Figure 83-1. Anatomy of the cardiac circulation. A: Anterior view. B: Posterior view.

Venous anatomy is more predictable, and very little pathology within this system is encountered.

Three named venous branches can be identified: the middle cardiac vein in the posterior interventricular

groove, the posterior cardiac vein along the obtuse margin of the heart, and the great (or anterior)

cardiac vein along the anterior interventricular groove. All three drain into one confluence known as the

coronary sinus along the posterior atrioventricular groove (Fig. 83-1). The coronary sinus empties

posteriorly into the right atrium between the inferior vena cava and the annulus of the tricuspid valve.

In addition to these identifiable named veins, the myocardium also drains directly into all chambers of

the heart via thebesian veins.

1 Myocardial work consumes an enormous amount of energy substrate. In fact, only 10% to 20% of

myocardial energy requirements are related to basal functions; the remainder is utilized during the

continuous energy-dependent calcium mobilization and myofilament cross-linking from cyclic

contraction and relaxation. Even at rest, the heart maximally extracts oxygen delivered from the

bloodstream, leaving venous saturation in the coronary sinus typically 20% or less. Thus, increased

energy requirements must be met with augmentation in blood oxygen delivery. Contrarily, other less

oxygen-dependent tissues, where venous saturation can be as high as 80%, can extract additional oxygen

during stress. When insufficient supply of oxygen is available, as may be the case with extreme

consumption or limited blood flow, anaerobic metabolism cannot generate enough energy substrate to

perform myocardial contraction.2 As a result, cardiac function deteriorates immediately and can be

observed clinically essentially within heartbeats. Increases in cardiac oxygen consumption must be met

with proportional increases in myocardial blood flow.

The heart and its coronary circulation have a unique capacity to dramatically increase blood flow, and

thus oxygen delivery, during periods of increased needs.3 While basal coronary blood flow is

approximately 10 mL/kg, this value can increase up to sixfold with exercise by autoregulatory

mechanisms and feedback loops. Specifically, adenosine accumulates from the breakdown of the energy

substrate adenosine triphosphate (ATP). Vasodilatory receptors within the media of coronary arteries

are particularly avid for adenosine, increasing blood flow to myocardial regions with increased energy

consumption. In addition, increased myocardial activity activates nitric oxide synthase within coronary

endothelial cells, producing the powerful vasodilator nitric oxide. By immediately altering the vessel

diameter and thus changing the resistance properties of epicardial vessels, these two short-acting

mediators can rapidly alter coronary flow rates to meet changing energy requirements.

In addition to the high metabolic requirements of the heart and its dependence on responsive changes

in blood flow, the coronary circulation is further uniquely challenged. During systole, increased cavitary

pressure compresses intramyocardial vessels and virtually eliminates forward flow. As a result, blood

flow to the left ventricle occurs only during diastole, so that myocardial perfusion depends not only on

coronary arterial patency and caliber, but also on the diastolic pressure gradient and the duration of

diastole. Tachycardia not only increases oxygen consumption, but also reduces the time available for

myocardial perfusion, increasing the demands for epicardial flow. The rise in ventricular diastolic

pressure seen in heart failure also reduces perfusion pressure and can jeopardize ischemia in vulnerable

territories. With an understanding of cardiac perfusion needs and mechanics, it is apparent why

occlusive lesions in coronary arteries can restrict blood flow, producing ischemia and infarction.

CORONARY ATHEROSCLEROSIS

Atherosclerosis is a progressive multifocal disease of medium and large muscular arteries of the

systemic circulation. Atherosclerotic plaques or atheromas can occur anywhere in the systemic

circulation, but tend to present clinically in varying quantities in the coronary circulation, carotid

arteries, splanchnic vessels, and lower extremities. The lesions tend to occur predominantly at vessel

bifurcations, sharp curvatures, and other regions creating pressure wave reflections and recirculation.4

All plaques consist of smooth muscle proliferation and intracellular and extracellular lipid deposition

within the arterial intima (Fig. 83-2). The predecessor “fatty streaks” seen in the first two decades of

life are small and unobstructing. However, under certain clinical circumstances, endothelial injury from

cigarette smoke, hypercholesterolemia, hyperglycemia, hypertension, or other causes of inflammation

initiates a cascade of events. These include endothelial dysfunction with expression of adhesion

molecules, which bind circulating inflammatory cells like monocytes. The activated monocyte

transmigrates into the vessel wall and ingests accumulated lipids. In turn, they release cytokines, which

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enhance endothelial cell adhesion molecule expression; alter endothelial cell nitric oxide production,

promoting vasoconstriction and platelet activation; and stimulate activation of other inflammatory cells

including neutrophils and T lymphocytes. The activated monocytes accelerate further lipid accumulation

and smooth muscle cell proliferation. The end result is an enlarging plaque encroaching on the arterial

lumen, separated from the bloodstream by a collagen-rich fibrous plaque.

Figure 83-2. The atherosclerotic plaque. A: The normal muscular artery consists of an internal intima with endothelium and

internal elastic lamina. The smooth muscle of the vessel wall is in the media, and the thin adventitial layer contains connective

tissue and the vasa vasorum. B: The first phase of an atherosclerotic lesion consists of focal thickening of the intima with smooth

muscle cells and extracellular matrix and an initial accumulation of intercellular lipid deposits. C: Extracellular lipid may also

develop. D: Intercellular and extracellular lipid in the earliest phase is referred to as a fatty streak. E: A fibrous plaque results as

fibroblasts that cover the proliferating smooth muscle cells laden with lipids and cell debris continue to accumulate. The lesion

becomes more complex as continuing cell degeneration leads to an ingress of blood constituents and calcification.

2 Within the coronary circulation, atherosclerotic stenotic lesions are generally restricted to the

proximal regions of the large epicardial coronary arteries. In particular, stenosis found in the LAD and

circumflex vessels are frequently isolated, short, and in the proximal segments. The right coronary

artery, however, develops diffuse obstructions, although rarely extending into the posterior descending

or intramural branches. For reasons that are unclear, atherosclerosis is rarely found within

intramyocardial segments of the coronary arteries. Symptoms from these atherosclerotic plaques can

occur from a variety of proposed mechanisms. First, the lesion can cause flow limitations, particularly

when the luminal cross-sectional area is reduced by at least 75%. With this degree of obstruction, the

vasodilatory reserve required during increased myocardial demand is restricted, resulting in transient

myocardial ischemia until demand returns to baseline, also known as exertional angina. The

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atherosclerotic plaque also causes coronary ischemia when the lesion becomes unstable. The fibrous

plaque can fracture or rupture, exposing the bloodstream to the highly thrombogenic internal plaque

contents. This can lead to complete epicardial thrombosis, the presumed mechanism of ST-segment

elevation myocardial infarction (STEMI). Additionally, subtotal plaque disruption can cause

vasoconstriction, platelet activation, and embolization, resulting in ischemia without total occlusion of

the epicardial vessel. This is the presumed mechanism of unstable angina and non–ST-segment elevation

myocardial infarction (NSTEMI). Some plaques are more prone to rupture than others, and the

composition of the fibrous cap may be an identifiable feature of an unstable lesion. Activation of

inflammatory cells may increase the activity of matrix metalloproteinases, which degrade components

of the fibrous cap. Some theorize that certain stressors can stimulate activation of these inflammatory

cells, such as acute infections, extreme cold, and even emotional distress.5 The inflammatory component

of coronary artery disease has been demonstrated by the strong relationship between C-reactive protein

and the incidence of acute myocardial infarctions.6

Although the characteristics, locations, and severity of lesions in each person can vary, a number of

established risk factors appear to predispose to atherosclerosis. These include advanced age, family

history, male sex, hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking. Recognizing the

presence of these risk factors can help identify patients at risk of coronary atherosclerosis. In addition,

some of these risk factors are modifiable, and simple interventions can reduce their risk of future

cardiac events.

Hypertension is strongly associated with the development of atherosclerotic heart disease and the risk

of death from cardiovascular causes. Although the mechanism is uncertain, it has been suggested that an

increase in shear stress at particular vessel locations may injure the vascular endothelium, predisposing

to lipid deposition and plaque development. Systolic hypertension appears to be more predictive than

diastolic hypertension, particularly in elderly patients. Numerous interventions can control

hypertension, but the most effective appears to be lifestyle modifications including reduction in dietary

sodium, exercise, and weight loss. Several classes of medications are used for blood pressure control,

and each is variably efficacious in different populations of patients.7 Unequivocally, reduction in

elevated systolic blood pressure reduces the risk of death from cardiovascular disease, and in particular

of atherosclerotic coronary artery disease.

Patients with diabetes are two to four times more likely to have coronary artery disease, and even

more so when they are insulin dependent and in diabetic women. In addition, patients with diabetes and

coronary disease have worse outcomes than age-matched nondiabetics. Unfortunately, rigorous control

of elevated blood glucose concentrations by insulin does not appear to affect coronary mortality as well

as control of other risk factors such as hypertension, dyslipidemia, and smoking cessation does.8

Dyslipidemia is associated with accelerated coronary artery disease. This includes both elevation of

total cholesterol levels and an imbalance in the ratio of the subcomponents of cholesterol: high-density

lipoprotein (HDL) and low-density lipoprotein (LDL).9 HDL levels appear to be protective, as the total

HDL level is inversely proportional to the risk for the development of coronary artery disease.

Conversely, LDL levels are directly proportional to cardiovascular risk. Importantly, alteration in total

cholesterol and the ratio of HDL to LDL by dietary changes, medications, and exercise can reduce the

risk of cardiovascular events.10

Cigarette smoking is one of the most important risk factors for coronary artery disease. Carbon

monoxide and nicotine directly adversely affect endothelial cell function. In addition, cigarette smoke

can increase LDL levels, reduce HDL levels, increase fibrinogen levels, and increase platelet

aggregation. Regular smokers have a four to five times higher rate of cardiovascular death than

nonsmokers, and there appears to be a dose relationship, with heavier smokers having a higher

prevalence of coronary disease than lighter smokers. Fortunately, the risk of developing coronary artery

disease is reduced by 50% after 1 year of smoking abstinence, and at 10 years the risk is no different

from that of those who never smoked.11

PATIENT PRESENTATION

The clinical manifestations of ischemic heart disease result from an imbalance of myocardial oxygen

supply and consumption. The symptoms and acuity depend on the severity and nature of the patient’s

occlusive lesions, but also on his or her other medical comorbidities. As many as 25% of patients

diagnosed with coronary artery disease have no clear symptoms. The diagnosis is often made based on

abnormalities identified on screening tests obtained because of the presence of worrisome risk factors.

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3 Chronic stable angina is the most frequent complaint of the patient with coronary artery disease. At

rest, coronary blood flow is adequate to meet myocardial demand, and patients are without symptoms.

However, during exercise or stress, as myocardial oxygen demand increases, the autoregulatory

mechanisms to vasodilate and increase myocardial blood flow are constrained. Significant coronary

obstructing atheromas become flow limiting, resulting in an imbalance of oxygen demand and supply.

Chest pain develops rapidly and builds up quickly, typically described as tightness, squeezing,

constricting, or aching. It is usually midsternal and radiates to the left shoulder, arm, jaw, or neck. The

classically described Levine sign with a clenched fist over the sternum is a common finding. Some

patients, however, will describe symptoms that are collectively referred to as “anginal equivalents.”

These include dyspnea, diaphoresis, nausea, abdominal pain, heartburn, and dizziness or presyncope.

Although the differential diagnoses of these “atypical” symptoms are broad, they should prompt the

clinician to think of coronary disease, particularly if risk factors predominate. Interestingly, women are

more likely to describe atypical symptoms, resulting in late or missed diagnosis of coronary

atherosclerosis. Although the clinical manifestations of angina are variable, the pathognomonic feature

of chronic stable angina is that the symptoms occur predictably with exertion and are always relieved

with rest. Symptoms of patients with coronary atherosclerosis can be categorized according to the

Canadian Heart Association Classification scheme. Class I patients have no symptoms, class II patients

have angina with significant exertion, class III patients describe angina with mild exertion, and class IV

patients have angina at rest.

Acute coronary syndromes (ACSs) refer to a spectrum of accelerated coronary occlusive disease states

and include unstable angina, NSTEMI, and STEMI. Approximately 1 million people are hospitalized in

the United States each year with a diagnosis of ACS. Unstable angina refers to patients with chest pain

or an anginal equivalent that is new in onset, occurs at rest, or occurs with increasing severity and

frequency from their baseline chronic stable symptoms, also referred to as crescendo angina. Patients

who develop an NSTEMI have evidence of myocardial injury with elevated blood levels of myocardial

enzymes (troponin and the MB fraction of creatine kinase). Unstable angina and NSTEMI are important

prognostic indicators, as 10% of patients will die of cardiovascular causes within 6 months.

STEMI represents the consequences of large epicardial vessel occlusion, typically associated with

plaque rupture. Patients describe a severe retrosternal pain that persists for at least 30 minutes, but

usually for several hours. The pain is frequently characterized as crushing, squeezing, or boring, and can

radiate down the left arm or into the jaw. Patients with previous chronic stable angina will report that

the current pain is similar to but more intense than their baseline symptoms and has not resolved with

rest or nitroglycerine. However, many patients that present with an STEMI never had chronic stable

angina. Patients will often describe additional symptoms such as diaphoresis, nausea, dizziness, and

epigastric pain. In emergency departments, the pain is often mistaken for gastroenteritis or indigestion,

particularly in women. Often in elderly patients and those with diabetes, chest pain may not be present

at all, and the only symptom associated with STEMI is heart failure from progressive loss of myocardial

contractile function. Although improvements in health systems have drastically increased survival from

myocardial infarction, mortality for STEMI remains near 10%.

COMPLICATIONS OF ACUTE MYOCARDIAL INFARCTIONS

4 STEMIs can create widespread myocyte necrosis, often resulting in catastrophic complications that

require urgent intervention. Anticipation and early diagnosis can improve outcomes. These

complications include cardiogenic shock, postinfarct ventricular septal defect (VSD), free wall rupture,

and acute mitral valve regurgitation (Table 83-1).

Cardiogenic Shock

Cardiogenic shock is a state in which cardiac output is insufficient to meet metabolic demands, despite

adequate intravascular filling pressures. Between 5% and 10% of patients with acute myocardial

infarctions develop cardiogenic shock. A large proportion of these patients progress to shock not upon

arrival, but more than 24 hours after initial presentation.12 Overall mortality is approximately 60%,

with very little improvement over recent decades. Treatments include fluids and inotropic agents to

optimize myocardial contraction. Insertion of an intra-aortic balloon counterpulsation pump (IABP) can

improve coronary perfusion by diastolic augmentation of perfusion pressure. This can have a profound

impact by improving contractile function of peri-infarct territories. Although there is significant

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afterload reduction afforded by the IABP, cardiac output typically increases by only 15% to 20%.

Emergent salvage revascularization can reduce mortality, with sustained benefits seen over long-term

follow-up.13 When shock persists despite using these aggressive strategies, consideration must be made

regarding the patient’s candidacy for mechanical circulatory support using ventricular assist devices or

extracorporeal membrane oxygenation.14 While these options may only be available in selected regional

medical centers, durable long-term survival can be obtained in a highly selected patient population.15

Postinfarction Ventricular Septal Defect

A postinfarction VSD is an infrequent complication occurring after fewer than 1% of acute myocardial

infarctions. The infarct is most commonly in the LAD territory, with the defect in the distal septum.

Alternatively, a postinfarct VSD can form from acute right coronary occlusion, with the infarct

predominantly in the posterobasilar septum. They typically present 5 to 10 days following initial

presentation, but can occur earlier, particularly if late thrombolytic therapy was administered. The

diagnosis should be considered in a patient in whom cardiogenic shock with refractory hypotension and

pulmonary edema develops suddenly following a myocardial infarction. On physical examination, an

unmistakable holosystolic murmur can be heard over the entire precordium. The diagnosis is confirmed

with echocardiography using Doppler techniques to demonstrate flow across the interventricular

septum. Right heart catheterization will reveal a step-up in oxygen saturation from the right atrium to

the pulmonary artery. Medical therapy involves stabilization to optimize cardiac output and end-organ

perfusion. Refractory hypotension is typical, excluding the use of afterload reducing agents. Intra-aortic

balloon counterpulsation can occasionally be helpful for afterload reduction and to optimize coronary

perfusion. Emergent surgical intervention is required if there is any hope of survival. Infarcted muscle is

débrided, and the defect is typically closed using prosthetic material. For surgical candidates, survival

rates of approximately 50% can be expected.16

Papillary Muscle Rupture

Severe regurgitation of the mitral valve can occur after acute myocardial infarctions, with a frequency

of less than 1%. The mechanism is related to infarction of the tip or trunk of one of the papillary

muscles, with resultant disruption of the mitral subvalvar apparatus and failed leaflet coaptation.

Posteroinferior MIs lead to this complication two to three times more frequently than anterior

infarctions, presumably because there is more collateral blood flow to the anterolateral papillary muscle

compared to the posteriomedial. While chronic mitral regurgitation can be well tolerated through

adaptive changes in the left atrium and pulmonary vascular bed, severe acute mitral regurgitation

results in immediate heart failure, as the small left atrium offers little compliance for the massive

volume overload. Papillary muscle rupture develops typically between the third and fifth days following

myocardial infarction, when infarcted myocardium is at its weakest. However, it can present within the

first 24 hours. Patients will describe acute-onset dyspnea, pulmonary edema, and possibly signs of

cardiogenic shock. The diagnosis should be suspected in any patient after myocardial infarction with a

new holosystolic murmur heard at the apex, associated with dyspnea and hypotension. Bedside surface

echocardiography typically demonstrates the mitral regurgitation, and the flail leaflet may be seen. For

more definitive imaging, transesophageal echocardiography (TEE) can be performed. Not only will the

mitral valve pathology be clearly seen, but also alternative diagnoses such as a postinfarct VSD can be

excluded. In addition to the treatments typically employed for myocardial infarctions, immediate

medical therapy of ruptured papillary muscles involves afterload reduction when tolerated, with

infusions of nitroglycerine or nitroprusside. If cardiac output cannot be maintained, intra-aortic balloon

counterpulsation can be helpful. Definitive therapy involves prompt surgical correction. Although

mortality rates are generally high, there are no survivors without surgical correction.17 If coronary

angiography demonstrated occlusive epicardial lesions in territories other than the acute infarction,

simultaneous coronary bypass grafting can be performed. Under most circumstances, the diseased mitral

valve is excised and replaced. Because the ventricular cavity is typically small, the valve is usually

replaced with a low-profile mechanical prosthesis to avoid left ventricular outflow obstruction from the

protruding struts of stented bioprosthetic valves.

Table 83-1 Complications of Acute Myocardial Infarctions

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Ventricular Free Wall Rupture

Ventricular free wall rupture after myocardial infarction is infrequently encountered clinically, likely

because of the exceedingly high mortality. The actual incidence is unknown, but may represent up to

30% of all deaths after acute myocardial infarctions. Like postinfarct VSD and papillary muscle ruptures,

they tend to occur between the third and sixth days after infarction, when the myocardium is at its

weakest. Free wall ruptures can present in essentially one of two ways: (a) a simple full-thickness tear

with catastrophic hemorrhage and death from tamponade or (b) a complex serpiginous tear, partially

contained. The latter is more likely to require surgical intervention, often presenting weeks from the

initial infarction with symptoms of delayed cardiac tamponade. In rare cases, it is completely contained

and may go unrecognized until a pseudoaneurysm develops, which is often diagnosed at a later date.

Patients with free wall rupture will typically present with cardiogenic shock and may have features

suggesting tamponade. Echocardiography will demonstrate a large pericardial effusion, frequently with

echo-dense clot or ventricular wall defects. Urgent surgical intervention is required, often without

coronary angiography or other time-consuming diagnostic tests. Once the pericardium is opened and

cardiac tamponade is relieved, hemodynamic stability is often achieved. The site of hemorrhage is

identified by the necrotic-appearing myocardium and adherent thrombus. The defect can be closed with

large mattress sutures reinforced with Teflon felt strips. Care must be taken while tying the suture, as

the necrotic muscle is weak and friable. Some have advocated covering the defect with a large Teflon

felt patch using biologic adhesives, avoiding sutures altogether.18 Whatever the technique, outcomes are

likely determined by the hemodynamic status of the patient prior to arrival in the operating room and

the quality of the remaining viable myocardium.

Figure 83-3. The electrocardiogram in an acute myocardial infarction.

DIAGNOSIS

The initial diagnostic tool for patients presenting with chest pain is the resting electrocardiogram

(ECG). Although the majority of patients with chronic stable angina will have a normal ECG pattern,

evidence of previous myocardial infarctions may be identified, either with the presence of Q waves or

conduction abnormalities. Patients with an acute myocardial infarction may demonstrate ST-segment

elevation (Fig. 83-3), prompting urgent intervention. Occasionally, more subtle ECG findings may

provide clues that the chest pain is ischemic in etiology. Although nonspecific, these changes may

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