ALU Chapter 13 Coronary Artery Disease

Ultimately, the prognosis in CAD will be directly related to the amount of damage that could occur, termed the

"myocardium at risk," should a coronary lesion undergo sudden and total occlusion. This, in turn, is linked to coronary stenosis severity and location.

Main Growth Mechanism: 1. Growth mainly by lipid addition 2. Increased smooth muscle and collagen increases 3. Thrombosis and or hematoma

1. Initial lesion-atheroma 2. Fibroatheroma 3. Complicated lesions

Clinical Collerlation: 1. Clinically Silent 2. Clinically silent or overt

1. Initial lesion-intermediate lesion 2. Atheroma-complicated lesion

Reference is usually made to left and right systems based on where the take-off from the aorta occurs.

1. Left main artery 2. Left anterior descending artery 3. Left circumflex artery 4. Right coronary artery

The possibility of stabilizing or retarding the progression of human atherosclerosis or even causing its regression is one of the current challenges. Several approaches are being pursued:

1. One is aimed at reducing risk factors, especially cholesterol levels. Preliminary evidence suggests that lipid-lowering therapy can act on the lipid-laden plaques more prone to rupture, possibly preventing their progression and inducing their regression thereby reducing the risk of acute coronary events. 2. Because thrombus formation seems to be an important factor in the initiation of an acute cardiac event and in the progression of disease after the acute event has subsided, another promising medical approach is the use of anti thrombotic therapy.

Complicated clinical scoring systems have been developed to quantitate the amount of myocardium at risk, but, in general, several broad rules apply:

1. Prognosis in CAD is related in large part to the number of coronary arteries with significant stenoses. Survival is best in single-vessel disease where obstruction is limited to one artery and is intermediate in two-vessel or double-vessel disease. Involvement of three vessels or triple-vessel disease carries the worst prognosis and usually is an indication for stenting or bypass. 2. Lesions in the left main artery are almost always prognostically significant. An occlusion in that artery could potentially cut off circulation to both the left anterior and left circumflex systems and would result in a massive myocardial infarction. 3. Proximal lesions are associated with greater risk than mid or distal lesions. 4. LAD lesions are usually associated with a large amount of myocardium at risk, as this artery provides blood flow to the functionally important anterior, septal, and apical walls of the left ventricle. 5. The importance of LCx and RCA stenoses depends, in part, on the dominance of the system as well as severity and location. In general, there is less myocardium at risk linked to lesions in these arterial systems.

Myocardial infarctions often present with ST elevation on the ECG and are classified as STEMI (ST elevation MI). A global cardiology task force established a new sub-classification of STEMI by cause:

1. Type 1 2. Type 2 3. Type 3 4. Type 4 and 5

Silent myocardial ischemia is classified as follows:

1. Type 1 2. Type 2 3. Type 3

This syndrome, now known as Prinzmetal's angina or variant angina, can be associated with:

1. acute myocardial infarction 2. severe cardiac arrhythmias, including ventricular tachycardia and fibrillation 3. sudden death.

Alternatively, echocardiography/doppler studies can be done during exercise and compared with resting studies. Myocardial ischemia is detected:

1. as a decrease in left ventricular ejection fraction during exercise 2. by the development of regional ventricular wall motion abnormalities not present at rest.

The major determinants of prognosis in patients with CAD are:

1. coronary obstruction 2. left ventricular function 3. presence of ischemia 4. risk factor analysis

Management of survivors of an SCD episode includes a detailed evaluation including:

1. definition of coronary anatomy by angiography 2. LV function 3. electrophysiologic testing (EPS).

False negatives are also seen in which 10%-15% of individuals with important coronary artery disease fail to demonstrate diagnostic EKG abnormalities. Possible explanations for false negative tests include:

1. failure to achieve an adequate heart rate ("submaximal" test) 2. baseline EKG changes that limit interpretation of exercise tracings 3. medications that suppress the development of ischemia

The approach to these goals is based on the:

1. frequency and severity of ischemic episodes 2. level of left ventricular function 3. clinical assessment of risk factors and comorbid conditions.

While a complex host of factors will determine myocardial oxygen supply, myocardial oxygen demand is rather simply controlled by:

1. heart rate 2. contractility of the myocardium 3. left ventricular wall tension.

The coronary arterial wall is composed of three layers:

1. intima 2. media 3. adventitia.

The early classification used for unstable angina was based on a description of the symptoms and included three subgroups:

1. new onset angina in a person previously free of symptoms 2. crescendo angina and pain at rest occurring in someone with known stable angina 3. acute coronary insufficiency, with episodes of chest pain at rest, 15 minutes or more in duration, not related to any previous precipitating factors.

Current definitions of these acute syndromes rely on the diagnostic electrocardiogram (EKG) and cardiac enzyme pattern on initial presentation:

1. non-ST elevation syndromes 2. ST elevation syndromes

When no effective medical regimen is identified, antiarrhythmic therapy includes:

1. radiofrequency ablation 2. surgical suppression of the arrhythmia 3. implantation of an automatic internal cardiac defibrillator (AICD).

The test is terminated by:

1. reaching a "maximal heart rate," determined individually by age and gender 2. marked EKG changes early in exercise 3. significant blood pressure changes, either markedly hypertensive, or severely hypo tensive 4. reproduction of typical chest pain.

Possible explanations for false positive tests include:

1. ventricular hypertrophy 2. mitral valve prolapse 3. conduction abnormalities (e.g., bundle branch blocks and WPW syndrome).

In contrast to the prognosis in individuals with coronary atherosclerosis, the survival in cardiac syndrome X is usually excellent, and it is important for the underwriter to recognize this. This group of individuals can constitute up to

20% of those undergoing coronary angiography because of the strong suspicion of angina. True myocardial ischemia can be demonstrated in some of these individuals by special tests.

High-risk groups are identified based on low exercise capacity, failure to have systolic blood pressure (BP) rise, and presence of Ischemic ST-segment depression at a low workload, whether accompanied by angina or not. The first-year mortality can range up to

25% in such people in the absence of intervention. In those who have good exercise tolerance, who have no exercise-induced ST change and a good BP response, the risk of cardiac events is 12% annually.

Computed tomography (CAT or CT) is now widely used in cardiac diagnosis. The CT scan is a computer-assisted imaging method that assembles anatomically accurate pictures from a huge number of standard x-rays. Recent developments in rapid CT systems that allow for up to

256 cardiac image "slices" per second have eliminated the blurring that occurs with a regular CT scan of the heart. The results are two important cardiac testing modalities - the coronary calcium scan and the CT angiogram.

Which of the following statements regarding adenosine stress testing is/are correct? A. lt's results are typically less accurate than the results of standard exercise testing. B. It is used for individuals who are unable to undergo standard exercise testing C. It requires concurrent radionuclide or echocardiographic imaging. 1. A only is correct. 2. B only is correct 3. B and C only are correct. 4. A, B, and Care correct

3. B and C only are correct.

When myocardial oxygen supply cannot meet demand, it is: 1. angina 2. hypoxia 3. ischemia 4. infarction

3. ischemia

A coronary artery lesion that would typically place the most myocardium at risk would be located: 1. mid 2. distal 3. proximal 4. dorsal

3. proximal

All the following findings on a post-myocardial infarction exercise test can help identify individuals at high risk for a recurrent event EXCEPT: 1. angina symptoms 2. low exercise capacity 3. rising systolic blood pressure 4. ischemic ST-segment depression at low workloads

3. rising systolic blood pressure

Possible explanations for a false positive result on an exercise stress test include which of the following? A. ventricular hypertrophy B. mitral valve prolapse C. bundle branch block 1. A and B only are correct. 2. A and C only are correct. 3. B and C only are correct. 4. A, B, and C are correct.

4. A, B, and C are correct.

Which of the following are found in the coronary artery wall? A. media B. adventitia C. intima A and B are correct A and C are correct B and C are correct A, B and C are all correct

A, B and C are all correct

Which of the following is/are major determinants of prognosis in patients with CAD? A. level of coronary obstruction B. presence of ischemia C. genetic predisposition A only is correct And B are correct B and C are correct A, B, and C are all correct

A, B, and C are all correct

Cardiac test findings that can be indicative of myocardial ischemia include which of the following? A. reversible defect on a thallium scan B. wall motion abnormality on an echocardiogram C. 1 mm ST segment depression on an exercise stress test A and B only are correct A and C only are correct B and C only are correct A, B, and C are correct

A, B, and C are correct

Which of the following statements regarding adenosine stress testing is/are correct? A. Its results are typically less accurate than the results of standard exercise testing. B. It is used for individuals who are unable to undergo standard exercise testing. C. It requires concurrent radionuclide or echocardiographic imaging. A only is correct B only is correct B and C only are correct A, B, and C are correct

B and C only are correct

Class III

Angina walking one or two blocks on the level at a normal pace.

Class II

Angina with walking more than two blocks or climbing one flight of stairs at a normal pace; angina walking uphill, in the wind or cold, with undue emotional stress, or after meals.

Which of the following statements regarding coronary artery anatomy is/are correct? A. The term "dominance" is used to describe which artery is the largest. B. The left anterior descending artery supplies the lateral ventricular wall. C. Any significant obstruction of the left main could result in severe myocardial damage. C only is correct A and B are correct A and C are correct B and C are correct

C only is correct

Differences between PTCA and CABG include all of the following EXCEPT: PTCA is less traumatic and requires a shorter hospital stay. PTCA of multiple vessels can leave individuals with incomplete revascularization. CABG offers a cure to CAD in those with progressive disease. In individuals with unstable angina, CABG is quite successful.

CABG offers a cure to CAD in those with progressive disease.

The indication for CABG that is least controversial is that of angina pectoris unrelieved by medical therapy and not amenable to PTCA. Other indications for

CABG that have been clearly accepted include left main coronary artery stenosis of more than 50%, failed PTCA, and triple vessel coronary disease, especially when large amounts of myocardium are at risk due to proximal stenoses.

The original report from the Framingham Heart Study indicated that the predictive power of both total cholesterol and LDL-cholesterol waned with age. However, more recent data from the same study have shown that HDL-cholesterol and total cholesterol/HDL ratio maintain their association with

CAD incidence in both sexes between the ages of 65-84 years. Several subsequent studies have supported this conclusion. There are also reports suggesting reduction in cardiac events with statin lipid-lowering therapy up to age 75.

Most studies conclude that there is higher perioperative mortality for CABG in the elderly. Data from the CASS show perioperative mortality for CABG of 1.5% for those under age 65, about 5% for those aged 65-74, and about 10% for those over age 75. However, those elderly

CAD patients who successfully undergo CABG surgery and who experience an uneventful recovery period have been shown to have excellent subsequent survival, often equivalent to those of similar age with no known CAD.

The past several decades have also witnessed rapid advances in the medical treatment of coronary artery disease.

Cardio-selective beta-blockade and calcium channel blockers are used extensively, as well as angiotensin-converting enzyme (ACE) inhibitors and, more recently, antiplatelet, and anticoagulant drugs such as clopidogrel (Plavix®).

The severity of stable angina is classified according to the degree of physical activity required to bring on chest discomfort. A classification system, developed by the Canadian Cardiovascular Society, is commonly used worldwide and is as follows:

Class I, II, III or IV

Risk factor analysis includes:

age and gender genetic predisposition such as the familial dyslipidemias lipids, including cholesterol, triglycerides, and apo-lipoprotein sub-fractions obesity hypertension diabetes homocysteine and c-reactive protein (CRP).

Although non-arrhythmic sudden cardiac deaths have been described, most

EKG-documented sudden cardiac deaths appear to be arrhythmic. Among arrhythmias, ventricular tachycardia and fibrillation seem to be the initiating electrical disturbance in most cases.

Onset: Earliest Onset From Third Decade: From Fourth Decade

EO: initial lesion-fatty streak 3rd: intermediate lesion-atheroma 4th: fibroatheroma-complicated lesion

Sensitivity and specificity of exercise tests for CAD. Exercise, Sensitivity, Specificity Pharmacologic, Sensitivity, Specificity

Exercise EKG, 66%, 84% Exercise Echo, 81%, 89% Exercise Nuclear (SPECT), 90%, 72% Dobutamine, 81%, 83% Dipyridamole nuclear, 90%, 70% Adenosine nuclear, 89%, 83%

Important stress testing parameters

Exercise duration (Bruce protocol stage; MET level) ST-segment change with exercise Blood pressure response to exercise Symptoms with exercise ( chest pain, leg cramps) Ejection fraction, resting and exercise Thallium/SPECT detects Echocardiographic wall motion abnormalities.

Individuals with CAD can be classified into several clinically and prognostically distinct categories.

History, initial findings, and early course distinguish these various CAD or angina syndromes.

Right coronary artery:

In 85% of cases, the posterior descending artery arises from the right coronary artery, supplying the inferior and posterior wall of the left ventricle as well as the right ventricle.

presence of ischemia -

In addition to a clinical history consistent with angina, there are invasive and non-invasive cardiac studies that serve to further define the frequency and severity of ischemic episodes. Evidence of ongoing ischemia will usually predict reduced survival in the absence of medical or surgical intervention.

Class IV

Inability to perform any physical activity without angina.

risk factor analysis

Increased understanding of the pathophysiology of atherosclerosis will highlight the importance of CAD risk factor evaluation.

All of the following statements regarding the pathology of atherosclerosis are correct EXCEPT: The adventitia gives the vascular wall a fair amount of stability by connecting the artery to its surrounding tissue. A lesion produced by plaque rupture can result in thrombosis and myocardial infarction. The media's smooth muscle cells and connective tissue are responsible for vasodilation. It affects mainly small-sized coronary arteries on the epicardial surface of the heart.

It affects mainly small-sized coronary arteries on the epicardial surface of the heart.

A high degree of correlation exists between the level of left ventricular function and the propensity toward future arrhythmic SCD. Patients with an

LV ejection fraction of less than 30% are at significantly greater risk than those who have ejection fractions of 30% or more.

Finally, significant progress in the treatment of CAD has been in revascularization (i.e., restoring blood flow to obstructed or blocked coronary arteries).

Microsurgical bypass graft implantation techniques (CABG surgery), balloon angioplasty (PTCA), and most recently, drugeluting (DES) coronary stenting have all proven effective in the treatment of the angina syndromes and myocardial infarction.

Type 1

Myocardial infarction caused by acute plaque disruption and thrombosis the most common cause of acute MI

Type 2

Myocardial infarction due to oxygen supply/demand imbalance this includes coronary artery dissection and vasospasm

Type 3

Myocardial infarction in the setting of chronic stable or unstable angina

Type 4 and 5

Myocardial infarctions occurring after procedures such as stenting or CABG surgery.

Class I

No angina with ordinary physical activity such as walking or stair climbing.

The cardiac syndrome where chest pain occurs almost exclusively at rest and is associated with EKG ST segment elevation is: angina pectoris Prinzmental's angina cardiac syndrome X silent myocardial infarction

Prinzmental's angina

The term "dominance" is often used to describe the anatomic configuration of the blood supply to the posterior descending artery.

Right dominance, with the posterior descending artery emerging from the right coronary artery, occurs in 85% of cases; the left circumflex (i.e., left dominance) provides the posterior descending circulation in the remaining 15%.

Left anterior descending artery

The left anterior descending (LAD) artery supplies the anterior and septal walls of the left ventricle. It gives rise to the septal perforating arteries that go deep into the muscular septum and to the diagonal arteries that course over the anterolateral free wall of the left ventricle. The LAD and its branches are usually considered the most important coronary artery system after the LMCA and obstruction or occlusion of this system could also result in extensive myocardial injury.

Left circumflex artery:

The left circumflex (LCx) artery is responsible for blood supply to the lateral ventricular wall. The artery can terminate in one or more large obtuse marginal (OM) branches, which course over the lateral to posterolateral left ventricular free wall. In 10-15% of cases, the LCx gives rise to a posterior descending artery, providing circulation to the inferior and posterior walls of the left ventricle.

Left main artery:

The left main coronary artery (LMCA) arises from the upper portion of the left aortic sinus. It then usually bifurcates by giving off the left circumflex artery (LCx) at right angles and continues in a straight line as the left anterior descending artery (LAD). Any significant obstruction of blood flow within the left main artery could result in severe myocardial damage.

All of the following statements regarding coronary artery disease in the elderly are correct EXCEPT: Isolated systolic hypertension is the most common form of hypertension. Advanced disease is often displayed as disease in more than one site. Smoking cessation reduces the risk just as it does in the young and middle-aged. The likelihood of having extensive CAD remains stable with advancing age.

The likelihood of having extensive CAD remains stable with advancing age.

left ventricular function -

The normal heart can pump over half of its blood volume with each stroke. This is measured by ventriculography, echocardiography, or nuclear scan as the ejection fraction, and is normally 50% or greater. Left ventricular dysfunction (abnormal function), particularly in the setting of myocardial ischemia or infarction, is an important factor in predicting survival outcomes.

coronary obstruction

The prognosis of CAD is dependent on the number of coronary vessels obstructed by plaque, as well as the severity of obstruction ( or occlusion) at each site, an indication of the amount of myocardium at risk. This relationship will be explored further following an overview of angiography and the coronary circulation.

ST elevation syndromes-

This is the classic pattern for acute myocardial infarction. Infarct Q waves on EKG can develop during or after the acute event.

non-ST elevation syndromes-

Within this group are those individuals classified as having unstable angina without infarction as well as those with non-Q wave infarctions (to be discussed with classic infarctions in the following section).

Over the past several decades, advances in the understanding and treatment of

acute and chronic coronary artery disease (CAD) have led to a steady decline in the mortality of this impairment.

During the first six months after their presentation, many with variant angina go through an

acute, active phase with frequent episodes of angina and cardiac events. Over this period, nonfatal myocardial infarction occurs in up to 20% of these individuals and death in up to 10%. Those who have serious arrhythmias or conduction disturbances during attacks have higher maximal ST - segment elevations and are at higher risk for sudden death.

During the early phase of an acute MI, it is logistically impossible to

admit, assess, and prepare a person for emergency CABG within the six-hour time frame for acceptable myocardial salvage. Thrombolytic therapy, with the option of emergent PTCA/stenting, remains the mainstay of therapy in this situation.

The cause of the syndrome is unknown. Several studies have demonstrated an abnormally reduced capacity to increase coronary flow in response to increased myocardial oxygen demand (i.e., abnormal vasodilator reserve). This abnormality appears to

affect the smaller resistance vessels that are not visible angiographically, while the large proximal conductance vessels appear to be normal. Such individuals can have positive exercise stress tests.

Serum NT-proBNP levels vary with

age, gender, build, and renal function and so require underwriting guidelines that take these into account Ultimately, underwriting cardiac mortality risk should benefit from the additional prognostic information that NT-proBNP screening provides.

It has been recognized for many years that stress testing for CAD is associated with a lower sensitivity and specificity in females than in males. However, when the .

age, symptom, and EKG status of the individuals have been properly classified, the predictive value of stress testing in females compares favorably with males when coronary angiography is used as the gold standard.

The same factors that affect the risk of CAD in males apply to females; however, not

all risk factors are equivalent between the sexes. Some risk factors, such as menopausal status and hormone use, are unique to females.

The limitations of the early forms of angioplasty equipment confined PTCA to selected individuals with

anatomically suitable single-vessel disease. As the equipment has become more sophisticated and operators more experienced, it has become possible to manage more complex, multivessel coronary disease with PTCA.

Treated in the past with thrombolytic agents, reperfusion of the infarct-related artery is now usually achieved by a catheter-based strategy. Percutaneous coronary intervention (PCI) includes

angioplasty and stent insertion. PCI has assumed an important role particularly in the treatment of those with a STEMI. There is little evidence of benefit with PCI in the acute coronary syndromes of unstable angina and NSTEMI infarctions.

All of the following medications can be used to treat angina pectoris EXCEPT: nitrates beta-blockers anticardiolipin antibodies calcium channel blockers

anticardiolipin antibodies

Risk factor assessment and control are crucial, both in

apparently healthy individuals (primary prevention) as well as in individuals with known CAD (secondary prevention), to reduce CAD risk. Not surprisingly, risk factor analysis is essential to critically interpret the results of cardiac testing in the insurance applicant.

Aging produces a variety of changes in cardiac structure and function. These include increased

arterial and myocardial stiffness, fibrosis, and cell loss within the cardiac conduction system, thickening and calcification of cardiac valves, and reduction in the maximal heart rate. The elderly are more likely to require cardiac medications and yet are also more likely to experience medication side effects and adverse drug interactions.

A complete cardiac catheterization study usually includes ventriculography with injection of contrast medium directly into the left ventricle. This procedure is used to

assess left ventricular size and function, the presence and degree of regional wall motion abnormalities, and the presence and severity of mitral regurgitation. In the past, this test had been the gold standard for left ventricular analysis, but has, for the most part, been supplanted by newer radionuclide and echocardiogram/Doppler techniques.

Aspirin, when used as an antiplatelet agent, can reduce the risk of myocardial infarction and cardiac death in stable angina patients, particularly in

association with other antiplatelet agents such as clopidogrel. The implications of these findings for long-term mortality assessment await further studies.

Silent myocardial ischemia is defined as episodes of

asymptomatic ischemia, with objective evidence of coronary insufficiency provided by exercise testing or Holter monitoring, usually occurring in someone with known CAD. While not a new topic, silent ischemia has generated considerable interest recently.

Underwriting mortality risk assessment in those individuals with known angina or CAD is relatively straightforward compared to the greater challenge in assessing those who are

asymptomatic or with atypical symptoms on presentation. In these situations, CAD risk factor assessment along with the results of cardiac testing are useful tools, confirming (or excluding) the presence of CAD and providing an estimate of disease severity.

This is largely the result of the advances in ambulatory 24-hour monitoring that revealed that many people with CAD and relatively stable angina had frequent episodes of

asymptomatic, ischemic-type ST-segment depression during daily life. Surprisingly, these silent episodes occurred at relatively low activity and heart rates compared with data from treadmill exercise tests for the same individuals, suggesting that changes in myocardial oxygen supply, as well as demand, might be responsible for these asymptomatic episodes of ischemia.

EBCT scans can detect

atherosclerosis before the buildup of arterial plaque has advanced enough to disrupt blood flow. While it cannot show actual plaque, it can show flecks of calcium in coronary arteries, which appear as bright white flakes on the dark gray x-ray films. It is these calcium deposits that are associated with plaque and coronary artery disease.

Coronary angiography identifies the presence, site, extent, and severity of coronary obstruction. When obstruction is present, angiography identifies

atherosclerosis, thrombus, spasm, or various combinations. More specifically, coronary angiography can identify anatomic characteristics (such as left main stenosis, severe three-vessel disease with abnormal left ventricular function) associated with high risk for death if left untreated.

By increasing their content of lipid material, these plaques can rupture through the thin fibrotic cap or can fissure with subsequent exposure of the internal constituents of the

atherosclerotic plaque to the flowing blood. Because of the highly thrombogenic properties of these components, the ruptured or fissured plaques represent a major risk for mural or occlusive thrombosis, the so-called complicated plaque.

Despite these sobering statistics, CAD mortality rates have been falling since 1969 and the number of people alive with CAD (and seeking life insurance) has been increasing each year. This presumably reflects the

awareness and treatment of CAD risk factors, the improving survival rates of the acute coronary syndromes, and technical advances in revascularization strategies, as well as advances in the medical treatment of the aging population.

Nitrates, both intravenous and oral, are the mainstays of the initial treatment of unstable angina. Along with nitrates,

calcium channel blockers and beta-blockers have been shown to be useful in reducing the number of ischemic episodes. Both aspirin and heparin are useful in reducing complications, emphasizing the importance of platelets and thrombosis in the unstable phase.

CT angiogram represents the next step in the evolution of CAT scan imaging in CAD. Rapid sequence images timed to the

cardiac cycle and reconstructed by computer are able, for the first time, to reveal coronary artery anatomy non-invasively (i.e., without resorting to arterial catheters as in cardiac catheterization). Current generation scanners can detect small nonobstructive atherosclerotic plaques as well as flow-limiting larger stenotic coronary lesions.

What is the syndrome of angina or angina-like chest pain with a normal coronary angiogram? cardiac syndrome X myocardial ischemia sudden cardiac death stable angina pectoris

cardiac syndrome X

Most survivors of out-of-hospital cardiac arrest remain at significant risk for a recurrence and fewer than 1/4 will have

evidence of an acute myocardial infarction. A cardiac arrest unassociated with a reversible cause such as myocardial infarction or electrolyte disturbance is associated with a risk of recurrence of up to 35% within the first year.

At times, the chest pain history is that of "atypical" angina and will include some, but not all, of these classic features. The pain can occur with exercise, for example, but be sharp rather than dull and achy. Atypical angina predicts only about a 50% chance of CAD, with the

chest complaint often eventually attributed to non-cardiac causes. Finally, non-anginal chest pain identifies a clinical history in which the symptoms described in no way resemble that of classic angina; the prevalence of CAD in this group approaches that of the general population.

Equally important is the exclusion of the CAD diagnosis as a cause of

chest pain in patients with normal coronaries at angiography. One rare exception to this conclusion is cardiac syndrome X, in which chest pain occurs without objective evidence of atherosclerotic disease.

Angina is more likely to be attributed to less significant causes of

chest pain in the elderly. Acute myocardial infarction is more difficult to diagnose in the elderly and many MIs occur with virtually no symptoms.

Calcium channel blockers are popular for

chronic therapy in classic stable angina pectoris. In addition, these agents are useful in vasospastic (i.e., Prinzmetal's variant) angina and angina suspected to be related to limited coronary vasodilator reserve (i.e., cardiac syndrome X).

Even in the setting of right dominance, however, the left

circumflex artery will supply a very significant portion of the left ventricle. ln most cases, therefore, obstructive disease of the LCx is considered more of a risk than isolated RCA disease.

Brain natriuretic hormone (BNP) and its metabolite NT-proBNP, are relatively new laboratory markers that have been found to be useful in

clinical and insurance medicine. Although originally isolated in brain tissue, BNP is synthesized predominantly by the cardiac ventricles in response to cardiac stress.

Risk stratification is determined from

clinical findings (e.g., age, previous MI, presence or absence of heart failure, and ventricular arrhythmias) and noninvasive studies. If a symptom limited exercise test performed two to four weeks after the infarction is available, this can be a post-effective method for determining low-and high-risk individuals.

Indeed, there is a recent trend toward earlier AICD implantation without EPS testing. This is

clinically justified as a potentially safer, more cost-effective strategy, but certainly makes medical risk assessment more difficult.

Given the prevalence of CAD and its considerable cost to society, the selection of the optimal approach to treatment for everyone is an important health care issue. Several large clinical trials have

compared medical therapy with coronary artery bypass graft surgery (CABG). These studies demonstrated that surgery improved survival and reduced the risk of myocardial infarction mainly for patients with left main or three-vessel coronary disease, particularly when their disease was accompanied by left ventricular dysfunction.

One large study, the Heart and Estrogen/Progestin Replacement Study (HERS), included the troubling finding of increased coronary disease events in known CAD patients in the first year after initiation of HRT therapy. Additional analysis showed that this increased CAD risk was

confined to older women more than 10 years after menopause. There also appears to be a slightly increased atherogenic risk in females taking oral contraceptives; this risk is only clinically significant in females who smoke or who have known thrombotic disease.

The previous discussion of the pathophysiology of myocardial ischemia stressed the important role of thrombosis and platelet aggregation, especially in the

conversion of chronic stable CAD to the acute ischemic syndromes of unstable angina, myocardial infarction, and sudden cardiac death. Despite this, therapy with anticoagulants has not yet been shown to have a role in the treatment of stable angina pectoris.

Although noninvasive procedures (such as exercise electrocardiography, radioisotope tests, and echocardiography) are important tools in CAD risk assessment, they do not define

coronary anatomy. Coronary angiography is the "gold standard" to define the extent of CAD. A specialized catheter is passed into the coronary artery and radiographic contrast material is injected into the artery while a special x-ray or video film is taken.

What testing is the "gold standard" for the detection of coronary artery disease? positron emission tomography (PET) exercise stress test coronary angiography magnetic resonance imaging (MRI)

coronary angiography

Positron emission tomography (PET) is a very accurate method for identifying how much the heart has been

damaged by infarction and how much is still viable. Until recently, it had been confined to research applications, but its use in clinical medicine is increasing. The test is performed by the injection of radionuclide "tracer'' and then detection of radioactive decay by use of a scanner.

Sudden cardiac death (SCD) is a major health problem in the United States, accounting for more than 300,000 deaths each year, and is a major cause of death for people with CAD. It is usually defined as

death from cardiac disease within one hour of the onset of symptoms in someone who was not expected to die. Most sudden cardiac deaths are due to arrhythmias occurring in the presence of chronic coronary or structural heart disease.

All reversible triggers, such as acute

ischemia and electrolyte abnormalities, need to be addressed as well to remove the arrhythmogenic substrate.

The history differs from that of typical angina in that the principal finding is angina at rest. The key to the diagnosis of variant angina lies in the

development of ST-segment elevations with pain. Exercise testing in individuals with variant angina is of limited value since the responses are so variable. The coronary anatomy in individuals with variant angina has been defined both at autopsy and during coronary angiography.

Cardiac syndrome X is the syndrome of angina or angina-like chest pain with a normal coronary angiogram. It is an important clinical entity to be

differentiated from classic CAD (and from the metabolic syndrome X of early diabetes). It can also be differentiated from variant angina by the absence of EKG changes or provokable arterial spasm at angiography.

The calcium channel blockers are available in oral and intravenous forms, both as short-acting and long-acting preparations and are a

diverse group of drugs with different chemical, pharmacologic, and physiologic actions. Anti-ischemic agents from these three drug classes (nitrates, betablockers, and calcium blockers) are frequently used as combination therapy to enhance their effects or minimize their side effects.

One-year mortality is similar in both types of MI. STEMI infarctions also have a high likelihood of coronary thrombus at

early angiography (85% of patients studied within four hours of onset of symptoms) compared with those who have NSTEMI infarction (30% or less). Thus, the individual with NSTEMI infarction has limited initial damage but a high frequency of residual ischemia and its attendant risk.

While plaque progression can be slow in some lesions, it is probable that for most, the progression from

early lesion to occlusion is very rapid by means of plaque rupture, resulting in blood clot formation that occludes the coronary artery.

The pathophysiology and coronary angiographic morphology of unstable angina have been intensely studied in recent years. Many of these individuals have acute active angiographic lesions with

eccentricity, overhanging edges, or irregular scalloped borders. Some appear to be sites of ulceration or ruptured plaques. Such lesions are rarely seen in people with stable angina pectoris. In addition, thrombi are commonly seen. These arteriographic impressions have been confirmed by direct coronary angioscopy.

Attempts to improve the diagnostic accuracy of exercise testing have led to the use of supplementary radionuclide and

echocardiographic/Doppler imaging during testing. Myocardial distribution of radioisotopes following intravenous injection at rest, during exercise, or following administration of a coronary vasodilator (e.g., dipyridamole and adenosine) is related to regional blood flow and myocardial viability.

There is now good evidence that both systolic and diastolic hypertension are formidable risk factors for stroke and CAD in the elderly and that treatment can be

effective. There appears to be particular risk associated with an elevated pulse pressure (i.e., systolic minus diastolic blood pressure), which may be related to increased arterial shear stress.

Patients with stable angina pectoris have chest pain with

effort, exercise, or during other conditions in which myocardial oxygen demand is increased. This occurs in a predictable manner and is usually relieved promptly by rest or sublingual nitroglycerin. When studied angiographically, one or more coronary stenoses, often calcified, are usually found.

Ongoing medical research has increased our understanding of the

etiology and pathogenesis of atherosclerosis and its clinical sequelae. Indeed, risk factor analysis and intervention are major weapons in the fight against atherosclerotic disease.

In the United States, stents are currently implanted post-balloon angioplasty in

most angioplasty procedures. Most studies have shown marked improvement in early restenosis rates with the newer generation of coronary stents.

An association of the chest pain with

exercise, effort, and emotion, and of relief with rest or nitroglycerin, is presumptive evidence that the chest pain represents typical angina pectoris. This implies a 90% likelihood of angiographically significant disease involving at least one major coronary artery.

CAD is the number one cause of death in those over age 65. While traditional risk factors identify elderly individuals at risk for CAD, these

factors lose some of their predictive power in the elderly. Advanced age is such a potent risk factor for CAD that it weakens the relative effect of other clinical variables.

In contrast to earlier reports, most recent studies have shown similar PTCA success rates for males and females. After successful angioplasty,

females have similar symptomatic improvement, decreased requirement for additional revascularization, restenosis, and similar survival rates as males.

Recent studies have also suggested that there appears to be a referral bias that works against females in their selection for thrombolytic therapy, cardiac catheterization, and revascularization. The lower prevalence of CAD in

females often leads the clinician to look for other causes of chest pain. Also, CAD in females often presents with atypical symptoms such as abdominal bloating or breathlessness. Recognition of this will probably result in a more aggressive approach to the early and later management of CAD in females.

Microscopically, they are composed of a

fibrotic cap and a necrotic core containing cellular debris, extracellular lipids, cholesterol crystals, calcium deposits, and blood-borne material. These deposits of calcium contribute to the sensitivity of coronary calcium scans (i.e., electron beam CT or EBCT) in detecting early atherosclerosis.

A characteristic daily variation in the frequency and duration of silent ischemic episodes has been documented. Increased activity is seen shortly after waking, with

higher peaks around noon, plateaus in the afternoon, and minimal activity late at night and in the early morning hours. This variation is the same as the variation observed in the frequency of acute MIs and out-of-hospital deaths, suggesting a common mechanism between transient ischemia and these life-threatening events.

This differs from a thallium scan or radionuclide angiography in the radiation emitting substances used. The advantage of PET is the

higher resolution or detail leading to improved localization of areas of decreased blood flow. Disadvantages are the limited availability and relatively high cost of the tracers and imaging equipment. PET may also be performed as a "stress test" after the administration of intravenous dipyridamole which acts to increase cardiac workload.

Myocardial ischemia is indicated by EKG ST-segment depression, radionuclide imaging defects, or wall motion abnormalities on echocardiogram. An exercise EKG is considered positive if there is

horizontal or down sloping ST -segment depression of 1 mm or greater, 0.08 seconds after the 1 point. False positive results can occur, in which the individual, despite an abnormal test, is found to be free of CAD.

Isolated systolic hypertension is the most common form of hypertension in people between the ages of 65 to 89, affecting two thirds of individuals with

hypertension. The recent report of Systolic Hypertension in the Elderly Program demonstrated that treatment of these individuals results in a significant reduction in cardiovascular disease events.

The major limitations to balloon angioplasty (PTCA) alone are related to the significant restenosis rate and need for repeat revascularization procedures. To address these problems,

increasingly sophisticated coronary artery stents have been developed. These stents are devices with metal structural supports infused with anti-coagulant medication (i.e., drug-eluting stents) that are inserted at sites of atherosclerotic narrowing. Once in place, the stent provides structural support and improved arterial flow, often to near-normal levels.

More prolonged (30-60 minutes) disruptions in the myocardial supply and demand balance, such as that resulting from coronary thrombosis, will result in myocardial

injury and cell death (myocardial infarction). Ischemic injury will usually produce cardiac dysfunction when cardiac testing will reveal a reduced ventricular ejection fraction. More extensive cardiac dysfunction can progress to "heart failure" and death.

The intima is the

innermost layer and is in direct contact with the flowing blood. The open space through which blood flows is known as the lumen. The most important structure in the intima is the endothelium, a layer of endothelial cells lining the whole vascular wall. The normal endothelium plays an important role in protecting against atherosclerosis. It acts as a selective barrier to prevent plasma lipid accumulation within the vessel wall and has also been shown to prevent blood clot formation and arterial spasm.

Revascularization with percutaneous transluminal coronary angioplasty (PTCA) is an effective method to treat individuals with CAD. A balloon-tipped catheter is

inserted percutaneously into the coronary circulation. The balloon, inflated at high pressure at the site of a coronary stenosis, creates a fracture of the plaque and splits the plaque from the wall of the vessel to allow an increase in the area through which blood can flow.

Not long thereafter, researchers began to explore the possibility that BNP could be useful as a screening tool for cardiac disease in asymptomatic people. Favorable results in this arena led to

interest from insurance companies in the use of BNP as an underwriting requirement. NT-proBNP was chosen for insurance screening based on its longer half-life and greater stability in collection and transport. Initial reports suggest that NT-proBNP levels can effectively identify increased mortality risk in proposed insureds, providing value over and above that of classic risk factor analysis.

Since PTCA with stenting is now performed even in patients with multivessel coronary disease, it must be compared with CABG. The operative mortality for elective CABG has fallen consistently and is about 1-3% in most centers. The

internal mammary artery (IMA) bypass graft is a superior conduit with improved long-term patency when compared with vein bypass grafts. Recent studies indicate an IMA patency rate of over 90% at 10 years is likely, while 50% of vein bypass grafts are likely to occlude within 10 years.

In general, the diagnosis of MI is based on a clinical presentation characterized by prolonged and severe chest pain. However, at least 25-30% of all Mis are probably silent or unrecognized. These are detected only by

interval electrocardiograms showing residual Q wave evidence of MI. Approximately one-half of silent Mis are truly asymptomatic and one-half causes mild or atypical symptoms that the patient does not recognize as being due to infarction. Those in the elderly age group, with diabetes or with hypertension, are at highest risk for silent infarction.

Clinical and pathological progression of atherosclerosis Atheroma

intracellular lipid accumulation core of extracellular lipid

Type 2

is seen in individuals who have been asymptomatic after a proven acute myocardial infarction. In this group, the one-year mortality can range up to 25% if not treated or revascularized. It is the presence of ischemia, rather than the presence or absence of symptoms, that appears to be prognostically important.

Type 3

is seen in individuals with angina in whom episodes of both symptomatic and silent ischemia are detected. The mortality in individuals with unstable angina and silent ischemia is significantly increased and represents a very high-risk group. In those with stable angina, left untreated, the presence of silent ischemia increases the mortality by a factor of two to four times.

The condition where myocardial oxygen demand exceeds supply is: angina hypoxia ischemia infarction

ischemia

MIs are rare in pre-menopausal females, but the incidence increases sharply with menopause and is two to three times that of pre-menopausal females the same age. Normally, females' risk lags 10 years behind that of males; however, 10 years after menopause, the

ischemic event rate approximates that of males. As compared to the gradual increase in cardiac risk seen in natural menopause, the risk rises sharply if surgical menopause is induced by a total hysterectomy with removal of the ovaries.

Fissuring or rupture of complicated atherosclerotic plaques with subsequent occlusive thrombi plays a fundamental role in development of the acute

ischemic syndromes. In addition, emerging evidence suggests that vicious cycles of plaque disruption, thrombosis, and scarring can also be important in the progression of atherosclerosis in asymptomatic individuals and in those with stable angina.

The differences between PTCA and CABG are obvious. Successful PTCA is less traumatic, less costly initially, and requires a shorter hospital stay than CABG. PTCA of multiple vessels, though, can

leave individuals with incomplete revascularization, and long-term follow-up of these individuals has indicated a higher recurrence of symptoms.

The likelihood of having extensive CAD increases progressively with advancing age. In the Coronary Artery Surgery Study (CASS), the incidence of

left main disease was 15% vs. 9%, and three-vessel disease was 61 % vs. 46% in patients over age 65 versus those aged 64 or younger.

Clinical and pathological progression of atherosclerosis. Fatty Streak

mainly intracellular lipid accumulation

The coronary arteries are

major blood vessels that emerge from the aortic root to supply the heart muscle with oxygen and nutrients.

For individuals with less extensive CAD, bypass surgery offered no survival advantage over the already excellent results with

medical therapy. However, it did effectively relieve severe angina that proved refractory to medical therapy.

Atherosclerosis affects mainly the

medium-sized coronary arteries on the epicardial (outer) surface of the heart.

The media is the

middle layer of the vascular wall. Its smooth muscle cells and connective tissue are responsible for the vasodilatory properties of the blood vessel.

Myocardial infarction (MI) refers to the irreversible

myocardial cell injury and death that occurs following prolonged ischemia. Muscle necrosis occurs when an ischemic episode is prolonged beyond 30-40 minutes. Almost all acute myocardial infarctions result from coronary atherosclerotic lesions, generally with superimposed thrombosis.

The number one killer of women in North America is: breast cancer diabetes myocardial infarction lung cancer

myocardial infarction

While the ultimate goals are the prevention of

myocardial infarction and death, relief of chest pain and improvement in the quality of life are important objectives in the management of stable angina.

A rapidly progressive coronary lesion produced by plaque rupture and resultant thrombosis can also be responsible for

myocardial ischemia, infarction, and sudden cardiac death. This new lesion could potentially lead to decreased blood flow, myocardial hypoperfusion, and increasing susceptibility to fatal ventricular arrhythmias.

Brief periods of oxygen supply/demand imbalance (as short as several minutes) will promptly result in

myocardial ischemia. At the same time, reversible regional myocardial wall motion abnormalities and perfusion defects appear, detectable with echocardiography and radionuclide imaging (thallium or sestamibi (SPECT)).

Most often, unstable angina is an active intracoronary process (i.e., thrombus formation and/or vasospasm) leading to acute reduction in myocardial blood flow and oxygen supply. An inappropriate increase in

myocardial oxygen needs, such as with severe anemia, fever, or hypoxia, can also cause a rapidly aggravating anginal syndrome. As a group, if untreated, within three months, 15-20% will experience refractory angina, MI, or death. Fifty-seven percent of individuals who enter the hospital with a myocardial infarction give a history of recent, unstable angina.

The basic process by which CAD produces morbidity and mortality and alters quality of life is acute myocardial ischemia. Myocardial ischemia occurs when

myocardial oxygen supply cannot meet myocardial oxygen demand in a region of the ventricle. Coronary artery disease is often called ischemic heart disease (IHD) because it is only when the coronary atherosclerotic process causes ischemia that it manifests clinically.

The acute coronary syndromes encompass a range of clinical syndromes that includes

new or worsening chronic angina, "rest" angina, and, finally, acute myocardial infarction.

What is usually used as initial treatment for stable angina? nitrates Beta-blockers calcium channel blockers lithium

nitrates

Advanced disease is often displayed as disease in more than one site. The elderly with

noncoronary atherosclerosis (for example, cerebrovascular disease, peripheral vascular disease, abdominal aortic aneurysm) are much more likely to have CAD, whether or not it is clinically apparent. Many of these individuals die from CAD rather than their non-coronary atherosclerotic vascular disease.

If the clinical features are atypical, or if an estimate of severity and prognosis is required, then further cardiac testing can be indicated. The resting EKG is

normal in 25-50% of individuals with stable angina pectoris. Even when abnormal, the findings such as ST -T changes or bundle branch block are nonspecific. For this reason, tests that provoke myocardial ischemia pharmacologically or with exercise are utilized.

In the remaining individuals, many will be experiencing their first infarction and will be minimally or completely asymptomatic. Most will have ejection fractions in the

normal or near normal range, the exception being those people who have suffered a larger anterior MI as their first event. In this large group, post-MI exercise testing has been shown to be superior to coronary angiography to identify individuals at risk for recurrent infarction and death.

The cardiac troponins are the most sensitive and specific biomarkers and can be elevated when other biomarkers are not. In very early MI presentations, the serum troponin elevation can precede all other enzyme evidence of MI. Troponins are

not detected in the peripheral circulation under normal circumstances. Even minor elevations of troponin concentrations are thought to indicate myocardial necrosis. In short-and long-term follow-up studies, the magnitude of troponin elevations has correlated with the risk of death and the composite risk of death or nonfatal MI, irrespective of whether the individuals had ST elevation or non-ST elevation acute coronary syndrome.

Medical therapy with beta-blockers, and calcium channel blockers offers a diverse choice of drugs to relieve symptoms of stable angina pectoris. It has

now been shown that drugs that improve exercise tolerance and relieve symptoms will favorably improve outcomes.

The degree of stenosis is recorded as a reduction in the lumen diameter expressed as a percentage, with total

occlusion being 100%. From the standpoint of surgically significant disease, a stenosis with greater than 50-70% reduction in diameter (10-40% in the left main stem coronary artery) is a lesion that can produce myocardial ischemia. Lesions in series or a long stenosis are of added importance.

Type 1

occurs in individuals who are apparently well and totally asymptomatic. Detection is usually by means of an exercise EKG, and the prevalence ranges from 2.5-12% in different studies. In the absence of intervention, mortality risk in these people compared to those with no exercise EKG abnormalities is increased by 200%-500%, depending on association with other known CAD risk factors.

At present, many people with single- and multivessel CAD are now being

offered PTCA and coronary stenting as an alternative to medical therapy rather than as an alternative to CABG. PTCA, therefore, has achieved widespread acceptance for single-vessel and multivessel CAD, while data to support this therapeutic protocol are only recently being published.

In the United States, over 700,000 people suffer from acute myocardial infarction (MI) annually and approximately one-fourth of all deaths are due to MI. More than 50% of the deaths associated with MI occur within

one hour of the event and are attributable to arrhythmias, most often ventricular fibrillation. Before the introduction of thrombolytic therapy for MI, the mortality rates during hospitalization and the year following infarction were in excess of 10%. However, in the past 20 years there has been a significant decline in the mortality from MI due to both a 25%decrease in incidence of MI and a similarly marked fall in case fatality rate once an MI has occurred.

Mortality in the first year after an MI, especially in the first six to nine months, is 6-10% (versus 2-4% overall annual mortality in CAD without recent MI). Within the post-MI population, up to

one-third of people have coronary anatomy (i.e., left main or three-vessel disease) for which coronary artery bypass graft (CABG) surgery has been shown to improve prognosis.

Late myocardial infarction rate is low and late survival of these individuals is good, similar to findings in people with chronic stable angina after CABG. However,

operative mortality in individuals with unstable angina is approximately twice that expected with those who have stable angina pectoris before surgery.

For all drugs, there is a wide individual variation in drug dose required for

optimum symptomatic response while keeping side effects to a minimum. Newer preparations are designed to provide better dosing schedules and bioavailability with fewer side effects.

The adventitia is the

outermost layer of the vascular wall. It consists of fibroelastic tissue without smooth muscle cells. It also houses nutrient vessels (i.e., vasa vasorum) of the vascular wall and nerve fibers. ln addition to carrying nutrients to the inner layers of the vessel, the adventitia gives the vascular wall a fair amount of stability by connecting the artery to its surrounding tissue.

Myocardial oxygen supply is determined by the amount of

oxygen delivered by coronary blood flow. Since oxygen extraction by the myocardium is nearly maximal at rest, myocardial oxygen supply is very dependent on the ability to increase coronary artery size and, thus, blood flow (coronary flow reserve).

Clinical trials to date have confirmed that the larger the evolving MI is, the sooner that reperfusion is attempted, and the higher the

patency rate achieved, the greater will be the benefit on mortality and left ventricular function, provided chronic vessel patency is maintained. The risks of this therapy are low and are less in younger patients than in older patients.

Numerous studies have confirmed the long-term survival benefit of CABG surgery. Most recently, studies on post-CABG patients reported a survival rate of 85%-90% at 5 years. Symptomatic improvement has been demonstrated in 70% of

patients and complete absence of angina pectoris in 50% after five years. However, about 30% require repeat revascularization by 10 years. Reoperation CABG is somewhat riskier, with perioperative mortality somewhat higher than first-time surgery-1-2% first-time versus 5-7% reoperation mortality.

Intra-luminal masses (tumors or clots) are easily shown. Special MRI techniques are available that can illustrate abnormal blood flow patterns that allow for MRI angiographic studies of the cerebral and peripheral vessels. MRI imaging is now

performed along with exercise testing but does not yet have the resolution required for identification of coronary stenoses. In addition, the strong magnetic fields, however, limit the use of the MRI to those who do not have pacemakers, metallic objects or implants, or certain prosthetics.

ln individuals who cannot undergo exercise testing, myocardial ischemia has been diagnostically induced with a variety of

pharmacologic agents, among them dipyridamole and adenosine. Imaging, either radionuclide or echocardiographic, is required for this type of testing, as the usual heart rate, blood pressure, and EKG findings of exercise testing are absent with the pharmacologic approach. ln reliable laboratories, these pharmacologic stress tests have proven equal in value to standard exercise testing in the detection of myocardial ischemia.

Magnetic resonance imaging (MRI) produces cross-sectional images of anatomy by

placing individuals in a strong magnetic field and bombarding them with radio waves, A super- conducting magnet circles around the body, causing the hydrogen nuclei in the body to align with the magnetic field. Hydrogen nuclei emit their own signals, which are then converted to computerized images.

Myocardial infarction is the number one killer of North American females. In fact, in many studies, the

post-MI death rate in females surpasses that of males. Females present a unique set of problems in terms of risk factor modification, acute presentation, and subsequent management.

The second component of risk stratification post-MI is residual LV function. Individuals with an ejection fraction of 50% or greater have a low event rate of approximately 5% over the next five years. Long-term

post-infarct survival decreases when the ejection fraction (EF) falls below 50%, and significantly deteriorates in those with ejection fractions less than 35-40%. Unfortunately, a severely reduced ejection fraction also predicts a high surgical mortality and poor long-term survival, despite revascularization.

Nevertheless, heart attacks occur in over 700,000 people in the United States every year. It remains the most common cause of death in adults overall and, tragically, the most common cause of

premature death in adults before the age of 65. In 15-20% of adults with CAD, their first symptom is their last symptom, in that they fall victim to the syndrome of sudden unexpected death as the first manifestation of this impairment.

Individuals with post-MI angina should have coronary angiography on an urgent basis. In addition, a large percentage of people with

previous infarction merit early coronary angiography because of higher likelihood of diminished L V function and multiple lesions. Individuals with a prior MI have significantly increased mortality in the year following a recurrent infarction.

A coronary artery lesion that would typically place the most myocardium at risk would be located: mid distal proximal dorsal

proximal

Management of individuals with MI has undergone remarkable evolution over the past several years. Coronary angiography and other complex manipulations can now be done in a relatively

rapid and safe manner in the individual with MI. The time interval between onset of abrupt coronary occlusion and the institution of any intervention to limit damage is critical.

PTCA and coronary stenting in the elderly has a primary success rate comparable to results observed in younger groups. However, angina is more likely to

recur in the elderly and to recur sooner than it would after CABG surgery. Procedure-related morbidity and mortality increases with age. Long--term results after CABG in the elderly mirror those seen in the younger populations.

Coronary obstructions identified on CTA require further confirmation and quantitation with conventional coronary angiography before proceeding with revascularization. Dense calcium particles in the arterial walls will

reduce the image quality. Another limiting factor is the significant radiation exposure that occurs during the CT imaging process. However, the CT angiogram represents a major advance in cardiac testing, particularly when the coronaries are "clean," thus excluding the presence of significant CAD in those presenting with chest pain or shortness of breath.

The location of an obstruction will be described in

relation to the origin of that coronary artery. Thus, a proximal lesion implies that the stenosis is close to the origin of the artery. Somewhat further along, after significant branching has occurred, lesions are referred to as mid lesions. Finally, distal lesions are those that occur near the terminal portions of the imaged artery.

Similar ST-segment changes were seen in people hospitalized for unstable angina even after apparent

relief of chest pain. Additional studies confirmed those episodes of silent ischemia occurred in many people, from those who were totally asymptomatic to those who were post myocardial infarction.

MRI can visualize the heart and large vessels in the abdomen and chest. It is an effective tool for cardiac diagnosis, with improved

resolution and anatomic clarity leading to rapid expansion in the use of the MRI. Aortic aneurysms, lesions in the aorta and other large arteries, congenital heart abnormalities, chest tumors, pericardial diseases, and myocardial scar from prior infarction are all well-visualized.

Several studies have suggested that coronary artery bypass surgery is less successful in females, related to operative mortality and graft closure and angina post-operatively. Subsequent studies have suggested that these

results can be explained by factors other than gender, including age, disease severity, body size, and coronary vessel size.

Individuals who appear to be at high risk, or who present with symptoms unresponsive to medical management, are considered for

revascularization therapy (e.g., coronary angioplasty or bypass grafting). Successful coronary revascularization offers high probability (over 85%) for relief or improvement of symptoms over an intermediate period (i.e., five to ten years).

All of the following findings on a post-myocardial infarction exercise test can help identify individuals at high risk for a recurrent event EXCEPT: angina symptoms low exercise capacity rising systolic blood pressure ischemic ST-segment depression at low workloads

rising systolic blood pressure

Early studies confirmed an association between increased BNP levels and heart failure. More recently, clinical BNP testing has found a

role in the treatment and monitoring of patients with a wide variety of cardiac impairments, including heart failure, congenital heart disease, aortic and valvular heart disease, and cardiomyopathy.

Reversible defects on nuclear scans generally reflect ischemic myocardium, whereas nonreversible defects often indicate

scarring from previous myocardial infarction. Technetium 99M (Tc99M) labeled agents, such as Tc99M sestamibi (SPECT), demonstrate improved imaging characteristics and have replaced thallium as the imaging agents of choice for most myocardial perfusion studies.

In most individuals with myocardial infarction, some change can be documented when

serial electrocardiograms are compared. The EKG changes are those of ischemia, injury, and cellular death (necrosis) and are, within limits, reflected by T wave changes, ST-segment elevation, and the appearance of Q waves, respectively.

Individuals suspected of unstable angina pectoris are placed at rest, usually in a hospital. Acute myocardial infarction is ruled out by

serial enzyme and EKG studies. Most data suggest that the more extensive and severe that the EKG changes are during chest discomfort, the more likely complications are to develop.

In all cases, the diagnosis of MI must be supported by objective laboratory findings. These findings include electrocardiographic or serum enzyme evidence of myocardial necrosis. Over the past 10 years,

serum enzymes and isoenzyme levels have become the final arbiters by which acute myocardial necrosis is documented and the diagnosis of MI is confirmed or excluded. If MI is suspected, levels of creatine kinase (CPK) and its MB fraction (CPK-MB), as well as myoglobin and cardiac-specific troponins (T and I), are measured and repeated approximately eight to 24 hours later.

The association of serum lipids with clinical CAD dates back to the 1940s and 1950s when total cholesterol and triglycerides were linked to atherosclerotic disease in both cross-sectional and prospective studies. In the 1960s and 1970s, focus shifted to the

serum lipoprotein cholesterol fractions, emphasizing the protective value of high-density lipoprotein (HDL) and the proatherogenic association of low-density lipoprotein (LDL) cholesterol.

Angina, myocardial ischemia, and myocardial infarction have been correlated with the presence of angiographically significant CAD (i.e., 50-70% narrowing of one or more coronary arteries). Whereas the likelihood of

significant CAD in the asymptomatic male population might be 5%, the individual with typical angina will have a 90% likelihood of angiographically significant CAD.

Clinical and pathological progression of atherosclerosis Fibroatheroma

single or multiple lipid cores fibrotic/calcific layers

CABG is also often used in double-vessel CAD not amenable to PTCA, especially if the LAD artery is involved and a large amount of myocardium is at risk. Less often, individuals with

single-vessel CAD can be candidates for CABG, especially those with a very proximal LAD lesion before the first septal perforator, just beyond the left main coronary artery, not amenable to PTCA, and with evidence of ischemia in the anterior wall and septum.

Compared with individuals with STEMI infarctions, those infarctions presenting without ST elevation (non-STEMI or NSTEMI) appear to have a

smaller infarction size and a reduced early mortality; however, they appear to be at a higher risk for re-infarction and continuing angina.

Smoking is the third major risk factor for CAD. There is now good evidence that

smoking cessation reduces the risk of cardiovascular events in the elderly, just as it does in the young and middle-aged.

Ultrafast CT scanners (also referred to as electron beam CT or EBCT) take x-ray images of the heart so quickly that they can freeze the motion of the heart and

snap the pictures between beats, avoiding the blurring that would occur with normal CT scans. Conventional scanners require about two seconds to form an image, during which time the heart has contracted twice. The ultrafast CT scanner can take a picture in a tenth of a second.

The classic atheroma or plaque appears as a rounded, raised lesion, white with a yellow core. Usually these plaques cause some degree of

stenosis, narrowing the vascular lumen.

Apolipoproteins (e.g., B, A1, E, Lp[a]), metabolic products (homocysteine), and serum inflammatory markers (C-reactive protein) have also been found to be additional markers of CAD. Genetic markers can also be included as even

stronger predictors of later atherosclerotic sequelae. Similar trends can be identified for other risk factors such as hypertension, diabetes, and obesity.

At autopsy, significant narrowing of two or more coronary arteries is usually seen. Evidence of acute myocardial infarction is found at autopsy in 40-70% of victims of

sudden cardiac death, but various acute triggers can ultimately precipitate a malignant arrhythmia. These triggers include acute myocardial ischemia, hemodynamic factors, electrolyte abnormalities, autonomic influences, and even drug interactions.

In addition, those individuals with severe fixed obstructive coronary artery lesions, upon which coronary artery spasm is

superimposed, are at a greater risk for persistent anginal syndromes, acute myocardial infarction, and death. Long-term survival in variant angina at five years is excellent (89-97%) but will be adversely affected by the extent and severity of CAD.

Clinical and pathological progression of atherosclerosis Complicated lesion

surface defect hematoma-hemorrhage thrombosis

The degree of left ventricular dysfunction is the factor most likely to predict preoperative and long-term mortality. CABG prolongs

survival in high-risk patients when compared with medical therapy alone, but does not "cure" CAD, since these individuals can develop progressive disease in other vessels not grafted or within the bypass grafts themselves.

Coronary angiography will establish the severity and location of coronary artery obstructions. Severity of obstruction refers to

the extent of stenosis and is expressed as a percentage of the coronary artery diameter. A 50-70% stenosis or greater is usually considered significant, implying that the artery has been narrowed to one-quarter of its normal diameter with a concomitant severe decrease in blood flow.

Post-surgical and post-menopausal hormone replacement therapy (HRT) has been recommended in the past, in part based on

theoretical protective effects on atherogenic risk. While previous observational studies had suggested a protective role for estrogen replacement, these results have yet to be confirmed in a published randomized trial.

In almost all cases, coronary angiography is usually performed, with further

therapeutic options, including coronary stenting and CABG surgery, determined based on the individual's response to therapy and the angiographic findings.

Variant angina pectoris has been demonstrated convincingly to be due to coronary artery spasm. Spasm is a

transient, abrupt, marked reduction in the diameter of an epicardial coronary artery resulting in myocardial ischemia. This reduction in the diameter can usually be reversed by nitroglycerin and can occur in either normal or diseased coronary arteries.

Exercise stress tests, the most frequently performed tests for diagnosis and assessment of CAD, are usually done on a

treadmill using standardized protocols (e.g., Bruce, Balke, Naughton) of walking speed and gradients. The individual starts at low workloads and progresses to higher ones, with blood pressure and pulse monitored throughout and multi-lead EKGs obtained prior to, during, and after exercise.

Other, less frequent causes include cardiomyopathy and inherited repolarization abnormalities. The factors that produce fatal arrhythmic events are complex but usually include a

triggering acute event, superimposed on an arrhythmogenic substrate. The anatomic substrate for sudden cardiac death is most frequently a chronically abnormal myocardium harboring various degrees of fibrosis. In most cases, the underlying cause is coronary artery disease.

Severe proximal coronary atherosclerosis of at least one major vessel occurs in approximately

two-thirds of these individuals, and, in those individuals, spasm usually occurs within one centimeter of the organic obstruction. The remaining individuals have normal coronaries in the absence of ischemia.

More recently, this descriptive classification of unstable angina has been extended to include the clinical background for its presentation (e.g., unstable angina after myocardial infarction, post bypass, or post-angioplasty). In these circumstances,

unstable angina possesses specific clinical characteristics, has a different natural history, and can require a different treatment. Finally, special forms of unstable angina can also be individualized because of their distinctive nature·' these include Prinzmetal's variant angina and cocaine intoxication.

Most individuals with unstable angina have multivessel CAD, similar in severity to those with chronic stable effort angina. In approximately 10% of individuals with

unstable angina, coronary angiograms show no significant obstruction. Presumably, most of these people have coronary artery spasm as the basis for ischemia.

In 1959, Prinzmetal described an

unusual syndrome of cardiac pain that occurs almost exclusively at rest, usually is not precipitated by physical exertion or emotional stress and is associated with electrocardiographic ST-segment elevation.

In individuals with unstable angina, CABG is quite successful. Relief of angina pectoris is excellent and prolonged. As with chronic stable angina, however, the beneficial effect diminishes with time. Late return of symptoms after CABG

usually indicates disease of the bypass graft or progression of disease in previously uninvolved native vessels. The recurrence of angina is not influenced by the existence of stable or unstable symptoms before surgery.

In addition, individuals with anatomical factors such as left main stenosis or three-vessel CAD with reduced

ventricular function (ejection fraction 35% or less) have significantly improved survival for up to 15 years after revascularization. People with less severe anatomy can be expected to experience symptom relief, but survival benefit with revascularization is less certain.

Many physicians use a beta-blocker as initial therapy for stable angina, due to its relatively low cost as well as its cardioprotective effects in post-myocardial infarction studies. Most betablockers are generally

well tolerated and are effective in reducing angina frequency and improving exercise tolerance. The choice between the agents is based largely on side effects and personal preference. Important but uncommon adverse effects of beta-blockers include excessive bradycardia, heart block, heart failure, aggravation of claudication, asthma, and depression.

In summary, both the evaluation and treatment of unstable angina are like those for stable angina but are greatly accelerated. The unstable phase is over

when the individual's symptoms have disappeared or become predictable. It is assumed that the active endothelial lesions heal in two or three months, and the individual has entered the stable phase with improved prognosis.

Clinical and pathological progression of atherosclerosis. Initial lesion

• histologically "normal" • macrophage infiltration • isolated foam cells

Clinical and pathological progression of atherosclerosis Intermediate lesion

• intracellular lipid accumulation • small extracellular lipid pools