eMedicine Specialties > Radiology > Cardiac

Coronary Artery Disease

Justin D Pearlman, MD, PhD, ME, MA, Director of Advanced Cardiovascular Imaging, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center

Updated: Nov 3, 2009

Introduction

Background

Coronary artery disease (CAD) is a complex disease that causes reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. The disease may be focal or diffuse. Apart from rare congenital anomalies (birth defects), CAD is usually a degenerative disease, uncommon as a clinical problem before the age of 30 years and common by the age of 60 years. One in four people will have a heart attack. The first recognized symptom may be death. The term coronary is derived from crown, referring to the way these arteries sit on the heart.

X-ray angiography is the criterion standard for delineating the coronary anatomy, but it is inferior to MRI and CT in identifying myocardium with impaired blood delivery, in assessing the functional consequences, and in identifying the development of microvascular collaterals.

MRIs of the coronaries can be used to build 4-dimensional images (3-dimensional beating heart). These images show a single frame, including a cutaway view to show the cardiac interior, the outer surface (no thresholding), and the extracted coronary artery tree including the aortic root.

Elastic-match imaging automatically identifies differences between image volumes. The acquisition of 1 set of contrast-enhanced chest CT images via the coronaries and a nonenhanced set provides a 3-dimensional view of the coronary-artery tree. The nonenhanced volume data were rendered as holographic projections to provide the anatomic context, and the elastic-match coronary tree was overlaid. In addition to automation, this method avoids thresholding so that small branches and filling defects, if present, are represented properly.

When the heart has inadequate blood supply (ie, ischemia), pressure may be felt in the chest that moves to the left arm; one may feel weak, sweaty, or short of breath or nauseated; palpitations (ie, change in heart rhythm) may occur; or there may be a sensation of pressure or tightness just in the chest, neck, or arms. Many patients mistake the heart warning symptoms for heartburn or gas. If symptoms occur that may represent inadequate blood supply to the heart one should rest immediately and take nitroglycerin, if available. If symptoms last more than 5 minutes, occur at rest, or keep coming back, one should call 911, chew a full-sized aspirin (325 mg) if not allergic, and continue taking nitroglycerin every 5 minutes as long as it does not cause dizziness or light-headedness.

For excellent patient education resources, see eMedicine's Cholesterol Center. Also, visit eMedicine's patient education articles Chest Pain, Coronary Heart Disease, and Heart Attack.

Severity of CAD

The severity of CAD is defined several ways: (1) anatomically, by visualizing the blood vessel branches and any blockages to blood flow along the pathways; (2) functionally, by estimating blood delivery to tissue supplied by each branch vessel; and (3) clinically, by determining what symptoms correspond to inadequate blood delivery, what level of activity causes them, what relieves them, and the pattern of occurrences. Such patterns are described as unstable if the pattern includes variable or accelerating frequency, variable or increasing severity or changing character of symptoms, or variable or decreasing exercise threshold or if symptoms continue or recur just after a heart attack.

In addition, one examines the consequences, including the location and extent of reversible and of permanent impairment, motion and thickening of affected segments of the heart, and whether the damage is causing or sustaining life-threatening arrhythmias. One also evaluates the patient's overall cardiac performance, which is typically expressed as the ejection fraction (EF), or percentage of the contents the left ventricle pumps forward in a heartbeat, and exertion tolerance, graded 1-4 (1=normal, 4=bedridden).

The TIMI (Thrombolysis in Myocardial Infarction) risk score looks at 7 factors that point to bad outcomes: age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation greater than 0.5 mm, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. TIMI risk scores have the following risk of all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization within the first 2 weeks: 1=5%, 2=8%, 3=13%, 4=20%, 5=26%, 6/7=41%.¹

Imaging of CAD

At present, achieving the best resolution on images of the coronary arteries requires catheterization, injection of an iodinated contrast agent, and use of a radiographic technique. As an alternative, multidetector-row CT (MDCT) or MRI may be used to clarify coronary anatomy and to determine whether a vessel is occluded.

Stress imaging has a complementary role in depicting zones with inducible ischemia (blood supply inadequate for the demands of the tissue). Stress may be produced with exercise, an infusion of a medication that increases the strength of cardiac contractions (eg, dobutamine), or an infusion of a medication (eg, adenosine, dipyridamole) that dilates the vessels and thereby reduces the delivery of blood to diseased branches.

More than a decade ago, MRI was shown to be capable of imaging the coronary arteries and demonstrating stenoses without catheterization or injection of contrast material.² More recently, MDCT is proving to be a fast and useful alternative for defining the coronary anatomy.³ MRI takes more time than MDCT and generally provides less detail of the coronary anatomy, but it avoids ionizing radiation and the use of iodinated contrast agent.

Advances in MRI and CT have markedly improved the speed and resolution of imaging, making these modalities useful in the clinical evaluation of CAD while improving their safety and convenience. In addition to defining the anatomy, both MRI and CT can be used to identify zones of impaired blood supply by timing of the arrival of contrast agent–labeled blood.

In addition, MRI is useful in identifying the location and thickness of myocardial scars. Although neither MRI nor CT has replaced x-ray angiography (XRA) as the clinical standard for the diagnosis of coronary stenosis, their use in determining if a vessel is open is increasing. Recently, 64-slice multidetector-row CT angiography (CTA) has shown potential as an alternative to x-ray angiography for the identification of coronary blockages.⁴

Assessment of tissue viability

The amount of impairment or damage caused by stenosis obstructing a coronary artery depends on how much of the myocardium the vessel supplies, the severity of the stenosis and any superimposed spasm, the level of demand in the tissue it supplies, and the condition of the tissue it supplies.

When demand exceeds supply, the tissue becomes ischemic, which means blood supply is insufficient to maintain normal metabolism. Myocardial ischemia may cause chest pain, fatigue, shortness of breath, or another form of reduced exertion tolerance. Ischemia may have no symptoms but may be detected as impaired blood delivery, impaired contractile function (wall motion or wall-thickening abnormality on dynamic cardiac imaging series), or interference with the movement of ions (resulting in depolarization and repolarization abnormalities on EKGs as ST-segment shifts, changes in ST and T waves, and/or rhythm abnormalities); and/or it may be detected when a blood test shows a release of enzymes (creatine kinase-MB [CK-MB], troponin-I, troponin-T) from the heart muscle.

Ischemia may deplete high-energy phosphate carriers (eg, creatine, adenosine) that are needed for muscle contraction. Depletion may occur to the point that impaired motion may persist even when ischemia is relieved. Transiently impaired contractile function of muscle that persists after the relief from ischemia is called stun, and long-term dysfunction of viable muscle is called hibernation.

Dead tissue converted to scar likewise loses contractile function. Therefore, a key issue when a region of heart wall shows loss of function is the determination of whether the myocardium is still viable. Persistent wall-motion abnormality at rest shown by imaging (echocardiography, MRI, CT, x-ray angiography) can raise the issue of tissue viability and, in particular, whether repairing a blockage in the blood supply is likely to be beneficial.

If a region is thin and akinetic (no motion), it is more likely to scar (dead myocardium) than if it is not. However, when in doubt, viability tests are appropriate. For example, viability can be identified by performing phosphorus-31 MRI and by reporting for each region the relative concentrations of creatine phosphate; inorganic phosphate; and adenosine monophosphate, diphosphate, and triphosphate.

Although MRI of phosphorylated metabolites and positron emission tomography (PET) of metabolic activity (to assess glucose utilization) can be used to assess tissue viability, an alternative method of equal, if not better, clinical value is imaging by MRI with contrast to identify contrast retention by damaged myocardium. We first observed that phenomenon over a decade ago when studying an animal model of ischemia and infarction while looking at angiogenesis (treatments to promote development of the blood supply).

Another way to identify viability is to examine wall motion at rest and with light stress. Dobutamine stress imaging may be performed with MRI or echocardiography. Dobutamine stress tests are used to detect viability by demonstrating dose-related increases in contractility if the tissue is viable. An increase in the dose of dobutamine may subsequently elicit a decline in contractility associated with induced ischemia — that is, a biphasic response, indicating viable but threatened myocardium.

Early in the development of perfusion imaging^5,6 , we observed retention of gadolinium contrast by injured myocardium. Normally, a bolus of contrast agent washes out of the heart walls within 5-10 minutes. Any contrast agent seen in the heart after the agent has washed out of normal zones demarcates injured myocardium. This technique has since been called MRI scar mapping or delayed enhancement imaging. The fraction of wall thickness that retains gadolinium-based contrast agent 10-20 minutes after a bolus infusion of 20 mL/75 kg indicates viability. The result is an excellent predictor of potential for functional recovery. If the scar is less than one third the thickness of the wall, improvement with revascularization is likely. However, if the scar is more than two thirds the thickness of the wall, improvement after revascularization is unlikely.

MRI scar maps depict contrast retention due to cell disruption. Although acute injury results in slightly enlarged zones of retained contrast agent on MRI, after a week, the defined zone appears the same months to years later and it corresponds on pathology to dead tissue.

Unfortunately, in patients with poor renal function, gadolinium contrast may stay in the body long enough to cause a potentially disabling inflammatory reaction called nephrogenic systemic sclerosis, also known as nephrogenic fibrosing dermopathy (NSF/NFD). That condition has been linked to all the gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape. Patients with poor renal function undergoing dialysis have been imaged with coordinated extra dialysis runs to clear the agent.

Pathophysiology

Injury and inflammation

In coronary artery disease (CAD), injury to the endothelial lining of arteries, active uptake by the vascular wall of cholesterol esters, inflammatory reaction, thrombosis, calcification, and hemorrhage all contribute to arteriosclerosis or hardening of an artery wall. Levels of the acute-phase reactant inflammation markers, C-reactive protein and serum amyloid-A protein, are elevated in patients with unstable angina and infarction. Inflammatory cells, including abnormal T-lymphocytes, are seen during autopsy in patients with coronary disease or inflammatory diseases. Patients undergoing a heart attack have elevated white blood counts. Statin medications, which have anti-inflammatory activity, reduce the risk of death from heart attack even when given acutely, without time for the benefit from lowering LDL (low-density lipoprotein cholesterol). Thus, inflammation plays a major role in CAD and heart attacks.^7,8

Whether inflammation causes and promotes the disease or whether it is merely a consequence and marker for a poor prognosis is not entirely clear. In a study of 121,700 women, those with rheumatoid arthritis had twice as many heart attacks as did women without inflammatory disease.⁹ Inflammation has also been implicated in elevating the risk of coronary disease in association with metabolic syndrome (obesity, hypertension, insulin resistance, and dyslipidemia). Hostility (presumably because of changes in hormone levels) is also a risk factor.¹⁰ Patients older than 65 years with antibodies to herpes simplex virus have increased risk of heart attack. The CD3+ lymphocytes, inflammatory cells that accumulate in atherosclerotic plaque, often have DNA to the bacteria Chlamydia pneumoniae, suggesting infection may also contribute to CAD.

Platelets and lipoproteins

In a study of patients with a heart attack who underwent coronary angiography within the previous year, one half of the culprit lesions were narrowed less than 70%; and with non-Q wave MI, less than half had a definite culprit stenosis. Other studies have had differing results, but it is clear that a lesion causing mild stenosis may rupture suddenly and cause bleeding into the wall of the vessel (plaque hemorrhage), promoting occlusion of the vessel because of thrombosis. The final step explains why antiplatelet medications, such as aspirin, can help in preventing heart attack. Thrombotic occlusion of the vessel occurs when platelets stick together to form an obstructive plug; therefore, the inhibition of platelet adhesion by aspirin can prevent thrombosis.

Cholesterol-lowering medications work by reducing or reversing the lipid deposition into the arterial wall in areas of flow stress, and many also have anti-inflammatory effects. Lipid levels can be improved by decreasing the amount of circulating low-density lipoprotein cholesterol (LDL-C) by changing the person's diet, by inhibiting the production of LDL-C in the liver, and/or by decreasing the absorption of LDL-C in the intestines. Furthermore, the rate of uptake of LDL-C into the vessel wall is sensitive to oxidation status, because oxidized LDL-C has a 50-fold increased rate of uptake.

Antioxidants have been suggested as a means to slow the process. In the Women's Health Initiative, patients who took vitamin C supplements had nearly one third fewer heart attacks than those who did not (relative risk of 0.72 and 95% confidence interval of 0.61-0.86 after adjustments were made for age, smoking, and other risk factors).¹¹ Consuming omega-3 fatty acids and drinking a glass of grape juice or red wine a day may help avert heart attacks by similar means. However, trials with vitamin E as an antioxidant have not lowered risk. 

High-density lipoprotein cholesterol (HDL-C) transports lipids from the body back to the liver. Exercise that keeps a heart rate above 130 bpm for at least 10 minutes every other day increases HDL-C levels. Niacin at 2000-3000 mg per day also helps elevate HDL-C values, as well as improve another risk factor, lipoprotein(a). Many patients experience a hot flash or flushed feeling with supplemental niacin, which is often reduced by taking it with 2 glasses of water, with dinner, or a half-hour after taking 325 mg of aspirin. No-flush niacin may not release enough niacin to be effective.

A new class of medication, cholesteryl ester transfer protein (CETP) inhibitors (eg, torcetrapib), was specifically designed to elevate HDL-C concentrations.¹² It was removed from the market after study in combination with atorvastatin showed increased mortality. Each study arm (atorvastatin alone vs torcetrapib + atorvastatin ) had 7500 patients enrolled; the arm receiving atorvastatin alone had 51 deaths, while the torcetrapib + atorvastatin arm had 82 deaths.

Calcification

Chronic lesions may become calcified and therefore provide evidence of the disease process, as seen on CT or electron-beam tomography (EBT). However, the calcification does not necessarily indicate the lesions that pose the greatest risk. In fact, calcified lesions may be more stable than noncalcified ones. However, evidence also suggests that a soft plaque has an increased capacity to remodel outward; therefore, calcification of a vessel is a significant risk factor. Once the degree of narrowing exceeds 50%, stable narrowing of an artery typically results in exercise limitations, which is often experienced as a squeezing chest tightness that may radiate to the jaw or left arm. This tightness (Heberden angina ) is predictable at a specific level of activity.

Angina Pectoris

Angina pectoris (constrictive discomfort in the chest) represents the classic symptoms of CAD.
Many patients do not have classic symptoms. CAD symptoms in patients who have no tightness or pressure in the chest are described as "angina equivalents."

Heberden described tightness in the chest predictable with exertion as a symptom of a dangerous disease that he classified as spasmodic:

"But there is a disorder of the breast marked with strong and peculiar symptoms, considerable for the kind of danger belonging to it, and not extremely rare, which deserves to be mentioned more at length. The seat of it, and sense of strangling, and anxiety with which it is attended, may make it not improperly be called angina pectoris. They who are afflicted with it, are seized while they are walking, (more especially if it be up hill, and soon after eating) with a painful and most disagreeable sensation in the breast, which seems as if it would extinguish life, if it were to increase or continue; but the moment they stand still, all this uneasiness vanishes. "¹³

Patients with diabetes or those who are older than 60 years commonly have no chest pain during ischemia but instead have impaired wall function, which may result in shortness of breath or changes in rhythm that may remain unnoticed or may cause palpitations or syncope. Therefore, stress imaging may help in identifying exercise-inducible ischemia with no symptoms.

Angina lasting more than 10 minutes may actuate a heart attack (by producing ischemia sufficient to cause permanent damage, whereby scar replaces the heart muscle). The mechanism of permanent injury is called apoptosis (cell suicide). Teleologically, it is better to build scar tissue and remove the injured muscle than to have just injured muscle incapable of self-repair that may cause a rupture of the heart wall.

A threatened heart attack is an emergency because it is life threatening and because remaining threat of injury may be reversible with prompt appropriate intervention. The diagnosis should be achieved as quickly as possible. At the early stages, simply chewing an aspirin tablet and/or taking nitroglycerin can often stop the immediate threat.

Appropriate and timely treatment

When symptoms suggestive of a possible threatened heart attack are present (persisting chest pain or pressure radiating to 1 or both arms or jaw; or unexplained shortness of breath, weakness, sudden sweating, or a serious arrhythmia), an electrocardiogram should be obtained promptly, with continual monitoring for arrhythmia or ischemia (impaired blood supply).

Ambulances have both EKG and rhythm and oxygenation monitoring equipment, as do emergency departments. The EKG can show ST segment shifts and/or T-wave inversions as signs of heart ischemia or injury. However, there are electrically silent areas in the standard monitors. A 12-lead EKG does not detect all of the electrical warning signs of heart damage; more extensive thoracic coverage is desirable.

Emergency care offers additional medications that can stop a threatened heart attack (eg, intravenous nitrates, beta-blockers, thrombolytics, anticoagulants), as well as quick transport of the patient to the catheterization laboratory for definitive diagnosis and treatment. Experienced cardiac catheterization laboratories are prepared to repair coronary arteries typically within an hour at any time of the day or night on an emergency basis. One hour has been described as equipoise, or a crossover point; if it will take longer than an hour to get coronary intervention by catheter, then lytics are favored. Contraindications to lytics (clot-busting medication) include the following:

• Prior intracranial hemorrhage
• Cerebral AV malformation 
• Cerebral neoplasm
• Ischemic stroke within 3 months
• Closed head trauma/subdural hematoma within 3 months
• Recent spinal surgery
• Uncontrolled severe hypertension

There is some evidence that in cases of acute ST-elevation MI, if there is a moderate likelihood that it will take longer than an hour to get a catheter intervention, half-dose lytics should be provided, followed promptly by percutaneous catheter intervention (PCI). That strategy is called facilitated PCI. However, the FINESSE¹⁴ and ASSENT¹⁵ clinical trials have argued against that approach. In those studies, patients who went directly to catheterization without half-dose lytic plus abciximab, or abciximab alone, did as well or better even if time to PCI was 1-4 hours. If a regimen is developed with a much lower incidence of bleeding complications (particularly intracranial hemorrhage), facilitated PCI may regain support. If symptoms were prominent and then stopped, that suggests the damage has been curtailed.

If threatened heart attack goes untreated, the tissue that depends on the interrupted blood supply eventually dies, and progressive amounts of irreversible damage accrue. The damaged area is typically small even after occlusion if it is effectively treated within an hour. Delay of more than an hour after occlusion is sufficient to produce life-threatening permanent damage to the heart wall, yet some benefit can still be obtained after 6 hours, or longer, if the damage is incomplete at that time.

Even if revascularization does not prevent damage, it may improve repair in terms of the strength of the scar and the quality of heart remodeling to compensate for the damage (open-artery hypothesis). The duration of chest pain, the timing and pattern of EKG changes, and the timing and area under the curve of enzyme elevation are clues to duration of ongoing damage.

Frequency

United States

Coronary artery disease (CAD) accounts for more than 650,000 deaths per year in the United States, including more than 25% of deaths in persons older than 35 years. Each year, 1.25 million acute myocardial infarctions (MIs) occur. Of these, more than one half occur without previously recognized symptoms. Cardiovascular disease is responsible for more than 3 times as many deaths as all forms of cancer combined. In the United States, spending on CAD exceeds $80 billion per year. One third of people who have a heart attack and who do not receive immediate medical attention die.

International

Coronary artery disease (CAD) is the leading cause of death in developed countries. The incidence is rising in Central Europe and in Eastern Europe, but it is low in Japan. Epidemiologic studies of differences among countries and regions revealed dietary and environmental factors that contribute to disease (eg, saturated fat, cholesterol, abdominal obesity, smoking, exposure to second-hand smoke) and also factors that protect against it (eg, fish oils, vitamin C and other antioxidants, red wine or grape juice, anti-inflammatory agents).

Mortality/Morbidity

In one half of the population, the first recognized symptom of CAD is MI, which is fatal in nearly one half of patients. Taking aspirin at the onset of a heart attack reduces mortality rates.

For individuals who arrive awake at a hospital, short-term survival is good, but long-term survival depends on the anatomy of the coronary arteries and on treatment. Survival after a heart attack has been continually improving over the last 30 years, but the incidence of new heart attacks has recently stabilized.

With the obstruction of 3 vessels, the left main coronary artery, or the equivalent combination of proximal anterior descending and circumflex disease plus reduced heart function (abnormal ejection fraction [EF]), bypass surgery may provide a survival benefit. However, similarly good results may be achievable with drug-eluting stents and complete revascularization by percutaneous intervention (PCI, catheterization).

With 1- or 2-vessel disease that is not equivalent to involvement of the left main coronary artery, medical treatment and catheter interventions are equally good, except in patients with diabetes, in whom surgery has provided the best long-term results. At some centers, catheter intervention may be used to manage 3-vessel disease (eg, with normal function). However, when catheter intervention is used in an acutely ill patient, the focus is on the culprit lesion, and repair of other blockages is deferred.

Morbidity depends on the patient's exercise tolerance and on the amount of damage, which is commonly assessed by using the EF. An EF below 40% typically limits a person's activity, an EF below 30% results in severe limitations plus significantly increases the risk of deadly arrhythmias, and an EF below 20% causes problems at rest.

In patients in whom damage is severe enough to cause clinically significant congestive heart failure, one half die within 5 years. The outlook is improving with rapid access to healthcare and with advancements in treatment. As shown in experimental studies, injected muscle precursor cells may be able to repair dead regions.¹⁶ In clinical studies, implantation of an automated defibrillator prolonged life, reducing the post-MI mortality rate by 31% in patients with persistently low EF.¹⁷

Race

Mortality rates in men do not differ by race, but African-American women have the highest risk of death from heart disease, and their rate of heart attacks is increasing. Native Americans, particularly those living in North Dakota and South Dakota, also have a higher risk for heart disease than do whites. Hispanics have the lowest risk for heart disease compared with all these groups.

African Americans have particular biologic and social risks, including the following:

• High prevalence of diabetes and hypertension
• Poor diet
• High stress levels
• Poor access to health care
• Possible genetic trait that increases the danger of triglycerides, especially in women
• Possibly decreased production of nitric oxide (which is critical for increasing blood flow) in response to stress

To study the effect of discrimination, actors portrayed patients presenting with symptoms of heart disease in 1 study.¹⁸ African-American women were 60% less likely to receive aggressive (and expensive) diagnostic tests than African-American men or whites. More recently, referral rates for intervention were similar for white or black individuals, but African-American patients accepted surgery less often than white patients.¹⁹

African Americans account for 13% of the United States population but only 2-9% of control subjects in most major research trials. Therefore, major studies have been focused more on the treatment of white patients than on black patients, and knowledge of what is best for patients of other races is limited.

Sex

In individuals younger than 65 years who do not smoke and who avoid second-hand smoke, CAD is primarily a disease of men. The difference is attributed to the protective effects of estrogen. Risk factors for significant coronary obstructions that affect both men and women are smoking; exposure to second-hand smoke; diabetes; poor diet; elevated levels of homocysteine, LDL-C, or triglycerides; low HDL-C levels; hypertension; use of birth control pills; and a sedentary lifestyle.

Because more research has been completed in men than in women, less is known about the reliability of screening women. In addition, vascular tone or spasm may play a larger role in women than in men. Therefore, many recommend a decreased threshold for imaging of the coronary arteries in any woman who complains of chest pain, without a consideration of whether the pain is predictable at a particular level of exercise.

Case-fatality rates are higher in women than men. Noninvasive testing in women has been controversial because of a perception of diminished accuracy, limited female representation, and technical limitations (eg, breast artifact). Exercise treadmill testing has an improved accuracy when multiple risk parameters (eg, ST deviation, chest pain, exercise time) are included in the interpretation. For women, a low-risk Duke treadmill score is predictive of a 5-year survival rate of 97%, and fewer than 20% of patients have obstructive disease.

Calcium scoring in women has a sensitivity of 88% and specificity of 49%; values for exercise echocardiography are 86% and 79%, respectively. A quantitative evaluation of perfusion may improve the precision of risk assessment.

Age

• Fatty streaks in vascular walls are observed in people of all ages, even infants. Children may have cardiac ischemia as a result of a stenotic or acutely angled origin of a vessel or another anomaly, such as a vessel pinched between the aorta and pulmonary artery or trapped under a myocardial bridge.
• In an autopsy series of 19-year-old soldiers, coronary lesions were prevalent but amounted to only mild stenosis.
• After the age of 35 years, clinically significant coronary artery disease (CAD) is prevalent in men. Serious disease at that age typically results from cocaine use; smoking or exposure to second-hand smoke; diabetes; or other predisposing factors, such as low HDL, high LDL, beta-subtype of LDL (determined by LDL fractionation), lipoprotein(a), C-reactive protein (CRP), or homocysteine. The lifetime incidence of CAD after the age of 35 years exceeds 1 in 4 people. Autopsy series revealed that 25% of men younger than 25 years and 75% of men older than 25 years have a clinically significant coronary lesion. One in every 4 adults has clinically significant atherosclerotic disease.

Anatomy

Coronary artery disease (CAD) may affect a large coronary artery near the vessel origin at the aortic root (proximal segment) or a small branch vessel far from its origin (distal segment). CAD may affect all 3 of the major supply arteries to the heart: the left anterior descending (LAD) artery, the left circumflex artery (LCX), and the right coronary artery (RCA). Therefore, a simple ranking of disease severity is 1-, 2-, or 3-vessel disease. For this purpose, disease is defined as the presence of 1 or more areas of narrowing of a vessel or major branch by 50% or more from its expected normal diameter (eg, compared with a nearby proximal normal segment without intervening branches). Therefore, 50% narrowing in the LAD, LCX, and RCA is considered 3-vessel disease comparisons of surgery, medical therapy, and catheter interventions.

A 50% reduction in vascular diameter is a reasonable definition of a clinically significant lesion because lesions with 50% or greater stenosis are commonly responsible for heart attacks. The definition is imperfect in that an unstable lesion with only 30% stenosis can also cause a heart attack, and lesions that cause angina are typically stenoses of 70% or greater. It is also imperfect in that stenosis based on diameter does not account for the length of the lesion or its entrance and exit effects (funnel versus abrupt), all of which affect flow reduction. Therefore, clinical judgment is also need in assessing the clinical significance of a lesion, such as whether it supplies a territory with demonstrated jeopardy on stress testing or perfusion assessment. In addition, a Doppler flow wire or intravascular ultrasonography (IVUS) may be applied and/or flow reserve may be estimated to assess the hemodynamic significance of a coronary lesion.

In most people, the LAD and LCX have a common origin from the left coronary sinus of the aortic root, a short vessel called the left main coronary artery. A third of the population has a third artery between these 2 called the ramus intermedius. In uncommon cases, the LAD and LCX have separate origins, both of which arise from the left coronary sinus; or in rare cases (1 in 1000 people), the LCX may originate in another sinus.

In as many as 20% of individuals, the origins are higher than usual, at the junction with the tubular portion of the aorta (sinotubular junction, or STJ). The RCA has a separate origin in the right coronary sinus, but sometimes its origin is at the sinotubular junction (9%) or higher (1%). The aortic cusps corresponding to the coronary arteries normally are anterior and face the pulmonary valve. The third cusp (posterior cusp), just above the aortic valve, typically has no arterial branch, but in a quarter of the population, it gives rise to the right conus artery, a small vessel that is usually the highest branch of the right coronary artery. Anatomic variants are common.

The branches of the LAD are called diagonals and are successively labeled D1, D2, etc. The portion from the left main coronary artery to the first diagonal is called the proximal segment of the LAD. The portion between D1 and D2 is the middle segment, and that beyond D2 is called the distal segment. The distal segment typically covers the anterior aspect of the apex of the left ventricle (LV). However, in 12% of the population, it wraps around to cover the inferior surface of the apex as well (wrap-around LAD). In addition to diagonal branches, the LAD gives off numerous, small septal perforators that supply the anterior two thirds of the intraventricular septum.

The branches of the LCX are called obtuse marginal branches and numbered sequentially (OM1, OM2, etc). The LCX often courses around the base of the heart near the atrioventricular (AV) groove. In 20% of patients, the LCX reaches the crux, where the AV groove meets the posterior interventricular septum and turns to supply the inferior surface of the heart as the posterior descending artery, also known as the posterior interventricular artery. In 85% of people, this artery is a distal continuation of the RCA. If the posterior descending artery stems from the RCA, the circulation is described as right dominant, and if it comes from the LCX, the supply system is called left dominant. In about 5% of patients, both the RCA and the LCX contribute to the PDA (posterior descending artery) territory, a condition described as codominance. The dominant artery delivers blood to the posterior one third of the septum and the AV node, which penetrates the center of the heart from the crux.

The proximal RCA usually (in 60% of the population) supplies the sinoatrial node via a branch that runs between the aortic root and the superior vena cava. In a third of the population, the sinoatrial node comes from the left, and in some individuals, it is supplied form both the right and the left. The RCA courses near the AV groove, extending inferiorly to the right toward the crux (the intersection of the AV groove and the interventricular node). The RCA gives off a large branch called the acute marginal branch before it reaches the crux. The RCA may continue in the AV groove past the crux with LV extension branches, or it may terminate short of the crux. The proximal RCA branches typically include the left atrial artery, the conus artery, the sinoatrial node artery (in 55% of the population), the right atrial artery, and the right or acute marginal artery.

Presentation

Risk factors for coronary artery disease (CAD) are classified as modifiable or unmodifiable.

Modifiable risk factors include smoking, exposure to second-hand smoke, hypertension, high levels of low density cholesterol (LDL-C) levels, low levels of high density cholesterol (HDL-C) levels, high triglyceride levels, high levels of lipoprotein(a), diabetes, abdominal obesity, sedentary lifestyle, avoidance or sudden challenges or stresses, snow shoveling, inadequate beta-blockade, high homocysteine levels, high levels of C-reactive protein (which indicates inflammation), and poor recognition of symptoms and the need to relieve them promptly and fully. HDL should be high (>40 mg/dL or >1 mMol/L in men, >50 or 1.25 in women) and LDL should be low (recommended target ranging from <160 in patients with low risk to <70 in patients with CAD).

Although some physicians are guided by the ratio of HDL to LDL, these function as independent factors that can be optimized separately. LDL is typically lowered by statins, and HDL raised by exercise and niacin. Although high homocysteine is a marker for elevated risk of atherosclerosis and CAD and it is modifiable (lowered by B-12 and folate), trials of treatment have not shown that lowering the homocysteine level reduces the risk of CAD. For patients with a triglyceride concentration of less than 400 mg/dL (<4.5 mmol/L), the LDL-C value can be estimated from a fasting sample of total cholesterol, HDL, and triglycerides by using the following equation:

LDL-C concentration = Total cholesterol concentration - HDL-C concentration - (triglyceride concenration/5).

Alternatively, LDL can be measured directly (D-LDL) without requiring fasting.

Treatment before evidence of disease appears is called primary prevention; treatment afterward is called secondary prevention.

Target levels for LDL-C have been lowered from 160 mg/dL to <100 mg/dL, depending on overall risk, down to a target of <70 mg/dL for patients with known CAD, because the lower levels have proved to help reduce recurrence of heart attack²⁰ .

Cholesterol synthetase inhibitors confer a benefit even in patients with normal LDL-C levels, possibly because of an anti-inflammatory effect. Skin flushing may limit the use of niacin; effects may be lessened if niacin is taken with 2 glasses of water, with dinner, or half an hour after aspirin or if slow-release preparations are used. However, no-flush versions of niacin may not work because it may not release enough niacin to be effective.

Unmodifiable risk factors include age, male sex, and family history. Aggressive lowering of cholesterol levels has reduced individual morbidity and mortality rates in some groups but not the cardiovascular death rate for the overall population.

CAD should be suspected in a patient with any symptoms that may represent cardiac ischemia, such as an ache, pressure, pain, other discomfort, or possibly just decreased activity tolerance due to fatigue, shortness of breath, or palpitations. Discomfort or pressure is especially suggestive when it occurs in the chest, left arm, jaw, or upper abdomen, particularly if it is triggered by exertion, exposure to cold, or shaving and if it is relieved by rest or nitrates. The feeling of discomfort or pressure often radiates from 1 location to another, such as from behind the sternum and down the left arm. Nausea, diaphoresis, and a duration longer than 10 minutes suggest that the episode is turning into a heart attack (cell death).

Cardiac ischemia without chest pain represents a defective warning system regarding angina; this presentation is not uncommon in people older than 60 years or in those with diabetes. Patients may have only decreased exertion tolerance, dyspnea, or palpitations triggered by exertion. Although a timely EKG may show silent ischemia, some areas of the heart are electrically silent, which means that they are not represented on the standard 12-lead EKG (more complete thoracic coverage has been shown to be superior).

Perfusion or wall-motion imaging can help in identifying the problem. Such patients can establish a regular exercise program, such as going easy on even dates and performing a 10-minute reproducible challenge on odd dates, to serve both as a minimal prescription for cardiovascular fitness and as a screening exercise challenge for painless inducible ischemia (a daily regimen and alternating with a light, no-target workload improves compliance for many patients, and an every-other-day cardiovascular challenge suffices for cardiovascular fitness). If the level of challenge is limited by dyspnea (shortness of breath) and fatigue, the patient should notify the physician for consideration of a formal stress test with imaging or evaluation for other possible causes of decreased exertion tolerance, such as salt overload or pulmonary disease.²¹

Preferred Examination

Elastic-match imaging can be used to identify collateral-dependent myocardium. Left and middle images are baseline and peak-arrival collateral-sensitive MRIs demarcating microvascular development. Right image, based on CT imaging of the heart, was obtained with and without back pressure to nullify collateral-dependent perfusion; white volume on represents collateral-dependent myocardium. The extent of collateral-dependent myocardium corresponds well on MRI and CT (r = 0.95).

Contrast-labeled blood to the heart is used to identify the territory at risk. The results of this assessment of the delayed arrival compares favorably to the findings of radionuclide stress imaging, and stress induction of ischemia is not required to identify the zone at risk.

Space-time maps show the history of blood arrival to all layers of myocardium on a 2-dimensional map. The indentation indicates the severity of the defect in blood delivery, and the length indicates the size as a percentage of the myocardium, without the need for stress induction of ischemia. In addition to the safety advantage, this method is also more reproducible than stress testing, which is useful in assessing the effect of therapy.

Compared with radionuclide images of blood delivery, MRIs and CT scans improve resolution, depiction of the functional effect and the relationship to the coronary supply, and identification of the area at risk without stress. The advantage of radionuclide imaging is primarily its predictive value; stress echocardiography has similar predictive value. MRI and CT have been less available than other studies; therefore, data on their value are relatively limited.

X-ray angiography is the criterion standard for delineating the coronary anatomy, but it is inferior to MRI and CT in identifying myocardium with impaired blood delivery, in assessing the functional consequences, and in identifying the development of microvascular collaterals.

The patient's clinical history (age, symptoms, risk factors) provides an estimate of disease likelihood. The basic screening test is stress EKG, which can adjust prognosis depending on the pretest likelihood of disease. Generally, if the patient has no symptoms and the resting and stress EKGs are normal, the risk of mortality in the next year is low. However, the predictive accuracy of EKG even at peak stress as part of stress testing overall is not good, with as much as one half of all cases of disease missed by EKG. The simple addition of stress testing of B-type natriuretic peptide (BNP) levels in the blood markedly improves the predictive accuracy.²² Other ways to improve accuracy are nuclear imaging, echocardiography, MRI, or CT.

Stress nuclear imaging is widely used to assess the patient's exercise tolerance and to identify zones of inducible ischemia (jeopardized myocardium), which is useful information, even after x-ray angiography is performed. PET offers similar rest-stress data and is superior for identifying viable myocardium. Jeopardy and viability are important issues, because if the myocardium is not at risk or if it is not viable, revascularization (bypass or angioplasty) will not help that part of the heart.

Echocardiography to identify wall motion abnormalities has a similar predictive accuracy in patients with intermediate suspicion of CAD, estimated at 80-90%. Echocardiography avoids radiation exposure, which may cause as much as 1 new cancer for every thousand patients studied, but radionuclide imaging (thallium, sestamibi) is preferred if the patient already has old wall motion abnormalities or has poor echo windows (lung blocks the views). Exercise stress echo may be performed before and after treadmill exercise or during exercise on a supine bicycle. The latter requires more cooperation but allows imaging at every stage, so it may avoid false negatives from rapid recovery or from involvement of all areas (balanced ischemia).

MRI and CT have markedly improved the ability to depict zones of impaired blood supply and to display the coronary anatomy. MRI and CT do not require stress; they offer sensitivity and specificity similar to those of nuclear imaging; they achieve resolution better than that of nuclear imaging; and they can demonstrate the 3-dimensional (3D) coronary anatomy.²³ Therefore, MRI and CT complement the combination of stress test and catheterization, and in some settings, MRI and/or CT may replace them (eg, by demonstrating normal results).

EBT offers similar value. EBT is a form of CT in which an electron beam, rather than the entire x-ray source, is rotated around the patient. Also, EBT and CT have been used as a screening test to screen for calcifications in the coronary arteries as a marker for risk of coronary disease in young patients.

To monitor angiogenesis, collateral-sensitive and delayed-arrival MRI appear to be far more sensitive than any other technique. Collateral-sensitive MRI generates a dark flare of susceptibility effect due to sparse neovascular development at an early stage while suppressing a similar effect from the LV. This finding is a strong predictor (r = 0.93) of improved blood delivery.

Data from quantitative studies of the extent of delayed arrival in humans and from double-blind postmortem evaluations in porcine models of chronic myocardial ischemia and angiogenesis have validated this method.⁵ This finding clearly distinguishes angiogenic treatment from control at 4 weeks after treatment, and the benefit is followed by improvements in wall motion (serial motion assessment by reference tracking [SMART] measurements).²⁴

Limitations of Techniques

X-ray angiography is considered the criterion standard for evaluating coronary artery stenosis. Flow limitations may be estimated by using the TIMI (Thrombolysis in Myocardial Infarction)score and confirmed by using a flow wire or by performing IVUS.²⁵ If x-ray angiography fails to depict a culprit lesion and if cardiac ischemia is inducible, the patient may have syndrome X (microvascular disease).

X-ray angiography requires the use of iodine, which may cause serious allergic reactions, including anaphylaxis and also renal failure. Use of large volumes of saline and the antioxidant acetylcysteine may help prevent renal failure. The catheterization procedure can induce vessel spasm and/or tear the lining of a vessel, resulting in occlusion and, possibly, death in a patient who may not have had coronary artery disease (CAD). The procedure can also result in embolism, which may cause stroke or limb loss. Nerve damage, infection, and other complications are possible as well. The death rate is approximately 0.1%.

Nuclear imaging produces low-resolution images that may depict an apparent defect resulting from breast tissue, hiccups, paradoxical septal motion, or other confounding factors. Nuclear imaging may fail to depict disease because of submaximal stress. Tomographic imaging, attenuation correction, or PET substantively eliminate the problems resulting from breast attenuation. The newer combinations of nuclear imaging with CT enable the most accurate correction of nuclear event maps for attenuation by overlying tissues.

MRI requires special precautions in patients with pacemakers or recently placed aneurysm clip. Patients with claustrophobia require premedication, mirrors, and/or an open magnet. Many magnets do not accommodate patients who weigh more than 300 lb. Arrhythmias commonly lower image quality.

CT contrast agents usually contain iodine, which may cause an allergic reaction and possibly anaphylaxis. Nonionic contrast material reduces the risk of harm, as does pretreatment with steroids. Gadopentetate dimeglumine, the contrast agent used for MRI, may be used for CT if patients are allergic to iodine-based media. CT uses X-rays typically equivalent to the dose needed for about 200 chest radiographs. A single routine CT study in a child increases the lifetime risk of cancer by 0.35% per scan.²⁶ In adults, the lifetime risk of cancer may be as high as 2% with annual CT screening.

Differential Diagnoses

Radiography

X-ray angiography is the criterion standard for delineating the coronary anatomy, but it is inferior to MRI and CT in identifying myocardium with impaired blood delivery, in assessing the functional consequences, and in identifying the development of microvascular collaterals.

Findings

Coronary angiography shows where vessels originate, how they branch, whether they have obstructions or dissections or thrombi, the degree of any obstructions, and which territories they supply. Some key questions answered during an examination of the anatomy include the following:

• Does a coronary artery pass between the aorta and pulmonary artery where it may get pinched?
• Does a segment tunnel under a myocardial bridge?
• Which pathway supplies the posterior surface? Is it the right, left circumflex, or both? That is, is it right dominant, left dominant, or cdominant?
• Does the LAD wrap around the apex to supply the distal diaphragmatic surface?
• What vessel supplies the AV node? Is its blood supply impaired?
• If an infarct is present, which is the infarct-related artery?
• If abnormal wall motion is seen, which branch obstruction accounts for it?
• Are any bypass-graft vessels present? If so, where do they originate (left internal mammary, saphenous vein graft from anterior aortic root)? Are they long or short, where do they connect, and how (end to side, side to side)?

The caliber of vessels may be estimated by comparing them with the known diameter of the catheter if it appears on the image. The reviewer should take into account the fact that magnifications differ at different distances from the source to the intensifier with x-ray projection angiography.

After describing the anatomy, note the location, percent narrowing, and character of all focal obstructions (stenoses).

• For each lesion, is it concentric (symmetric) or eccentric (1 sided)?
• Is it long or short?
• Does it abut a branch vessel (which may be lost after intervention)?
• Is it calcified?
• Is any thrombus demonstrated?
• Is evidence of intimal tear demonstrated?
• Is evidence of vessel spasm demonstrated?
• Is diffuse narrowing demonstrated?

The flow of contrast agent–labeled blood offers useful information. TIMI criteria may be applied to determine whether the distribution of contrast material is TIMI 0 (incomplete, fails to fill branches and distal part of the vessel), TIMI 1 (slow but complete), or TIMI 2 (brisk and complete). When imaging is performed at a rate of 30 frames per second, the number of frames it takes for a vessel to completely fill may be assessed. The normal number is approximately 21 frames. Filling takes longer in patients with disease than in healthy people, not only in the diseased vessel but also in normal vessels.

Consider how findings may affect possible interventions and report them accordingly. Clinically significant narrowing in the left main coronary artery is a medical emergency because of the amount of myocardium at risk. Other patterns of disease can pose similar risk; examples are proximal disease in both the LAD and a dominant right or left circumflex vessel.

• What is the caliber of distal vessels that may support a bypass graft?
• Are they calcified?
• Is any stenosis near a branch point (such that balloon angioplasty of the lesion may obstruct a branch artery)?
• How long is the left main coronary artery?
• How much myocardium is at risk?

Examine images for ancillary findings.

• Which calcifications move with the heart?
• Is the mitral valve annulus calcified?
• Is the aortic root or the aortic valve calcified?
• Are valve rings, bypass vessel rings or clips, stents, sternal wires, or other evidence of prior surgeries noted?
• If pacer wires are noted, where do they end?
• Does evidence exist of chamber enlargement, aneurysm, cardiac displacement, abnormal pulmonary venous return, unusual persistence of fetal structures, or other variants?

If left ventriculography is performed, examine LV function for the EF, regional wall-motion abnormalities, and valve integrity. Hypokinesis indicates educed motion, akinesis indicates no motion, and dyskinesis indicates reversed motion, such as ballooning outward during systole. Note any leakage of contrast material back into the left atrium and any restriction of the valve leaflets.

At the time of coronary angiography, the same set of tools can be used to examine other vessels (eg, renal and carotid arteries).²⁷

Degree of Confidence

X-ray angiography (XRA) is the standard for identifying the coronary anatomy and stenoses. In select cases, alternative imaging may appear superior, but be careful to distinguish between high-quality or good-looking pictures and the reliability of the results. X-ray angiography may provide a false-negative result if a branch vessel is occluded at its origin, if the disease is asymmetrical, or if the lesion is cracked, such that the contrast agent can extend close to the full diameter of the vessel even though the vessel cross-sectional area is severely reduced (eg, a star-shaped lesion).

It is possible to miss a lesion that is hidden behind another vessel, but that problem is generally resolved by angled views and by moving the camera (panning) during image collection. If the significance of an obstruction is unclear by XRA, intravascular ultrasound (IVUS) or a flow wire may be used to clarify its spatial extent in relation to the vessel lumen or its impact on flow down a particular branch vessel. A vasodilator may be delivered to assess flow reserve. X-ray angiography is not a good detector of small vessel disease, epitomized by cardiac syndrome-X.

Stress EKG predictive accuracy can be as low as 50%, but it rises above 75% if combined with proBNP blood testing.²² Stress imaging accuracy for detection of coronary artery disease (CAD) ranges from 70-90% if the target stress level is achieved while off antianginal medications.

Treadmill or bicycle stress testing is generally preferred, followed by dobutamine stress testing, then adenosine combined with low level exercise. Adenosine or dipyridamole alone is less reliable. Chest pain during a dipyridamole stress test is not uncommon in the absence of CAD.²⁸ Target heart rate (peak HR) for exercise or dobutamine stress testing is 85% of the age-predicted maximum (85% of peak systolic BP × peak HR). Animal studies have shown that the rate-pressure product is a better predictor of the stress levels that should induce detectible ischemia. A 50% blockage should be detected with more than 50% confidence above a rate-pressure product of 20 kilotorr/min and with more than 85% confidence above 25 kilotorr/min.

False Positives/Negatives

Balloon angioplasty can disrupt an obstruction so that the vessel appears to recover its full diameter when, in fact, the cross-sectional area is improved only minimally and insufficiently. 3D imaging can be used to examine contrast-agent attenuation and the percentage narrowing. On occasion, this condition may be identified by looking at the lesion on different views or by performing IVUS or optical CT.

The introduction of a catheter or a wire can cause intimal dissection (a tear in the lining of a vessel), which may be mistaken for vascular spasm, thrombosis, or a long stenosis on cursory examination. A tissue flap in the endothelial lining may alternate between an open position and an obstructive one, mimicking a spasm; however, it is not responsive to nitrates. The distinction may be a matter of life or death. If clinically significant, stent placement, bypass, placement of a perfusion catheter, or other emergency treatment is typically required to treat a dissection. Sudden obstruction due to a dissection can be deadly, and it does not respond to medications.

Myocardial bridges, or small bands of muscle overlying a vessel, may be mistaken for stenoses; however, these are not amenable to angioplasty. The obstruction from a myocardial bridge is smooth and eccentric. Observation throughout the cardiac cycle shows that the obstruction occurs during systole.

Computed Tomography

Elastic-match imaging automatically identifies differences between image volumes. The acquisition of 1 set of contrast-enhanced chest CT images via the coronaries and a nonenhanced set provides a 3-dimensional view of the coronary-artery tree. The nonenhanced volume data were rendered as holographic projections to provide the anatomic context, and the elastic-match coronary tree was overlaid. In addition to automation, this method avoids thresholding so that small branches and filling defects, if present, are represented properly.

Elastic-match imaging can be used to identify collateral-dependent myocardium. Left and middle images are baseline and peak-arrival collateral-sensitive MRIs demarcating microvascular development. Right image, based on CT imaging of the heart, was obtained with and without back pressure to nullify collateral-dependent perfusion; white volume on represents collateral-dependent myocardium. The extent of collateral-dependent myocardium corresponds well on MRI and CT (r = 0.95).

Findings

CT imaging of the coronary arteries is achievable with fast CT and EBT systems triggered or gated by ECG to accumulate data when the heart is in diastole. 64-section multidetector-row CT is the newest technology.^29,30,31,32

With a section thickness of 1 or 0.5 mm or less, the coronary anatomy is laid out in a 3D volume. Image processing can greatly facilitate visualization of the course of vessels and branches and the presence and degree of stenoses. The coronary-artery tree may be viewed as a solid rendering of the surface of the heart, but portions may be obstructed from view.

Proper viewing of each coronary-artery branch should include clean views in which the LV blood pool, aortic root, and all extracardiac structures are removed, and vascular projections are limited to the zones that include the vessel of interest and a margin for partial-volume effects. Do not rely on threshold-based renderings, which can cause false-stenosis and false-obstruction and which can cause an intravascular thrombus to be missed. The use of a pair of volumes before and after the administration of contrast material for elastic matching³³ greatly facilitates the evaluation by automatically isolating the coronary tree without thresholding.²³

CT also enables superb evaluation of blood delivery. In principle, CT combined with catheterization permits accurate definition of the extent of collateral-dependent myocardium.²³

Pizzuto et al found that transthoracic Doppler echocardiography can improve the diagnostic accuracy of multidetector computed tomography (MDCT) for detecting left anterior descending (LAD) coronary artery stenosis. In 144 consecutive patients, coronary anatomy was assessed with MDCT, and echocardiography was used to calculate coronary flow reserve (CFR), by measuring the ratio of hyperemic to baseline peak flow velocity; results of both methods were verified with invasive coronary angiography. In a univariate model, the prediction of significant LAD stenosis was slightly, but significantly, better with coronary flow reserve (sensitivity 90%, specificity 96%, positive predictive value 84%, negative predictive value 97%, diagnostic accuracy 94%, chi-square = 97.5) than with MDCT (sensitivity 80%, specificity 93%, positive predictive value 71%, negative predictive value 95%, diagnostic accuracy 90%, chi-square = 63.2). When the findings from transthoracic Doppler echocardiography and MDCT agreed, thediagnosticaccuracy increased (96%; chi-square = 86.1, p <0.0001). In the 13 patients missed by MDCT, transthoracic Doppler echocardiography proved 100% accurate at predicting significant LAD stenosis.³⁴

Degree of Confidence

The ability of MRI and CT to depict the anatomy and the absence of notable obstructions is improving rapidly, but it is not uniform. The value of MRI and CT must be assessed in a truly double-blind fashion for each center until standardized, reliable methods are widely established. Whether MRI and CT results match in terms of the percentage of stenosis is relatively unimportant. Most important is whether MRI and CT reliably depict normal tissue and culprit lesions and, then, whether they establish the severity and the territories supplied by the culprit vessel. Both MRI and CT offer the significant advantage of direct assessment of the zones of impaired blood delivery.

False Positives/Negatives

MRI shows calcifications as black or signal voids, whereas CT shows calcifications as white and similar to contrast-filled blood. These appearances can influence the estimation of stenoses. Heavy calcification causes a beam-hardening artifact on CT that can interfere with visualization. Stents cause a local disturbance stronger on MRI than on CT. Also, with 3D MRI or CT, be certain to understand how the images account for local curvature in and out of the imaging planes. In finding the best plane to show a vessel, radiologists can mistake a local curve that is out of plane for an apparent stenosis. Proper image processing resolves this problem.

Magnetic Resonance Imaging

Findings

Coronary MRI has improved from the early methods² and equipment sufficient to identify normal proximal coronary arteries and courses, but it is not a clinical replacement for XRA apart from ruling out aberrant coronary origins, demonstrating graft or native vessel patency, or follow-up on specific lesions.  Coronary MRI may be performed by using a 3D volume, but the trade-off in time and resolution favors imaging in selective planes that address each branch of interest. As a 3D volume, MRIs may show the coronary tree in a way similar to the methods described for CT. Background tissue may be suppressed with fat saturation, tissue saturation, magnetization transfer, and/or T2 preparation (90°-180°-180°- ... -180°-90°).³⁵

The vessel-plane approach is as follows: Any desired target plane can be obtained by specifying 3 points to include in the plane, by drawing the lines of intersection with 2 previous images at different angles, or (commonly) by drawing a single line of intersection with a previous image that is perpendicular to the desired view. For example, to obtain a short-axis view of the coronary sinus, first obtain a long-axis view of the LV parallel to the septum and perpendicular to the AV groove, then prescribe a plane in the AV groove perpendicular to that view passing through the 2 observed points of intersection on the first view with the coronary sinus, seen as bright dots anterior and posterior to the mitral valve.

Other points regarding MRI to evaluate CAD are the following:

• A transverse stack of images covering the aortic root depicts the origin of the RCA and the left main coronary artery. The typical section thickness should be 3 mm or less. A bright- or dark-blood technique can be applied with the use of single frames or with a dynamic movie series.
• An additional distal transverse image shows a cross-section of the RCA, LAD, and LCX.
• From 2 points along the proximal vessel and from 1 point from the distal vessel, a plane that captures the desired segment is selected. The plane may be adjusted to be thick enough to encompass out-of-plane bends. As an alternative, it may be subdivided into a stack of thin imaging planes for a localized 3D stack of images.
• The course of the RCA in the AV groove can quickly be ascertained from a 4-chamber long-axis view of the heart by obtaining 1 preliminary image perpendicular to the AV groove and parallel to the septum through the mid RV. This provides 2 points of intersection with the RCA: 1 anterior and 1 posterior in the AV groove. Prescribing a plane through those 2 points from the long axis image gives the desired view.
• The posterior descending artery requires a different imaging plane, as do the LAD, LCX, and major branches. The course of the LCX in the AV groove is assessed in a way similar to that used for imaging the RCA, by acquiring a scout image parallel to the septum to identify 2 points to include in one final short-axis image. However, in this case, the scout image should be laterally displaced to the outer third, because the distal LCX is often hard to identify.
• The authors routinely identify the proximal course of the coronary arteries in young patients who have had syncope to look for aberrant origins. A complete absence of abnormalities suggests a good prognosis.
• MRI with contrast is an excellent method to identify myocardial scar (infarction) as small as 1% of the myocardium, which is a very strong prognostic factor³⁶ , while also assessing perfusion and precise function of left and right ventricles. It can also be combined with stress testing and coronary imaging for a "one stop shop."
• MRI is the preferred test for right ventricular injury or infarction.
• Apparent stenosis must be distinguished from an out-of-plane bend.
• A signal void from flow disturbance may exaggerate apparent stenosis.
• MRI is well established as a means to assess the patency of a bypass graft.

Degree of Confidence

MRI offers high sensitivity to changes in wall function, eg, wall thickening and radial motion.²⁴ MRI may be useful in identifying and quantifying impaired blood delivery and wall function in response to interventions.^{5,37,38,39,40,41,42,43} Such applications are perhaps more vital than visualizing the percentage of stenosis.

Confidence in the data depends on the speed and quality of the imaging method, the cooperation of the patient (shallow regular breathing or several matching breath holds), the accuracy of EKG triggering or gating, and the anatomic knowledge and judgment of the person directly supervising data collection.

Usual EKG signal in MRI is markedly distorted by competing signals from movement in a magnetic field and by moving magnetic fields, particularly from blood flow in the great vessels, called the magnetohydrodynamic effect. That distortion makes it difficult to perform electrographic safety monitoring for ischemic changes.

Cardiac MRI with the vessel-chasing approach requires highly informed decision making as the data are being acquired. If the operator acquiring the data understands what the x-ray angiogram demonstrates, the views may be manipulated for the best match. This consideration is not necessarily positive, because the operator may exaggerate the agreement.

The ability of MRI and CT to identify anatomy and the absence of clinically significant obstructions is improving rapidly, but it is not uniform. The value of MRI and CT must be assessed in a truly double-blind fashion for each center until standardized and reliable methods are widely established. Whether MRI and CT results match in terms of the percentage of stenosis is relatively unimportant. Most important is whether MRI and CT reliably depict normal tissue and culprit lesions and, then, whether they help in establishing their severity and in depicting the territories supplied by the culprit vessel. Both MRI and CT offer the notable advantage of enabling direct assessment of the zones with impaired blood delivery.

False Positives/Negatives

In an apparent stenosis, be certain that it is not a partial-volume artifact or a velocity-shear effect. Because local differences in velocity can cause a signal void, estimates of stenosis may be exaggerated.

Magnetic susceptibility artifacts may produce signal voids. Stents, clips, and wires cause local disturbances.

The presence of pacemaker wire is considered a relative contraindication to MRI because the rapidly changing magnetic fields may induce a voltage that can trigger an arrhythmia, induce a burn, or shorten the battery life. Also, when the patient enters and leaves the magnet, the magnetic reed switch on most pacemakers will switch it to fixed mode, and the temperature may rise in metal devices. For example, a pacemaker generator may warm by 1-2°C. However, with informed consent, careful pulse monitoring, and a readiness to promptly abort a pulse sequence if an arrhythmia is induced, patients with pacers have undergone MRI with no apparent consequence and no change in their pacer thresholds. In the dozen reports of mishaps related to pacemakers and MRI, none were caused by MRI.

On MRIs, calcification is depicted as a black area or signal void, whereas CT shows calcifications as white, similar to blood filled with contrast agent. These appearances can influence the estimation of stenoses. Also, with 3D MRI or CT, be certain to understand how the images account for local curvature in and out of the imaging planes. In finding a best MRI plane for showing a vessel, radiologists can mistake a local curve that is out of plane for an apparent stenosis. Proper image processing resolves this problem.

With MRI, flow disturbances that cause velocity shear (range of phases in each picture element or pixel resulting from different rates of motion of blood) cause a local decrease in signal intensity, which may create or exaggerate an apparent stenosis.

Ultrasonography

Findings

Echocardiography can be used to identify the left main coronary artery. In some patients, much of the RCA and LAD can be viewed; however, in most patients, the imaging window is inadequate for useful coronary imaging from outside the chest.

In the catheterization laboratory, IVUS may be performed to examine the coronary arteries from the inside and to characterize plaque. However, the diameter of the device limits the ability to pass through tight stenoses. Also, the injection of a sonographic contrast agent (eg, agitated Renografin) into the coronary arteries, combined with transthoracic or esophageal ultrasonography, can be useful in identifying perfusion territories.

Nuclear Imaging

Findings

Nuclear medicine study does not depict the coronary arteries, but it does demonstrate various metabolites useful in identifying perfusion defects and tissue viability. Thallium-201 and technetium-99m sestamibi are widely used and may be combined to shorten the study of myocardial uptake of radioactive tracer at rest and during stress. Although a rest-and-stress thallium study takes more than 4 hours, a combined study performed with thallium and sestamibi may be completed in less than 2 hours.

By using PET, a rest-and-stress study with rubidium-82 may be completed in 30 minutes, because the agent has a half-life of less than 5 minutes. A defect during stress that is not evident at rest indicates a zone of induced ischemia. A defect at rest and also during stress indicates persisting metabolic dysfunction, either from infarction (scar) or hibernation (prolonged dysfunction). PET with ammonia, fluorinated glucose, or other agents may be used to determine if the tissue with a defect at rest is viable.

Degree of Confidence

Nuclear medicine tests for CAD improve the predictive accuracy over that of stress tests alone, to approximately 90%. The utility of these tests depends on the previous probability of disease and on whether they are being used to identify CAD or to clarify the pathophysiology of known disease.

False Positives/Negatives

Breast attenuation may cause an apparent defect on radionuclide images. Attenuation correction and multiplanar imaging mitigate the problem.

Unusual motion, such as that from a bundle branch block or coughing during imaging, may cause false-positive results. A persisting defect is commonly interpreted as a fixed defect or a scar, but it may represent prolonged yet still-reversible ischemic impairment of tracer uptake.

The low resolution of nuclear medicine studies compared with that of other modalities may result in false-negative results. Also, global disease may be missed because defects are generally identified by comparing them to regions with high uptake of the tracer.

Intervention

Imaging guidance of interventional procedures

X-ray angiography is widely used to guide interventions, such as balloon angioplasty, atherectomy, laser treatment, stent placement, and other procedures. Current practice indicates the use of x-ray angiography in patients with potentially treatable lesions to confirm the findings and to perform interventions. Both tasks may be accomplished in a single procedure.

Cardiac catheterization is recommended for patients with mild angina (class I or II) plus an EF of less than 45%, including patients with noninvasive test results indicating a high risk, those with an uncertain diagnosis after noninvasive testing, patients with serious ventricular arrhythmias, and those who survive an episode of sudden death. The only indication with submaximal support is mild angina with reduced EF; this is a class IIa recommendation. The classification of indications by the American College of Cardiology indicates the weight of evidence in support of the recommendation. Mild angina with no reduction in EF might be managed with medication as a therapeutic trial.

As an experiment, MRI, CT, or echocardiography may be used to guide interventional procedures. MRI does not involve ionizing radiation; therefore, imaging may be active throughout the procedure. However, special guidewires and other equipment compatible with the magnet and the rapidly changing magnetic field must be used, and staff must be trained to ensure that no magnetic objects are brought near the magnet.

CT uses ionizing radiation and is slower than x-ray angiography, but it provides 3D information that may facilitate localization, especially for newer interventions such as the intramyocardial injection of angiogenic growth factors or stem cells. 3D ultrasonography similarly facilitates accurate injections, with convenience of portability and without a need for lead shielding from x-rays.

Prevention, treatment, repair, and new therapies

Prevention aims to slow or reverse the process that causes disease—for example, by lowering serum LDL-C levels (with statins); by increasing HDL-C levels (with exercise and niacin); by lowering lipoprotein(a) with niacin, fibrates, or other medication; and by counteracting the oxidation of LDL-C that accelerates wall uptake of the lipid (with vitamin C and selenium). Vigorous exercise every other day promotes overall health and the development of new vessels.

High levels of homocysteine are associated with the rapid development of disease. High homocysteine levels are as important as high cholesterol levels, and they can be treated by simply administering supplemental doses of folate and B-vitamins, adjusted to effect, but such treatment has not been shown to reduce the associated risk.
 
Growth factors, such as basic fibroblast growth factor 1 (bFGF1), basic fibroblast growth factor 2 (bFGF2), and vascular endothelial growth factor (VEGF) may stimulate the development of new vessels. These factors are administered experimentally either directly or by means of DNA-based therapies.^{5,39,40,41,42,43}

Medical treatments aim to improve the blood supply as needed by dilating the vessels, typically with nitrates, and/or by decreasing the demand, typically with beta-blockers. Other medical treatments include thrombin inhibitors, IIb/IIIa inhibitors, and high-dose statins.

Repair aims to crack or crush a lesion (with angioplasty), remove a portion of the obstruction (with atherectomy or laser treatment), remove clot (with thrombectomy, passage of a wire, or thrombolysis), hold the vessel open at an increased diameter (with stent placement), apply local medication (with drug-eluting stent placement), provide new pathways (with bypass surgery), and/or stimulate the growth of new vessels (with therapeutic angiogenesis).

New site-specific drug-eluting stents chemically inhibit the reactive endothelial growth that causes early restenosis after angioplasty. The failure of vein grafts after mechanical intervention continues to pose a challenge. New devices (eg, Front Runner and Safe-Cross devices) have been developed to improve the ability to open totally occluded vessels, even chronic occlusions. One area of investigation is the protection of the distal vessel from debris during the treatment of acute MI or degenerating vein grafts. A current trend is to use PCI and complete revascularization, even in high-risk elderly patients.⁴⁴

The typical clinical approach to CAD is an abnormal stress test followed by cardiac catheterization. If the catheterization identifies significant lesions (corresponding to inducible ischemia or to an acute coronary syndrome, or deemed significant by appearance or flow wire), then revascularization is planned either as part of the same catheterization or as a separate intervention. Intervention by catheterization is called percutaneous intervention (PCI) and by surgery is called coronary artery bypass grafting (CABG). If the patient was unstable from an acute threatened or actual myocardial infarction, the initial procedure by percutaneous intervention focuses on the culprit lesion.

Prior to the invention of drug eluting stents (DES), PCI was performed as plain-old balloon angioplasty (POBA), which might be supplemented by a bare metal stent (BMS), originally used to treat biliary stenoses. POBA was plagued by a high frequency of restenosis within months. BMS improved that for large diameter vessels in nondiabetics. Patients with 3-vessel CAD or left main disease or diabetes did better with CABG. The benefit of surgery over medical treatment was best demonstrated for severe CAD with reduced ejection fraction (EF) and for diabetics. POBA was only demonstrated to reduce symptoms. However, that data predates DES. Diabetics do well with DES, and now PCI with DES is performed not only on isolated one-vessel CAD but also on 3-vessel CAD and left main disease. 

DES had a rocky initial experience that caused controversy, but now it is generally preferred treatment, particularly in high-risk lesions, small-caliber vessels, and patients with diabetes. DES prevents endothelial growth that may occlude a bare metal stent (BMS), but that also means that there is continued exposure of blood to metal and collagen, resulting in thromboemboli. That risk is offset by administering Plavix (clopidogrel) as well as aspirin, even in patients who are taking warfarin. Clopidogrel added to aspirin clearly lowers the risk of thrombosis and thromboembolus from a stent; clopidogrel alone has not been studied in any large trials.

Patients allergic to clopidogrel (1-2% of patients may develop a severe rash, itching, hives, or angioedema) may take Ticlid (ticlopidine), but ticlopidine may also cause an allergic reaction and may be markedly less effective; therefore, many patients may undergo clopidogrel desensitization concurrently so as to be able to resume taking clopidogrel. With BMS, clopidogrel is essential for the first 1-2 months. With DES, risk is high for the first 6 months, and there is a risk of sudden thrombosis for 1-2 years after clopidogrel.

Surgery is deferred for 2-3 months with BMS and for 6-12 months with DES. After DES, if there are no contraindications, clopidogrel plus aspirin is often continued indefinitely. Experimental new stents are under development that may allow a protective lining to grow over a stent without risk of obstruction of blood flow from endothelial overgrowth, which may eliminate the long-term need for antiplatelet therapy with concomitant risk of a serious bleeding event.^{45,46,47,48,49,50,51}

Medicolegal Pitfalls

• Failure to perform timely screening and/or catheterization in a patient referred for evaluation may create liability for the physician if the patient subsequently has a cardiovascular event that might have been prevented if the disease had been discovered earlier.
• Other pitfalls are listed below:
  • Performing a routine stress test in a patient with symptoms from severe aortic stenosis
  • Giving nitrates to a patient in the upright position who is taking Viagra or Cialis without also giving intravenous saline, performing careful BP monitoring, and advising the patient about a possible life-threatening hypotension
  • Failure to obtain promptly an EKG or otherwise properly evaluate and treat a patient with an angina-equivalent condition or silent MI who presents with painless shortness of breath, fatigue, or other painless angina-equivalent symptoms
  • Failure to promptly relieve ischemia by applying the relevant treatment options
  • Misinterpreting intimal dissection as stenosis or thrombosis, which may result in the avoidable death of a patient
  • Failure to identify spasm and to promptly initiate appropriate treatment
  • Failure to treat stenosis of the left main coronary artery or its equivalent with appropriate urgency and use of precautionary measures
  • Complications from performing an intervention in a nonculprit lesions in an acute setting

Multimedia

Media file 1: Selective injection image of the left coronary arteries. D1 = first diagonal, LAD = left anterior descending artery, LCX = left circumflex, LM = left main coronary artery, and OM1= first obtuse marginal.

Media file 2: MRIs of the coronaries can be used to build 4-dimensional images (3-dimensional beating heart). These images show a single frame, including a cutaway view to show the cardiac interior, the outer surface (no thresholding), and the extracted coronary artery tree including the aortic root.

Media file 3: Elastic-match imaging automatically identifies differences between image volumes. The acquisition of 1 set of contrast-enhanced chest CT images via the coronaries and a nonenhanced set provides a 3-dimensional view of the coronary-artery tree. The nonenhanced volume data were rendered as holographic projections to provide the anatomic context, and the elastic-match coronary tree was overlaid. In addition to automation, this method avoids thresholding so that small branches and filling defects, if present, are represented properly.

Media file 4: Elastic-match imaging can be used to identify collateral-dependent myocardium. Left and middle images are baseline and peak-arrival collateral-sensitive MRIs demarcating microvascular development. Right image, based on CT imaging of the heart, was obtained with and without back pressure to nullify collateral-dependent perfusion; white volume on represents collateral-dependent myocardium. The extent of collateral-dependent myocardium corresponds well on MRI and CT (r = 0.95).

Media file 5: Contrast-labeled blood to the heart is used to identify the territory at risk. The results of this assessment of the delayed arrival compares favorably to the findings of radionuclide stress imaging, and stress induction of ischemia is not required to identify the zone at risk.

Media file 6: Space-time maps show the history of blood arrival to all layers of myocardium on a 2-dimensional map. The indentation indicates the severity of the defect in blood delivery, and the length indicates the size as a percentage of the myocardium, without the need for stress induction of ischemia. In addition to the safety advantage, this method is also more reproducible than stress testing, which is useful in assessing the effect of therapy.

Media file 7: Compared with radionuclide images of blood delivery, MRIs and CT scans improve resolution, depiction of the functional effect and the relationship to the coronary supply, and identification of the area at risk without stress. The advantage of radionuclide imaging is primarily its predictive value; stress echocardiography has similar predictive value. MRI and CT have been less available than other studies; therefore, data on their value are relatively limited.

Media file 8: X-ray angiography is the criterion standard for delineating the coronary anatomy, but it is inferior to MRI and CT in identifying myocardium with impaired blood delivery, in assessing the functional consequences, and in identifying the development of microvascular collaterals.

References

1. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. Aug 16 2000;284(7):835-42. [Medline]. [Full Text].

2. Pearlman JD. NMR imaging and spectroscopy studies of the coronary arteries: II. 3-D reconstruction of in vivo coronary arteries. In: Sideman S, Beyar R, eds. Image Analysis and Simulation of the Cardiac System: Proceedings of 5th Henry Goldberg Workshop on Analysis. London, England: Freund;. 1990: 451-64.

3. Aviram G, Finkelstein A, Herz I, et al. Clinical value of 16-slice multi-detector CT compared to invasive coronary angiography. Int J Cardiovasc Intervent. 2005;7(1):21-8. [Medline].

4. Flohr T, Stierstorfer K, Raupach R, et al. Performance evaluation of a 64-slice CT system with z-flying focal spot. Rofo. Dec 2004;176(12):1803-10. [Medline].

5. Pearlman JD, Laham RJ, Simons M. Coronary angiogenesis: detection in vivo with MR imaging sensitive to collateral neocirculation--preliminary study in pigs. Radiology. Mar 2000;214(3):801-7. [Medline].

6. Pearlman JD, Hibberd MG, Chuang ML, et al. Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis. Nat Med. Oct 1995;1(10):1085-9. [Medline].

7. Hansson GK. Inflammation, Atherosclerosis, and Coronary Artery Disease. NEJM. 2005/04;352:1685-1695. [Full Text].

8. Bhattacharyya MR, Steptoe A. Emotional triggers of acute coronary syndromes: strength of evidence, biological processes, and clinical implications. Prog Cardiovasc Dis. Mar-Apr 2007;49(5):353-65. [Medline].

9. Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. Mar 11 2003;107(9):1303-7. [Medline].

10. Todaro JF, Con A, Niaura R, et al. Combined effect of the metabolic syndrome and hostility on the incidence of myocardial infarction (the Normative Aging Study). Am J Cardiol. Jul 15 2005;96(2):221-6. [Medline].

11. Osganian SK, Stampfer MJ, Rimm E, et al. Vitamin C and risk of coronary heart disease in women. J Am Coll Cardiol. Jul 16 2003;42(2):246-52. [Medline].

12. Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. Apr 8 2004;350(15):1505-15. [Medline].

13. Heberden, William. Pectus Dolor. Commentaries on the History and Cure of Diseases. 1802;Medical Transactions 2, 59-67 (1772):[Full Text].

14. Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. May 22 2008;358(21):2205-17. [Medline].

15. Bainey KR, Fu Y, Wagner GS, Goodman SG, Ross A, Granger CB, et al. Spontaneous reperfusion in ST-elevation myocardial infarction: comparison of angiographic and electrocardiographic assessments. Am Heart J. Aug 2008;156(2):248-55. [Medline].

16. Baklanov DV, Demuinck ED, Thompson CA, Pearlman JD. Novel double contrast MRI technique for intramyocardial detection of percutaneously transplanted autologous cells. Magn Reson Med. Dec 2004;52(6):1438-42. [Medline].

17. Zareba W, Piotrowicz K, McNitt S, Moss AJ; MADIT II Investigators. Implantable cardioverter-defibrillator efficacy in patients with heart failure and left ventricular dysfunction (from the MADIT II population). Am J Cardiol. Jun 15 2005;95(12):1487-91. [Medline].

18. Schulman KA, Berlin JA, Harless W, et al. The effect of race and sex on physicians'' recommendations for cardiac catheterization. N Engl J Med. Feb 25 1999;340(8):618-26. [Medline].

19. Kelly RF, Hashim AS, Al-Dallow R. Recommendations and performance of coronary revascularization procedures in black and white patients. Am J Cardiol. Jul 15 2005;96(2):215-7. [Medline].

20. O'Keefe JH, Cordain L, Harris WH, et al. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. Jun 2 2004;43(11):2142-6. [Medline].

21. Núñez J, Núñez E, Sanchis J, Bodí V, Llàcer A. Prognostic value of leukocytosis in acute coronary syndromes: the cinderella of the inflammatory markers. Curr Med Chem. 2006;13(18):2113-8. [Medline].

22. Foote RS, Pearlman JD, Siegel AH, Yeo KT. Detection of exercise-induced ischemia by changes in B-type natriuretic peptides. J Am Coll Cardiol. Nov 16 2004;44(10):1980-7. [Medline].

23. Pearlman JD. Three- (and more) dimensional imaging of the heart, great vessels, and coronary arteries. In: Cardiovascular Radiology. Dallas, TX: American Heart Association;. 1997: 5-8.

24. Pearlman JD, Gertz ZM, Wu Y, et al. Serial motion assessment by reference tracking (SMART): application to detection of local functional impact of chronic myocardial ischemia. J Comput Assist Tomogr. Jul-Aug 2001;25(4):558-62. [Medline].

25. Schoenhagen P, Nissen SE. Intravascular ultrasonography: using imaging end points in coronary atherosclerosis trials. Cleve Clin J Med. Jun 2005;72(6):487-9, 493-6. [Medline].

26. Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR Am J Roentgenol. Feb 2001;176(2):289-96. [Medline].

27. Rigatelli G, Rigatelli G. Screening angiography of supraaortic vessels performed by invasive cardiologists at the time of cardiac catheterization: indications and results. Int J Cardiovasc Imaging. Apr-Jun 2005;21(2-3):179-83. [Medline].

28. Pearlman JD, Boucher CA. Diagnostic value for coronary artery disease of chest pain during dipyridamole-thallium stress testing. Am J Cardiol. Jan 1 1988;61(1):43-5. [Medline].

29. Liu H, Huang MP, Liang CH, Zheng JH, Wu ZB. [Detection and its clinical value of myocardial bridging with 64-slice spiral CT coronary angiography.]. Nan Fang Yi Ke Da Xue Xue Bao. Feb 2009;29(2):236-8. [Medline].

30. Tsiflikas I, Drosch T, Brodoefel H, Thomas C, Reimann A, Till A, et al. Diagnostic accuracy and image quality of cardiac dual-source computed tomography in patients with arrhythmia. Int J Cardiol. Feb 24 2009;[Medline].

31. Halon DA, Dobrecky-Mery I, Gaspar T, Azencot M, Yaniv N, Peled N, et al. Pulse pressure and coronary atherosclerosis in asymptomatic type 2 diabetes mellitus: A 64 channel cardiac computed tomography analysis. Int J Cardiol. Feb 24 2009;[Medline].

32. Ito H, Dajani KA. A case with noncompaction of the left ventricular myocardium detected by 64-slice multidetector computed tomography. J Thorac Imaging. Feb 2009;24(1):38-40. [Medline].

33. Pearlman JD, Raptopoulos VD, Kleefield J. Three-dimensional elastic subtraction spiral CT angiography. Radiology. 1995;197:143-4.

34. Pizzuto F, Voci P, Bartolomucci F, Puddu PE, Strippoli G, Broglia L, et al. Usefulness of coronary flow reserve measured by echocardiography to improve the identification of significant left anterior descending coronary artery stenosis assessed by multidetector computed tomography. Am J Cardiol. Sep 1 2009;104(5):657-64. [Medline].

35. Kaya MG, Okyay K, Yazici H, Sen N, Tavil Y, Turkoglu S, et al. Long-term clinical effects of magnetic resonance imaging in patients with coronary artery stent implantation. Coron Artery Dis. Feb 25 2009;[Medline].

36. Kwong RY, Sattar H, Wu H, Vorobiof G, Gandla V, Steel K, et al. Incidence and prognostic implication of unrecognized myocardial scar characterized by cardiac magnetic resonance in diabetic patients without clinical evidence of myocardial infarction. Circulation. Sep 2 2008;118(10):1011-20. [Medline]. [Full Text].

37. Pearlman JD, Gazit Y. Accurate quantification of atheroma inside arterial walls by 1H-NMR. In: Woodford FP, Davignon J, Sniderman A, eds. Atherosclerosis X: Proceedings of the 10th International Symposium on Atherosclerosis, Montreal, Canada, October 9-14 1994. Elsevier;1995:1008-17.

38. Pearlman JD, Yaseen ZS. Multiplexed space-time maps for time-series data visualization: application to 4D cardiac imaging. In: Erbacher RD, Pang A, eds. Visual Data Exploration and Analysis V. Proceedings of the SPIE. Vol 3298. Bellingham, WA: The International Society for Optical Engineering;1998:153-9.

39. Sellke FW, Laham RJ, Edelman ER, et al. Therapeutic angiogenesis with basic fibroblast growth factor: technique and early results. Ann Thorac Surg. Jun 1998;65(6):1540-4. [Medline].

40. Lopez JJ, Laham RJ, Stamler A, et al. VEGF administration in chronic myocardial ischemia in pigs. Cardiovasc Res. Nov 1998;40(2):272-81. [Medline].

41. Laham RJ, Rezaee M, Post M, et al. Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia. J Pharmacol Exp Ther. Feb 2000;292(2):795-802. [Medline].

42. Laham RJ, Chronos NA, Pike M, et al. Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study. J Am Coll Cardiol. Dec 2000;36(7):2132-9. [Medline].

43. Sato K, Laham RJ, Pearlman JD, et al. Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia. Ann Thorac Surg. Dec 2000;70(6):2113-8. [Medline].

44. Scheidt S. Treatment of stable angina: medical and invasive therapy--implications for the elderly. Am J Geriatr Cardiol. Jul-Aug 2005;14(4):183-92; quiz 193-4. [Medline].

45. [Best Evidence] Abbate A, Biondi-Zoccai GG, Appleton DL, Erne P, Schoenenberger AW, Lipinski MJ, et al. Survival and cardiac remodeling benefits in patients undergoing late percutaneous coronary intervention of the infarct-related artery: evidence from a meta-analysis of randomized controlled trials. J Am Coll Cardiol. Mar 4 2008;51(9):956-64. [Medline].

46. Aquaro GD, Pingitore A, Strata E, Di Bella G, Palmieri C, Rovai D, et al. Relation of pain-to-balloon time and myocardial infarct size in patients transferred for primary percutaneous coronary intervention. Am J Cardiol. Jul 1 2007;100(1):28-34. [Medline].

47. Boden W, O'Rourke RA, Teo KK, et al. Optimal Medical Therapy with or without PCI for Stable Coronary Disease. NEJM. 2007/04;356:1503-1516.

48. Boomsma RA, Swaminathan PD, Geenen DL. Intravenously injected mesenchymal stem cells home to viable myocardium after coronary occlusion and preserve systolic function without altering infarct size. Int J Cardiol. Oct 31 2007;122(1):17-28. [Medline].

49. De Luca G, Suryapranata H, Marino P. Reperfusion strategies in acute ST-elevation myocardial infarction: an overview of current status. Prog Cardiovasc Dis. Mar-Apr 2008;50(5):352-82. [Medline].

50. Goldenberg I, Moss AJ. Implantable device therapy. Prog Cardiovasc Dis. May-Jun 2008;50(6):449-74. [Medline].

51. Seung KB, Park DW, Kim YH, et al. Stents versus Coronary-Artery Bypass Grafting for Left Main Coronary Artery Disease. NEJM. 2008/04;358:1781-1792. [Full Text].

52. Brown TA. Hibernating myocardium. Am J Crit Care. Mar 2001;10(2):84-91; quiz 92-3. [Medline].

53. Davis JA, Cecchin F, Jones TK, Portman MA. Major coronary artery anomalies in a pediatric population: incidence and clinical importance. J Am Coll Cardiol. Feb 2001;37(2):593-7. [Medline].

54. Edelman RR, Manning WJ, Pearlman J, Li W. Human coronary arteries: projection angiograms reconstructed from breath-hold two-dimensional MR images. Radiology. Jun 1993;187(3):719-22. [Medline].

55. Fuessl RT, Kranenberg E, Kiausch U, et al. Vascular remodeling in atherosclerotic coronary arteries is affected by plaque composition. Coron Artery Dis. Mar 2001;12(2):91-7. [Medline].

56. Goldstein JA. Angiographic Plaque Complexity: The Tip of the Unstable Plaque Iceberg. JACC. 2002/05;39:1464-1467. [Full Text].

57. Gottdiener JS. Overview of stress echocardiography: uses, advantages, and limitations. Prog Cardiovasc Dis. Jan-Feb 2001;43(4):315-34. [Medline].

58. Haberl R, Becker A, Leber A, et al. Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients. J Am Coll Cardiol. Feb 2001;37(2):451-7. [Medline].

59. Kailasnath P, Sinusas AJ. Technetium-99m-labeled Myocardial Perfusion Agents: Are They Better than Thallium-201?. Cardiol Rev. May-Jun 2001;9(3):160-72. [Medline].

60. Lu B, Mao SS, Zhuang N, et al. Coronary artery motion during the cardiac cycle and optimal ecg triggering for coronary artery imaging. Invest Radiol. May 2001;36(5):250-6. [Medline].

61. Pearlman JD, Laham RJ, Simons M, et al. Extent of myocardial collateralization: determination with three-dimensional elastic-subtraction spiral CT. Acad Radiol. Oct 1997;4(10):680-6. [Medline].

62. Pearlman JD, Southern JF, Ackerman JL. Nuclear magnetic resonance microscopy of atheroma in human coronary arteries. Angiology. Sep 1991;42(9):726-33. [Medline].

63. Pearlman JD, Zajicek J, Merickel MB, et al. High-resolution 1H NMR spectral signature from human atheroma. Magn Reson Med. Jul 1988;7(3):262-79. [Medline].

64. Servoss SJ, Januzzi JL, Muller JE. Triggers of acute coronary syndromes. Prog Cardiovasc Dis. Mar-Apr 2002;44(5):369-80. [Medline].

65. Shaw LJ, Hachamovitch R, Redberg RF. Current evidence on diagnostic testing in women with suspected coronary artery disease: choosing the appropriate test. Cardiol Rev. Jan-Feb 2000;8(1):65-74. [Medline].

66. Toyama T, Hoshizaki H, Isobe N, et al. Detecting viable hibernating myocardium in chronic coronary artery disease--a comparison of resting 201Tl single photon emission computed tomography (SPECT), 99mTc-methoxy-isobutyl isonitrile SPECT after nitrate administration, and 201Tl SPECT after 2. Jpn Circ J. Dec 2000;64(12):937-42. [Medline].

67. Umarji SI. Myocardial infarction in a 25-year-old woman. Eur J Emerg Med. Jun 2000;7(2):145-6. [Medline].

68. Weinstein AR, Sesso HD, Lee IM, et al. Relationship of physical activity vs body mass index with type 2 diabetes in women. JAMA. Sep 8 2004;292(10):1188-94. [Medline].

69. Yao SS, Rozanski A. Principal uses of myocardial perfusion scintigraphy in the management of patients with known or suspected coronary artery disease. Prog Cardiovasc Dis. Jan-Feb 2001;43(4):281-302. [Medline].

Keywords

coronary artery disease, CAD, heart disease, coronary angiography, coronary angioscopy, coronary artery imaging, magnetic resonance angiography, MRA, stress test, perfusion imaging, collateral-sensitive imaging, heart attack, myocardial infarction, MI, acute myocardial infarction, AMI, angina, UA, unstable angina, stent, DES, drug-eluting stent

Contributor Information and Disclosures

Author

Justin D Pearlman, MD, PhD, ME, MA, Director of Advanced Cardiovascular Imaging, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center
Justin D Pearlman, MD, PhD, ME, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America
Disclosure: Nothing to disclose.

Medical Editor

Justin D Pearlman, MD, PhD, ME, MA, Director of Advanced Cardiovascular Imaging, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center
Justin D Pearlman, MD, PhD, ME, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

John D Newell Jr, MD, Professor of Radiology, Co-Director of Thoracic Imaging, Department of Radiology, University of Colorado Health Sciences Center; Professor of Medicine, Medical Director of Lung Imaging Center, National Jewish Medical and Research Center
John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians, American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association of University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology
Disclosure: Siemens Medical Grant/research funds Consulting; Forevision Technologies Ownership interest Consulting; Vida Corporation Ownership interest Board membership; TeraRecon Grant/research funds Consulting; eMedicine Honoraria Consulting

CME Editor

Robert M Krasny, MD, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Consulting Radiologist, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

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