include mild ST-segment depression or T-wave inversions.

During a myocardial infarction, the dying myocytes release enzymes specific to cardiac muscle into

the bloodstream. These enzymes can be detected from laboratory analysis and are pathognomonic of

myocardial infarction. The MB fraction of creatine kinase is cardiac specific and rises within 8 to 24

hours of infarction and returns to baseline within 2 days. Cardiac troponin has even greater specificity

and serum levels rise faster than creatine kinase, improving both the speed and accuracy in the

laboratory diagnosis of an acute myocardial infarction in the absence of clear ECG changes.19

For asymptomatic patients, or those with chronic stable angina, the most widely used diagnostic test

to evaluate for coronary artery disease is exercise electrocardiography, or a “stress test.” Using

standardized protocols, patients are exercised on a treadmill while the 12-lead ECG is continuously

recorded. Alternatively, for those patients unable to walk, a bicycle ergometer may be used. Testing is

continued until patient symptoms are noted or until the development of significant downward-sloping

ST-segment depression, suggesting myocardial ischemia (Fig. 83-4). The diagnostic accuracy of exercise

stress ECG testing can be enhanced with myocardial perfusion imaging. Several radioactive tracers are

used clinically, the most frequent of which is thallium-201. Because of its similarities to potassium ions,

it is taken up preferentially by viable cardiac myocytes. Its distribution within the myocardium is

proportional to the rate of perfusion. During stress, regions of underperfused myocardium will take up

less thallium, resulting in a visible defect. Following a period of rest and reperfusion, thallium uptake

normalizes, demonstrating a “reversible defect.”

Figure 83-4. Electrocardiogram during an exercise test showing precordial leads V1

through V6

. A: During exercise, depression of

the ST segment and ischemia are seen in leads V4

through V6

. B: These resolve after exercise is stopped.

In some cases, patients are unable to exercise because of additional physical or psychological

limitations. Pharmacologic agents can substitute for exercise by increasing myocardial oxygen demand

(dobutamine) or by directly vasodilating coronary arteries (adenosine or dipyridamole), thus

demonstrating regions with fixed restrictions in myocardial blood flow. Echocardiography can be used

as an alternative to nuclear perfusion imaging to improve the accuracy of exercise ECG testing.

Regional changes in wall motion will be observed during myocardial ischemia, followed by restoration

of normal myocardial contraction after rest or discontinuation of dobutamine. Echocardiography can

also identify valvular abnormalities or other conditions that may influence treatment choices.

Coronary angiography, also known as cardiac catheterization, is the definitive tool for diagnosing

coronary atherosclerotic disease. Indications include symptomatic patients with typical angina

refractory to medical treatments, patients with significant ischemia on exercise or pharmacologic stress

testing, patients with a STEMI, or patients with an NSTEMI and persistent pain despite medical

treatment. Patients with valvular heart disease who are scheduled to undergo surgical correction should

also undergo coronary angiography to identify coexisting coronary occlusions, which can be addressed

at the time of the valve surgery. After percutaneous access is obtained in the femoral, brachial, or radial

arteries, preformed catheters of varying sizes are advanced fluoroscopically to selectively engage the

ostia of the left and right coronary arteries. Radio-opaque contrast is injected with imaging of the

opacified coronary artery. Standardized views are obtained of both the right and left coronary systems

to provide different projections to clearly define the vascular anatomy and to quantify the severity of

occlusive lesions (Fig. 83-5). Automated computer analysis systems can calculate area reduction,

improving interobserver consistency. Additionally, catheters can be inserted across the aortic valve into

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the left ventricular cavity, providing information about ventricular pressure throughout the cardiac

cycle. Contrast injection for ventriculography can illustrate ventricular systolic function, cavity size, and

the presence of left-sided valvular abnormalities. New microtipped pressure sensors can be advanced

across coronary lesions and document a clinically significant drop in perfusion pressure, either at rest or

after provocation with vasodilating agents.20 In addition, intravascular ultrasound imaging sensors can

now be loaded onto tiny catheters and advanced into the left main coronary artery, helping to clarify

the significance of lesions that may appear equivocal in severity on standard angiography.21

Newer imaging techniques using high-resolution multislice computed tomography (CT) scanning with

three-dimensional reconstruction and magnetic resonance imaging are increasingly being utilized. These

noninvasive approaches have the potential to improve the safety and convenience of coronary imaging;

however, resolution remains inferior to standard coronary angiography. These techniques are often used

as screening tests and are frequently followed up with traditional angiography.22

MEDICAL TREATMENT

5 Medical therapy of coronary artery disease is designed to slow the rate of progression of coronary

artery atherosclerosis, to reduce the rate of complications from these lesions, and to control symptoms.

Treatments are aimed at slowing plaque growth, reducing risk of plaque rupture, and reducing

myocardial oxygen consumption. While advances in pharmacologic agents have improved the treatment

of atherosclerosis and reduced mortality, lifestyle modification remains the most important intervention

and the most difficult to achieve. These lifestyle modifications include cessation of cigarette smoking,

weight loss, dietary control of diabetes, salt restriction, reduction in the consumption of foods high in

cholesterol and fat, and exercise.

Medical therapy begins with controlling risk factors that contribute to formation and destabilization

of the atherosclerotic plaque. Medical treatment alone is often satisfactory for many patients with

coronary artery disease affecting only one or two epicardial vessel territories. Statins can decrease

cholesterol levels and improve the ratio of LDL to HDL and have been demonstrated to reduce rates of

myocardial infarction and death.23 Statins also appear to reduce macrophage accumulation within

atheromatous plaques, matrix metalloprotease activity, and collagen degradation. Angiotensinconverting enzyme (ACE) inhibitors have been shown to reduce mortality and myocardial infarction in

patients with coronary artery disease.24 Aspirin inhibits cyclooxygenase-1 (COX-1) activity and

thromboxane production, irreversibly inhibiting platelet aggregation by inhibiting platelet activity, and

should be prescribed to all patients unless significant contraindications exist. Aspirin has been shown to

reduce death and myocardial infarctions in patients with significant coronary artery disease. By binding

the catecholamine-mediated B1 receptor on cardiac myocytes, beta-blocking agents reduce myocardial

oxygen consumption by reducing heart rate and contractility, and increase perfusion by extending

diastolic perfusion time. Beta blockers are effective at controlling angina26 and, in selected patients,

reduce cardiovascular mortality.27 Nitrates also reduce myocardial oxygen demand by decreasing

cardiac preload via venodilation and by reducing afterload via arterial vasodilation. Some epicardial

coronary vasodilation will occur, improving coronary blood flow. Nitrates can be given sublingually for

immediate relief or as an oral long-acting agent for continuous control of symptoms. Headaches and

tolerance are notable side effects. For patients who have refractory angina despite all revascularization

and traditional medical options, a newer agent, ranolazine, has recently been introduced. It alters

cardiac myocyte membrane ion channel permeability and can relieve angina with few side effects.28

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Figure 83-5. Coronary angiography. A: Left anterior oblique view of the left coronary artery. B: Right anterior oblique view of the

left coronary artery. C: Left anterior oblique view of the right coronary artery. (Images courtesy of Brahmajee Nallamothu.)

A patient admitted to the hospital with a diagnosis of acute myocardial infarction or possible ACS

should be placed in an environment with continuous ECG monitoring and the capacity to perform

emergent defibrillation, since these patients are at risk of life-threatening malignant ventricular

arrhythmias. Patients with evidence of ST-segment elevation should undergo emergent cardiac

catheterization when possible, as will be discussed later. For those patients in which the ECG is normal

but an ACS is suspected, a stress test should be performed expeditiously to identify their risk for future

coronary events and to identify patients in need of urgent cardiac catheterization.

Unless there is a strong contraindication, aspirin should be administered immediately, ideally chewed

to increase the rate of bioavailability. Typically, aspirin is given by emergency transport personnel.

Patients may be instructed by 911 operators to take aspirin if they describe chest pain. Institution of

oxygen therapy is important to maximizing oxygen delivery, particularly for patients in whom

hypoxemic respiratory dysfunction is also present. Intravenous nitroglycerine as a continuous infusion is

typically effective at controlling symptoms of pain, which is essential in reducing unnecessary

myocardial strain. Small randomized trials have suggested that nitroglycerine can reduce hospital

mortality, although this has not been validated in larger trials.29 When necessary, narcotics should be

added, as unrelenting pain not only increases myocardial oxygen consumption, but also may contribute

to plaque instability. Beta-blocking agents can reduce myocardial oxygen consumption but can also

exacerbate heart failure, particularly in the setting of severely decreased systolic ventricular function.

They should be considered cautiously in hemodynamically stable patients. ACE inhibitors reduce

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mortality after acute myocardial infarctions, particularly those with decreased ventricular function.30

Benefits are not just restricted to the afterload reduction effects. Some evidence suggests they have a

role in alteration of the myocardial intercellular matrix and scar formation.31

Anticoagulation is among the most important interventions in patients presenting with an acute

myocardial infarction. In recent years, patients with myocardial infarctions were placed on newer

antiplatelet glycoprotein (Gp) IIb/IIIa inhibitors, which affect adenosine diphosphate (ADP)-mediated

platelet adhesion. Thienopyridines are a newer class of antiplatelet agents that act by binding to the

ADP receptors on the platelet surface and inhibiting the GpIIb/IIIa pathway. Specific agents include

clopidogrel (Plavix) and ticlopidine (Ticlid). There is strong evidence that the addition of clopidogrel to

aspirin reduces death, myocardial infarction, and stroke in the setting of ACS.32 Clopidogrel is

irreversible and has a long half-life, resulting in bleeding complications, particularly if surgery is

required. Surgical intervention should ideally be delayed for 3 to 5 days.33 Abciximab (ReoPro) is a

murine antibody that binds directly to the GpIIb/IIIa receptor on platelet surfaces, preventing

fibrinogen binding and activation. The half-life is short, and platelet activity generally returns to normal

within 24 hours. Eptifibatide (Integrilin) is a synthetic antagonist of the GpIIa/IIIb receptor and has a

half-life of 3 to 4 hours. The benefit of these agents in patients with ACS treated medically is unclear,

but they have become routine in the setting of percutaneous treatment of coronary stenoses. Unless

contraindications exist, inhibition of the coagulation cascade is also recommended for patients with

acute myocardial infarctions. Although standard unfractionated heparin has been used for many years,

newer low–molecular-weight agents and direct Xa inhibitors may have advantages and are used with

increasing frequency.34,35

With STEMI, significant myocardium is at risk, potentially resulting in either cardiogenic shock or

ventricular arrhythmias. Emergency recanalization of acutely occluded vessels can salvage cardiac

function and save lives. Various fibrinolytic drugs, which convert plasminogen to plasmin, can be given

emergently and restore flow in vessels obstructed by acute thrombus. A number of clinical trials were

performed in the 1980s using streptokinase and demonstrated reduced survival when it was given

within 12 hours.36 Newer agents are now available including tissue plasminogen inhibitor (tPA) and

reteplase, which are faster in onset and may further improve outcomes, although they are more costly.

The main drawbacks of fibrinolytic therapy are bleeding complications and failure of recanalization.

Systemic intravenous thrombolytic therapy unquestionably decreases morbidity and mortality after MI

and continues to be used in 40% to 50% of eligible patients. The earlier the treatment, the greater the

impact, with the greatest benefit accruing in patients treated within 1 to 2 hours after the onset of

symptoms.

In 1977, Dr. Andreas Gruentzig performed the first percutaneous intervention (PCI) with balloon

angioplasty on a stenotic lesion in the LAD. This pioneer laid the foundation for a revolution in the

treatment of coronary artery disease worldwide. Percutaneous treatment of acute STEMI is now

standard practice in centers in which this therapy is available, with outcomes that are superior to

pharmacologic reperfusion.37 Although percutaneous intervention may be better than fibrinolysis, the

treatment requires numerous experienced personnel and highly technologic equipment, which is not

always available in every facility. Complex interhospital and intrahospital systems are now in place to

improve the efficiency and application of this treatment strategy, and guidelines have defined minimum

“door to balloon” times to salvage myocardium at risk.38

PERCUTANEOUS CORONARY INTERVENTIONS

6 Since the inception of percutaneous transcoronary balloon angioplasty (PTCA), catheter-directed

treatment of coronary artery disease has evolved into one of the most commonly performed procedures

worldwide. Advances in technology have improved outcomes and expanded the indications, particularly

for the acutely ischemic heart. Using the same techniques described for cardiac catheterization, small,

highly flexible and steerable guide wires can be advanced through the lumen of epicardial coronary

arteries. Over this guide wire, balloon-tipped catheters can be advanced and centered across discrete

stenotic lesions and inflated to 4 to 10 atmospheric pressures, stretching and dilating the affected vessel

(Fig. 83-6). Typically, the vessel tears or cracks at the junction of the plaque and the normal vessel wall.

Acute thrombosis or coronary dissection could result in immediate closure of the vessel, often

necessitating emergent surgical coronary bypass grafting in approximately 5% of cases. Restenosis is

common, occurring in nearly 40% to 50% of patients, either from mechanical elastic recoil or

progressive neointimal hyperplasia.

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The addition of stents, nitinol scaffolding devices, has nearly eliminated acute vessel occlusion, and

the need for salvage surgical revascularization is below 1%. In addition, stents have greatly reduced

restenosis rates down to nearly 20% and are used in nearly 90% of percutaneous procedures in the

United States. The stents are delivered crimped onto a deflated balloon. With balloon inflation, the stent

expands, restoring the vessel lumen to its anatomic dimensions. The stent prevents elastic recoil and

coronary dissection, improving immediate outcomes, but the problem of neointimal hyperplasia

remains, resulting in the persistent rates of restenosis. Stents have been improved even further by

impregnating antiproliferative drugs onto the scaffolds. Sirolimus and paclitaxel are

immunosuppressants that act by different mechanisms. Paclitaxel is a mitotic inhibitor, which retards

microtubule breakdown. Sirolimus binds intracellularly to FK-binding protein and inhibits interleukin-2

(IL-2) production via the target of rapamycin pathway. Both sirolimus- and paclitaxel-eluting stents

have further reduced the rate of target vessel restenosis and the need for repeat interventions.39

However, reports of late stent thrombosis have raised concerns, and indefinite use of antiplatelet

regimens has been recommended.40

CORONARY BYPASS GRAFTING

Indications

Coronary artery bypass grafting (CABG) is one of the most common and most studied surgical

procedures performed in the United States. As one might expect, CABG consumes more resources than

any other single cardiovascular procedure. Dozens of multicenter, prospective, randomized trials have

been performed comparing the surgical treatment of coronary artery disease to both medical and

percutaneous options. Some of these landmark studies will be discussed in detail later in the chapter, as

proper understanding of these trials is important in determining appropriate treatment strategies for

individual patients. In summary, these studies consistently demonstrate that CABG continues to be the

best revascularization strategy, reducing rate of both myocardial infarctions and the need for repeat

revascularization in patients with a broad degree of occlusive disease. A task force made up of

numerous medical societies including the American College of Cardiology, the American Heart

Association, the Society of Thoracic Surgeons (STS), and the American Association of Thoracic Surgeons

recently published guidelines on the indications for coronary artery revascularization and made

recommendations regarding the mode of revascularization.41 The group considered a number of

variables, including clinical symptoms and mode of presentation, the degree of ischemia determined by

noninvasive imaging, and the severity of coronary disease based on angiographic imaging. In summary,

patients are more likely to benefit from surgical revascularization if they have worse symptoms, more

severe myocardial ischemia, and more extensive coronary artery occlusions. The recommendations are

summarized in Figure 83-7, where recommendations are categorized as “appropriate,” “uncertain,” and

“inappropriate.” Interestingly, these guidelines have not changed markedly over the last several

decades, despite vast improvements in both medical treatment and percutaneous technology. Today,

CABG remains the best mode of cardiac revascularization in symptomatic patients.

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Figure 83-6. Percutaneous coronary intervention. A: A stenotic midright coronary artery lesion. B: Balloon angioplasty. C:

Postintervention result. (Images courtesy of Brahmajee Nallamothu.)

Standard Technique

7 The basic principles in coronary bypass grafting are to restore normal unimpeded perfusion of

ischemic myocardial territories by providing alternative routes for blood flow. Previous approaches to

surgically revascularize the myocardium-included creation of intramyocardial tunnels and arterialization

of the coronary sinus. However, it was the aortocoronary bypass pioneered by a surgeon named Rene

Favaloro at the Cleveland Clinic in the late 1960s that revolutionized the treatment of coronary

atherosclerosis. The technique has evolved considerably over the decades, and there remains significant

variability in how this complex procedure is conducted even today.

The heart is typically exposed via a median sternotomy. This incision allows exposure of the anterior

surface of the heart, as well as the great vessels, for initiation of cardiopulmonary bypass (CPB). Except

for the severely hypertrophic heart, the entire epicardial surface can be exposed with manipulation and

traction on the left ventricle. Alternatively, a left lateral thoracotomy can be used. This limits

visualization to the obtuse margin of the heart but can be advantageous, particularly if the patient has

previously had a median sternotomy with dense adhesions hazarding catastrophic injury during sternal

reentry. Another alternative has been a limited left anterior thoracotomy, which exposes only a small

portion of the anterior wall of the left ventricle, usually limited to revascularization of the LAD. This

approach will be discussed later in the section describing minimally invasive approaches to surgical

revascularization.

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Figure 83-7. 2009 consensus recommendations regarding coronary artery revascularization. A, appropriate; CABG, coronary artery

bypass grafting; I, inappropriate; LAD, left anterior descending; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary

intervention; U, uncertain. (Reproduced with permission from Patel MR, Dehmer GJ, Hirshfeld JW, et al.

ACCF/SCAI/STS/AATS/AHA/ASNC 2009 appropriateness criteria for coronary revascularization. Circulation 2009;119:1330–1353.)

The key to constructing a durable and reproducible anastomosis to small diseased epicardial vessels is

creation of a quiet and bloodless surgical field. The advent of CPB using extracorporeal circulation along

with cardiac standstill using cardioplegia has allowed precisely this environment. The epicardial vessels

are motionless and can be brought directly into the surgical field. Epicardial blood flow is eliminated,

allowing direct visualization of the lumen without arterial control, avoiding potential clamp or snare

injury to the fragile vessels.

After anticoagulation with 300 IU/kg of heparin is confirmed with an activated clotting time (ACT),

the patient is cannulated in the distal ascending aorta. Patients may have significant atherosclerotic

disease, and the cannulation site should be carefully inspected for mobile lesions using TEE and manual

palpation. Some centers advocate epiaortic ultrasonic imaging for more accurate visualization. After

insertion, the cannula is manually deaired and connected to the arterial limb of the CPB circuit (Fig. 83-

8). Venous drainage is accomplished with a cannula in the right atrium, typically in the atrial

appendage. Bleeding from the cannulation sites is controlled by pursestring sutures around the cannulas.

Bypass is initiated by venous drainage into a reservoir, emptying the heart of venous return. Blood is

pumped into a membrane oxygenator and returned into the aortic cannula, typically at a blood flow rate

of 2.4 L/min per m2 of body surface area. With full flow, ventilation of the patient can be discontinued,

further improving visualization and minimizing motion in the surgical field. The extracorporeal blood is

cooled, creating mild hypothermia, varying from 28°C to 32°C. Systemic cooling minimizes end-organ

injury from relative hypotension or hypoperfusion from nonpulsatile blood flow.

After adequate CPB is confirmed, the heart is arrested by applying a clamp across the midascending

aorta, proximal to the aortic cannulation site. This clamp isolates the native coronary vessels from the

remainder of the systemic circulation. Cardioplegia is then delivered to the myocardium via a needle or

catheter in the aortic root. There are a variety of cardioplegia solutions commercially available, but the

most important components are dilute blood, cold temperature (8°C to 15°C), potassium at 15 to 30

mM/L, citrate for calcium binding, dextrose for myocardial substrate, and pH buffers. The cold

temperature and potassium maintain the heart in diastolic arrest, reducing myocardial oxygen

consumption. Cardioplegia is typically delivered intermittently, approximately every 15 to 20 minutes,

to provide adequate oxygen and nutrient delivery and to minimize myocardial activity. Additionally,

some surgeons utilize cardioplegia delivered in a retrograde fashion via a specially designed balloontipped catheter inserted into the coronary sinus. Protocols relying entirely upon antegrade delivery of

cardioplegia hazard incomplete myocardial protection, particularly in territories of severe coronary

artery stenosis or total occlusions. In addition, an incompetent aortic valve will limit cardioplegia

delivery down the coronaries, and leaking into the left ventricle will result in significant ventricular

distention. Furthermore, antegrade cardioplegia can be delivered under supraphysiologic pressures from

the extracorporeal mechanical blood pumps. This can result in epicardial vessel injury and embolization

of atheromatous debris, particularly in the reoperative setting in which old vein grafts often contain

mobile and highly friable lesions. The use of retrograde cardioplegia can overcome these limitations,

and some evidence suggests outcomes can be improved.

Conduits used for coronary bypass grafting are variable. The oldest and most frequently chosen

conduit is the greater saphenous vein because of its availability, accessibility, reasonable size match, the

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