2060 PART 6 Disorders of the Cardiovascular System

more common when patients require invasive procedures, unnecessary venous or arterial interventions should be avoided in patients

receiving fibrinolytic agents. Hemorrhagic stroke is the most serious

complication and occurs in ~0.5–0.9% of patients being treated with

these agents. This rate increases with advancing age, with patients

>70 years experiencing roughly twice the rate of intracranial hemorrhage as those <65 years. Large-scale trials have suggested that the rate

of intracranial hemorrhage with tPA or rPA is slightly higher than with

streptokinase.

■ INTEGRATED REPERFUSION STRATEGY

Evidence has emerged that suggests timely performance of PCI is the preferred reperfusion strategy in the management of STEMI. Prior approaches

that segregated the pharmacologic and catheter-based approaches to

reperfusion have now been replaced with an integrated approach to triage

and transfer STEMI patients to receive PCI (Fig. 275-5). To achieve the

degree of integration required to care for a patient with STEMI, all

communities should create and maintain a regional system of STEMI

care that includes assessment and continuous quality improvement of

emergency medical services and hospital-based activities.

Cardiac catheterization and coronary angiography should be carried

out after fibrinolytic therapy if there is evidence of either (1) failure of

reperfusion (persistent chest pain and ST-segment elevation >90 min),

in which case a rescue PCI should be considered; or (2) coronary

artery reocclusion (re-elevation of ST segments and/or recurrent chest

pain) or the development of recurrent ischemia (such as recurrent

angina in the early hospital course or a positive exercise stress test

before discharge), in which case an urgent PCI should be considered.

Routine angiography and elective PCI even in asymptomatic patients

following administration of fibrinolytic therapy are used with less frequency, given the numerous technologic advances that have occurred

in the catheterization laboratory and the increasing number of skilled

interventionalists. Coronary artery bypass surgery should be reserved

for patients whose coronary anatomy is unsuited to PCI but in whom

revascularization appears to be advisable because of extensive jeopardized myocardium or recurrent ischemia.

HOSPITAL PHASE MANAGEMENT

■ CORONARY CARE UNITS

These units are routinely equipped with a system that permits continuous monitoring of the cardiac rhythm of each patient and hemodynamic monitoring in selected patients. Defibrillators, respirators,

noninvasive transthoracic pacemakers, and facilities for introducing

pacing catheters and flow-directed balloon-tipped catheters are also

usually available. Equally important is the organization of a highly

trained team of nurses who can recognize arrhythmias; adjust the

dosage of antiarrhythmic, vasoactive, and anticoagulant drugs; and

perform cardiac resuscitation, including electroshock, when necessary.

Patients should be admitted to a coronary care unit early in their

illness when it is expected that they will derive benefit from the sophisticated and expensive care provided. The availability of electrocardiographic monitoring and trained personnel outside the coronary care

unit has made it possible to admit lower-risk patients (e.g., those not

hemodynamically compromised and without active arrhythmias) to

“intermediate care units.”

The duration of stay in the coronary care unit is dictated by the

ongoing need for intensive care. If symptoms are controlled with oral

therapy, patients may be transferred out of the coronary care unit. Also,

patients who have a confirmed STEMI but who are considered to be at

low risk (no prior infarction and no persistent chest discomfort, CHF,

hypotension, or cardiac arrhythmias) may be safely transferred out of

the coronary care unit within 24 h.

Activity Factors that increase the work of the heart during the initial hours of infarction may increase the size of the infarct. Therefore,

patients with STEMI should be kept at bed rest for the first 6–12 h.

However, in the absence of complications, patients should be encouraged, under supervision, to resume an upright posture by dangling

their feet over the side of the bed and sitting in a chair within the first

24 h. This practice is psychologically beneficial and usually results in a

reduction in the pulmonary capillary wedge pressure. In the absence of

hypotension and other complications, patients typically are ambulating

in their room with increasing duration, anticipating that they may be

discharged after 3–5 days.

Diet Because of the risk of emesis and aspiration soon after STEMI,

patients should receive either nothing or only clear liquids by mouth

for the first 4–12 h. The typical coronary care unit diet should provide ≤30% of total calories as fat and have a cholesterol content of

≤300 mg/d. Complex carbohydrates should make up 50–55% of total

calories. Portions should not be unusually large, and the menu should

be enriched with foods that are high in potassium, magnesium, and

fiber, but low in sodium. Diabetes mellitus and hypertriglyceridemia

are managed by restriction of concentrated sweets in the diet.

Bowel Management Bed rest and the effect of the narcotics used

for the relief of pain often lead to constipation. A bedside commode

rather than a bedpan, a diet rich in bulk, and the routine use of a stool

softener such as dioctyl sodium sulfosuccinate (200 mg/d) are recommended. If the patient remains constipated despite these measures, a

laxative can be prescribed. Contrary to prior belief, it is safe to perform

a gentle rectal examination on patients with STEMI.

Sedation Many patients require sedation during hospitalization to

withstand the period of enforced inactivity with tranquility. Diazepam

(5 mg), oxazepam (15–30 mg), or lorazepam (0.5–2 mg), given three

to four times daily, is usually effective. An additional dose of any of

the above medications may be given at night to ensure adequate sleep.

Attention to this problem is especially important during the first few

days in the coronary care unit, where the atmosphere of 24-h vigilance may interfere with the patient’s sleep. However, sedation is no

substitute for reassuring, quiet surroundings. Many drugs used in the

coronary care unit, such as atropine, H2

 blockers, and narcotics, can

produce delirium, particularly in the elderly. This effect should not be

confused with agitation, and it is wise to conduct a thorough review of

the patient’s medications before arbitrarily prescribing additional doses

of anxiolytics.

PHARMACOTHERAPY

■ ANTITHROMBOTIC AGENTS

The use of antiplatelet and anticoagulant therapy during the initial

phase of STEMI is based on extensive laboratory and clinical evidence

that thrombosis plays an important role in the pathogenesis of this

condition. The primary goal of treatment with antiplatelet and anticoagulant agents is to maintain patency of the infarct-related artery, in

conjunction with reperfusion strategies. A secondary goal is to reduce

the patient’s tendency to thrombosis and, thus, the likelihood of mural

thrombus formation or deep-venous thrombosis. The degree to which

antiplatelet and anticoagulant therapy achieves these goals partly

determines how effectively it reduces the risk of mortality from STEMI.

As noted previously (see “Management in the Emergency Department” earlier), aspirin is the standard antiplatelet agent for patients

with STEMI. The most compelling evidence for the benefits of antiplatelet therapy (mainly with aspirin) in STEMI is found in the comprehensive overview by the Antiplatelet Trialists’ Collaboration. Data

from nearly 20,000 patients with MI enrolled in 15 randomized trials

were pooled and revealed a relative reduction of 27% in the mortality

rate, from 14.2% in control patients to 10.4% in patients receiving

antiplatelet agents.

Inhibitors of the P2Y12 ADP receptor prevent activation and aggregation of platelets. The addition of the P2Y12 inhibitor clopidogrel to

background treatment with aspirin to STEMI patients reduces the

risk of clinical events (death, reinfarction, stroke) and, in patients

receiving fibrinolytic therapy, has been shown to prevent reocclusion

of a successfully reperfused infarct artery. Newer P2Y12 ADP receptor

antagonists, such as prasugrel and ticagrelor, are more effective than

clopidogrel in preventing ischemic complications in STEMI patients

ST-Segment Elevation Myocardial Infarction

2061CHAPTER 275

undergoing PCI but are associated with an increased risk of bleeding.

Glycoprotein IIb/IIIa receptor inhibitors are useful for preventing

thrombotic complications in patients with STEMI undergoing PCI.

The standard anticoagulant agent used in clinical practice is unfractionated heparin (UFH). The available data suggest that when UFH is

added to a regimen of aspirin and a non-fibrin-specific thrombolytic

agent such as streptokinase, additional mortality benefit occurs (about

5 lives saved per 1000 patients treated). The immediate administration

of intravenous UFH, in addition to a regimen of aspirin and relatively

fibrin-specific fibrinolytic agents (tPA, rPA, or TNK), helps to maintain

patency of the infarct-related artery. This effect is achieved at the cost

of a small increased risk of bleeding. The recommended dose of UFH

is an initial bolus of 60 U/kg (maximum 4000 U) followed by an initial

infusion of 12 U/kg per h (maximum 1000 U/h). The activated partial

thromboplastin time during maintenance therapy should be 1.5–2

times the control value.

Alternatives to UFH for anticoagulation of patients with STEMI are

the low-molecular-weight heparin (LMWH) preparations, a synthetic

version of the critical pentasaccharide sequence (fondaparinux), and

the direct antithrombin bivalirudin. Advantages of LMWHs include

high bioavailability permitting administration subcutaneously, reliable

anticoagulation without monitoring, and greater anti-Xa:IIa activity.

Enoxaparin has been shown to reduce significantly the composite endpoints of death/nonfatal reinfarction and death/nonfatal reinfarction/

urgent revascularization compared with UFH in STEMI patients who

receive fibrinolysis. Treatment with enoxaparin is associated with

higher rates of serious bleeding, but net clinical benefit—a composite

endpoint that combines efficacy and safety—still favors enoxaparin

over UFH. Interpretation of the data on fondaparinux is difficult

because of the complex nature of the pivotal clinical trial evaluating

it in STEMI (OASIS-6). Fondaparinux appears superior to placebo

in STEMI patients not receiving reperfusion therapy, but its relative

efficacy and safety compared with UFH is less certain. Owing to the

risk of catheter thrombosis, fondaparinux should not be used alone

at the time of coronary angiography and PCI but should be combined

with another anticoagulant with antithrombin activity such as UFH or

bivalirudin. Trials of bivalirudin used an open-label design to evaluate

its efficacy and safety compared with UFH plus a glycoprotein IIb/

IIIa inhibitor. Bivalirudin was associated with a lower rate of bleeding,

largely driven by reductions in vascular access site hematomas ≥5 cm

or the administration of blood transfusions.

Patients with an anterior location of the infarction, severe LV

dysfunction, heart failure, a history of embolism, two-dimensional

echocardiographic evidence of mural thrombus, or atrial fibrillation

are at increased risk of systemic or pulmonary thromboembolism.

Such individuals should receive full therapeutic levels of anticoagulant

therapy (LMWH or UFH) while hospitalized, followed by at least

3 months of warfarin therapy.

■ BETA-ADRENOCEPTOR BLOCKERS

The benefits of beta blockers in patients with STEMI can be divided

into those that occur immediately when the drug is given acutely and

those that accrue over the long term when the drug is given for secondary prevention after an infarction. Acute intravenous beta blockade

improves the myocardial O2

 supply-demand relationship, decreases

pain, reduces infarct size, and decreases the incidence of serious ventricular arrhythmias. In patients who undergo fibrinolysis soon after

the onset of chest pain, no incremental reduction in mortality rate is

seen with beta blockers, but recurrent ischemia and reinfarction are

reduced.

Thus, beta-blocker therapy after STEMI is useful for most patients

(including those treated with an angiotensin-converting enzyme

[ACE] inhibitor) except those in whom it is specifically contraindicated

(patients with heart failure or severely compromised LV function, heart

block, orthostatic hypotension, or a history of asthma) and perhaps

those whose excellent long-term prognosis (defined as an expected

mortality rate of <1% per year, patients <55 years, no previous MI, with

normal ventricular function, no complex ventricular ectopy, and no

angina) markedly diminishes any potential benefit.

■ INHIBITION OF THE RENIN-ANGIOTENSINALDOSTERONE SYSTEM

ACE inhibitors reduce the mortality rate after STEMI, and the mortality benefits are additive to those achieved with aspirin and beta blockers. The maximum benefit is seen in high-risk patients (those who are

elderly or who have an anterior infarction, a prior infarction, and/or

globally depressed LV function), but evidence suggests that a shortterm benefit occurs when ACE inhibitors are prescribed unselectively

to all hemodynamically stable patients with STEMI (i.e., those with a

systolic pressure >100 mmHg). The mechanism involves a reduction

in ventricular remodeling after infarction (see “Ventricular Dysfunction” later) with a subsequent reduction in the risk of CHF. The rate of

recurrent infarction may also be lower in patients treated chronically

with ACE inhibitors after infarction.

ACE inhibitors should be continued indefinitely in patients who

have clinically evident CHF, in patients in whom an imaging study

shows a reduction in global LV function or a large regional wall motion

abnormality, or in those who are hypertensive.

Angiotensin receptor blockers (ARBs) should be administered to

STEMI patients who are intolerant of ACE inhibitors and who have

either clinical or radiologic signs of heart failure. Long-term mineralocorticoid receptor inhibition (spironolactone, eplerenone) should be

prescribed for STEMI patients without significant renal dysfunction

(creatinine ≥2.5 mg/dL in men and ≥2.0 mg/dL in women) or hyperkalemia (potassium ≥5.0 mEq/L) who are already receiving therapeutic

doses of an ACE inhibitor, have an LV ejection fraction ≤40%, and

have either symptomatic heart failure or diabetes mellitus. A multidrug

regimen for inhibiting the renin-angiotensin-aldosterone system has

been shown to reduce both heart failure–related and sudden cardiac

death–related cardiovascular mortality after STEMI.

■ OTHER AGENTS

Favorable effects on the ischemic process and ventricular remodeling

(see below) previously led many physicians to routinely use intravenous

nitroglycerin (5–10 μg/min initial dose and up to 200 μg/min as long

as hemodynamic stability is maintained) for the first 24–48 h after the

onset of infarction. However, the benefits of routine use of intravenous

nitroglycerin are less in the contemporary era where beta-adrenoceptor

blockers and ACE inhibitors are routinely prescribed for patients with

STEMI.

Results of multiple trials of different calcium antagonists have failed

to establish a role for these agents in the treatment of most patients

with STEMI. Therefore, the routine use of calcium antagonists cannot

be recommended. Strict control of blood glucose in diabetic patients

with STEMI has been shown to reduce the mortality rate. Serum

magnesium should be measured in all patients on admission, and

any demonstrated deficits should be corrected to minimize the risk of

arrhythmias.

COMPLICATIONS AND THEIR

MANAGEMENT

■ VENTRICULAR DYSFUNCTION

After STEMI, the left ventricle undergoes a series of changes in shape,

size, and thickness in both the infarcted and noninfarcted segments.

This process is referred to as ventricular remodeling and generally precedes the development of clinically evident CHF in the months to years

after infarction. Soon after STEMI, the left ventricle begins to dilate.

Acutely, this results from expansion of the infarct, i.e., slippage of

muscle bundles, disruption of normal myocardial cells, and tissue loss

within the necrotic zone, resulting in disproportionate thinning and

elongation of the infarct zone. Later, lengthening of the noninfarcted

segments occurs as well. The overall chamber enlargement that occurs

is related to the size and location of the infarct, with greater dilation

following infarction of the anterior wall and apex of the left ventricle

and causing more marked hemodynamic impairment, more frequent

heart failure, and a poorer prognosis. Progressive dilation and its clinical consequences may be ameliorated by therapy with ACE inhibitors

and other vasodilators (e.g., nitrates). In patients with an ejection

2062 PART 6 Disorders of the Cardiovascular System

fraction <40%, regardless of whether or not heart failure is present,

ACE inhibitors or ARBs should be prescribed (see “Inhibition of the

Renin-Angiotensin-Aldosterone System” earlier).

■ HEMODYNAMIC ASSESSMENT

Pump failure is now the primary cause of in-hospital death from

STEMI. The extent of infarction correlates well with the degree of

pump failure and with mortality, both early (within 10 days of infarction) and later. The most common clinical signs are pulmonary rales

and S3

 and S4

 gallop sounds. Pulmonary congestion is also frequently

seen on the chest roentgenogram. Elevated LV filling pressure and elevated pulmonary artery pressure are the characteristic hemodynamic

findings, but these findings may result from a reduction of ventricular

compliance (diastolic failure) and/or a reduction of stroke volume with

secondary cardiac dilation (systolic failure) (Chap. 257).

A classification originally proposed by Killip divides patients into

four groups: class I, no signs of pulmonary or venous congestion;

class II, moderate heart failure as evidenced by rales at the lung

bases, S3

 gallop, tachypnea, or signs of failure of the right side of the

heart, including venous and hepatic congestion; class III, severe heart

failure, pulmonary edema; and class IV, shock with systolic pressure

<90 mmHg and evidence of peripheral vasoconstriction, peripheral

cyanosis, mental confusion, and oliguria. When this classification was

established in 1967, the expected hospital mortality rate of patients in

these classes was as follows: class I, 0–5%; class II, 10–20%; class III,

35–45%; and class IV, 85–95%. With advances in management, the

mortality rate in each class has fallen, perhaps by as much as one-third

to one-half.

Hemodynamic evidence of abnormal global LV function appears

when contraction is seriously impaired in 20–25% of the left ventricle.

Infarction of ≥40% of the left ventricle usually results in cardiogenic

shock (Chap. 305). Positioning of a balloon flotation (Swan-Ganz)

catheter in the pulmonary artery permits monitoring of LV filling pressure; this technique is useful in patients who exhibit hypotension and/

or clinical evidence of CHF. Cardiac output can also be determined

with a pulmonary artery catheter. With the addition of intraarterial

pressure monitoring, systemic vascular resistance can be calculated as

a guide to adjusting vasopressor and vasodilator therapy. Some patients

with STEMI have markedly elevated LV filling pressures (>22 mmHg)

and normal cardiac indices (2.6–3.6 L/[min/m2

]), while others have

relatively low LV filling pressures (<15 mmHg) and reduced cardiac

indices. The former patients usually benefit from diuresis, while the

latter may respond to volume expansion.

■ HYPOVOLEMIA

This is an easily corrected condition that may contribute to the

hypotension and vascular collapse associated with STEMI in some

patients. It may be secondary to previous diuretic use, to reduced fluid

intake during the early stages of the illness, and/or to vomiting associated with pain or medications. Consequently, hypovolemia should

be identified and corrected in patients with STEMI and hypotension

before more vigorous forms of therapy are begun. Central venous pressure reflects RV rather than LV filling pressure and is an inadequate

guide for adjustment of blood volume because LV function is almost

always affected much more adversely than RV function in patients with

STEMI. The optimal LV filling or pulmonary artery wedge pressure

may vary considerably among patients. Each patient’s ideal level (generally ~20 mmHg) is reached by cautious fluid administration during

careful monitoring of oxygenation and cardiac output. Eventually, the

cardiac output plateaus, and further increases in LV filling pressure

only increase congestive symptoms and decrease systemic oxygenation

without raising arterial pressure.

TREATMENT

Congestive Heart Failure

The management of CHF in association with STEMI is similar to

that of acute heart failure secondary to other forms of heart disease

(avoidance of hypoxemia, diuresis, afterload reduction, inotropic

support) (Chap. 257), except that the benefits of digitalis administration to patients with STEMI are unimpressive. By contrast,

diuretic agents are extremely effective, as they diminish pulmonary

congestion in the presence of systolic and/or diastolic heart failure.

LV filling pressure falls and orthopnea and dyspnea improve after

the intravenous administration of furosemide or other loop diuretics. These drugs should be used with caution, however, as they can

result in a massive diuresis with associated decreases in plasma

volume, cardiac output, systemic blood pressure, and, hence, coronary perfusion. Nitrates in various forms may be used to decrease

preload and congestive symptoms. Oral isosorbide dinitrate, topical

nitroglycerin ointment, and intravenous nitroglycerin all have the

advantage over a diuretic of lowering preload through venodilation

without decreasing the total plasma volume. In addition, nitrates

may improve ventricular compliance if ischemia is present, as ischemia causes an elevation of LV filling pressure. Vasodilators must be

used with caution to prevent serious hypotension. As noted earlier,

ACE inhibitors are an ideal class of drugs for management of ventricular dysfunction after STEMI, especially for the long term. (See

“Inhibition of the Renin-Angiotensin-Aldosterone System” earlier.)

■ CARDIOGENIC SHOCK

Prompt reperfusion, efforts to reduce infarct size, and treatment

of ongoing ischemia and other complications of MI appear to have

reduced the incidence of cardiogenic shock from 20 to ~7%. Among

those who exhibit cardiogenic shock, only 10% of patients with this

condition present with it on admission, while 90% develop it during

hospitalization. Typically, patients who develop cardiogenic shock have

severe multivessel coronary artery disease with evidence of “piecemeal”

necrosis extending outward from the original infarct zone. The evaluation and management of cardiogenic shock and severe power failure

after STEMI are discussed in detail in Chap. 305.

■ RIGHT VENTRICULAR INFARCTION

Approximately one-third of patients with inferior infarction demonstrate at least a minor degree of RV necrosis. An occasional patient with

inferoposterior LV infarction also has extensive RV infarction, and rare

patients present with infarction limited primarily to the RV. Clinically

significant RV infarction causes signs of severe RV failure (jugular

venous distention, Kussmaul’s sign, hepatomegaly [Chap. 239]) with

or without hypotension. ST-segment elevations of right-sided precordial

ECG leads, particularly lead V4

R, are frequently present in the first 24 h in

patients with RV infarction. Two-dimensional echocardiography is helpful in determining the degree of RV dysfunction. Catheterization of the

right side of the heart often reveals a distinctive hemodynamic pattern

resembling constrictive pericarditis (steep right atrial “y” descent and an

early diastolic dip and plateau in RV waveforms) (Chap. 270). Therapy

consists of volume expansion to maintain adequate RV preload and

efforts to improve LV performance with attendant reduction in pulmonary capillary wedge and pulmonary arterial pressures.

■ ARRHYTHMIAS

(See also Chaps. 244 and 246) The incidence of arrhythmias after

STEMI is higher in patients seen early after the onset of symptoms. The

mechanisms responsible for infarction-related arrhythmias include

autonomic nervous system imbalance, electrolyte disturbances, ischemia, and slowed conduction in zones of ischemic myocardium. An

arrhythmia can usually be managed successfully if trained personnel

and appropriate equipment are available when it develops. Since

most deaths from arrhythmia occur during the first few hours after

infarction, the effectiveness of treatment relates directly to the speed

with which patients come under medical observation. The prompt

management of arrhythmias constitutes a significant advance in the

treatment of STEMI.

Ventricular Premature Beats Infrequent, sporadic ventricular

premature depolarizations occur in almost all patients with STEMI and

do not require therapy. Whereas in the past, frequent, multifocal, or

early diastolic ventricular extrasystoles (so-called warning arrhythmias)

ST-Segment Elevation Myocardial Infarction

2063CHAPTER 275

were routinely treated with antiarrhythmic drugs to reduce the risk of

development of ventricular tachycardia and ventricular fibrillation,

pharmacologic therapy is now reserved for patients with sustained

ventricular arrhythmias. Prophylactic antiarrhythmic therapy (either

intravenous lidocaine early or oral agents later) is contraindicated for

ventricular premature beats in the absence of clinically important ventricular tachyarrhythmias because such therapy may actually increase

the mortality rate. Beta-adrenoceptor blocking agents are effective

in abolishing ventricular ectopic activity in patients with STEMI

and in the prevention of ventricular fibrillation. As described earlier

(see “Beta-Adrenoceptor Blockers”), they should be used routinely

in patients without contraindications. In addition, hypokalemia and

hypomagnesemia are risk factors for ventricular fibrillation in patients

with STEMI; to reduce the risk, the serum potassium concentration

should be adjusted to ~4.5 mmol/L and magnesium to ~2.0 mmol/L.

Ventricular Tachycardia and Fibrillation Within the first

24 h of STEMI, ventricular tachycardia and fibrillation can occur

without prior warning arrhythmias. The occurrence of ventricular

fibrillation can be reduced by prophylactic administration of intravenous lidocaine. However, prophylactic use of lidocaine has not been

shown to reduce overall mortality from STEMI. In fact, in addition to

causing possible noncardiac complications, lidocaine may predispose

to an excess risk of bradycardia and asystole. For these reasons, and

with earlier treatment of active ischemia, more frequent use of betablocking agents, and the nearly universal success of electrical cardioversion or defibrillation, routine prophylactic antiarrhythmic drug

therapy is no longer recommended.

Sustained ventricular tachycardia that is well tolerated hemodynamically should be treated with an intravenous regimen of amiodarone

(bolus of 150 mg over 10 min, followed by infusion of 1.0 mg/min for

6 h and then 0.5 mg/min). A less desirable but alternative regimen is

procainamide (bolus of 15 mg/kg over 20–30 min; infusion of 1–4 mg/

min). If ventricular tachycardia does not stop promptly, electroversion

should be used (Chap. 246). An unsynchronized discharge of 200–300 J

(monophasic waveform; ~50% of these energies with biphasic waveforms) is used immediately in patients with ventricular fibrillation

or when ventricular tachycardia causes hemodynamic deterioration.

Ventricular tachycardia or fibrillation that is refractory to electroshock

may be more responsive after the patient is treated with epinephrine

(1 mg intravenously or 10 mL of a 1:10,000 solution via the intracardiac

route) or amiodarone (a 75–150-mg bolus).

Ventricular arrhythmias, including the unusual form of ventricular

tachycardia known as torsades des pointes (Chaps. 252 and 254), may

occur in patients with STEMI as a consequence of other concurrent

problems (such as hypoxia, hypokalemia, or other electrolyte disturbances) or of the toxic effects of an agent being administered to the

patient (such as digoxin or quinidine). A search for such secondary

causes should always be undertaken.

Although the in-hospital mortality rate is increased, the long-term

survival is excellent in patients who survive to hospital discharge after

primary ventricular fibrillation; i.e., ventricular fibrillation that is a

primary response to acute ischemia that occurs during the first 48 h

and is not associated with predisposing factors such as CHF, shock,

bundle branch block, or ventricular aneurysm. This result is in sharp

contrast to the poor prognosis for patients who develop ventricular

fibrillation secondary to severe pump failure. For patients who develop

ventricular tachycardia or ventricular fibrillation late in their hospital

course (i.e., after the first 48 h), the mortality rate is increased both

in-hospital and during long-term follow-up. Such patients should

be considered for electrophysiologic study and implantation of a

cardioverter-defibrillator (ICD) (Chap. 252). A more challenging issue

is the prevention of sudden cardiac death from ventricular fibrillation

late after STEMI in patients who have not exhibited sustained ventricular tachyarrhythmias during their index hospitalization. An algorithm

for selection of patients who warrant prophylactic implantation of an

ICD is shown in Fig. 275-6.

Accelerated Idioventricular Rhythm Accelerated idioventricular rhythm (AIVR, “slow ventricular tachycardia”), a ventricular

rhythm with a rate of 60–100 beats/min, often occurs transiently

during fibrinolytic therapy at the time of reperfusion. For the most

part, AIVR, whether it occurs in association with fibrinolytic therapy

or spontaneously, is benign and does not presage the development of

classic ventricular tachycardia. Most episodes of AIVR do not require

treatment if the patient is monitored carefully, as degeneration into a

more serious arrhythmia is rare.

Supraventricular Arrhythmias Sinus tachycardia is the most

common supraventricular arrhythmia. If it occurs secondary to

another cause (such as anemia, fever, heart failure, or a metabolic

derangement), the primary problem should be treated first. However,

if it appears to be due to sympathetic overstimulation (e.g., as part of a

hyperdynamic state), then treatment with a beta blocker is indicated.

Other common arrhythmias in this group are atrial flutter and atrial

fibrillation, which are often secondary to LV failure. Digoxin is usually the treatment of choice for supraventricular arrhythmias if heart

failure is present. If heart failure is absent, beta blockers, verapamil,

and diltiazem are suitable alternatives for controlling the ventricular

rate, as they may also help to control ischemia. If the abnormal rhythm

persists for >2 h with a ventricular rate >120 beats/min or if tachycardia

induces heart failure, shock, or ischemia (as manifested by recurrent

pain or ECG changes), a synchronized electroshock (100–200 J monophasic waveform) should be used.

Accelerated junctional rhythms have diverse causes but may occur

in patients with inferoposterior infarction. Digitalis excess must be

ruled out. In some patients with severely compromised LV function,

the loss of appropriately timed atrial systole results in a marked reduction of cardiac output. Right atrial or coronary sinus pacing is indicated

in such instances.

Sinus Bradycardia Treatment of sinus bradycardia is indicated

if hemodynamic compromise results from the slow heart rate. Atropine is the most useful drug for increasing heart rate and should be

given intravenously in doses of 0.5 mg initially. If the rate remains

<50–60 beats/min, additional doses of 0.2 mg, up to a total of 2.0 mg,

may be given. Persistent bradycardia (<40 beats/min) despite atropine

may be treated with electrical pacing. Isoproterenol should be avoided.

Atrioventricular and Intraventricular Conduction Disturbances

(See also Chap. 244) Both the in-hospital mortality rate and the postdischarge mortality rate of patients who have complete atrioventricular

(AV) block in association with anterior infarction are markedly higher

than those of patients who develop AV block with inferior infarction.

This difference is related to the fact that heart block in inferior infarction is commonly a result of increased vagal tone and/or the release

of adenosine and therefore is transient. In anterior wall infarction,

however, heart block is usually related to ischemic malfunction of

the conduction system, which is commonly associated with extensive

myocardial necrosis.

Temporary electrical pacing provides an effective means of increasing the heart rate of patients with bradycardia due to AV block. However, acceleration of the heart rate may have only a limited impact on

prognosis in patients with anterior wall infarction and complete heart

block in whom the large size of the infarct is the major factor determining outcome. It should be carried out if it improves hemodynamics.

Pacing does appear to be beneficial in patients with inferoposterior

infarction who have complete heart block associated with heart failure,

hypotension, marked bradycardia, or significant ventricular ectopic

activity. A subgroup of these patients, those with RV infarction, often

respond poorly to ventricular pacing because of the loss of the atrial

contribution to ventricular filling. In such patients, dual-chamber AV

sequential pacing may be required.

External noninvasive pacing electrodes should be positioned in a

“demand” mode for patients with sinus bradycardia (rate <50 beats/

min) that is unresponsive to drug therapy, Mobitz II second-degree

AV block, third-degree heart block, or bilateral bundle branch block

(e.g., right bundle branch block plus left anterior fascicular block).

Retrospective studies suggest that permanent pacing may reduce the

long-term risk of sudden death due to bradyarrhythmias in the rare

2064 PART 6 Disorders of the Cardiovascular System

patient who develops combined persistent bifascicular and transient

third-degree heart block during the acute phase of MI.

■ OTHER COMPLICATIONS

Recurrent Chest Discomfort Because recurrent or persistent

ischemia often heralds extension of the original infarct or reinfarction

in a new myocardial zone and is associated with a near tripling of mortality after STEMI, patients with these symptoms should be referred

for prompt coronary arteriography and mechanical revascularization.

Administration of a fibrinolytic agent is an alternative to early mechanical revascularization.

Pericarditis (See also Chap. 270) Pericardial friction rubs and/or

pericardial pain are frequently encountered in patients with STEMI

involving the epicardium. This complication can usually be managed

with aspirin (650 mg four times daily). It is important to diagnose

the chest pain of pericarditis accurately because failure to recognize it

may lead to the erroneous diagnosis of recurrent ischemic pain and/or

infarct extension, with resulting inappropriate use of anticoagulants,

nitrates, beta blockers, or coronary arteriography. When it occurs,

complaints of pain radiating to either trapezius muscle is helpful

because such a pattern of discomfort is typical of pericarditis but rarely

occurs with ischemic discomfort. Anticoagulants potentially could

cause tamponade in the presence of acute pericarditis (as manifested by

either pain or persistent rub) and therefore should not be used unless

there is a compelling indication.

Thromboembolism Clinically apparent thromboembolism complicates STEMI in ~10% of cases, but embolic lesions are found in

20% of patients in necropsy series, suggesting that thromboembolism

is often clinically silent. Thromboembolism is considered to be an

important contributing cause of death in 25% of patients with STEMI

who die after admission to the hospital. Arterial emboli originate from

LV mural thrombi, while most pulmonary emboli arise in the leg veins.

Thromboembolism typically occurs in association with large

infarcts (especially anterior), CHF, and an LV thrombus detected by

echocardiography. The incidence of arterial embolism from a clot

originating in the ventricle at the site of an infarction is small but real.

Two-dimensional echocardiography reveals LV thrombi in about onethird of patients with anterior wall infarction but in few patients with

inferior or posterior infarction. Arterial embolism often presents as a

major complication, such as hemiparesis when the cerebral circulation

is involved or hypertension if the renal circulation is compromised.

When a thrombus has been clearly demonstrated by echocardiographic

or other techniques or when a large area of regional wall motion

abnormality is seen even in the absence of a detectable mural thrombus, systemic anticoagulation should be undertaken (in the absence of

contraindications), as the incidence of embolic complications appears

to be markedly lowered by such therapy. The appropriate duration of

therapy is unknown, but 3–6 months is probably prudent.

Left Ventricular Aneurysm The term ventricular aneurysm is

usually used to describe dyskinesis or local expansile paradoxical wall

motion. Normally functioning myocardial fibers must shorten more

if stroke volume and cardiac output are to be maintained in patients

with ventricular aneurysm; if they cannot, overall ventricular function

is impaired. True aneurysms are composed of scar tissue and neither

predispose to nor are associated with cardiac rupture.

The complications of LV aneurysm do not usually occur for weeks

to months after STEMI; they include CHF, arterial embolism, and

ventricular arrhythmias. Apical aneurysms are the most common and

the most easily detected by clinical examination. The physical finding

Yes*

Yes Yes No No

No

Yes

No

Reassess LVEF >40 d after MI

and/or >90 d after

revascularization

Yes Primary prevention in pts with IHD,

LVEF ≤40%

EP study

(especially in

the presence

of NSVT)

Inducible

sustained

VT

ICD

(Class I)

ICD

(Class I)* ICD

(Class I)

ICD

(Class IIa) GDMT ICD should not

be implanted

(Class III:

No benefit)

GDMT

(Class I)

WCD

(Class IIb)

MI <40 d

and/or

revascularization

<90 d

NYHA

class I

LVEF ≤30%

NYHA

class II or III

LVEF ≤35%

LVEF ≤40%,

NSVT, inducible

sustained VT on

EP study

NYHA

class IV

candidate for

advanced HF

therapy†

FIGURE 275-6 Primary prevention of SCD in patients with ischemic heart disease, including recent MI. Colors correspond to class of recommendation in the guideline (green =

Class I; yellow = Class IIa; amber = Class IIb; red = Class III). *Scenarios exist for early ICD placement in select circumstances such as patients with a pacing indication

or syncope. †

Advanced HF therapy includes CRT, cardiac transplant, and left ventricular assist device. CRT, cardiac resynchronization therapy; EP, electrophysiologic;

GDMT, guideline-directed management and therapy; HF, heart failure; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease, LVEF, left ventricular

ejection fraction; MI, myocardial infarction; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association; pts, patients; SCD, sudden cardiac death; VT,

ventricular tachycardia; WCD, wearable cardioverter-defibrillator. The available evidence does not suggest there is a survival advantage to the use of an ICD early after

MI, and the WCD is a potential option while waiting until the ejection fraction is reassessed (see figure). While the WCD appears to be effective in patients who wear the

device, it is associated with frequent alarms, skin irritation, and emotional distress, which results in reduced wear time in a large number of patients. (Reproduced with

permission from SM Al-Khatib et al: 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death.

Circulation 138:e272, 2018.)

ST-Segment Elevation Myocardial Infarction

2065CHAPTER 275

of greatest value is a double, diffuse, or displaced apical impulse. Ventricular aneurysms are readily detected by two-dimensional echocardiography, which may also reveal a mural thrombus in an aneurysm.

Rarely, myocardial rupture may be contained by a local area of pericardium, along with organizing thrombus and hematoma. Over time,

this pseudoaneurysm enlarges, maintaining communication with the

LV cavity through a narrow neck. Because a pseudoaneurysm often

ruptures spontaneously, it should be surgically repaired if recognized.

POSTINFARCTION RISK STRATIFICATION

AND MANAGEMENT

Many clinical and laboratory factors have been identified that are

associated with an increase in cardiovascular risk after initial recovery from STEMI. Some of the most important factors include persistent ischemia (spontaneous or provoked), depressed LV ejection

fraction (<40%), rales above the lung bases on physical examination

or congestion on chest radiograph, and symptomatic ventricular

arrhythmias. Other features associated with increased risk include a

history of previous MI, age >75, diabetes mellitus, prolonged sinus

tachycardia, hypotension, ST-segment changes at rest without angina

(“silent ischemia”), an abnormal signal-averaged ECG, nonpatency of

the infarct-related coronary artery (if angiography is undertaken), and

persistent advanced heart block or a new intraventricular conduction

abnormality on the ECG. Therapy must be individualized on the basis

of the relative importance of the risk(s) present.

The goal of preventing reinfarction and death after recovery from

STEMI has led to strategies to evaluate risk after infarction. In stable

patients, submaximal exercise stress testing may be carried out before

hospital discharge to detect residual ischemia and ventricular ectopy

and to provide the patient with a guideline for exercise in the early

recovery period. Alternatively, or in addition, a maximal (symptomlimited) exercise stress test may be carried out 4–6 weeks after infarction. Evaluation of LV function is usually warranted as well. Recognition of a depressed LV ejection fraction by echocardiography or

radionuclide ventriculography identifies patients who should receive

medications to inhibit the renin-angiotensin-aldosterone system.

Patients in whom angina is induced at relatively low workloads, those

who have a large reversible defect on perfusion imaging or a depressed

ejection fraction, those with demonstrable ischemia, and those in

whom exercise provokes symptomatic ventricular arrhythmias should

be considered at high risk for recurrent MI or death from arrhythmia

(Fig. 275-6). Cardiac catheterization with coronary angiography and/

or invasive electrophysiologic evaluation is advised.

Exercise tests also aid in formulating an individualized exercise prescription, which can be much more vigorous in patients who tolerate

exercise without any of the previously mentioned adverse signs. In

addition, predischarge stress testing may provide an important psychological benefit, building the patient’s confidence by demonstrating

a reasonable exercise tolerance.

In many hospitals, a cardiac rehabilitation program with progressive exercise is initiated in the hospital and continued after discharge.

Ideally, such programs should include an educational component that

informs patients about their disease and its risk factors.

The usual duration of hospitalization for an uncomplicated STEMI

is about 3–5 days. The remainder of the convalescent phase may be

accomplished at home. During the first 1–2 weeks, the patient should

be encouraged to increase activity by walking about the house and outdoors in good weather. Normal sexual activity may be resumed during

this period. After 2 weeks, the physician should regulate the patient’s

activity on the basis of exercise tolerance. Most patients will be able to

return to work within 2–4 weeks.

SECONDARY PREVENTION

Various secondary preventive measures are at least partly responsible for

the improvement in the long-term mortality and morbidity rates after

STEMI. Long-term treatment with an antiplatelet agent (usually aspirin)

after STEMI is associated with a 25% reduction in the risk of recurrent

infarction, stroke, or cardiovascular mortality (36 fewer events for every

1000 patients treated). An alternative antiplatelet agent that may be

used for secondary prevention in patients intolerant of aspirin is clopidogrel (75 mg orally daily). ACE inhibitors or ARBs and, in appropriate

patients, aldosterone antagonists should be used indefinitely by patients

with clinically evident heart failure, a moderate decrease in global ejection fraction, or a large regional wall motion abnormality to prevent late

ventricular remodeling and recurrent ischemic events.

The chronic routine use of oral beta-adrenoceptor blockers for at

least 2 years after STEMI is supported by well-conducted, placebocontrolled trials.

Evidence suggests that warfarin lowers the risk of late mortality and

the incidence of reinfarction after STEMI. Most physicians prescribe

aspirin routinely for all patients without contraindications and add

warfarin for patients at increased risk of embolism (see “Thromboembolism” earlier). Several studies suggest that in patients <75 years

old a low dose of aspirin (75–81 mg/d) in combination with warfarin

administered to achieve an international normalized ratio >2.0 is more

effective than aspirin alone for preventing recurrent MI and embolic

cerebrovascular accident. However, there is an increased risk of bleeding and a high rate of discontinuation of warfarin that has limited

clinical acceptance of combination antithrombotic therapy. There is an

increased risk of bleeding when warfarin is added to dual antiplatelet

therapy (see Chap. 273). However, patients who have had a stent

implanted and have an indication for anticoagulation should receive

dual antiplatelet therapies in combination with warfarin. (See Chap.

273 for further discussion.) Such patients should also receive a proton

pump inhibitor to minimize the risk of gastrointestinal bleeding and

should have regular monitoring of their hemoglobin levels and stool

hematest while on combination antithrombotic therapy.

Finally, risk factors for atherosclerosis (Chap. 237) should be discussed with the patient and, when possible, favorably modified.

■ FURTHER READING

Cherney DZ et al: Sodium glucose cotransporter-2 inhibition and

cardiorenal protection: JACC review topic of the week. J Am Coll

Cardiol 74:2511, 2019.

Gershlick AH, Price MJ: Full revascularization in the patient with

ST-segment elevation myocardial infarction: The story so far. J Am

Coll Cardiol 74:2724, 2019.

Krumholz HM et al: Twenty-year trends in outcomes for older adults

with acute myocardial infarction in the United States. JAMA Netw

Open 2:e191938, 2019.

Levine GN et al: 2015 ACC/AHA/SCAI focused update on primary

percutaneous coronary intervention for patients with ST-elevation

myocardial infarction: An update of the 2011 ACCF/AHA/SCAI

guideline for percutaneous coronary intervention and the 2013

ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology/

American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 133:1135, 2016.

Libby P et al: The myocardium: more than myocytes. J Am Coll Cardiol 74:3136, 2019.

Mehta SR et al: Complete revascularization with multivessel PCI for

myocardial infarction. N Engl J Med 381:1411, 2019.

O’Gara PT et al: 2013 ACCF/AHA guideline for the management of

ST-elevation myocardial infarction: executive summary: A report of

the American College of Cardiology Foundation/American Heart

Association Task Force on Practice Guidelines. Circulation 127:529,

2013.

Olgin JE et al: Wearable cardioverter-defibrillator after myocardial

infarction. N Engl J Med 379:1205, 2018.

Park J et al: Prognostic implications of door-to-balloon time and

onset-to-door time on mortality in patients with ST-segmentelevation myocardial infarction treated with primary percutaneous

coronary intervention. J Am Heart Assoc 8:e012188, 2019.

Sugiyama T et al: Differential time trends of outcomes and costs of

care for acute myocardial infarction hospitalizations by ST elevation

and type of intervention in the United States, 2001–2011. JAMA

4:e001445, 2015.

2066 PART 6 Disorders of the Cardiovascular System

Percutaneous transluminal coronary angioplasty (PTCA) was first

introduced by Andreas Gruentzig in 1977 as an alternative to coronary

bypass surgery. The concept was initially demonstrated by Charles Dotter in 1964 in peripheral vessels. The development of a small inelastic

balloon catheter by Gruentzig allowed expansion of the technique into

smaller peripheral and coronary vessels. Initial coronary experience

was limited to single-vessel coronary disease and discrete proximal

lesions due to the technical limitations of the equipment. Advances in

technology with smaller profile balloon catheters and movable steerable guidewires and greater operator experience allowed the procedure

to grow rapidly with expanded use in patients with more complex

lesions and multivessel disease. The introduction of coronary stents in

1994 was one of the major advances in the field. These devices reduced

acute complications and reduced by half the significant problems of

acute thrombosis and late restenosis (or recurrence of the stenosis).

Further reductions in restenosis were achieved by the introduction of

drug-eluting stents in 2003. These stents slowly release antiproliferative

drugs directly into the plaque over a few months. Percutaneous coronary intervention (PCI) is the most common revascularization procedure in the United States and is performed more than twice as often as

coronary artery bypass surgery: >900,000 patients a year.

276 Percutaneous Coronary

Interventions and Other

Interventional Procedures

David P. Faxon, Deepak L. Bhatt

A B C D

FIGURE 276-1 Schematic diagram of the primary mechanisms of balloon angioplasty and stenting. A. A balloon angioplasty catheter is positioned into the stenosis over

a guidewire under fluoroscopic guidance. B. The balloon is inflated, temporarily occluding the vessel. C. The lumen is enlarged primarily by stretching the vessel, often

resulting in small dissections in the neointima. D. A stent mounted on a deflated balloon is placed into the lesion and pressed against the vessel wall with balloon inflation

(not shown). The balloon is deflated and removed, leaving the stent permanently against the wall acting as a scaffold to hold the dissections against the wall and prevent

vessel recoil. (Reproduced with permission from EJ Topol: Textbook of Cardiovascular Medicine, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 2002.)

Szummer K et al: From early pharmacology to recent pharmacology

interventions in acute coronary syndromes: JACC state-of-the-art

review. J Am Coll Cardiol 74:1618, 2019.

Vernon ST et al: ST-segment-elevation myocardial infarction (STEMI)

patients without standard modifiable cardiovascular risk factors:

How common are they, and what are their outcomes? J Am Heart

Assoc 8:e013296, 2019.

Virani SS et al: Heart Disease Statistics - 2021 Update: A Report from

the American Heart Association. Circulation 143:e254, 2021.

Interventional cardiology is a separate discipline in cardiology that

requires a dedicated 1- or 2-year interventional cardiology fellowship

following a 3-year general cardiology fellowship in order to obtain

a separate board certification. The discipline has also expanded to

include interventions for structural heart disease including treatment

of congenital heart disease and valvular heart disease; it also includes

interventions to treat peripheral vascular disease, including atherosclerotic and nonatherosclerotic lesions in the carotid, renal, aortic, and

peripheral arterial and venous circulations.

TECHNIQUE

The initial procedure is performed in a similar manner as a diagnostic

cardiac catheterization (Chap. 242). Arterial access is obtained via the

radial or femoral artery. To prevent thrombotic complications during

the procedure, patients who are anticipated to need an angioplasty

are given aspirin (325 mg) and may be given a platelet P2Y12 inhibitor

such as clopidogrel (loading dose of 600 mg), prasugrel (loading dose

of 60 mg), or ticagrelor (loading dose of 180 mg) before the procedure.

Cangrelor, a potent IV P2Y12 inhibitor, is approved for use in patients

who have not received an oral agent prior to the procedure. During the

procedure, anticoagulation is achieved by administration of unfractionated heparin, enoxaparin (a low-molecular-weight heparin), or

bivalirudin (a direct thrombin inhibitor). In patients with ST-segment

elevation myocardial infarction (STEMI), high-risk acute coronary

syndrome, or a large thrombus in the coronary artery, an intravenous

glycoprotein IIb/IIIa inhibitor (abciximab, tirofiban, or eptifibatide)

may also be given, although cangrelor appears to be as effective with

less bleeding risk.

Following placement of an introducing sheath into the artery, preformed guiding catheters are used to cannulate selectively the origins of

the coronary arteries. Through the guiding catheter, a flexible, steerable

guidewire is negotiated down the coronary artery lumen using fluoroscopic guidance; it is then advanced through the stenosis and into the

vessel beyond. This guidewire then serves as a “rail” over which angioplasty balloons, stents, or other therapeutic devices can be advanced to

enlarge the narrowed segment of coronary artery. The artery is usually

dilated with a balloon catheter followed by placement of a stent. The

catheters and introducing sheath are removed and the artery manually

held, or in the case of radial access, an inflatable cuff is used. One of

several femoral arterial closure devices can also be used to achieve

hemostasis. Because PCI is performed under local anesthesia and mild

sedation, it requires only a short (1-day or less) hospitalization.

Angioplasty works by stretching the artery and displacing the plaque

away from the lumen, enlarging the entire vessel (Figs. 276-1 and

276-2). The procedure rarely results in embolization of atherosclerotic

Percutaneous Coronary Interventions and Other Interventional Procedures

2067CHAPTER 276

permanent polymers in preventing late stent thrombosis. In addition,

the first-generation everolimus-eluting biodegradable vascular scaffold

(BVS) stent had been shown to be reasonably safe with gradual degradation over several years, although concerns about late and very late

stent thrombosis ultimately led to its withdrawal from clinical practice.

Additional bioresorbable stents are under investigation. Drug-coated

balloons are covered with an antiproliferative drug that can also reduce

restenosis and are used primarily to treat in-stent restenosis.

Other interventional devices include atherectomy devices and

thrombectomy catheters. These devices are designed to remove atherosclerotic plaque or thrombus and are used in conjunction with

balloon dilatation and stent placement. Rotational atherectomy is the

most commonly used adjunctive device and is modeled after a dentist’s

drill, with small round burrs of 1.25–2.5 mm at the tip of a flexible

wire shaft. The burr is passed over the guidewire up to the stenosis

and drills away atherosclerotic material. Because the atherosclerotic

particles are ≤25 μm, they pass through the coronary microcirculation

and rarely cause problems. The device is particularly useful in heavily

calcified plaques that are resistant to balloon dilatation. Given the

current advances in stents, rotational atherectomy is infrequently used.

Orbital atherectomy is a newer approach to calcified lesions that also

relies on a spinning burr. Directional atherectomy catheters that slice

off the plaque and remove it are not used in the coronaries any longer

but are sometimes used in peripheral artery disease. In acute STEMI,

specialized catheters without a balloon can be used to aspirate thrombus in order to prevent embolization down the coronary vessel and to

improve blood flow before angioplasty and stent placement. Current

studies show that manual catheter thrombus aspiration should not be

used routinely but, in certain cases of a large thrombus burden, can

improve blood flow in primary PCI.

PCI of degenerated saphenous vein graft lesions has been associated

with a significant incidence of distal embolization of atherosclerotic

material, unlike PCI of native vessel disease. A number of distal protection devices have been shown to significantly reduce embolization

and myocardial infarction in this setting. Most devices work by using a

collapsible wire filter at the end of a guidewire that is expanded in the

distal vessel before PCI. If atherosclerotic debris is dislodged, the basket captures the material, and at the end of the PCI, the basket is pulled

into a delivery catheter, and the debris safely removed from the patient.

SUCCESS AND COMPLICATIONS

A successful procedure (angiographic success), defined as a reduction of the stenosis to less than a 20% diameter narrowing, occurs

in 95–99% of patients. Lower success rates are seen in patients with

tortuous, small, or calcified vessels or chronic total occlusions. Chronic

total occlusions have the lowest success rates and their recanalization is

significantly better if the occlusion is recent (within 3 months) or there

are favorable anatomic features. Improvements in equipment and complex antegrade and retrograde techniques have increased the success

rates of recanalization of chronic total occlusions to 70–80%.

Serious complications are rare but include a mortality rate of 0.1–0.3%

for elective cases, a large myocardial infarction in <3%, and stroke in

0.1–0.4%. Patients who are older (>65 years), undergoing an emergent

or urgent procedure, have chronic kidney disease, present with STEMI,

or are in shock have significantly higher risk. Scoring systems can help

to estimate the risk of the procedure. Myocardial infarction during PCI

can occur for multiple reasons including an acute occluding thrombus,

severe coronary dissection, embolization of thrombus or atherosclerotic

material, or closure of a side branch vessel at the site of angioplasty or

stent placement. Most myocardial infarctions are small and only detected

by a rise in the creatine phosphokinase (CPK) or troponin level after the

procedure. Only those with significant enzyme elevations (>10 times

the upper limit of normal) are associated with a less favorable long-term

outcome. Coronary stents have largely prevented occlusive coronary

dissections due to the scaffolding effect of the stent.

All types of stents are prone to stent thrombosis (1–3%), either

acute (<24 h) or subacute (1–30 days), which can be ameliorated by

greater attention to full initial stent deployment and the use of dual

antiplatelet therapy (DAPT) (aspirin, plus a platelet P2Y12 receptor

A

B

FIGURE 276-2 Pathology of acute effects of balloon angioplasty with intimal

dissection and vessel stretching (A) and an example of neointimal hyperplasia and

restenosis showing renarrowing of the vessel (B). (Panel A reprinted from M Ueda et

al: The early phenomena of restenosis following percutaneous transluminal coronary

angioplasty. Eur Heart J 12:937, 1991; with permission. Panel B reprinted from CE

Essed, M Van den Brand, AE Becker: Transluminal coronary angioplasty and early

restenosis. Fibrocellular occlusion after wall laceration. Br Heart J 49:393, 1983; with

permission.)

material. Owing to inelastic elements in the plaque, the stretching of

the vessel by the balloon results in small localized dissections that can

protrude into the lumen and be a nidus for acute thrombus formation.

If the dissections are severe, then they can obstruct the lumen or induce

a thrombotic occlusion of the artery (acute closure). Stents have largely

prevented this complication by holding the dissection flaps up against

the vessel wall (Fig. 276-1).

Stents are currently used in >90% of coronary angioplasty procedures. Stents are wire meshes (usually made of stainless steel or other

metals, such as cobalt chromium or nitinol) that are compressed over

a deflated angioplasty balloon. When the balloon is inflated, the stent

is enlarged to approximate the “normal” vessel lumen. The balloon is

then deflated and removed, leaving the stent behind to provide a permanent scaffold in the artery. Owing to the design of the struts, these

devices are flexible, allowing their passage through diseased and tortuous coronary vessels. Stents are rigid enough to prevent elastic recoil

of the vessel and have dramatically improved the success and safety of

the procedure as a result.

Drug-eluting stents further enhanced the efficacy of PCI. An antiproliferative agent is attached to the metal stent by use of a thin polymer coating. The antiproliferative drug elutes from the stent over a 1- to

3-month period or longer after implantation. Drug-eluting stents have

been shown to reduce clinical restenosis by 50%, so that in uncomplicated lesions, symptomatic restenosis occurs in 5–10% of patients. Not

surprisingly, this led to the rapid acceptance of these devices; currently

>90% of all stents implanted are drug-eluting. The first-generation

devices were coated with either sirolimus or paclitaxel. Second-generation drug-eluting stents use newer agents such as everolimus, biolimus,

and zotarolimus. These second-generation drug-eluting stents appear

to be more effective with fewer complications, such as early or late

stent thrombosis, than the first-generation devices and, therefore, have

replaced the first-generation stents. Biodegradable polymers that are

used to attach the drugs to the stents may be theoretically superior to

2068 PART 6 Disorders of the Cardiovascular System

blocker [clopidogrel, prasugrel, or ticagrelor]). Late (30 days–1 year)

and very late (>1 year) stent thromboses occur very infrequently

with stents but are slightly more common with first-generation drugeluting stents, necessitating DAPT for up to 1 year or longer. Use of the

second-generation stents is associated with lower rates of late and very

late stent thromboses, and shorter durations of DAPT (6 months) are

recommended for the stent, although longer durations may be useful

depending on the underlying atherothrombotic and bleeding risks.

Premature discontinuation of DAPT, particularly in the first month

after implantation, is associated with a significantly increased risk for

stent thrombosis (three- to ninefold greater). Stent thrombosis results

in death in 10–20% and myocardial infarction in 30–70% of patients.

Elective surgery that requires discontinuation of antiplatelet therapy

after drug-eluting stent implantation should be postponed until after

3 months and preferably after 6 months, if at all possible.

Restenosis, or renarrowing of the dilated coronary stenosis, is the

most common complication of angioplasty and occurs in 20–50% of

patients with balloon angioplasty alone, 10–30% of patients with bare

metal stents, and 5–15% of patients with drug-eluting stents within

the first year. The fact that stent placement provides a larger acute

luminal area than balloon angioplasty alone reduces the incidence

of subsequent restenosis. Drug-eluting stents further reduce restenosis through a reduction in excessive neointimal growth over the

stent. If restenosis does not occur, the long-term outcome is excellent

(Fig. 276-3). Clinical restenosis is recognized by recurrence of angina

or symptoms within 12 months of the procedure. Less frequently,

patients with restenosis can present with non-ST-segment elevation

myocardial infarction (NSTEMI) (10%) or STEMI (2%) as well. Very

late stent thrombosis and restenosis after 1 year is more likely to be

due to neoatherosclerosis than intimal hyperplasia seen within the first

year. Clinical restenosis requires confirmation of a significant stenosis

at the site of the prior PCI. Target lesion revascularization (TLR) or target vessel revascularization (TVR) is defined as angiographic restenosis

with repeat PCI or coronary artery bypass grafting (CABG). By angiography, the incidence of restenosis is significantly higher than clinical

restenosis (TLR or TVR) because many patients have mild restenosis

that does not result in a recurrence of symptoms. The management of

clinical restenosis is usually to repeat the PCI with balloon dilatation

and placement of another drug-eluting stent. Once a patient has had

restenosis, the risk of a second restenosis is further increased. The risk

factors for restenosis are diabetes, myocardial infarction, long lesions,

small-diameter vessels, and suboptimal initial PCI result. Treatments

for symptomatic recurrent restenosis include re-stenting (three layers

of stent), brachytherapy, drug-coated balloons, or coronary bypass

surgery.

INDICATIONS

The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines extensively review the indications for PCI in

patients with stable angina, unstable angina, NSTEMI, and STEMI and

should be referred to for a comprehensive discussion of the indications.

Briefly, the two principal indications for coronary revascularization

in patients with chronic stable angina (Chap. 273) are (1) to improve

angina symptoms in patients who remain symptomatic despite adequate medical therapy and (2) to reduce mortality rates in patients

with severe and extensive coronary disease. In patients with stable

angina who are well controlled on medical therapy, studies such as the

Clinical Outcomes Utilizing Revascularization and Aggressive Drug

Evaluation (COURAGE) and Bypass Angioplasty Revascularization

Investigation 2 Diabetes (BARI 2D) trials have shown that initial

revascularization does not lead to better outcomes (death or myocardial infarction) and can be safely delayed until symptoms worsen or

evidence of severe ischemia on noninvasive testing occurs. The International Study of Comparative Health Effectiveness with Medical and

Invasive Approaches (ISCHEMIA) trial was the largest trial comparing

optimal medical therapy to revascularization with PCI or CABG in

stable patients with moderate ischemia on stress testing but without left

main or reduced left ventricular function (<35% ejection fraction). It

showed that optimal medical therapy was similar to revascularization

in a composite of cardiovascular death or hospitalization or in cardiovascular death and myocardial infarction at a median of 3.3 years. This

trial confirms prior studies and supports conservative management in

most stable patients. When revascularization is indicated due to unacceptable symptoms, the choice of PCI or CABG depends on a number

of clinical and anatomic factors.

The Synergy between Percutaneous Coronary Intervention with

Taxus and Cardiac Surgery (SYNTAX) trial compared PCI with the

paclitaxel drug-eluting stent to CABG in 1800 patients with three-vessel

coronary disease or left main disease. The study found no difference in

death or myocardial infarction at 1 year, but repeat revascularization

was significantly higher in the stent-treated group (13.5 vs 5.9%), while

stroke was significantly higher in the surgical group (2.2 vs 0.6%). The

primary endpoint of death, myocardial infarction, stroke, or revascularization was significantly better with CABG, particularly in those

FIGURE 276-3 Long-term results from one of the first patients to receive a sirolimus-eluting stent from early Sao Paulo experience. (From GW Stone, in D Baim [ed]:

Cardiac Catheterization, Angiography and Intervention, 7th ed. Philadelphia, Lippincott Williams & Wilkins, 2006; with permission.)

Percutaneous Coronary Interventions and Other Interventional Procedures

2069CHAPTER 276

with the most extensive coronary artery disease such as three-vessel

disease. The 10-year results confirm these findings. The Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal

Management of Multivessel Disease (FREEDOM) trial randomized

1900 patients with diabetes and multivessel disease and found a significantly lower primary endpoint of death, myocardial infarction, or

stroke with CABG than PCI. Recent trials comparing PCI with CABG

have shown similar outcomes for those with less extensive disease, but

a better outcome when the coronary disease is severe and extensive.

These studies support CABG for those with the most severe left main

and three-vessel disease or those with diabetes. Lesser degrees of multivessel disease in patients with or without diabetes have an equal outcome with PCI, including left main disease with favorable angiographic

characteristics.

The choice of PCI versus CABG is also related to the anticipated

procedural success and complications of PCI and the risks of CABG.

For PCI, the characteristics of the coronary anatomy are critically

important. The location of the lesion in the vessel (proximal or distal),

the degree of tortuosity, and the size of the vessel are considered. In

addition, the lesion characteristics, including the degree of the stenosis,

the presence of calcium, lesion length, and presence of thrombus, are

assessed. The most common reason to decide not to do PCI is that

the lesion(s) felt to be responsible for the patient’s symptoms is not

treatable. This is most commonly due to the presence of a chronic total

occlusion (>3 months in duration) with unfavorable characteristics. A

lesion classification to characterize the likelihood of success or failure

of PCI has been developed by the ACC/AHA. Lesions with the highest

success are called type A lesions (such as proximal noncalcified subtotal lesions), and those with the lowest success or highest complication

rate are type C lesions (such as chronic total occlusions). Intermediate

lesions are classified as type B1 or B2 depending on the number of

unfavorable characteristics. Approximately 25–30% of patients will not

be candidates for PCI due to unfavorable anatomy, whereas only 5%

of CABG patients will not be candidates for surgery due to coronary

anatomy. The primary reason for being considered inoperable with

CABG is the presence of severe comorbidities such as advanced age,

frailty, severe chronic obstructive pulmonary disease (COPD), poor

left ventricular function, or lack of suitable surgical conduits or poor

distal targets for bypass.

Another consideration in choosing a revascularization strategy is

the degree of revascularization. In patients with multivessel disease,

bypass grafts can usually be placed to all vessels >2 mm with significant

stenosis, whereas PCI may be able to treat only some of the lesions due

to the presence of unfavorable anatomy. Assessment of the significance

of intermediate lesions using fractional flow reserve (FFR) or the

instantaneous wave-free ratio (iFR) (Chap. 242) can assist in determining which lesions should be revascularized. The Fractional Flow

Reserve versus Angiography for Multivessel Evaluation (FAME) trial

showed a 30% reduction in adverse events when revascularization by

PCI was restricted to those lesions that were hemodynamically significant (FFR ≤0.80) rather than when guided by angiography alone. Trials

have shown that iFR is as predictive as FFR but is quicker and easier to

perform, especially if there are sequential lesions or multivessel disease.

Thus, complete revascularization of all functionally significant lesions

should be favored and considered when choosing the optimal revascularization strategy. Given the multiple factors that need to be considered in choosing the best revascularization for an individual patient

with multivessel disease, it is optimal to have a discussion among the

cardiac surgeon, interventional cardiologist, and the physicians caring

for the patient (so-called Heart Team) to weigh the choices properly.

Patients with acute coronary syndrome are at excess risk of shortand long-term mortality. Randomized clinical trials have shown that

PCI is superior to intensive medical therapy in reducing mortality

and myocardial infarction, with the benefit largely confined to those

patients who are high risk. High-risk non-ST-segment elevation acute

coronary syndrome patients are defined as those with any one of the

following: refractory ischemia, recurrent angina, positive cardiacspecific enzymes, new ST-segment depression, transient ST-segment

elevation, low ejection fraction, severe arrhythmias, or a recent PCI

or CABG. PCI is preferred over surgical therapy in most high-risk

patients with acute coronary syndromes unless they have severe

multivessel disease or the culprit lesion responsible for the unstable

presentation cannot be adequately determined or treated. In STEMI,

thrombolysis and PCI (primary PCI) are effective methods to restore

coronary blood flow and salvage myocardium within the first 12 h after

onset of chest pain. Because PCI is more effective in restoring flow

than thrombolysis, it is preferred if readily available within 90 min of

presentation to the hospital. PCI is also performed following thrombolysis to facilitate adequate reperfusion or as a rescue procedure in

those who do not achieve reperfusion from thrombolysis, who cannot

be rapidly transferred to a hospital that can perform primary PCI, or

who develop cardiogenic shock. The Complete Versus Culprit-Only

Revascularization Strategies to Treat Multivessel Disease After Early

PCI for STEMI (COMPLETE) trial supports complete revascularization of nonculprit lesions in STEMI either in the hospital or in the few

weeks after discharge.

OTHER INTERVENTIONAL TECHNIQUES

■ STRUCTURAL HEART DISEASE

Interventional treatment for structural heart disease (adult congenital

heart disease and valvular heart disease) is a significant and growing

component of the field of interventional cardiology.

The most common adult congenital lesion to be treated with percutaneous techniques is closure of atrial septal defects (Chap. 269). The

procedure is done as in a diagnostic right heart catheterization with the

passage of a catheter up the femoral vein into the right atrium. With

echo and fluoroscopic guidance, the size and location of the defect can

be accurately defined, and closure is accomplished using one of several

approved devices. All devices use a left atrial and right atrial wire mesh

or covered disk that are pulled together to capture the atrial septum

around the defect and seal it off. The Amplatzer Septal Occluder device

(AGA Medical, Minneapolis, Minnesota) is the most commonly used

in the United States. The success rate in selected patients is 85–95%,

and the device complications are rare and include device embolization,

infection, or erosion. Closure of patent foramen ovale (PFO) is done in

a similar way. PFO closure may be considered in patients who have had

recurrent paradoxical stroke or transient ischemic attack (TIA) despite

adequate medical therapy including anticoagulation or antiplatelet

therapy or who are at high risk for recurrent stroke. The CLOSURE

I trial (Evaluation of the STARFlex Closure System in Patients with a

Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical

Embolism Through a Patent Foramen Ovale) randomized 909 patients

with cryptogenic stroke or TIA who had a PFO. Closure did not reduce

the primary endpoint of death within 30 days or death following a neurologic cause during 2 years of follow-up or stroke/TIA within 2 years.

Other short-term trials confirmed these findings. However, the 10-year

follow-up from the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) trial did find a benefit of closure in reducing the risk

for recurrent cryptogenic stroke, as have meta-analyses examining the

longer-term effects of closures in appropriate patients. The use in the

treatment of migraine is not supported by the current data.

Similar devices can also be used to close patent ductus arteriosus

and ventricular septal defects. Other congenital diseases that can be

treated percutaneously include coarctation of the aorta, pulmonic

stenosis, peripheral pulmonary stenosis, and other abnormal communications between the cardiac chambers or vessels.

The treatment of valvular heart disease is the most rapidly growing

area in interventional cardiology. In the past, the only available techniques were balloon valvuloplasty for the treatment of aortic, mitral,

or pulmonic stenosis (Chap. 261). Mitral valvuloplasty is the preferred

treatment for symptomatic patients with rheumatic mitral stenosis

who have favorable anatomy. The outcome in these patients is equal to

that of surgical commissurotomy. The success is highly related to the

echocardiographic appearance of the valve. The most favorable setting

is commissural fusion without calcification or subchordal fusion and

the absence of significant mitral regurgitation. Access is obtained from

2070 PART 6 Disorders of the Cardiovascular System

A B

FIGURE 276-4 A. An example of a high-risk patient who requires carotid revascularization but who is not a candidate

for carotid endarterectomy. B. Carotid artery stenting resulted in an excellent angiographic result. (From M Belkin, DL

Bhatt: Carotid stenting in the elderly: Is 80 the new 60? Circulation 119:2302; 2009; with permission.)

the femoral vein using a transseptal technique in which a long metal

catheter with a needle tip is advanced from the femoral vein through

the right atrium and atrial septum at the level of the foramen ovale

into the left atrium. A guidewire is advanced into the left ventricle,

and a balloon-dilatation catheter is negotiated across the mitral valve

and inflated to a predetermined size to enlarge the valve. The most

commonly used dilatation catheter is the Inoue balloon. The technique

splits the commissural fusion and commonly results in a doubling

of the mitral valve area. The success of the procedure in favorable

anatomy is 95%, and severe complications are rare (1–2%). The most

common complications are tamponade due to puncture into the

pericardium during the transseptal puncture or the creation of severe

mitral regurgitation due to damage to the valve leaflets.

Severe mitral regurgitation can be treated percutaneously using

the MitraClip (Abbott, Abbott Park, Illinois) device. The procedure

involves the passage of a catheter into the left atrium using the transseptal technique. A special catheter with a metallic clip on the end is

passed through the mitral valve and retracted to catch and clip together

the mid portion of the anterior and posterior mitral valve leaflets.

The clip creates a double opening in the mitral valve and thereby

reduces mitral regurgitation similar to the surgical Alfieri repair. In

the Endovascular Valve Edge-to-Edge Repair Study (EVEREST II)

trial, the device was less effective than surgical repair or replacement but

was shown to be safe. Subsequent trials have shown it to be reasonably

effective for patients who are not good candidates for surgical repair,

particularly when the regurgitation is due to functional causes. The

Cardiovascular Outcomes Assessment of the MitraClip Percutaneous

Therapy for Heart Failure Patients with Functional Mitral Regurgitation

(COAPT) trial showed that, in patients with heart failure and functional

mitral regurgitation who were carefully selected based on clinical and

echocardiographic features, the procedure can reduce mortality.

Severe aortic stenosis can be treated with balloon valvuloplasty as

well. In this setting, the valvuloplasty balloon catheter is placed retrograde across the aortic valve from the femoral artery and briefly inflated

to stretch open the valve. The success is much less favorable, with only

50% achieving an aortic valve area of >1 cm2

 and a restenosis rate of

25–50% after 6–12 months. This poor success rate has limited its use to

patients who are not surgical candidates or as a bridge to surgery or transcatheter aortic valve replacement (TAVR). In this setting, the intermediate-term mortality rate of the procedure is high (10%). Repeat aortic

valvuloplasty as a treatment for aortic valve restenosis has been reported.

Percutaneous TAVR has been shown to be an effective treatment

for low-, intermediate-, and high-risk patients and inoperable patients

with aortic stenosis. Currently, three valve models, the Edwards

SAPIEN valve (Edwards Lifescience, Irvine, California), the CoreValve ReValving system (Medtronic, Minneapolis, Minnesota), and the

Lotus valve (Boston Scientific, Natick, Massachusetts), are available. Data to date show excellent durability of the valves, although long-term

outcomes of 10 years are not yet available. The

CoreValve and Lotus valves are self-expanding,

whereas the Edwards valve is balloon expanded.

The cannulas are large (14–22 French), and

retrograde access via the femoral artery is most

commonly chosen, if possible. In patients with

peripheral artery disease, access via the subclavian artery, aorta, or transapically through a

surgical incision can be used. Following balloon

valvuloplasty, the valve is positioned across

the valve and deployed with postdeployment

balloon inflation to ensure full contact with the

aortic annulus. The success rate is >90%, and

the 30-day mortality rate is 2–15% based on

preoperative risk. The Placement of Aortic Transcatheter Valve (PARTNER) randomized trial

of the Edwards valve showed a 55% reduction

in 1-year mortality and major adverse events in

the extreme-risk group randomized to TAVR

compared with medical therapy. In separate

randomized trials, low-, moderate-, and high-risk patients had similar

outcomes to surgical valve replacement at 1 year. As a result, this valve

is approved for low-, intermediate-, high-, and extreme-risk patients

with severe symptomatic aortic stenosis.

Aortic and mitral bioprosthetic valve degeneration can be treated with

repeat surgery or, in high-risk patients, with a valve-in-valve procedure

where a percutaneous valve is placed inside of the prior surgical valve. It

has been shown to be effective for aortic and mitral valves.

Pulmonic stenosis can also be effectively treated with balloon valvuloplasty and percutaneously replaced with the Melody valve (Medtronic). Tricuspid valve interventions are increasingly being performed.

■ PERIPHERAL ARTERY INTERVENTIONS

The use of percutaneous interventions to treat symptomatic patients

with arterial obstruction in the carotid, renal, aortic, and peripheral vessels is an effective alternative to vascular surgery. Randomized clinical

trial data support the use of carotid stenting in patients at high risk of

complications from carotid endarterectomy (Fig. 276-4). Recent trials

suggest similar outcomes with carotid stenting and carotid endarterectomy in patients at average risk, although depending on the patient’s

risk for periprocedural stroke or myocardial infarction, one procedure

may be preferred over the other. The success rate of peripheral artery

interventional procedures has been improving, including treatment

for long segments of occlusive disease historically treated by peripheral bypass surgery (Fig. 276-5). The use of drug-coated balloons and

drug-eluting stents has shown to reduce restenosis when compared with

balloon angioplasty alone. Peripheral intervention is increasingly part of

the training of an interventional cardiologist, and most programs now

require an additional year of training after the interventional cardiology

training year. The techniques and outcomes are described in detail in

the chapter on peripheral vascular disease (Chap. 281).

■ CIRCULATORY SUPPORT TECHNIQUES

The use of circulatory support techniques is indicated for the management of patients with shock or hemodynamic instability and occasionally is needed in order to safely perform PCI on hemodynamically

unstable patients. It also can be useful in helping to stabilize patients

before surgical interventions. The most commonly used device is the

percutaneous intraaortic balloon pump developed in the early 1960s.

A 7- to 10-French, 25- to 50-mL balloon catheter is placed retrograde

from the femoral artery into the descending aorta between the aortic

arch and the abdominal aortic bifurcation. It is connected to a helium

gas inflation system that synchronizes the inflation to coincide with

early diastole with deflation by mid-diastole. As a result, it increases

early diastolic pressure, lowers systolic pressure, and lowers late diastolic pressure through displacement of blood from the descending