lower LDL-C levels:the lower the better with diminishing return. But recent studies show that the benefit of lowering LDL-is almost a straight line.

Goal for Patients with previous angioplasty, bypass, MI it should since you have been already established having CHD: o LDL-C <70mg/dl

LDL CHOLESTEROL GOALS FOR THERAPEUTIC LIFESTYLE CHANGES (TLC) and DRUG THERAPY ACCORDING TO NCEP ATP III Risk LDL-C LDL-C LDL-C Level Category Goal Level for (mg/dL) for Considerati initation on fo Drug of TLC Therapy (mg/dL) (mg/dL CHD or <100 >=100 >=130 (100-

The above grapg shows that a 1% decrease in LDL-C reduces the risk of CHD by 1% and a 1% increase in HDL-C reduces CHD risk by 3%. However, Total cholesterol 10mg increase = increase risk by 9-10% , TAG 1mmol = increase risk by 75%, and a 1mg HDL decrease = increases risk by 4% in females 5% in males CORONARY ARTERY DISEASE A story of a heart attack.. A normal artery has a clean, smooth internal lining that allows free flow of blood at any physical activity without symptoms. Cholesterol builds up on its wall gradually and may not produce significant impairment of 6 of 11 |Page

blood flow and therefore cause no symptoms even with exertion. Progressive growth of the cholesterol deposit(plaque) may restrict blood flow and may produce symptoms only on exertion (obstruction of the lumen = 75%). The plaque may rupture and a blood clot (thrombus) may cause total occlusion of the artery, cutting off blood supply to the heart muscles and may cause an acute heart attack (MI). CLINICAL CLASSIFICATION OF CHEST PAIN Not every chest pain is ischemic in nature 1.Typical angina (definite) 4 important characteristics to consider: 1)location (75% are on precordium.), 2)type of pain and onset 3) what precipitate and 4) relieves it

Substernal chest discomfort with a characteristic quality and duration, that is squeezing, compressing or heaviness. Develops gradually with increasing exertion (does not happen suddenly bec angina develops when there is discrepancy between supply and demand). Provoked by exertion or emotional stress, and relieved by rest or
nitroglycerine. Atypical angina (probable) Meets only 2 of the above criteria Non-cardiac chest pain Meets only one or none of the above UNSTABLE ANGINA THREE PRINCIPAL PRESENTATIONS Rest angina (recent onset rest angina) Angina occurring at rest and usually prolonged >20 minutes occurring within a week of presentation New onset angina Angina of at least CCSC (Candian classification) III severity with onset within 2 months of initial presentation Increasing angina (crescendo) Previously diagnosed angina that is distinctly more frequent, longer in duration or lower in threshold (i.e. increased by at least one CCSC class within 2 months of initial presentation to at least CCSC Class III severity)=less exercise/exertion precipitates the chest pain. THE Sequence of Unstable Angina The atheroma/plaque ruptures and forms a thrombosis, which causes symptoms of an Acute Coronary Syndrome (ACS). Pathological studies shown that most heart attacks are not due to the progressive obstruction of a vessel, but 75% showed that it is due to a ruptured plaque. SIGNS AND SYMPTOMS OF A HEART ATTACK Chest pain o Described as heavy, squeezing and crushing; also stabbing or burning o Similar in character to the discomfort of angina pectoris but commonly occurs at rest, more severe and lasts longer o Usually involves the center portion of the chest and/or the epigastrium, sometimes radiates to the arms; also radiates to the abdomen, back, lower jaw and neck

Diaphoresis (abnormal sweating) Nausea and vomiting Shortness of breath Atypical chest pain (diabetics) Palpitations o A feeling of anxiety and sense of impending doom is usually present. How do we work these patients up? 1.Evaluate the lipid profile. 2. Evaluate the Electrocardiogram (ECG) Can demonstrate ischemic changes. However, a Normal ECG does not rule out Angina, because Angina is a clinical diagnosis and is not diagnosed by ECG. 3.If the ECG is normal, then perform a Stress/Treadmill test to provoke ischemia in the patient. Put patient on a treadmill, increasing the workload of the heart. If the vessels are not patent enough, symptoms of Angina will occur. 4.Perform Echocardiogram to see if the muscles are contracting normally, to see if there are any abnormalities with the myocardium 5. Radionucleide Scanning, can find out specifically what part of the heart is not receiving blood. 6. CT Scan, and MRI to see the viability of the tissue in relation to the blood flow. 7.CORONARY ANGIOGRAM Objectively, it is the Gold Standard of diagnostic tests. It can locate the obstruction and determine the degree of obstruction. Procedure: A catheter is inserted into the femoral artery and threaded into the root of the aorta and a dye is injected into the coronary vessels to find out which vessels are obstructed. 8.Intravascular Ultrasound (IVUS) A very small ultrasound, inserted into the coronary vessel. The advantage of IVUS is that you can see inside the vessel and see the atherosclerosis inside the vessel. But not done routinely bc it is expensive and is riskier than doing a coronary angiogram. TREATMENT PNEUMONIC: 10 most important elements of stable angina management(read about this in the book) A o Aspirin o Anti-anginals B o Beta-blockers o Blood pressure C o Cholesterol lowering Drugs o Cessation of Cigarette Smoking D o Diet o Diabetes, control DM E o Education o Exercise For Patients Needing more than just medications Not all people may respond well to medications, in these cases, the goal of therapy is to re-open the vessel, regain patency of the vessel. 1.Revascularization: PTCA (Percutaneous Transluminal Coronary Angioplasty) , a non surgical procedure Balloon dilatation with coronary stenting is usually done to revascularise myocardium in patients with symptomatic IHD. 7 of 11 |Page

Most common indication is angina pectoris with ischaemia during stress test despite medical therapy. 95% success rate. Recurrence may occur in ~20% of cases and is more common in patients with DM, with small-calibre arteries, incomplete dilation of stenosis, occluded vessels, obstructed vein grafts, dilation of ledt anterior descending coronary artery, and stenoses containing thrombi 2. CABG (Coronary Artery Bypass Grafting) If above is not possible, Anastomosis of one or both internal mammary arteries or a radial artery to the coronary artery distal to the obstructive lesion. The ideal candidate is male, <80 years of age, has no other complicating disease, has troublesome or disabling angina that is not adequately controlled by medical therapy and has severe stenoses of two or three epicardial coronary arteries. This procedure is lasts longer and is more effective than a stent Saphenous vein or Internal mammary artery may be used as a graft ACC/AHA Practice Guidelines for Management of Patients with ST Elevation MI(CHD) Smoking: Complete cessation Blood Pressure: <140/90 mmHg or <130/80 mmHg if chronic kidney disease or diabetes Physical activity: minimum 30 minutes 3-4 days per weekly optional daily Lipid management: o Primary goal is to keep LDL-C <100 mg/dL o TG < 200 mg/dL, Weight management BMI 18.5 to 24.9 kg/m2; WaistHip ratio, F=0.7, M=0.9 (level of umbilicus) Diabetes management: HbA1c <7 Secondary Prevention Medications and Measures Treatment Continue PostACS (acute coronary syndrome) Aspirin, ACE Indefinitely inhibitor Beta Blocker Indefinitely, unless contraindicated Cholesterol-lowering Indefinitely drug (Statin) Drugs for ischemia As needed in events: Nitrates, Selected Patients trimetazidine, ivabradin Others Aldosterone Antagonist Thienopyridine Post-PCI and possibly all THE ACUTE CORONARY SYNDROME Acute ischemic chest pain (discomfort) at rest or on minimal exertion or emotion (2 x 5 minute episodes or 1 episode > 10 minutes), AND

evidence of underlying coronary artery disease (at least one of the following) ECG: ST segment depression, T wave inversion or transient ST elevation Enzyme elevation: Troponin I or T, CK or CK-MB Evidence of coronary artery disease on angiography or perfusion scanning.

The above slide shows the formation of ACS. The basic element is plaque disruption/fissure/erosion which leads to thrombus formation which can lead to different outcomes such as 1)UA= unstable angina that later becomes stable 2)NQMI=not manifested by a Q wave MI which can be partial or incomplete obstruction or 3)STEMI(ST elevation Myocardial Infarction)= complete obstruction manifested as a ST elevation on the ECG. Because the ST segment is hallmark to the Injury we can term the following outcomes as: Non-ST Segment Elevation ACS (outcomes 1 and 2) and STE-MI (outcome 3). NSTE has a different treatment and management as STE-MI or STE ACS. PATHOPHYSIOLOGY OF ACS: Disrupted Plaque Sequence: Plaque ruptures and its contnets come in contact with the blood and forms a thrombosis. The thrombosis occludes the vessel and depending on the size of the thrombus, it can be labeled as a unstable angina,Non-STEMI ACS or STEMI ACS INITIAL LABS Immediate ECG ECG is sole test required to select patients for emergency reperfusion, whether an ST elevation or not Blood tests Serum Trop I or T levels ( or CK-MB if trop is not available) Most often used is Serum trop I, bc it is highly sensitive and specific and can be obtained rapidly (15-20mins) Full blood count Serum creatinine (eGFR) and electrolyte levels Serum creatine kinase (CK) levels if creatinine is elevated, you may have false positive results Serum lipid levels within 24 hours Blood glucose level Chest X-ray 8 of 11 |Page

Useful, but should not delay reperfusion treatment (does not tell you if px is with ACS only enlarged heart or Heart failure)

CARDIAC BIOMARKERS Troponin level (I or T) o The preferred biochemical markers for MI o May remain elevated for 7-10 days after STEMI Should be tested on arrival No need to repeat if positive (will remain positive for the next seven days) If a patient is initially negative, then repeat after 8 hours. If it is negative, then chances are the px has not had a ACS/MI and the px may be discharged) Do serial troponin measurements in patients with NSTEACS suspected to be at high risk CK-MB level (second best marker) Measure in all patients with an ACS if troponin assay is not available o It is not as specific as Troponin, but it is more specific vs Total CK) o Not present in significant concentrations in extracardiac tissues and therefore considerably more specific than Total CK Total CK level (if no other assays are availablecheck the level of Total CK) Total CK is not specific for MI, but Serial measurements performed for 48 hours in patients with MI and can be remeasured to confirm a second event if reinfarction is suspected. Rises within 4-8 hours and generally returns to normal by 48 72 From Harrisons Creatine Phosphokinase (CK) rises within 48 hrs and generally returns to normal by 4872 hrs. An important drawback of total CK measurement is its lack of specificity for STEMI, as CK may be elevated with skeletal muscle disease or trauma, including intramuscular injection. The MB isoenzyme of CK has the advantage over total CK that it is not present in significant concentrations in extracardiac tissue and therefore is considerably more specific.

Above slide shows examples of ST segment depression in graphs A and B. Graph C shows a T-wave inversion. This is classified as a NSTEMI, non-ST segment elevation MI.

Top ECG shows a ST segment elevation in relation to the baseline. Bottom ECG shows a depressed ST elevation in relation to the baseline.

Analyzing the ECG Analyzing ECG can help classify your patients condition as UA, High risk patient, or STEMI. It is important to identify because each treatment and management is different. a)Elevated ST segment = ST Elevation Miocardial Infarction (STEMI) b)Depressed ST Segment= patient is at high Risk for ischemia c)No changes=Unstable Angina (UA) Try to classify patients with acute ischemic chest pain into 1 of the 3 groups within 10 minutes using ECG.

The above ECG shows ST segment elevation in leads II, III, and AVF. This suggests that the patient has had an Acute Myocardial Infarction located in the Inferior wall of the heart. The Use of Biomarkers to help diagnose ACS If the ECG reading is inconclusive or normal, then use the Biomarkers to help diagnose your patient. (a normal ECG doe not mean your patient did not have a acute coronary event). In the early stages of an MI, biomarker levels are normal because there is minimal to no myocardial necrosis. 9 of 11 |Page

Once the extent of myocardial necrosis increases, then the biomarker levels increase too. If your patient has had an established Acute MI, then all biomarkers are abnormal and elevated. So for those patients who have normal troponin levels, repeat the test in 8 hours. If they remain normal, then no MI has occurred and you may send the patient home.

NSTEMI). If the second test is negative then the patient is calssified as Low risk (Dx: Unstable Angina). Treatment is either invasive or noninvasive. DIAGNOSIS AND RISK STRATIFICATION 1st step: initial evaluation Quality and character of the chest pain (hx) Assessment of likelihood of CAD (hx and pe) ECG (looking for ST elevation or other abnormalities) 2nd step: Validation and Risk Assessment Biochemistry(test your biomarkers) Responsiveness to sublinqual treatment (nitroglycerine ) ECG (repeat, continuous monitoring) Echocardiography, MRI, CTS Risk scoring using the APACHE scoring TREATMENT 3rd step: Anti-ischemic Management NTG (nitroglycerine) o Up to 3 doses of 0.4 mg of sublingual nitroglycerin administered at about 5minute intervals o Diminish/abolish chest discomfort, decrease myocardial demand (by lowering preload) and increasing myocardial oxygen supply (by dilating infarct-related coronary vessels or collateral vessels Morphine o Affective analgesic for the pain associated with STEMI o AE: diaphoresis, nausea, bradycardia, advanced degrees of heart block Beta-blockers o Control pain by diminishing oxygen demand o Reduce the risk of reinfarction and ventricular fibrillation o Metoprolol, 5 mg every 2 5 minutes for a total of 3 doses Oxygen 4th step: Decide if Invasive Management is needed Emergency angioplasty or emergency coronary bypass surgery Early surgical management (wait for 1-2 days before performing surgery) No surgery/elective surgery/or no invasive management 5th step: Decide whether to Revascularize When ST-segment elevation of at least 2 mm in two contiguous precordial leads and 1 mm in two adjacent limb leads is present, a patient should be considered a candidate for reperfusion therapy. Reperfusion, either pharmacologically (by fibrinolysis) or by PCI, accelerates the opening of infarct-related arteries in those patients in whom spontaneous fibrinolysis ultimately would have occurred and also greatly increases the number of patients in whom restoration of flow in the infarctrelated artery is accomplished. 6th step: Long-term management Rehabilitation 10 of 11 |Page

The above graph shows the Biomarkers associated with STEMI. Troponin rises the earliest (within 2 hours and remains elevated for a 7 days). CKMB rises early and begins to decrease after 24 hours. Testing for CKMB every day can establish if the patient has had a repeated attack.

The above slide shows the flow chart of management for a patient presenting with chest pain. Once admitted, obtain an ECG to see how the heart is functioning. If ECG readings are confirmatory for an STEMI (ST segment elevation), and enzymes are elevated,then patient is classified as having a STEMI and treatment is reperfusion(Angioplasty or Coronary By-Pass surgery). If ECG findings are inconclusive, then check the level of troponin. If levels are elevated then patient is classified as high risk (Dx:NSTEMI) and treatment is invasive. If troponin levels are negative then recheck levels after 8 hours. If the second test is positive then patient is classified as high risk (Dx:

Acute Management of ACS Possible ACS: Minimal tx is 2 tablets of Aspirin (antiplatelet, anticoagulant). Likely/Definite ACS: Aspirin + subcutaneous low moleculae weight Heparin (LMWH) or IV Unfractionated Warfarin + clopidogrel (anti-platelet, ok to combine with aspirin) LMWH is prefered High Risk or Definite ACS: Aspirin + subcutaneous low moleculae weight Heparin (LMWH) or IV Unfractionated Warfarin + IV platelet GP Iib/Iia antagonist + clopidogrel Platelet GP Iia/Aab antagonist is expensive EMERGENCY INVASIVE MANAGEMENT: After treating with medication decide if invasive management is needed (Angiopalsty or Bypass surgery) 1.Angiopalsty PCI, usually angioplasty and/or stenting without preceding fibrinolysis, referred to as primary PCI, is effective in restoring perfusion in STEMI when carried out on an emergency basis in the first few hours of MI. The fundamental indication for PCI is the presence of one or more coronary stenoses thought to be responsible for a clinical syndrome, that warrant revascularization, are approachable by catheterbased techniques, with risks and benefits that compare favorably with those of bypass surgery. 2.CORONARY ARTERY BYPASS Due to better technology, can perform surgery right away instead of having to wait 1 week or so. Bypass with an artery is preferred because it is long lasting and can give a better blood supply than a vein. END OF LECTURE TGM

11 of 11 |Page