Ebook Principles of ambulatory medicine (7th edition): Part 2

(BQ) Part 2 book Principles of ambulatory medicine presents the following contents: Cardiovascular problems, musculoskeletal problems, metabolic and endocrinologic problems, neurologic problems, selected general surgical problems, gynecology and women’s health, selected problems of the eyes, common disorders of the skin,...

65: Common Cardiac Disorders Revealed by Auscultation of the Heart

66: Heart Failure 67: Hypertension

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• C h a p t e r 6 2 •

Nisha Chandra-Strobos and Glenn A Hirsch

General Therapeutic Considerations 958

Postmenopausal Hormone Replacement Therapy 959

CAD caused by atherosclerosis is one of the most mon ailments in the Western world, and it remains theleading nontraumatic cause of disability and death in theUnited States Increased public awareness and health ed-ucation have reduced CAD mortality by>20% in the last

com-25 years However, CAD still affects approximately13,000,000 Americans Cardiovascular disease accountsfor 38% of the total mortality in the United States or ap-proximately the same number of deaths as the next fiveleading causes combined (cancer, chronic lower respira-tory diseases, accidents, diabetes mellitus, and influenzaand pneumonia) Of these cardiovascular deaths, coronaryheart disease accounts for 53% (1) Chest pain is one of themost common presenting symptoms of patients with CADwho seek medical attention Health care providers mustunderstand the appropriate diagnostic evaluation and sub-sequent therapeutic options for patients with chest pain

A detailed history and physical examination are essentialwhen evaluating patients with chest pain They cannot bereplaced by sophisticated procedures; rather, they guidethe clinician in selecting the most appropriate diagnosticevaluation

PATHOGENESIS

CAD presents in a variety of ways, largely related tothe underlying pathophysiology of plaque formation andatherosclerosis The endothelium plays an integral role

in defending against atherosclerosis, modulating vasculartone, and preventing intravascular thrombosis These en-dothelial functions are adversely affected by CAD risk fac-tors, even before the development of overt atherosclerosis

In the earliest stages of disease, circulating monocytes here to vascular endothelial cells (via adhesion molecules)and migrate into the intima of the blood vessel, where they

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ingest oxidatively modified low-density lipoprotein (LDL)

and become trapped as foam cells Collections of foam

cells, known as fatty streaks, may be present even in early

childhood Foam cells die, leading to the development of

a lipid core Smooth muscle cells are signaled to migrate

from the media, destroying the internal elastic lamina of

the vessel in the process Calcification of the plaque

oc-curs early and can be visualized noninvasively by

electron-beam computed tomography (EBCT; see later discussion)

The arterial wall progressively thickens and remodels

En-croachment of plaque into the lumen of a coronary artery

occurs late in the atherosclerotic process, reflecting

ad-vanced disease Arterial cross-sectional area is reduced by

approximately 40% before a lesion is visible as “significant”

CAD on catheterization, a finding demonstrated by use of

in vivo intravascular ultrasound (2)

Atherosclerotic progression is accelerated by three

pro-cesses: endothelial dysfunction, inflammation, and

throm-bosis Advanced lesions may be calcified and fibrotic, but

more concerning are plaques that have a core of lipid and

necrotic tissue surrounded by a thin fibrous cap This cap

contains collagen, and its characteristics are closely

re-lated to the risk of plaque rupture, the major cause of

acute coronary syndromes Specifically, a thinner fibrous

cap is more likely to rupture A ruptured plaque exposes

the highly thrombogenic underlying collagen matrix and

leads to rapid thrombus formation Complete occlusion

of a coronary vessel by thrombus on a ruptured plaque

typically causes an acute transmural MI characterized by

ST-segment elevation on the electrocardiogram (ECG)

Nonocclusive thrombus can cause unstable angina or an

MI without ST-segment elevation Nonocclusive thrombus

may not cause symptoms but instead may change plaque

geometry and lead to rapid plaque growth

MIs are classified by their appearance on 12-lead ECG

during the acute phase as either ST-segment elevation

or non–ST-segment elevation and are treated differently

(3–6) It is important to recognize that an acute MI

of-ten arises from rupture of an atherosclerotic plaque that

caused<50% luminal reduction by angiography prior to

plaque rupture (7,8) On the other hand, a coronary artery

that is narrowed by ≥70% is more likely than is a less

severe narrowing to cause exertional angina The

discor-dance between plaque severity and the development of an

acute MI indicates that coronary disease is not simply a

mechanical problem but instead occurs as the end result

of the interplay between mechanical stresses,

inflamma-tion, cholesterol deposiinflamma-tion, and thrombosis

Most patients with classic exertional angina by history

have fixed atherosclerotic lesions of≥70% in at least one

major coronary artery Fundamentally, angina is caused

by a mismatch between myocardial oxygen supply and

de-mand Supply is affected by coronary perfusion pressure,

coronary vascular resistance, and the oxygen-carrying

ca-pacity of blood Flow is autoregulated over a wide

vari-ety of perfusion pressures; therefore, most of the changes

in flow result from changes in resistance (i.e., tion) However, the coronary bed beyond a significant flow-limiting stenosis already is maximally vasodilated suchthat small increases in demand (e.g., increased heart rateand blood pressure during exercise) may result in myocar-dial ischemia Oxygen demand is related to heart rate,systolic blood pressure, and wall tension Wall tension isdetermined by ventricular pressure, cavity size, and wallthickness Physical exertion and emotional stress have po-tent effects on these variables and, not coincidentally, arethe common triggers for ischemic chest pain

vasodila-RISK FACTORS

Both genetic and environmental risk factors influence thedevelopment of atherosclerotic heart disease The recogni-tion of risk factors is especially important because many

of these conditions can be modified to prevent disease

Landmark epidemiologic surveys, such as the ham Heart Study, have helped to define levels of risk forindividual risk factors Treatment guidelines have beenrevised to include the important interactions betweenindividual risk factors and age Risk calculators (CADevent risk over 10 years) are available on the Internet athttp://www.intmed.mcw.edu/clincalc/heartrisk.html The27th Bethesda Conference was designed to bring atten-tion to specific patients at high risk for development ofCAD events (9) This work has been incorporated into theNational Cholesterol Education Program (NCEP) ExpertPanel on Detection, Evaluation and Treatment of HighBlood Cholesterol in Adults (Adult Treatment Panel III[ATP-III]) (see Chapter 82) (10) The concepts of “risk”

Framing-and “risk factor” are important in understFraming-anding Framing-and ing the guidelines The Bethesda Conference outlined fourcategories of risk based on observational studies and effi-cacy studies (clinical trials) Table 62.1 summarizes theserisk factors

us-Category I risk factors are those for which interventions

have been proven to reduce the risk of CAD events Theyinclude smoking, elevated LDL cholesterol, diet high insaturated fat, hypertension, left ventricular hypertrophy,and “thrombogenic factors,” which are unnamed but havethe potential of being reduced by aspirin

Category II risk factors are those for which interventions

are likely to lower CAD risk They include diabetes mellitus,physical inactivity, low levels of high-density lipoprotein(HDL) cholesterol, increased levels of triglycerides, obe-sity, and postmenopausal estrogen deficiency Since thepublication of these findings, diabetes has been reclassi-fied as a CAD “risk equivalent” based on data suggestingthat diabetic patients without known CAD have survivalrates similar to those of nondiabetic patients who have ex-perienced an MI The ATP-III guidelines focus attention

◗TABLE 62.1 Risk Factors for Cardiovascular

Disease Category I (Factors for which Interventions Have Been Proved to

Left ventricular hypertrophy

Thrombogenic factors (as affected by aspirin)

Category II (Factors for which Interventions Are Likely to Lower

Postmenopausal status (women)

Category III (Factors Associated with Increased CVD Risk That,

if Modified, Might Lower Risk)

Low socioeconomic status

Family history of early-onset coronary artery disease

aMay now be considered a category I risk factor; see text.

CVD, cardiovascular disease; HDL, high-density lipoprotein LDL;

low-density lipoprotein.

Adapted from Pasternak RC, Grundy SM, Levy D, et al 27th Bethesda

Conference: matching the intensity of risk factor management with the

hazard for coronary disease events Task Force 3 Spectrum of risk

factors for coronary heart disease J Am Coll Cardiol 1996;27:978.

on the “metabolic syndrome,” which incorporates

abdom-inal obesity, atherogenic dyslipidemia (elevated

triglyc-erides, small LDL particles, low HDL cholesterol), elevated

blood pressure, insulin resistance (with or without

glu-cose intolerance), and prothrombotic and

proinflamma-tory states Patients with this syndrome now are

appropri-ately targeted for intensive risk factor modification Low

HDL cholesterol, with the publication of the Veterans

Af-fairs High-Density Lipoprotein Intervention Trial (VA-HIT)

(11), now may be considered a category I risk factor,

be-cause an intervention to raise HDL cholesterol (i.e., with

gemfibrozil) in this trial reduced the incidence of

cardio-vascular events (12) Although postmenopausal status

cor-rectly identifies a cardiac risk factor, evidence from

ran-domized trials demonstrates that hormone replacement

therapy may actually increase the risk of cardiovascular

events and therefore is not recommended for treatment orprevention of CAD (13,14)

Category III risk factors are those associated with

in-creased CAD risk that may, if modified, lower risk Theseinclude the “emerging” risk factors such as depression,elevated lipoprotein (a) levels, and hyperhomocysteine-mia This list probably should be expanded to includeinflammatory markers (elevated white blood cell count,high-sensitivity C-reactive protein, serum fibrinogen, sol-uble adhesion molecules), thrombotic risk factors (plas-minogen activator inhibitor-1), and sleep apnea Coronarycalcification as measured by EBCT (15) can correctly beconsidered a category III risk factor for now, but it mayneed to be reclassified (like diabetes mellitus) as a CADrisk equivalent because it is a measure of the subclinicalcoronary artery plaque burden

Category IV risk factors are those that are associated with

increased risk but cannot be modified They include age,male gender, low socioeconomic status, and family history

of early-onset CAD Positive family history has been fined as CAD in a male first-degree relative younger than

de-55 years or in a female first-degree relative younger than

65 years These factors usually are taken into considerationwith the available risk scoring systems

DIAGNOSIS History

Character and Location of Ischemic Pain

The discomfort of myocardial ischemia can be described

in a variety of ways Classically, the term angina pectoris

describes a “strangulation of the chest,” a helpful point toremember because many individuals describe somethingother than “pain” and instead mention chest tightness orheaviness Often it is more effective to ask the patient todescribe the discomfort Some patients may simply holdtheir clenched fist in the middle of their chest (Levine sign)

Angina typically begins and ends gradually over 2 to

5 minutes and usually is steady in character, although casionally it waxes and wanes If ischemic pain continues

likely to have occurred The discomfort of angina pectorisusually is midline and substernal, sometimes with radia-tion to the shoulder, arm, hand, or fingers, usually to theleft Radiation down the inside of the arm into the fin-gers supplied by the ulnar nerve is classic Pain also mayradiate into the neck, lower jaw, or interscapular region

Occasionally, a patient has pain only in a referred tion and experiences no chest discomfort at all The pain

loca-of myocardial ischemia is diffuse and cannot easily be calized Rarely is the patient able to point with one finger

lo-to the location When pain can be localized in this way,

it likely is noncardiac in origin The elderly, especially the

frail elderly, are more likely than are younger patients to

experience atypical symptoms such as dyspnea, confusion,

or dyspepsia rather than pain

The Canadian Cardiovascular Society (CCS)

Classifi-cation System was designed to provide a simple way of

grading anginal symptoms (16) Class I angina occurs with

strenuous, rapid, or prolonged exertion but not with

ordi-nary physical activity Patients with class II angina

experi-ence slight limitation of ordinary activity Class II angina

occurs on walking or climbing stairs rapidly; walking

up-hill; walking or climbing stairs after a meal, in cold, or in

wind; or under emotional stress Class III angina produces

marked limitations of ordinary physical activity Angina

occurs on walking one or two blocks on level terrain or

climbing one flight of stairs under normal conditions and

at a normal pace With class IV angina, the most severe

type, the patient is unable to carry on any physical

ac-tivity without discomfort, and anginal symptoms may be

present at rest A higher CCS class is associated with more

extensive CAD and a higher risk of CAD events

Precipitating Factors

The single most important diagnostic feature of the

dis-comfort of myocardial ischemia is its predictable

relation-ship to exertion, emotional stress, or other situations that

may either increase myocardial oxygen demand or reduce

supply The cause of atypical pain, pain in an unusual

lo-cation or of an unusual character, may be clarified by this

relationship Pain that is experienced at rest, if it is caused

by ischemia, suggests unstable angina or MI

Anxiety and mental stress are important and often

over-looked provoking factors in many patients Angina is more

likely to occur during cold or windy weather because of

in-creased peripheral vascular resistance and, consequently,

increased myocardial work Other triggers include sexual

intercourse or a heavy meal

Relief of Ischemic Pain

Because angina is fundamentally caused by a

discrep-ancy between oxygen supply and demand, relief of pain

is achieved by increasing coronary blood flow or

decreas-ing oxygen demand Most people must stop or at least slow

the activity responsible for precipitating the pain before it

is relieved Angina often is relieved by sublingual

nitro-glycerin, but the practitioner and the patient both need to

realize that relief of chest pain by nitroglycerin is not

spe-cific for myocardial ischemia (17) For example, the pain of

esophageal spasm can also be relieved by nitroglycerin

Physical Examination

The physical findings in patients with CAD are

nonspe-cific A complete cardiovascular examination should focus

on identifying markers of hypertension and dyslipidemia,peripheral vascular disease, or diabetes mellitus Severeaortic valve disease (stenosis or regurgitation) or pul-monary hypertension without CAD can cause angina pec-toris either from left or right ventricular wall strain,respectively, leading to myocardial ischemia

Electrocardiography

A 12-lead ECG should be obtained as soon as possible in

a patient with suspected CAD, although in many cases theECG is completely normal The most reliable ECG sign ofchronic ischemic heart disease is the presence of a prior MI

as manifested by two or more pathologic Q waves in a ticular myocardial territory (e.g., anterior, lateral, inferior,etc.) (Fig 62.1A) The differential diagnosis of Q waves onECG includes prior MI, healed myocarditis, hypertrophiccardiomyopathy, an infiltrative myocardial disorder such

par-as amyloidosis or sarcoidosis, and Wolff-Parkinson-Whitesyndrome (usually with characteristic findings of preexci-tation; see Chapter 64) Nonspecific ST-T wave changes,conduction abnormalities (except for left bundle-branchblock [LBBB], discussed later), and arrhythmias do nothelp establish the diagnosis of myocardial ischemia How-ever, ST-segment depression with a flat or downslop-ing ST segment is suggestive of subendocardial ischemia(Fig 62.1B) It is seldom present on the resting ECG ofpatients with ischemic heart disease unless they are ex-periencing angina at the time the tracing is recorded Onthe other hand, transient ischemic changes are seen com-monly when a patient with CAD is exercised to a point

at which chest pain develops Such ECG changes, ing with exercise or pain and resolving with rest or withthe resolution of pain, usually are an indication of my-ocardial ischemia Therefore, the necessity of repeating theECG at rest or after the chest pain has resolved cannot beoveremphasized ST-segment elevation during chest pain(Fig 62.1C) suggests acute myocardial injury (e.g., MI) orvariant angina (discussed later) T-wave inversion on anECG taken at rest is a nonspecific finding but can occurafter infarction or as a specific transient finding in a pa-tient experiencing angina Therefore, ECG changes notedduring episodes of chest pain not only can confirm thediagnosis of myocardial ischemia but also may indicatethe extent and location of the ischemic myocardium As

appear-a generappear-al rule, the more widespreappear-ad the chappear-anges on ECG,the greater the extent of myocardium that is involved ST-segment elevation in the absence of chest pain is common

on the resting ECG of healthy young adults and is caused

by rapid or “early” repolarization of the ventricle This tern (Fig 62.1D) usually is noted in the mid–left chestleads (V2–V4) but may be more widespread ST-segmentelevation from pericarditis is diffuse and can be associ-ated with PR-segment depression in the limb leads (exceptaVR, which may show PR-segment elevation)

pat-A B

waves suggestive of prior myocardial infarction B: ST-segment depression developing after exertion.

C: ST-segment elevation during coronary artery spasm (variant angina) D: Early repolarization

(a normal variant)

The presence of ST-T abnormalities in an otherwisehealthy person is a nonspecific finding and should not be

considered confirmation of CAD There is a high

associa-tion of LBBB with organic heart disease (see Chapter 64),

especially CAD Right bundle-branch block (RBBB), on the

other hand, is seen commonly in the absence of other

car-diac abnormalities

Cardiac Stress Testing

Exercise Electrocardiography

The exercise stress test is a means of establishing the

diagnosis of myocardial ischemia It also can be used

to assess the efficacy of antianginal therapy, to identify

patients who are likely to have more severe CAD and a

large area of myocardium at risk, and to assess serially

the degree of conditioning or exercise capacity in patients

of all age groups The American College of Cardiology

(ACC)/American Heart Association (AHA) exercise testing

guidelines outline the recommendations for the use of

exercise testing in establishing the diagnosis of CAD, in

assessing risk and prognosis in patients with symptoms

or a prior history of CAD, and the use of exercise testing

after MI (18,19) The usefulness of exercise testing in

es-tablishing the diagnosis of CAD is based in part on the

like-lihood that the patient has this condition (i.e., the “pretest

probability” of CAD) This can be determined by the

pa-tient’s age, gender, and symptoms For example, exercise

testing would not be expected to greatly improve the

ac-curacy of diagnosing CAD in an older patient with ical angina (who has a high pretest probability of CAD)nor in a young, asymptomatic individual (who has a lowpretest probability of CAD) The usefulness of stress testing

typ-in these situations would be limited by false-negative andfalse-positive findings, respectively The ACC/AHA guide-lines recommend exercise testing to diagnose CAD in adultpatients with an intermediate pretest probability of CADbased on gender, age, and symptoms (18,19) For patientswith known CAD, the guidelines recommend stress test-ing for those with a significant change in clinical status

Patients with unstable angina, decompensated heart ure, severe aortic stenosis, or uncontrolled hypertensionshould not be referred for stress testing because of an un-acceptably high risk for provoking a cardiac event duringexercise

fail-Exercise stress testing is based on the rationale that,

as the work performed by the patient increases, cardiacwork is increased The increased cardiac work results in in-creased myocardial oxygen utilization, with a subsequentincreased demand in coronary blood flow If narrowed orobstructed coronary arteries prevent the required increase

in coronary blood flow, myocardial ischemia may occurand be manifested as chest pain and/or ECG changes (20)

The simplest and least expensive exercise stress test isthe graded, symptom-limited exercise treadmill test Thetest requires 12-lead ECG monitoring of the patient whilewalking on a treadmill at workloads that can be progres-sively increased by increasing the speed and inclination ofthe treadmill A stationary bicycle ergometer (with hand

FIGURE 62.2.Algorithm for determining the appropriate stress

test See text for a description of the procedures

pedals) can be substituted for a treadmill, permitting the

patient to exercise with his or her arms instead of legs

Although it is not commonly used, this method of stress

testing permits exercise by a patient who may otherwise

be unable to do so because of lower-extremity

claudica-tion, arthritis, or amputation It also may be useful in

the evaluation of patients who have chest pain

predomi-nantly or exclusively with work that involves the arms and

shoulders

A simple algorithm can be used to decide the type of

stress test to recommend (Fig 62.2) First, the patient’s

ability to exercise should be assessed If the patient can

walk up a flight of stairs carrying laundry or groceries,

for example, a treadmill exercise protocol can generally be

chosen to allow the patient to achieve a level of cardiac

work that permits meaningful information to be obtained

from the test If the patient cannot perform this task, or

one that is comparable, a pharmacologic stress test with

cardiac imaging (discussed later) should generally be

rec-ommended The patient’s baseline ECG should be reviewed

to determine the presence of baseline ST-segment

abnor-malities that might lower the predictive value of

exercise-induced changes False-positive stress tests are often

en-countered in women, in patients taking medications such

as digoxin or amiodarone, and in patients with left

ventric-ular hypertrophy or mitral valve prolapse (21) For these

patients and in those with baseline ST-segment

abnormal-ities, intraventricular conduction defects (i.e., LBBB or

RBBB), or other conduction system disorders (e.g.,

Wolff-Parkinson-White syndrome), the diagnostic accuracy of

the exercise stress test can be enhanced by concurrent

ra-dioisotopic or echocardiographic imaging (see later

dis-cussion) The choice between radioisotopic or

echocardio-graphic imaging depends largely on the expertise of local

laboratories

Radioisotope Imaging

Radioisotope imaging can enhance the specificity of stress

testing by evaluating myocardial function or flow (22)

Ra-dioisotope imaging can be used in conjunction with

ei-ther treadmill exercise testing or pharmacologic stress

test-ing, using either dobutamine to increase cardiac work or

adenosine or dipyridamole to alter coronary blood flow(see later discussion) Commonly used imaging modalitiesinclude radioisotope imaging with thallium 201 (201Tl)–

and/or technetium 99 (99Tc)–based agents (e.g., 99msestamibi) The usefulness of 201Tl as a perfusion tracer

Tc-is based on its ability to function as an analogue of ionicpotassium It is very efficiently extracted by healthy my-ocardial cells, and uptake is proportional to regional per-fusion and myocardial viability 99mTc-sestamibi has ashorter half-life (6 hours) than does201Tl (73 hours), al-lowing administration of a larger tracer dose This andits higher emission energy make it an excellent agent forcardiac imaging.99mTc-sestamibi is particularly useful inobese patients and in patients with large breasts (because

of possible attenuation of the radioisotopic images in thearea of the anterior myocardium)

Both 201Tl and99mTc-sestamibi can be used to assessregional myocardial blood flow, either by planar imag-ing or by single-photon emission computed tomography(SPECT) Imaging usually occurs at two separate times:

the stress scan, obtained very shortly after the patient hasexercised or received a pharmacologic agent, and the restscan, obtained either before or several hours after stress

The radioisotope is injected intravenously at the time ofpeak exercise (or at the time of peak infusion during apharmacologic stress test), and scintigraphic images areobtained shortly thereafter, depicting regional myocardialperfusion at the time of peak stress The rest scan typically

is obtained several hours later and shows redistribution

of the isotope Ischemia is indicated by the filling in of acold spot defined on the stress images (i.e., normalization

or “redistribution” of a radioisotopic defect), and tion is indicated by a persisting cold spot or one with onlypartial redistribution

infarc-Radioisotope imaging with stress gated blood poolscans (multiple-gated acquisition [MUGA]) also can beused to assess myocardial ischemia To allow for continu-ous imaging during exercise, stress MUGA is performedwith the patient exercising on a semirecumbent bicy-cle The rationale for this test is based on the fact thatmyocardium that becomes ischemic during graded exer-cise develops regional wall-motion abnormalities that can

be detected by sequential image analyses This type ofimaging labels the blood pool with a radioisotope and gatesimage acquisition to the ECG Right and left ventricularvolumes, regional left ventricular wall motion, and globaland regional ejection fractions can be measured, both atrest and with stress

The cost of stress testing with radioisotope scanningusually is several times that of a standard exercise test

Stress Echocardiography

Two-dimensional echocardiography can be used instead

of radioisotope scanning to detect areas of regional ocardial dysfunction (as evidenced by a wall-motion

my-abnormality) with exercise or pharmacologic stress

(23,24) Typically, baseline images are first obtained at

rest to determine the adequacy of the echocardiographic

images If these images are technically inadequate (e.g.,

because of obesity or severe obstructive lung disease),

an intravenous ultrasound contrast agent can be used if

available; if not, radioisotope images are preferable If the

rest images are technically adequate, the patient

under-goes treadmill exercise stress and then images are

reac-quired immediately, using special software to allow for

direct comparison of pre-exercise and postexercise images

If pharmacologic stress testing with dobutamine (see

Phar-macologic Stress Testing) is used, the dose of dobutamine

is increased in stepwise fashion, and echocardiographic

images typically are obtained each time the dose is

in-creased The safety of dobutamine stress

echocardiogra-phy is comparable to that of a routine exercise stress test

(23,25,26) The sensitivity, specificity, and cost of the test

are similar to those of radioisotopic stress testing Stress

echocardiography may be preferred in some cases because

additional information is provided that is not obtained

with radioisotopic scanning (e.g., presence of pericardial

effusion, ventricular hypertrophy, or valvular

abnormal-ity) It also avoids exposure to radioactivity

Pharmacologic Stress Testing

Patients who are unable to exercise because of

physi-cal limitations can be evaluated after intravenous

admin-istration of dipyridamole, adenosine, or dobutamine in

conjunction with an imaging modality Dipyridamole and

adenosine dilate all coronary vessels and generally increase

flow to all areas of the heart Enhanced dilation of

nor-mal coronary arteries, compared to that of significantly

narrowed vessels, augments differences in flow that

usu-ally are not apparent at rest These agents are suitable for

use with radioisotopic imaging modalities that may

read-ily demonstrate this flow heterogeneity After

administra-tion of dipyridamole or adenosine followed by either201Tl

or 99mTc-sestamibi (i.e., the stress image), myocardium

supplied by a narrowed coronary artery typically

demon-strates a perfusion defect that “fills in” during the rest

im-age Because of its ultrashort duration of action, adenosine

is preferable to dipyridamole for this test

Dobutamine is a β1-receptor agonist that at highdosages (20–40 μg/kg/min intravenously) increases

myocardial contractility and heart rate in a similar

man-ner and extent to exercise Heart rate may not be affected

to the same extent as contractility, and atropine often is

administered intravenously to increase the heart rate to

the maximal predicted heart rate for age Dobutamine

can be used in conjunction with either echocardiography

or radioisotopic imaging for diagnosis of CAD

Mild side effects (e.g., nausea, flushing, and headache)are common with dipyridamole, adenosine, and dobuta-

mine Dipyridamole and adenosine (but not dobutamine)

can produce severe bronchospasm and therefore must beused with caution or not at all in patients with asthma

or chronic obstructive pulmonary disease Adenosine cancause transient heart block, typically lasting several sec-onds Because dobutamine increases atrioventricular con-duction, it should not be used in patients with atrial flutterand should be used carefully in patients with atrial fibril-lation

Implications of an Abnormal Stress Test

If treadmill exercise stress testing is performed, factorsaffecting prognosis include the degree of ST-segment de-pression, time to development of ST-segment depressionduring exercise, duration of the ST-segment depression inrecovery, and speed of heart rate decline during recovery

In addition, an ischemic ECG response that is nied by hypotension generally implies a large amount ofmyocardium at risk Prognostic information from phar-macologic stress testing-induced ECG abnormalities is lessreliable The number, size, and location of abnormalitiesevident on stress imaging studies reflect the location andextent of functionally significant coronary stenoses (27)

accompa-Both radioisotopic and echocardiographic imaging candetect left ventricular dilation with stress, a finding thatsuggests global, severe ischemia Lung uptake of a ra-dioisotopic tracer indicates stress-induced left ventriculardysfunction and suggests multivessel CAD Many studieshave shown that high-risk abnormal stress tests are asso-ciated with an increased risk for cardiac events On theother hand, normal radioisotopic or echocardiographicstress tests are associated with a favorable prognosis In

a review of 16 studies involving almost 4,000 patients over

2 years, a negative perfusion scan was associated with a0.9% rate of cardiac death per year, similar to that of thegeneral population (28)

Ambulatory Electrocardiography

The ambulatory ECG (Holter monitor) may be usefulfor detecting myocardial ischemia However, it is not agood tool for screening patients to make the diagnosis

of CAD In patients with CAD who are symptomatic ing ambulatory ECG monitoring, ST-segment elevation

dur-or depression can be observed during episodes of painand at other times as well (silent ischemia; see later dis-cussion) In patients with silent ischemia, the ambula-tory ECG is particularly useful for quantifying the degreeand frequency of ischemia and assessing the efficacy oftherapy

Electron-Beam Computed Tomography

Studies in the 1970s demonstrated that coronary tion (detected by cardiac fluoroscopy) was useful in identi-fying patients with angiographically significant CAD (29)

calcifica-A B

they would be seen on the angiogram No attempt has been made to convey the third dimension

Careful study of the changes in position of the various branches with rotation of the heart is essential

to intelligent interpretation of arteriograms A: Anteroposterior B: Lateral (Modified from Abrams HL,

Adams DF The coronary arteriogram: structural and functional aspects [First of two parts] N Engl JMed 1969;281:1276, with permission.)

EBCT is a highly sensitive technique for detecting coronary

artery calcium and may be useful for diagnosing CAD

non-invasively (11) ECG gating allows data acquisition within

one or two breath-holds, making it a rapid test with limited

radiation exposure The images obtained by this technique

allow the determination of a calcium score, which is an

index of calcium deposition in multiple arterial segments

and is a good approximation for overall plaque burden

in the coronary tree High calcium scores are associated

with increased risk for MI (30) The test offers improved

discrimination over conventional risk factors in the

iden-tification of people with CAD (31) The negative predictive

value of EBCT is high The test is particularly useful for

screening asymptomatic individuals with multiple risk

fac-tors, in whom an abnormal EBCT should prompt further

testing and/or treatment A very low EBCT score would be

reassuring (32)

Cardiac Catheterization and

Coronary Angiography

Coronary angiography is defined as the radiographic

vi-sualization of the coronary vessels after injection of

ra-diopaque contrast medium (33) This technique provides

direct information about the presence of CAD and defines

the distribution and severity of obstructive coronary

le-sions It is considered the “gold standard” to confirm the

diagnosis of CAD The images obtained are stored as

ei-ther 35-mm cine film or, more commonly, a digital

record-ing Percutaneous or cutdown techniques of the femoral or

brachial arteries allow insertion of sheaths for the

intro-duction of selective catheters for the right and left coronaryostia, saphenous bypass grafts, or internal mammary arter-ies Arteriography is performed as part of cardiac catheter-ization, which may include left ventriculography andhemodynamic assessment Figure 62.3 shows diagram-matically the coronary arteries and their branches as theyappear on coronary arteriography The three major coro-nary arteries are the left anterior descending, left circum-flex, and right coronary artery The coronary tree can bedivided into 29 segments, but the extent of disease usu-ally is defined as one-vessel, two-vessel, three-vessel, or leftmain disease, with significant disease taken to mean thepresence of≥50% reduction in diameter (some operatorsand texts use≥70% reduction in diameter)

The 1999 ACC/AHA Guidelines for Coronary raphy outline the indications and contraindications forthe procedure (33) The guidelines recommend arteriog-raphy for patients with CCS class III or IV angina whilereceiving medical treatment (marked limitations of ordi-nary physical activity because of angina or angina at rest,discussed earlier) and those with high-risk criteria on non-invasive testing regardless of angina severity It may be rea-sonable to consider coronary arteriography for patientswhose angina has improved with medical treatment butremains present, those in whom noninvasive testing hasshown evidence of worsening disease, those who cannottolerate medical therapy, those with angina who cannot beadequately risk stratified because of disability or illness,and those whose occupation involves the safety of others(e.g., pilots, bus drivers) and who have abnormal, but nothigh-risk, stress test results

Angiog-Inherent in the recommendation for coronary ography is the assumption that the patient is a potential

arteri-candidate for coronary revascularization If the patient’s

general medical condition or other medical problems

pre-clude revascularization, or if the patient refuses to consider

revascularization regardless of catheterization results,

ar-teriography is ill advised

Indications for percutaneous coronary intervention([PCI] including angioplasty and stenting) (34) and coro-

nary artery bypass surgery (35) are reviewed in

sepa-rate ACC/AHA guidelines and are discussed later in this

chapter

Patient Experience The patient may undergo cardiac

catheterization as part of an evaluation during a pitalization, but the test itself does not require that thepatient be admitted to the hospital The procedure isnot painful, and the patient remains awake through-out the study Approximately 1 hour before the proce-dure, the patient is given a sedative, often diazepam(Valium), 5 to 10 mg orally After the patient is brought

hos-to the catheterization laborahos-tory, either the area of thebrachial artery or the femoral artery is prepared for ster-ile procedure The site of introduction of the catheterusually is selected based on the preference of the oper-ator but also is guided by the presence and extent ofperipheral vascular disease Typically, a catheter isintroduced percutaneously through a wire that isthreaded through an introducer needle Under fluoro-scopic guidance, the catheter is threaded to the coro-nary sinuses, and the orifices of the right and left coro-nary arteries are injected sequentially with contrastmedium The patient is asked to hold his or her breathduring the few seconds of the injection In addition tothis part of the test, which visualizes the coronary arter-ies, studies are typically performed to measure ventric-ular pressures and to assess left ventricular contractionduring injection of dye directly into the left ventricu-lar cavity During ventriculography, focal wall-motionabnormalities, ventricular aneurysms, and valvular le-sions such as mitral regurgitation can be assessed inaddition to the measurement of overall left ventricularfunction and ejection fraction At the end of the proce-dure, the catheter is withdrawn, and pressure is applied

to the arteriotomy site to achieve hemostasis

During the procedure, the patient should feel relaxed or

even slightly drowsy from the sedation The patient usually

does not feel pain except for the moment when the needle is

initially introduced There is some pressure as the catheter

is held in place The patient may experience a sensation of

hot flushing when the dye is injected, particularly when the

larger bolus of dye is injected into the left ventricle during

ventriculography

Risks and Relative Contraindications

The major complications of coronary arteriography are

MI, stroke, and death These risks are related to the

ex-perience of the laboratory performing the study and to therisk profile of the patient undergoing the test Risks tend

to be lower in young, otherwise healthy patients Riskstend to be higher in older patients with poor left ventricu-lar function, diabetes mellitus, or peripheral vascular dis-ease, and those who are clinically unstable (e.g., patientswith cardiogenic shock, recent acute MI, or decompen-sated heart failure) at the time of the procedure In a sur-vey of almost 60,000 patients, mortality from angiographywas 0.11%, MI occurred in 0.05%, and stroke occurred in0.07% The most common complication was a problemwith vascular access, which occurred in 0.43% of patients(36)

There are no absolute contraindications to coronary teriography Relative contraindications include renal fail-ure, active gastrointestinal bleeding, acute stroke, severeanemia, coagulopathy, unexplained fever or active un-treated infection, severe uncontrolled hypertension, al-lergic reaction to angiographic contrast agents, anddecompensated congestive heart failure (CHF) Renal in-sufficiency has been the most well-studied complication

ar-It occurs in up to 5% of patients without preexisting nal dysfunction and in 10% to 40% of patients with base-line renal insufficiency More than 75% of patients whodevelop renal insufficiency recover normal renal function,although 10% of these patients may require dialysis tem-porarily Pretreatment with intravenous hydration (0.9%

re-saline) (37) and limiting the amount of intravenous trast material used are effective means to avoid contrast-induced renal dysfunction

con-For patients with underlying renal dysfunction,

pre-treatment with N-acetylcysteine (38) or intravenous

sodium bicarbonate (39) has been shown to reducecontrast-induced acute renal failure following cardiaccatheterization No direct comparison of these prophylac-tic measures has been performed to date Patients takingthe oral hypoglycemic metformin should be asked to with-hold it for 48 hours prior to the procedure, because the use

of iodinated contrast dye in patients taking metformin hasbeen associated with development of lactic acidosis (40)

The major predictors of contrast allergy are prior contrastallergy (50% risk of subsequent reaction), iodine allergy,and shellfish allergy These conditions should be discussedwith the patient before referral for angiography The use

of nonionic contrast medium along with pretreatment ing corticosteroids and antihistamines may reduce allergiccomplications

us-Computed Tomography Coronary Angiography

High-definition rapid CT scanning has evolved as a potentdiagnostic tool for identifying CAD noninvasively Newer

CT devices are able to rapidly scan through a patient’schest using many slices for image acquisition (the current

state of the art is to use a 64-slice scanner), quickly and

accurately identifying unique features of coronary and

car-diac anatomy Multislice carcar-diac CT scanning is extremely

accurate in detecting coronary narrowings in the proximal

two thirds of the coronary tree that are demonstrated by

conventional coronary angiography, but its resolution of

the distal third is less accurate However, it is superior to

conventional coronary angiography in identifying

extralu-minal vascular abnormalities that result in coronary

nar-rowings but cannot be seen by conventional techniques

Additionally, other noncardiac causes of chest pain, such

as aortic dissection, pneumonia, or pulmonary embolus,

may be diagnosed by this imaging technique CT

coro-nary angiography is particularly useful in patients with

peripheral vascular disease because it can minimize or

avoid catheter-related complications During CT

angiog-raphy, the patient receives intravenous radiographic

con-trast, and the total scanning time usually is≤15 minutes

Image quality is improved at slower heart rates and

pa-tients may receive low doses of β-blockers to facilitate

this Because iodinated contrast is used for this

proce-dure, the risks and precautionary treatment associated

with such therapy is the same as for cardiac

catheteri-zation

TREATMENT OF ANGINA PECTORIS

General Therapeutic Considerations

In evaluating and treating patients with angina, it is of

paramount importance to identify and treat underlying

contributing factors and to modify cardiac risk factors that

promote CAD progression if possible

Hypertension often is present in patients with angina.

There is a linear relationship between left ventricular work

and myocardial oxygen demand Left ventricular systolic

pressure increases in response to an increase in peripheral

vascular resistance Both systolic and diastolic

hyperten-sion can increase myocardial oxygen demand An attempt

should always be made to reduce resting blood pressure to

normal in patients with chronic hypertension, including

those with isolated systolic hypertension This can be of

crucial importance in reducing the frequency and severity

of angina pectoris in the hypertensive patient.β-Blockers

and calcium channel blockers (see Chapter 67) are

excel-lent choices in such patients because these agents have

other antianginal properties as well Agents such as

hy-dralazine and minoxidil, which cause a reflex tachycardia,

are less desirable

It is important to achieve a maximal level of pulmonary

compensation in patients with angina and coexisting lung

disease (see Chapter 60) Chronic hypoxemia, acidosis,

and the increased work of breathing in patients with

pul-monary disease increase myocardial oxygen demand,

de-crease myocardial oxygen delivery, or both Unfortunately,the treatment of angina in patients with severe lung dis-ease often is limited by a real, or perceived, need to avoidthe use ofβ-blockers (see later discussion).

Abstinence from tobacco products is essential because

nicotine in tobacco can cause coronary tion Chapter 27 describes techniques used to achievethis goal Similarly, passive tobacco smoke should beavoided

vasoconstric-The possibility of hyperthyroidism (see Chapter 80) in

patients with angina should never be overlooked, larly in older patients or in those with increasing angina

particu-Often, particularly in the older patient, other obvioussigns of hyperthyroidism are not present For example,hyperthyroidism may be manifested only by an increasedfrequency or severity of angina, an increase in heartrate in people with atrial fibrillation, or increasing heartfailure

Anemia is important to consider in patients with angina,

particularly if the hemoglobin concentration falls to

<7 g/dL, when cardiac output must increase to

main-tain adequate peripheral oxygen delivery at rest Obviously,this problem is exacerbated in patients with concomitantchronic lung disease and hypoxemia

Heart failure (see Chapter 66) in patients with angina

should always be optimally treated The real possibilitythat heart failure is producing angina at rest (see laterdiscussion) or nocturnal angina should be considered Di-uretics, vasodilators, andβ-blockers may be useful in pa-

tients with rest or nocturnal angina and may reduce thefrequency and severity of angina The calcium channelblocker amlodipine has been shown to be safe in patientswith left ventricular dysfunction and may be useful for pa-tients with angina in this setting because it has little nega-tive inotropic effect, reduces preload and afterload, helpsdecrease left ventricular end-diastolic pressure, and lowersperipheral vascular resistance

Lipids and Diet

Most of the recent decline in mortality from heart disease isbelieved to be related to primary and secondary risk factorreductions (41,42) Numerous randomized controlled tri-als involving cholesterol reduction have been performedand have supported the ability to reduce CAD morbidityand mortality with both primary and secondary preven-tion strategies The West of Scotland Coronary Preven-tion Study demonstrated significant mortality reductionwith treatment of hyperlipidemia with pravastatin inasymptomatic people; the greatest benefit occurred in pa-tients with other risk factors for CAD (43) The landmarkHeart Protection Study in the United Kingdom random-ized subjects with CAD, peripheral vascular disease, ordiabetes to 40 mg of simvastatin or placebo and demon-strated reductions in mortality in simvastatin-treated

patients regardless of baseline LDL cholesterol levels (44).

The value of secondary prevention was established by

the Scandinavian Simvastatin Survival Study (45) and

the Cholesterol and Recurrent Events (CARE) trial (46)

Both trials demonstrated a significant reduction in

mor-tality when LDL cholesterol levels were lowered to

ap-proximately 100 to 120 mg/dL Other trials also have

clearly demonstrated that coronary artery lesions did not

progress when elevated LDL cholesterol levels were

re-duced to <100 mg/dL (47,48) More recent trials have

compared the effects of more aggressive to less

ag-gressive lipid-lowering strategies, usually by examining

the effects of high-dose and lower-dose therapy with a

β-hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA)

re-ductase inhibitor or “statin.” One of these trials

demon-strated that 80 mg of atorvastatin reduced the frequency of

cardiovascular events to a greater degree than did 40 mg of

pravastatin by more intensive lowering of LDL cholesterol

(mean LDL cholesterol lowered to 62 mg/dL) (49) Another

study compared the effects of 80 mg and 10 mg of

atorva-statin in patients with stable CAD and demonstrated

clinical benefit with the more aggressive lipid-lowering

ap-proach, achieving mean LDL cholesterol levels of 77 mg/dL

and 101 mg/dL in the 80-mg and 10-mg groups,

respec-tively (50)

The NCEP guidelines indicate that the desirable LDLcholesterol level is <100 mg/dL in patients with estab-

lished CAD or with coronary heart disease risk equivalents

including diabetes mellitus, multiple risk factors that

con-fer a 10-year CAD risk>20%, or other clinical forms of

atherosclerotic disease (i.e., peripheral arterial disease,

ab-dominal aortic aneurysm, or symptomatic carotid artery

disease) (10) Updates recommend considering an LDL

cholesterol target <70 mg/dL in very-high-risk patients,

defined as those with an acute coronary syndrome or with

established CAD and multiple major CAD risk factors

(es-pecially diabetes mellitus), severe and poorly controlled

risk factors (especially cigarette smoking), or the metabolic

syndrome (51) Treatment of patients having low HDL

cholesterol levels with the fibrate gemfibrozil was shown to

reduce the risk of major cardiovascular events in patients

with CAD (12) In addition to pharmacologic options for

lipid-lowering drug therapy, the guidelines recommend a

multifaceted lifestyle approach to reduce CAD risk This

approach calls for reducing the intake of saturated fats

in-creasing physical activity also are advised These lifestyle

recommendations are an essential part of treatment for all

patients with coronary disease Chapter 82 discusses these

changes in more detail Obesity has emerged as a national

epidemic, with several studies confirming the increased

mortality and morbidity from this condition (52)

Cha-pter 83 discusses in detail the various treatment options

for this condition

associ-reduction in mortality with moderate alcohol use pared with 24% reduction from physical activity and 36%

(com-reduction with smoking cessation) (56)

Antioxidants

Although antioxidants may be important in inhibitingatherosclerosis, clinical trials of antioxidant therapy havenot demonstrated conclusive long-term benefit In theHeart Outcomes Prevention Evaluation (HOPE) study, forexample, approximately 9,500 patients at high risk for car-diovascular events were randomly assigned to therapy witheither 400 IU of vitamin E or placebo for an average of4.5 years There was no apparent effect of treatment withvitamin E on cardiovascular outcomes in this study (57)

More recently, a meta-analysis of 19 trials suggested thepossibility of increasing mortality with high-dosage vita-min E supplementation for CAD prevention, with risk in-creasing as the dosage of vitamin E exceeded 150 IU/day(58)

Fish Oil and ω-3 Fatty Acids

Fish oils (ω-3 fatty acids) have demonstrated

cardiovascu-lar benefit in people who have taken them by decreasingthe risk of potentially fatal arrhythmias, slowing plaqueprogression, decreasing levels of triglycerides, and mildlydecreasing blood pressure Currently, the AHA recom-mends two servings of fish per week Similarly, other foodsthat contain α-linolenic acid, which can be metabolized

soy products, and tofu, are recommended, but the benefit

not well delineated (59)

Postmenopausal Hormone Replacement Therapy

Earlier studies demonstrated improvements in surrogatemeasures such as endothelial function from hormone re-placement therapy (HRT) Observational studies suggested

a decreased risk for cardiovascular events in women ing HRT compared to women who did not (60,61) Thisfinding led to two randomized, placebo-controlled studies

tak-to definitively evaluate the role of HRT in postmenopausalwomen with chronic stable CAD The Heart and Estrogen/

Progestin Replacement Study (HERS) showed that HRT

did not result in a reduced risk for cardiovascular death

or nonfatal MI (13) The Estrogen Replacement and

Atherosclerosis Study (ERAS) failed to show an effect

of HRT on the angiographic progression of

atheroscle-rotic heart disease (62) There also is evidence that

post-menopausal HRT increases the risk of venous

throm-boembolic disease (13,63) and gallbladder disease (13) in

women with CAD Therefore, HRT is not recommended

for reducing cardiovascular morbidity or mortality in

post-menopausal women

Physical Conditioning

Physical conditioning can improve the exercise

toler-ance and psychological well-being of patients with

sta-ble angina Additionally, improvements in atherosclerotic

risk factors, such as hypertension, glucose intolerance, low

HDL cholesterol concentrations, elevated triglyceride

lev-els, and obesity, reduce CAD risk from the perspective of

both primary and secondary prevention The combination

of weight reduction and exercise lowers LDL cholesterol

concentrations (64) Studies confirm that moderate

exer-cise (20 minutes three times per week) is as effective for

weight loss as more vigorous exercise (65) Most large

com-munities have developed supervised exercise programs

for patients with CAD Chapter 63 details the benefits of

physical conditioning and exercise programs for patients

with heart disease The AHA-published guidelines for

ex-ercise in various patient groups are available on their

website (www.americanheart.org) Patients with angina

should be counseled to avoid physical activities that are

known to provoke their symptoms Health care providers

should specifically discuss the safety of sexual intercourse,

a subject that people often are reluctant to broach (see

Chapter 63) The appropriate level of sexual activity or

par-ticipation in any stressful physical activity ideally should

be based on the results of an exercise stress test The

en-ergy requirements for a broad range of activities are

sum-marized in Table 63.5

Medical Treatment

The basic objective in treating patients with angina

pec-toris is not only to relieve or prevent symptoms but also

to prevent disease progression The former goal may be

achieved by medical therapy that improves the

relation-ship between myocardial oxygen demand and supply The

latter goal may be accomplished by preventing platelet

ag-gregation and by decreasing the growth of atherosclerotic

plaque and the risk of plaque rupture The major advance

in the medical management of angina has been the

demon-stration that long-acting antiplatelet and antithrombotic

agents and vigorous lipid-lowering therapy can improve

outcomes in selected patients with CAD Table 62.2 lists

practical information about the drugs used most often fortreatment of angina

Nitrates

Traditionally, nitroglycerin and related compounds havebeen an inexpensive mainstay of treatment of patientswith angina pectoris Nitrates increase coronary bloodflow in patients with spasm, but the predominant mecha-nism of action in most patients is not an increase in bloodflow but rather a decrease in myocardial oxygen demandand peripheral vascular resistance These compounds pro-duce dilation of the venous circulation, reduced venousreturn, decreased ventricular volume, and decreased walltension These effects ultimately reduce myocardial oxy-gen demand Nitrates also produce arterial dilation to alesser degree and thereby reduce the resistance to ventric-ular ejection Therefore, the beneficial antianginal effect ofnitrates is caused primarily by peripheral vasodilation

Sublingual nitroglycerin is still the drug of choice in

most patients for the relief and prevention of discreteepisodes of angina pectoris The initial dose should besmall (0.4 mg) to minimize unpleasant side effects(flushing, headache, light-headedness) Patients should betaught the importance of relieving their pain as soon aspossible, and they should be instructed to take nitroglyc-erin whenever such symptoms appear If pain is not re-lieved by two to three tablets of nitroglycerin (the patientshould wait at least 5 minutes between doses) or if theneed for nitroglycerin increases suddenly and dramati-cally, the patient should be instructed to call his or herhealth care provider or go to an emergency facility imme-diately because of the danger of impending MI Becausenitroglycerin may lose potency on storage, patients should

be advised not to keep tablets longer than 3 to 4 monthsafter opening the bottle If the use of nitroglycerin doesnot result relieve the angina and the usual side effects arenot experienced, the problem may be caused by outdatedmedicine that has lost its potency rather than by a change

in cardiac status Prophylactic use of nitroglycerin is ofparticular value in patients who have angina in response

to specific and reproducible stress despite other therapies

For example, the patient who develops angina after ing from a car to a place of work can be instructed to takenitroglycerin after the car is parked, wait a few minutes,and then walk to work, thereby preventing pain altogether

walk-The most common side effects of nitroglycerin therapy areflushing and headache A nitroglycerin sublingual sprayhas been developed that is designed to deliver 0.4 mg of ni-troglycerin with each compression of the nebulizer Somepatients find this preparation more acceptable and morereliable than the tablet

Long-acting nitrates are available in a variety of

prepara-tions (Table 62.2) Careful studies confirm the clinical cacy of both nitroglycerin ointment and isosorbide tablets

(66,67) When selecting from among available oral

prepa-rations, the major considerations should be efficacy,

con-venience, and cost Using these criteria, long-acting

isosor-bide probably is the best choice for ambulatory patients.

A nitrate patch for once-daily use is available It provides

controlled release of 0.2, 0.4, or 0.6 mg of nitroglycerin

per hour through a semipermeable membrane applied to

the skin by means of an adhesive tape The patch delivers

a standardized dose, but constant serum levels of nitrate

predispose to the development of tolerance; therefore, the

patch should be removed for a period of the day (e.g., at

night) (68)

The side effects of all long-acting nitrates are similar

to those produced by sublingual nitrates Some patients

are unable to take long-acting nitrates because of

persis-tent headache, but for most patients this is not a problem

Nitrates can produce orthostatic hypotension and

occa-sionally syncope

Sildenafil (Viagra) is a drug used for treatment of

erectile dysfunction The drug inhibits cyclic

guano-sine monophosphate (cGMP)-specific phosphodiesterase

type 5, allowing accumulation of cGMP in the corpus

cav-ernosum of the penis Because nitrates increase cGMP

levels but sildenafil inhibits cGMP breakdown, the

com-bination of sildenafil and nitrates may result in severe

hy-potension Therefore, sildenafil should not be used by men

who are taking nitrates of any kind (see Chapter 63)

β-Blocking Agents

A number of β-blockers are currently available in the

United States These agents vary in their cardioselectivity,

their metabolism, and, to some degree, their side effects

(see later discussion and Chapters 64 and 67)

In many respects,β-blockade is an ideal approach to the

treatment of angina It decreases heart rate, myocardial

contractility, and systemic blood pressure These effects,

alone or in combination, significantly reduce myocardial

oxygen consumption and thereby attenuate the frequency

or severity of angina in most patients

An added benefit for patients with ischemic heart

disease is that β-blockade often effectively prevents

ar-rhythmias (see Chapter 64) It may decrease or eliminate

premature ventricular contractions (PVCs), and the

ven-tricular rate in patients with atrial fibrillation also may

be decreased Furthermore, when PVCs are frequent, the

number of hemodynamically effective ventricular

contrac-tions is diminished, which decreases coronary as well as

peripheral perfusion In patients who are in atrial

fibril-lation, decreasing the ventricular response improves left

ventricular dynamics by decreasing heart rate, increasing

diastolic filling period, and decreasing myocardial oxygen

consumption

The dosage of aβ-blocker can be rapidly increased over

hours or days until the desired effect is obtained The heart

rate is a useful guide to treatment, with sinus rhythm at aresting rate of 50 to 60 bpm a reasonable goal However,the ideal dosage is one that not only results in mild sinusbradycardia at rest but also blocks an increase in heartrate with exercise The dosage necessary to produce thiseffect and that necessary to relieve angina pectoris mayvary considerably

Althoughβ-blockers are an important part of the

man-agement of CHF (see Chapter 66), the acute effect ofthese drugs is to decrease myocardial contractility, andthey should not be used in patients with decompensatedCHF

β-Blockers are contraindicated in a patient with

second- or third-degree block (see Chapter 64) becauselife-threatening bradycardia can be precipitated in suchpatients

The nonselectiveβ-blockers (propranolol, nadolol,

pin-dolol, timolol, carvedilol) are relatively contraindicated

in patients with intrinsic asthma A history of allergicasthma or bronchospasm during pulmonary infectionsshould be sought in all patients for whom β-blockers

are being considered Patients with chronic obstructivelung disease may develop increased bronchospasm from

β-blockers even if they have no history of allergic or

in-trinsic asthma In such patients, a selectiveβ-blocker with

minimalβ2-blocking effects should be used Metoprololand atenolol both are cardioselective and often can be usedsafely in such patients and in patients with peripheral arte-rial disease, particularly Raynaud disease, in whom non-selectiveβ-blockers may exacerbate symptoms However,

even these agents have β2-blocking effects at moderateand high dosages and should be used cautiously in thesesituations

Although impotence occurs in ≤1% of the ble population, it is a major reason for discontinuingthe drug in young and middle-age men This side effectcan sometimes be overcome by prescribing a β-blocker

suscepti-with poor lipid solubility and therefore less penetration ofthe nervous system (e.g., atenolol instead of propranolol)

Atenolol may be less likely to cause depression and fusion or to alter sleep patterns, occasional reported sideeffects of otherβ-blockers.

con-Calcium Channel Blockers

Calcium channel blockers reduce the influx of calcium intothe slow channels of the myocardium and smooth mus-cle (see Chapter 64) and thereby cause several importanthemodynamic effects, including dilation of coronary ar-teries, prevention of coronary vasospasm, and production

of systemic vasodilation, thus effectively reducing preloadand afterload They have been shown to be effective in thetreatment of both stable and unstable angina, and theyare effective antihypertensive agents A number of cal-cium channel blockers are currently available (Table 62.2)

Although many are effective in the treatment of

hyperten-sion (see Chapter 67), only a few are currently approved

for use in patients with angina: nifedipine, nicardipine,

amlodipine, verapamil, and diltiazem A meta-analysis

suggested that use of short-acting calcium blockers,

when used to treat hypertension, is associated with

ad-verse outcomes (69) More recently, another meta-analysis

compared patients treated with diuretics, β-blockers,

angiotensin-converting enzyme (ACE) inhibitors, or

cloni-dine to those treated with intermediate-acting or

long-acting calcium channel blockers and showed that those

treated with calcium antagonists had a higher risk for MI,

CHF, and major cardiovascular events (70) Although

cal-cium channel blockers are effective in treating patients

with angina, it seems reasonable to consider other

ther-apies first and to use calcium antagonists only if other

an-tianginal medications do not relieve symptoms

Nifedipine is a potent coronary and systemic

vasodila-tor and may be used for angina and for treatment of

hyper-tension The common side effects of nifedipine are

dizzi-ness, flushing, headache, nausea, diarrhea, and peripheral

edema The major adverse effect is significant

hypoten-sion, which, in association with a reflex tachycardia, can

actually intensify myocardial ischemia in a few patients

All side effects usually can be controlled by reducing the

dosage of the drug Nifedipine and other calcium

chan-nel blockers should be used cautiously in patients taking

digoxin because digoxin excretion may be inhibited and

digitalis toxicity may be induced At higher dosages in

pa-tients with reduced left ventricular function, negative

in-otropy may be observed with nifedipine

Nicardipine is structurally similar to nifedipine but is

less likely to cause hypotension or left ventricular

dysfunc-tion It may be useful in patients with angina and

border-line blood pressure

Amlodipine has been shown to be an effective

antiangi-nal and antihypertensive agent Its safety in patients with

significant left ventricular dysfunction makes it a

particu-larly attractive anti-ischemic agent in patients with angina

and reduced left ventricular ejection fraction (71) Added

advantages are its once-daily dosing and the infrequent

incidence of side effects It has few, if any effects, on the

atrioventricular (AV) node Reflex tachycardia after

admin-istration is unusual

Verapamil is often prescribed for the treatment of

hyper-tension or arrhythmia but is also an effective antianginal

agent However, it has a more potent negative inotropic

ef-fect than other calcium channel blockers and significantly

retards AV conduction Therefore, it should not be used

in patients with compromised left ventricular function or

in those with sinus bradycardia, sick sinus syndrome, or

AV block (see Chapter 64) In these situations, amlodipine

or nicardipine are safer choices Verapamil may be

par-ticularly beneficial in the patient with a supraventricular

arrhythmia who also has angina

Diltiazem also significantly retards AV conduction, but it

has less of a negative inotropic effect than does verapamiland, in contrast to nifedipine, is unlikely to cause hypoten-sion or other side effects (e.g., flushing, headache, edema)

It is available as a twice-daily or once-daily preparation

Caution must be exercised when treating older patientswith calcium blockers, especially if they are used in con-junction with a β-blocker or other agents that slow AV

conduction (e.g., digitalis) or if used in patients with existing conduction system disease In such patients, sig-nificant heart block and bradycardia can be precipitatedbut usually resolve after stopping administration of the cal-cium blocker or after the administration of calcium intra-venously This effect, most commonly seen with verapamiland diltiazem, may occur with other calcium blockers butnot with amlodipine

pre-Anticoagulants and Antiplatelet Drugs

Aspirin (81–325 mg) remains the least expensive agentfor reducing platelet aggregation The AHA/ACC guide-lines on the management of chronic stable angina recom-mend daily aspirin, in the absence of contraindications,for all patients with the condition (72) If aspirin is ab-solutely contraindicated, clopidogrel (75 mg), an inhibitor

of adenosine 5-diphosphate (ADP)-induced platelet gation, may be used It is generally preferable to ticlopi-dine, a drug with a similar mechanism of action, becauseticlopidine has a slower onset of action and is more of-ten associated with the development of neutropenia and,rarely, thrombotic thrombocytopenic purpura Clopido-grel is commonly used for at least several months in pa-tients following PCI and has been shown to decrease therate of restenosis (73) Studies in patients with acute coro-nary syndromes have demonstrated improved clinical out-comes at 1 year in those taking clopidogrel (74) As withall antiplatelet drugs, clopidogrel is associated with an in-creased risk for bleeding Other than the increased bleed-ing risk, the most common side effect is a skin rash

aggre-Despite its significant cost compared to aspirin, severalstudies have demonstrated the cost effectiveness of clopi-dogrel in acute coronary syndromes and for percutaneousinterventions (75)

Angiotensin-Converting Enzyme Inhibitors

ACE inhibitors reduce morbidity and mortality in patientswith CHF (see Chapter 66) and should be part of the treat-ment regimen of patients with CHF and angina The HOPEstudy demonstrated that the ACE inhibitor ramipril re-duced mortality and the risk of MI and stroke in patientswith vascular disease or diabetes plus one other cardio-vascular risk factor who were not known to have left ven-tricular dysfunction or CHF (57) However, a later studyexamined the use of ACE inhibitors for patients having

stable CAD with preserved left ventricular function and

ob-served no cardiovascular benefit during almost 5 years of

followup (76) Although the routine use of ACE inhibitors

cannot be recommended for all patients with CAD and

pre-served left ventricular function, it certainly should be

con-sidered, particularly in patients with coexistent

hyperten-sion or diabetes mellitus

Initiating and Adjusting Long-Acting

Drugs for Angina

The choice of an antianginal regimen should be made after

evaluation of the patient’s age, angina frequency, lifestyle,

and possible mechanism of angina In addition, the

pa-tient’s financial resources should be considered because

many drugs, although effective, are expensive and are not

available in generic form In patients with stable angina,

prepara-tion may be used if β-blockers are contraindicated or if

β-blockers alone fail to prevent angina (Table 62.2) A

cal-cium channel blocker may be prescribed to patients who

have variable chest pain, in whom coronary artery spasm

(see Variant Angina) may be playing a role, and to those

intolerant ofβ-blockers If the patient does not improve,

the dosage may be increased weekly until a response is

achieved If the type of treatment selected initially fails to

help at a maximally tolerated dosage, another agent can

be added or substituted Because nitrates andβ-blockers

decrease myocardial oxygen demand by different

mech-anisms, concomitant use of the two types of therapy is

reasonable If it is necessary to stopβ-blocker therapy, it

should be tapered over several days to avoid the risk of

precipitating angina, which may occur when aβ-blocker

is abruptly discontinued

Patients who do not improve after maximal medical

management for angina pectoris often are considered

for coronary arteriography and possible revascularization

Therefore, it is important to ensure that maximally

toler-ated doses of medications are used before medical therapy

is considered unsuccessful In general, maximal medical

therapy for angina consists of a β-blocker, a long-acting

nitrate, and a calcium channel blocker in doses that either

achieve the desired effect or cannot be increased because

of the side effects In addition, all patients with angina

should take daily aspirin (or clopidogrel if aspirin is

abso-lutely contraindicated)

Percutaneous Coronary Intervention

PCI offers an important option for the treatment of CAD

that cannot be controlled by medical therapy PCI has the

ability to restore nearly normal coronary flow in diseased

native coronary arteries, without the cost and morbidity

of bypass surgery Various strategies are available, but all

generally involve mechanical treatment of the coronary

le-sion with balloon angioplasty alone, stenting with ical devices, varying combinations of atherectomy, plusstenting or laser-guided vessel recanalization Patients areidentified as candidates for PCI based on their coronaryanatomy determined by coronary angiography PCI ini-tially was used to treat patients with only single-vessel,proximal, discrete, noncalcific coronary lesions However,

mechan-in skilled hands and through improvements mechan-in the stentsthemselves, PCI has evolved as an appropriate treatmentfor multivessel CAD Although there are no absolute con-traindications to the procedure, patients with arterial dis-section or eccentric calcific and long stenotic lesions arepoor candidates and have a higher risk for complicationsand restenosis These patients are best treated with surgery

if medical therapy alone is ineffective

Patients who are appropriate candidates for PCI dergo the procedure either immediately after cardiaccatheterization or at a later time, depending on the clini-cal situation and the needs of the particular patient Thepatient’s experience with PCI is similar to that for cardiaccatheterization and coronary arteriography (described ear-lier in this chapter) The major complications of PCI areabrupt vessel closure and restenosis The usual restenosisrate after conventional balloon angioplasty is 30%, but therate can be as high as 40% to 50% Restenosis most com-monly occurs within the first 6 months and can be success-fully treated by a second angioplasty A lack of symptomsafter 6 to 8 months usually indicates a favorable long-term

un-prognosis The use of intracoronary stents has significantly

reduced the rates of both abrupt vessel closure and sis (77,78) Intracoronary stents typically are stainless steelcylindrical structures and often are self-expanding Theyare available in a variety of lengths and sizes, and severaltypes allow treatment of the target lesion with pharmaco-logic agents to retard restenosis Evidence demonstratesthat such drug-eluting stents have a lower rate of occlu-sion versus bare-metal stents (79) Stents are delivered anddeployed on balloon catheters using guiding catheters andguidewires

resteno-Barring complications, the patient’s experience duringPCI (with or without intracoronary stent placement) andthe time required for the procedure are the same as forcoronary angiography (see previous discussion) The onlyexception is that many patients experience chest pain dur-ing inflation of the balloon in the coronary artery The in-cidence of major side effects (including coronary arterydissection, MI, and sudden death) is related to the skilland experience of the operator and can be as low as 1%

to 4% Overall, the procedure is successful 80% to 90%

of the time Patients usually can be discharged the dayafter the procedure and often can return to work 1 weeklater After successful angioplasty and stent placement, pa-tients are prescribed aspirin indefinitely and clopidogrel

or ticlopidine for at least 4 to 6 weeks and often for atleast several months, depending on the type of procedure

and the patient’s clinical condition Patients who cannot

take clopidogrel and who require ticlopidine can develop

leukopenia, so blood counts should be checked at 2-week

intervals

Surgical Management

Coronary artery bypass graft (CABG) surgery is one of

the most common surgical procedures performed in the

United States country today However, advances in PCI

technology and expertise have reduced the number of

tients referred for CABG It is generally accepted that

pa-tients with incapacitating angina pectoris who have good

left ventricular function and who have not responded to

maximal medical therapy should be considered candidates

for coronary arteriography and subsequent surgery Early

studies demonstrated that CABG surgery prolongs survival

compared with medical therapy in patients with stable

angina who have ≥50% stenosis of the left main

coro-nary artery (80) or who have triple-vessel CAD and a left

ventricular ejection fraction between 35% and 50% (81)

Long-term followup indicates that, in patients with

nor-mal left ventricular function, surgery does not result in a

survival benefit compared to medical therapy, even in

pa-tients with left main or triple-vessel CAD (82) In diabetics,

CABG yields better long-term outcomes compared to

(usu-ally multiple) PCIs (83)

CABG surgery usually involves the use of saphenousvein bypass grafts and implantation of an internal mam-

mary artery into the native coronary artery circulation or

the placement of radial artery conduits as bypass grafts

Some surgeons also use radial or gastric arterial conduits

in patients undergoing repeat surgical procedures The

technique used is often based on the surgeon’s preference

and experience

CABG usually is performed through a median otomy using cardiopulmonary bypass and cardioplegic

stern-arrest Minimally invasive techniques use a limited

tho-racotomy incision and are associated with less

postopera-tive pain, a shorter stay in the intensive care unit, earlier

discharge from the hospital, and a more rapid

recupera-tion Alternatives to standard bypass procedures can be

performed on the beating heart using “off pump bypass

surgery” in an effort to avoid some of the embolic

compli-cations of traditional cardiopulmonary bypass surgeries

Some centers have little, if any, experience with these

techniques, and they are not available in every

commu-nity These operations may be technically more

challeng-ing and, understandably, there is a shortage of long-term

outcome data compared with conventional bypass

tech-niques

CABG surgery results in complete (or nearly complete)relief of angina pectoris initially in approximately 60% of

properly selected patients, and another 20% have a

signif-icant decrease in their angina (84) There is a

demonstra-ble increase in exercise tolerance after surgery in mately 60% to 80% of such patients

approxi-Patients with good left ventricular function have a 1%

to 2% mortality rate from surgery, and<4% of patients

develop evidence of MI during the perioperative period

Perioperative MI is more likely to occur in older patientsand in patients with severe disease distal to a proximal ob-struction Another major complication of bypass surgery

is stroke, which may be caused by cerebral sion, arterial embolization, or both The risk of periop-erative stroke varies from<1% to approximately 6%, de-

hypoperfu-pending on the patient’s risk factors (85,86) The risk

is highest in patients older than 70 years and in thosewith pre-existing cerebrovascular disease or a previousstroke (87–89) Patients with significant atherosclerosis ofthe proximal or ascending aorta or of the carotid or in-tracranial cerebral arteries are at increased risk Neuropsy-chiatric complications of CABG include problems withmemory and other cognitive functions The prevalence ofthese disturbances varies from approximately 10% to 80%

soon after surgery, depending on the manner in whichneurocognitive function is assessed (90,91) In general,neuropsychiatric disturbances resolve slowly over severalmonths

Historically, up to 30% of patients developed recurrentangina within 5 years after bypass surgery The diagnosis

of recurrent angina should be confirmed by exercise stresstesting The initial treatment is the same as it is for pa-tients who have not undergone bypass surgery:β-blockers,

nitrates, or calcium channel blockers Patients who prove

to be unresponsive to medical treatment should undergocoronary arteriography in an effort to delineate new le-sions that could be amenable to PCI or repeat CABG In anattempt to prevent formation of such lesions, it is critical

to administer aspirin to patients after bypass surgery (seeChapter 57) In all patients undergoing CABG, it is imper-ative to implement strict risk factor modification, specifi-cally smoking cessation and treatment of hyperlipidemia

to achieve an optimal LDL cholesterol level

The postpericardiotomy syndrome may develop after

by-pass surgery, usually within 2 to 4 weeks (but sometimes

as early as a few days or as late as 6 months after the eration) The syndrome is characterized by fever, fatigue,pleuritic chest pain, and often pleural and pericardial effu-sions Laboratory examination shows leukocytosis and anelevated erythrocyte sedimentation rate Large effusionsmay require drainage, but most patients respond to di-uretics and a nonsteroidal anti-inflammatory drug (e.g.,indomethacin 25–50 mg three times per day for 1–2 weeks)

op-Patients who are refractory to such treatment usually spond to prednisone, initially 60 mg/day for 2 to 3 days,with tapering of the dosage over 7 to 10 days Constrictivepericarditis is a late rare complication of the postpericar-diotomy syndrome; when it occurs, pericardial stripping

re-is often necessary

Atrial fibrillation is common after CABG surgery,

oc-curring in 30% to 40% of patients (and in >50% in

those older than 75 years) The arrhythmia often resolves

spontaneously without specific therapy, but it may persist

and require anticoagulation, cardioversion, or both The

incidence of postoperative atrial fibrillation may be

re-duced by prophylactic use of β-blockers or amiodarone

(92,93)

Dysesthesia, swelling, and itching are common in the

leg from which the vein was harvested and can persist for

several months The swelling usually responds to the use

of support hose or elevation of the legs periodically during

the day If the itching is severe and there is no evidence of

local infection, topical corticosteroid ointments often are

effective

CABG surgery has been shown to prolong life in

sev-eral patient subsets (see earlier discussion) In addition,

60% of patients who either were working just before

by-pass surgery or had discontinued work because of cardiac

symptoms return to work after surgery Early ambulation

is advisable, and the role of cardiac rehabilitation, as early

as 6 to 8 weeks postoperatively, cannot be overemphasized

(see detailed discussion in Chapter 63)

Patient Experience Most patients are discharged within

5 to 7 days after CABG if the operation and

postop-erative recuperation were uncomplicated Usually, the

patient is transferred from an intensive care unit to

an intermediate care unit within 24 hours; early and

aggressive mobilization is standard After discharge, a

structured, self-directed exercise program is commonly

used It is recommended that patients not operate a

mo-tor vehicle for 6 to 8 weeks after surgery

Other Therapies

Conventional medical therapy and improved

revascular-ization techniques result in improvement of angina in most

patients, but some patients do not improve despite these

therapies Others cannot be treated with certain classes

of medications or cannot tolerate maximal doses because

of the side effects In addition, some patients, particularly

those with diffuse and/or distal coronary disease, are not

appropriate candidates for either PCI or CABG If

conven-tional treatments cannot be used or fail to relieve

symp-toms, alternative therapies should be considered

Enhanced external counterpulsation (EECP) may be

considered in patients with class III or IV angina who

remain symptomatic despite maximally tolerated medical

therapy and who are not believed to be candidates for

ei-ther PTCA or CABG EECP is available only in practices

with specialized equipment It involves the use of

inflat-able pneumatic cuffs that are wrapped around the patient’s

lower legs and thighs and are sequentially inflated and

de-flated (using compressed air) in relation to the cardiac

cy-cle The use of high pressure (300 mm Hg) allows blood

to be pumped back to the heart during early diastole in

an attempt to increase coronary blood flow and possibly

to improve endothelial function and to promote the velopment of collateral coronary circulation The patientundergoes therapy for 1 hour per day, 5 days per week inthe office setting, usually for a total of 7 weeks EECP ap-pears to decrease the number of anginal episodes and toimprove exercise tolerance (94) EECP is reimbursed bymany insurance companies and by Medicare

de-Chelation therapy is designed to “leach” calcium out

of atherosclerotic plaque by repeated intravenous istration of ethylenediamine tetraacetic acid (EDTA) Al-though many patients with refractory angina undergo, orare interested in, this form of treatment, a review of pub-lished clinical studies of chelation therapy indicates that

admin-it is of no clinical benefadmin-it (95) Because chelation therapymay produce a number of serious adverse effects, it is notrecommended for treatment of patients with angina

Many new techniques are being studied in an attempt

to improve coronary blood flow in patients with tory angina who are not candidates for conventional revas-cularization procedures These include therapeutic angio-genesis (gene therapy to stimulate blood vessel growth in

refrac-the heart), stem cell refrac-therapies, and percutaneous in situ

coronary venous arterialization (percutaneous based coronary bypass) The percutaneous coronary by-pass procedure is a new, experimental approach that uses

catheter-a ccatheter-atheter catheter-and catheter-a self-expcatheter-anding connector to crecatheter-ate catheter-a tula between a critically narrowed coronary artery and anadjacent coronary vein (96) Whether these experimentaltechniques become part of the treatment regimen for pa-tients with angina will depend on the results of ongoingtrials

fis-Prompted by earlier animal and clinical studies thatimplied a potentially infectious contribution to CAD for-mation and progression, various antibiotic therapies havebeen tested in patients with CAD, but the results havebeen disappointing Therefore, use of antibiotic therapyfor treatment of CAD is not recommended

UNSTABLE ANGINA

Unstable angina is a term used to describe pain caused by

cardiac ischemia that is becoming more intense, is ring more frequently (often provoked by diminishing ef-fort, perhaps even at rest), and is relieved less readily by ni-troglycerin The syndrome has also been called “crescendoangina” and “preinfarction angina.” Most patients with un-stable angina have atherosclerotic plaque rupture and con-sequent platelet aggregation, leading to coronary hypoper-

occur-fusion The term acute coronary syndrome (ACS) is now

used to encompass the spectrum of conditions rangingfrom rest angina to non–ST-segment elevation MI Patientswith ACS are at very high risk and should be hospitalized

Although some cases of unstable angina can be

man-aged successfully with aspirin, heparin, β-blockers, and

other antianginal therapy alone (which may include

calcium channel blockers or nitroglycerin, as discussed

previously), others may benefit from more aggressive

an-tiplatelet therapy (e.g., an intravenous glycoprotein

IIb-IIIa inhibitor) and/or from early coronary arteriography

and revascularization Consultation with a cardiologist is

advised when evaluating and treating a patient with ACS

to assess risk and to decide on the optimal therapeutic

strategy Urgent PCI should be considered for patients

having rest angina on heparin, ST-segment changes on

β-blockers, those who do not respond to aspirin, and those

with extensive ECG changes, heart failure, or a high serum

troponin level

VARIANT ANGINA

Coronary artery spasm often plays a major role in

the pathogenesis of variant angina (also referred to as

Prinzmetal angina) This type of angina typically occurs at

rest and is not precipitated by exertion or emotional stress

Most patients with variant angina have a fixed, often

prox-imal obstruction of a major coronary artery Angina in this

group often is associated with spasm of the artery near the

site of obstruction and is marked by ST-segment elevation

at the time of the attack that resolves when the symptoms

abate The variant syndrome in this group of patients

com-monly occurs after months or years of stable typical angina

pectoris or after an MI

Some patients with variant angina (15%) have normalcoronary arteries but have spasm of one of the arteries,

which reduces blood supply to the myocardium, resulting

in ischemic pain These patients usually are younger and

predominantly are women These patients usually have no

history of typical angina or MI and rarely have a history of

a systemic arteritis syndrome The ST-segment elevation

observed during the anginal attack is a manifestation of

coronary artery spasm It occasionally can be confirmed

by arteriography It is important to perform arteriography

in such patients because those with normal coronary

ar-teries obviously are not candidates for CABG or PCI, and

most respond favorably to treatment with calcium channel

blockers, the drugs of choice in such patients If used

with-out calcium channel blockers,β-blockers may potentiate

coronary artery spasm because of unopposedα-adrenergic

vasoconstriction

Angina and MI, probably caused by coronary sospasm, have been reported in otherwise healthy pa-

va-tients who use cocaine Coronary vasospasm usually

oc-curs acutely after ingestion or inhalation of cocaine, but

it can be observed up to 1 hour after use as a result of

vasoactive byproducts of cocaine metabolism Prolonged

episodes of angina in such patients usually respond well

to treatment with calcium channel blockers and nitratesbecause concurrent hypertension is common

ANGINA WITH NORMAL CORONARY ARTERIES

Some individuals have chest pain that is characteristic

of angina but on arteriography are found to have mal coronary arteries Many different possible causes havebeen described, including coronary vasospasm, abnor-mal coronary vasodilator reserve (i.e., disease of smallcoronary vessels), and noncardiac chest pain (especiallyesophageal disease; see Chapter 42) The prognosis of thesepatients is generally favorable, with survival comparable tothat of age- and sex-matched controls (97) However, chestpain often is recurrent and may result in frequent visits tothe emergency department or practitioner’s office

nor-SILENT ISCHEMIA

Many episodes of myocardial ischemia are painless Such

“silent ischemia” may be detected either during cise treadmill testing or by continuous ECG monitor-ing Asymptomatic ischemic ST-segment changes on ECGmonitoring are common in patients with CAD and havebeen correlated with transient abnormalities in myocar-dial perfusion and function

exer-The presence of silent ischemia within the first 3 daysafter an MI has been shown to be associated with a greaterfrequency of recurrent ischemic events Although severalstudies have identified silent ischemia to be a poor prog-nostic factor for patients with CAD (98), whether treatment

of such patients in an attempt to eliminate these episodesimproves prognosis is unknown

CORONARY ARTERY DISEASE

IN WOMEN

Women with CAD have worse outcomes than do men withcomparable disease (21,99) CAD is the leading cause ofdeath in women in the United States The diagnosis ofCAD in women often is harder to establish because symp-toms often are atypical (i.e., different from those in men),and false-positive stress tests are more common Clini-cians must be alert to these potential differences in clin-ical presentations in women, and, if noninvasive testing

is warranted, stress testing with radioisotopic or diographic imaging should be considered The treatment

echocar-of angina in women is the same as that previously scribed Many studies confirm that women who sustain an

de-MI are less likely than men to receive treatments known

to improve survival after MI (e.g., aspirin andβ-blockers)

and are less likely to achieve optimal lipid control These

discrepancies are more evident in minority populations.

Women are less likely to undergo PCI or CABG and, if

re-ferred, generally have more advanced coronary disease at

the time of referral than do men

SUMMARY

Angina remains the cardinal manifestation of coronary

disease The mortality rate of patients with angina depends

on a number of factors, including age, the extent and

sever-ity of CAD, left ventricular function, and medical

comor-bidity The prognosis for older patients, those with

dia-betes mellitus, and women (see Coronary Artery Disease

In Women) is worse than for others with angina

In general, a 2-year mortality rate of approximately

1.3% has been reported (100) In contrast, the crude

first-year mortality rate remains between 10% and 30% for tients with unstable angina (see previous discussion), 8%

pa-to 10% for patients surviving 30 days after MI, and 5%

to 10% for those with stable angina of 2.5 years’ duration(101–104)

Newer diagnostic strategies permit earlier diagnosis

of CAD An improved understanding of the iology of CAD has led to a major emphasis on dis-ease prevention and modification, with the cornerstones

pathophys-of therapy being early identification pathophys-of high-risk tients (particularly those with diabetes mellitus) and ag-gressive risk factor modification Therapy must includestrategies to reduce platelet aggregation Specific ther-apy for patients with angina includesβ-blockers, nitrates,

pa-and calcium blockers This early pa-and aggressive CADmanagement strategy is rewarded by improved clinicaloutcomes

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80 Chaitman BR, Fisher LD, Bourassa MG, et al.

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81 Passamani E, Davis KB, Gillespie MJ, et al A

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93 Guarnieri T, Nolan S, Gottleib SO, et al.

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99 Chandra NC, Ziegelstein RC, Rogers WJ, et al.

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100 Thompson SG, Kienast J, Pyke SDM, et al.

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For annotated General References and resources related to this chapter, visit www.hopkinsbayview.org/PAMreferences.

Survivors of Myocardial Infarction 971

Survivors of Cardiac Arrest Who Have Not Had a

Risk Stratification before Hospital Discharge 974

Rehabilitation and Management after Myocardial

Referral for Cardiology Consultation 984

Management of Unstable Angina after Discharge

Cardiovascular diseases are the major cause of mortality

in the United States, accounting for more than one

mil-lion deaths annually These conditions are responsible forapproximately 40% of all deaths in this country (1) Ap-proximately 35% of these deaths are caused by myocar-dial infarction (MI) Approximately 25% of men and 38%

of women will die within 1 year after having an MI (1) though the overall death rate after MI has decreased, therate of hospitalizations for MI has been relatively stable

Al-The greater number of patients surviving an MI has creased the number of individuals with chronic heart fail-ure (see Chapter 66) and the number of individuals whoshould be considered for cardiac rehabilitation and sec-ondary prevention (2) In both older and younger patients,mortality after MI could be reduced still further with moreconsistent use of interventions known to benefit patientsafter MI, which is the focus of this chapter (3)

in-Patients who survive an acute MI are far more likely tosuffer recurring illness or death from coronary artery dis-ease (CAD) Approximately 7.1 million people alive today

in the United States have a history of heart attack (1) Two

of every three survivors of MIs do not make a completerecovery but still have a good long-term prognosis Thelongitudinal care of the patient who has survived an MIusually is the responsibility of the patient’s primary careprovider

num-Death rates from CAD are highest among AfricanAmerican men and women Whereas the mortality fromcardiovascular disease has declined for men over the lasttwo decades, it has increased for women during this pe-

riod (1) For patients hospitalized with an acute MI, women,

particularly African-American women, have higher casemortality than men both during hospitalization and in the

48 months after discharge (5) The higher mortality inwomen admitted for acute MI has been found in all agegroups irrespective of type of treatment (6)

PROGNOSIS OF PATIENTS DISCHARGED FROM CORONARY CARE UNITS

Survivors of Myocardial Infarction

Mortality

Over the last several decades, the in-hospital mortalityrate for patients with acute MI has decreased to approxi-mately 10% (1,7) Although the in-hospital mortality rate

is higher for patients with Q-wave MI, there is a higher

◗TABLE 63.1 Characteristics Associated with

Increased Mortality after Discharge

of Patients Who Have Had an MI

Left main, proximal left anterior descending, or three-vessel CAD

(arteriography)

Positive limited early post-MI ECG stress test (within 2–3 weeks

after MI)

Ventricular aneurysm developing in acute stage of MI

Characteristics after discharge

ECG abnormalities, especially ischemic ST-segment depression,

1 month after MI

Decreased heart rate variability

Cigarette smoking

Depression

aMortality risk highest when ECG shows ischemia at a distance (i.e.,

transient ischemic ST changes in myocardial location that is different

from the location of the patient’s MI).

bMultifocal premature ventricular contractions (PVCs), runs of two or more

sequential ectopic ventricular beats, or PVCs with R-on-T pattern CAD,

coronary artery disease; CHF, congestive heart failure; ECG,

electrocardiogram; LV, left ventricular; MI, myocardial infarction.

long-term mortality for those with non–Q-wave MI The

overall first-year mortality for hospital survivors of an MI

is approximately 10% to 15% (7,8) Most of the deaths in

the first year occur during the 3 months after discharge,

and they occur chiefly in patients with one or more of the

high-risk characteristics listed in Table 63.1

The classification of acute MI developed by Killip

accord-ing to the presence and severity of CHF on admission to the

hospital is one of the most useful prognostic indices Class

I patients have no evidence of CHF on admission, class

II patients have mild CHF, class III patients present with

pulmonary edema, and class IV patients have cardiogenic

shock Figure 63.1 shows the strikingly different survival

rates among patients in these four classes (9)

Improve-ment in survival rates in each of the Killip classes has been

observed, but the classification remains a valid index of

morbidity and mortality after MI (10,11)

Table 63.1 lists the clinical factors predictive of an

in-creased mortality after hospital discharge Patients with the

greatest risk of mortality during the first year after an MI

have one or more of the following factors: previous MI;

development of early (within 10 days) post-MI angina

on Killip classification (810 patients admitted to the Duke cal Center Coronary Care Unit from 1967 to 1978) (From Rosati

Medi-RA, Harris PJ Acute myocardial infarction In: Fries J, Ehrlich

GE, eds Prognosis: contemporary outcomes of disease Bowie,MD: Charles Press, 1981:275, with permission.)

companied by transient ST-segment or T-wave changes;

ejection fraction≤40%; late hospital phase (predischarge)complex ventricular arrhythmia; left main, proximal leftanterior, left anterior descending, or three-vessel CAD; pos-itive stress test at low workload within a few weeks afterMI; presence of ischemic ST changes on resting electrocar-diogram (ECG) taken≥1 month after MI; and low heartrate variability (amount of heart rate fluctuation aroundthe mean heart rate) (12) The Gruppo Italiano per lo Stu-dio della Sopravvivenza nell’Infarto Miocardico (GISSI)-2study also clearly showed that the significantly increasedrisk of in-hospital mortality with older age persists afterdischarge (13) Left ventricular (LV) aneurysm developingwithin 2 days of acute MI also brings a high risk of deathduring the first year, independent of LV function (14) In ad-dition to these cardiac complications, post-MI depression

is strongly associated with post-MI mortality, even aftercontrolling for other known predictors of survival (15)

In patients who are clinically stable 1 to 6 months ter hospitalization for an acute MI or unstable angina, the

af-presence of ischemic ST-segment depression on the restingECG is the strongest predictor of morbidity and mortalityover the ensuing 3 years Posthospitalization stress testing

is predictive of future coronary events in stable patientsonly when ischemia (≥1 mm ST-segment depression onexercise ECG) or a reversible perfusion defect (on thall-ium exercise test) is present at a low workload (5 metabolicequivalents [METs] or less) or when there is evidence ofexercise-induced LV dysfunction (LV cavity dilation and/orincreased thallium uptake by the lung during exercise)(16) Each of these high-risk subsets has made up<3% of

study populations

Morbidity

Postinfarction angina occurs during the year after an MI

in many patients, and cardiac stress testing can help

anticipate who will develop this symptom Stress

test-ing, during the hospitalization, after discharge, or both,

is recommended for many patients who have sustained

an MI (17,18) The American College of Cardiology (ACC)/

American Heart Association (AHA) guidelines list three

class I recommendations for stress testing after MI (19):

(a) before discharge for prognostic assessment, activity

prescription, and evaluation of medical therapy; (b) early

after discharge for prognostic assessment, activity

pre-scription, evaluation of medical therapy, and cardiac

reha-bilitation if the predischarge exercise test was not done;

and (c) late after discharge for prognostic assessment,

activity prescription, evaluation of medical therapy, and

cardiac rehabilitation if the early exercise test was

sub-maximal Despite these recommendations, only one of

every 10 patients hospitalized in this country undergoes a

stress test before hospital discharge (20) The limited

uti-lization of stress testing as part of the care of patients with

acute MI may relate to the perception that the test is not as

useful in patients who have received reperfusion therapy

(i.e., percutaneous coronary intervention or thrombolytic

therapy) as it was in patients in the pre-reperfusion era

However, exercise testing after contemporary reperfusion

therapies for MI still confers important prognostic

infor-mation (21)

Patients who can exercise to 5 to 6 METs or to 70%

to 80% of their age-predicted maximal heart rate without

an abnormal ECG or blood pressure response have a low

1-year mortality (22) Patients with a post-MI

symptom-limited stress test that shows early ischemic ST-segment

changes (≥1 mm exercise-induced ST-segment

depres-sion) or limited work capacity (≤5 METs) have two or more

times the risk of recurrent MI and of death over the ensuing

year (23)

Postinfarction medical complications other than angina

include CHF, life-threatening arrhythmias and sudden

death, intracavity thrombi with stroke and systemic

em-boli, and post-MI syndrome (Dressler syndrome)

The psychologic and social sequelae during the year after

an MI depend on both the severity of the patient’s MI and

the patient’s premorbid psychosocial situation (see later in

this chapter for a more detailed discussion of this topic)

Patients with Unstable Angina

Unstable angina is defined as pain caused by cardiac

is-chemia that is occurring more frequently, is being

pro-voked by less effort, is occurring at rest, or is being

re-lieved less readily by nitroglycerin Chapter 62 describes

other characteristics

Patients discharged from the cardiac care unit with thediagnosis of unstable angina have 1-year morbidity and

mortality rates similar to the rates of patients discharged

with the diagnosis of a completed MI (24) Studies show

that the resting ECG and the response to exercise stress

testing are especially helpful in predicting future events inpatients who are clinically stable after admission for unsta-ble angina (16) The lack of ischemic ST-segment changesduring exercise testing helps to identify patients at lowerrisk

In an individual patient with unstable angina, a moreprecise prognosis often can be given by defining the coro-

nary anatomy by cardiac catheterization and coronary giography In studies of patients with unstable angina, coro-

an-nary angiography has shown CAD in the left main artery

is more common in patients discharged with the sis of unstable angina than in patients discharged with thediagnosis of a completed MI (15% vs 5%, respectively) An-other 10% have diffuse CAD, 10% have normal coronaryarteries and are presumed to have coronary artery spasm

diagno-or small-vessel disease as the cause of their chest pain,and the remaining 65% are equally divided among single-vessel, double-vessel, and triple-vessel CAD (25) This infor-mation is clinically important because of the demonstratedsuperiority of surgical over medical treatment of CAD inthe left main artery Chapter 62 describes the prognosesassociated with each of the patterns and the management

of-hospital cardiac arrest followed for>4 years, the rate

of recurrence of ventricular fibrillation or sudden death

in patients without an acute MI was 31%, compared with5% for out-of-hospital survivors of cardiac arrest who sub-sequently evolved ECG changes of acute MI The mediantime to recurrent circulatory arrest was 20 weeks Morethan 70% of the episodes of ventricular fibrillation wereunexpected or occurred during sleep or during the usualactivities of daily living (26)

Because the survivors of ventricular fibrillation not sociated with an MI have a high risk of sudden death, theyrequire aggressive and highly individualized treatment

as-Advances in electrophysiology, antiarrhythmics, tic implantable defibrillators, and the many innovativesurgical approaches to ventricular dysrhythmias dictateprompt referral of such high-risk patients to a consult-ing cardiologist Survivors of ventricular fibrillation notassociated with an MI often receive an implantable cardi-overter-defibrillator (ICD) The widespread use of ICDs islikely to produce issues for primary care providers whocare for patients with these devices Increased levels ofanxiety and depression have been described in patients af-ter ICD placement (27–29) The experience of a shock may

automa-FIGURE 63.2.Flow diagram of risk

stratifi-cation after myocardial infarction CCU,

coro-nary care unit; CHF, congestive heart

fail-ure; LBBB, left bundle branch block; MI,

myocardial infarction; PTCA, percutaneous

transluminal coronary angioplasty; ST, ST

segment (From Clinical Guidelines Parts I

and II Guidelines for risk stratification

af-ter myocardial infarction [American College

of Physicians] Ann Intern Med 1997;126:561,

with permission.)

contribute to psychological distress and diminished

qual-ity of life (30,31) Chapter 64 discusses this topic in detail

RISK STRATIFICATION BEFORE

HOSPITAL DISCHARGE

The American College of Physicians has published

re-commendations for in-hospital risk stratification of MI

patients, and the recommendations are summarized in

Figs 63.2 and 63.3 (see American College of Physicians,

www.hopkinsbayview.org/PAMreferences) This

three-phase scheme delineates decision-making that is

suppor-ted by outcome data from clinical trials It was published

to guide the care of MI patients before they are

discha-rged from the hospital It draws on a mix of baseline

char-acteristics and findings from continuous reevaluation of

the patient Depending on clinical findings, a patient

may have undergone thrombolysis, revascularization, or

neither in the acute and nonacute phases of risk

strat-ification In the predischarge evaluation, patients at

intermediate or low risk (60%–70% of MI patients) shouldundergo assessment of LV function and noninvasive stresstesting Often, those patients can be discharged after stays

as short as 4 to 5 days The postdischarge prognosis of MIpatients and their appropriate management depend onthe predischarge evaluation, postdischarge reevaluations,and the rehabilitation and medical approaches described

in this chapter

REHABILITATION AND MANAGEMENT AFTER MYOCARDIAL INFARCTION

Most patients discharged after MI can expect to return

to most of their usual activities within a few weeks tomonths For a smaller number of patients, complications

of their MI make this outcome impossible In either ation, an organized plan for care should be followed (Ta-ble 63.2) This plan should include the education of the

situ-FIGURE 63.3.Flow diagram for predischarge risk stratification

after myocardial infarction LVEF, left ventricular ejection

frac-tion (From Clinical Guidelines Parts I and II Guidelines for risk

stratification after myocardial infarction [American College of

Physicians] Ann Intern Med 1997;126:561, with permission.)

patient and the patient’s family Because of shorter hospital

stays, much of the patient education previously included in

inpatient cardiac rehabilitation now is conducted in

out-patient programs

Patient Education

Many hospitals initiate education about MI when the

pa-tient is clinically stable The educational program often is

the responsibility of a cardiac rehabilitation professional

Patient education should cover the nature of coronary

heart disease, cardiac symptoms, cardiac drugs,

modifica-tion of major risk factors (smoking, hypertension,

hyper-lipidemia, obesity, and inactivity), and guidelines for

re-sumption of physical activities (including sexual activity)

and return to work It should be emphasized that MI is a

manifestation of a disease process that has been ongoing

for many years Many patients attribute their MI to what

they were doing at the moment it actually occurred

Pa-tients must understand that the MI very likely would have

occurred regardless of what they were doing that

particu-lar day and that the likelihood of a recurrence may best be

diminished by following prescribed medical therapy and

making lifestyle changes

Individualized information should be provided in a discharge conference at which the patient and the patient’s

Hospital Discharge

Understands disease process (damage to the heart that heals in

a few months, leaves a scar)Understands likely prognosis

Understands importance of controlling major risk factors(smoking, hypercholesterolemia, hypertension) and takesaction to control them

Knows how to recognize key cardiac symptoms (angina,tachycardia, heart failure, hypotension) and understands how

to use sublingual nitroglycerin

Gets answers to questions specific to his or her lifestyleMedical management

Review in-hospital course for prognosis characteristics (seeTable 63.1) and for medications prescribed at dischargeAssess and reinforce above patient education

Check periodically for complications of infarction (see Table 63.5)Check for behavioral/psychiatric complications

Check ECG 2–3 months after discharge

aEssential to include the patient’s partner in all aspects of education.

bSerial exercise stress tests can be used to plan progressive activity (see text).

cIf programs are available in the community.

dSee text for details.

ACE, angiotensin-converting enzyme; ECG, electrocardiogram; MI, myocardial infarction.

family members are encouraged to ask questions The ference should include review of any adverse prognos-tic features identified before discharge (Table 63.1); themedications prescribed at discharge; discussion of specificplans for cardiac rehabilitation, diet, and smoking modi-fication; a chance for ventilation about emotional stress-laden issues; and realistic appraisal of expectations of re-turn to work or usual levels of physical activity Because

con-of the possibility con-of postinfarction angina, it is important

to describe this symptom to patients who have never perienced it and to point out to all patients that postin-farction angina may occur with the increased activity rec-ommended for the coming weeks Every patient should begiven sublingual nitroglycerin, and the correct use of thisdrug should be reviewed

ex-It is important to provide written information and toassess and reinforce patient understanding of the informa-tion after discharge This has perhaps become even moreimportant as length of stay for MI has decreased, result-ing in fewer in-hospital opportunities for education andfor providing postdischarge recommendations The pa-

tient education booklet After a Heart Attack (single copies

available without charge from local chapters of the AHA)

gives a useful general account of the disease process,

prognosis, coronary risk factors, and rehabilitation

pro-cess

Many hospitals have developed group classes for MI

sur-vivors and their families Typically, they are invited to

par-ticipate in a number of weekly meetings during the first or

second month after discharge Sessions usually are led by

a cardiac rehabilitation professional such as a nurse, social

worker, clinical exercise physiologist, or cardiologist, with

the objective of having participants raise questions about

the recovery period to provide mutual support by sharing

experiences with each other Additional resources

avail-able in many communities are patient-run heart clubs and

supervised physical conditioning programs (see Physical

Conditioning After Myocardial Infarction) The American

Association of Cardiovascular and Pulmonary

Rehabilita-tion (401 North Michigan Avenue, Chicago, IL 60611-4267;

312-321-5146; http://www.aacvpr.org) publishes a national

directory of cardiac rehabilitation programs and is an

excellent source of patient materials and professional

pub-lications, such as Guidelines for Cardiac Rehabilitation

and Secondary Prevention Programs (see American

Asso-ciation of Cardiovascular and Pulmonary Rehabilitation,

www.hopkinsbayview.org/PAMreferences) In addition,

several resources for patients are available on the Internet,

including the sites of the Johns Hopkins Bayview

Medi-cal Center and Johns Hopkins Greenspring Station

(http://www.hopkinsbayview.org/cardiology) and of the

AHA (http://www.americanheart.org) Patients also can be

directed to support groups such as The Mended Hearts

(http://www.mendedhearts.org/) Many of these sites

pro-vide links to other sources of patient information, support,

and online newsletters

Postdischarge Appointments

In general, each patient who has had an MI should be

en-couraged to contact his or her primary care provider or

cardiologist at least once during the first week at home

to discuss any questions that arise An office visit should

be scheduled within 2 to 3 weeks Before this visit, it is

important to review the patient’s hospital summary to

de-termine whether adverse prognostic features were present

(Table 63.1) and to identify the medications prescribed at

discharge The visit should be divided between an

assess-ment of the patient’s progress in rehabilitation (physical

activity level, diet and smoking modifications, emotional

status, understanding of the overall plan of care,

expec-tation about return to work) and an assessment of the

patient’s medical status (manifestations of ischemia and

heart failure, blood pressure status, and review of

cur-rent medications) Two or more additional office visits,

similar to the first visit, should be scheduled during the

3 months after an MI, and the patient should be

encour-aged to telephone at any time about new symptoms orquestions

Risk Stratification at 3 to 6 Weeks

Approximately 3 to 6 weeks after MI, a maximal cise stress test should be considered, because this test can

exer-provide helpful therapeutic and prognostic informationregarding the patient’s disease (see discussion of stress test-ing after MI earlier in this chapter) Table 63.3 summa-rizes the criteria and recommendations of the AmericanCollege of Physicians, based on stratification into low-riskand moderate-risk findings in this stress test The stresstest is also used to assess functional capacity, to guidethe return to work, and to provide goals (e.g., targetheart rate, MET level) for an exercise prescription Ap-proximately 3 months after hospital discharge, an ECGshould be obtained and used as the patient’s new baselinetracing

Activity Schedule

Table 63.4 provides a practical summary of symptomrecognition for use by the patient and a schedule of pro-gressive physical activities for the first 2 months after MI

Stress Test Risk Stratification 3 to

6 Weeks After MI

Low-risk patients

of exercise-induced angina pectoris or ST-segmentdepression

Recommendations: Further diagnostic testing is unlikely to

identify patients at an even lower risk and therefore is notindicated The effect, if any, of medical or surgical therapy onthe prognosis of these patients is difficult to demonstratebecause of their very low risk Treatment should emphasize thereduction of risk factors, especially control of hypertension,smoking cessation, diet modification, and exercise training

Moderate-risk patients

Indication for coronary arteriography: In patients at moderate

risk, coronary arteriography is indicated

aMET (metabolic equivalent) is the energy requirement for a certain level of activity One MET is the energy requirement at rest METs for common activities are given in Table 16.1.

MI, myocardial infarction.

Data from American College of Physicians Evaluation of patients after recent acute myocardial infarction (position paper) Ann Intern Med 1989;110:485.

General points

All activities, including sitting and lying down, require energy The amount of energy required to perform a specific activity is expressed asMETs One MET is your resting energy requirement As activities become more strenuous, the amount of energy required (METs) alsoincreases, as does the workload imposed on your heart

The schedule recommended in this program is based on the number of METs needed for various activities Some specific recommendationsare given for each of the first 3 months after your return to home Table 16.1 gives the energy requirements for a wide variety of additionalactivities If the table omits your favorite activities, ask your doctor about them

Warnings: Generally the following activities impose an added strain on your heart and should be avoided, especially during the first 3 months

after a heart attack:

Taking very hot or cold showers or bathsExtended breath-holding while exercising, lifting, or strainingWorking in a bent or stooped position or with arms held above your headDoing work that requires continuous tensing of your muscles

Working or exercising during very hot, cold, humid, or windy weather (in bad weather, plan your regular exercise at a nearby shopping mall)Working or exercising during the first hour after a meal or after consuming alcohol

Walking or exercising on a hill or an inclined surfaceEngaging in any activity that creates emotional stress or worry for you

First month (1–3 METs)From discharge to 1 weekRegular exercise: Walk 5 min at a leisurely pace once per day on a level surface

Some specific advice: This week, primarily get used to being at home Occupy yourself with sit-down activities, such as watchingtelevision, playing cards, sewing, painting, or sketching Avoid lifting objects heavier than 5 lb or doing activities that requirereaching above your head You may go up and down the stairs However, take your time and limit the number of times you need toclimb them Do all of the things you were doing in the hospital Get up and get dressed each day You may be surprised at how tiredand weak you feel This is natural Be sure to take rest periods when you need them, particularly after meals and before you exercise

or climb the stairs

Week 2Regular exercise: Walk 10 min at a leisurely pace twice per day

Some specific advice: Continue all of your previous activities and add others, such as taking rides in the car (however, no driving yet),cooking a meal, washing clothes in a machine (have someone else remove them), making your bed, attending a relaxing movie, goingout to dinner, going shopping with your family (let others lift things from the shelves to the basket and carry the groceries), shootingpool, playing shuffleboard, throwing a softball underhand, and playing a piano or organ

Weeks 3 and 4Regular exercise: Advance gradually to walking 15 min at a leisurely pace twice per day

Some specific advice: Continue your previous activities and others, such as going to religious services, sweeping floors, polishingfurniture, and driving the car (beginning with short drives, avoiding heavy traffic)

Second month (3–5 METs)Regular physical exercise: Progressively increase leisurely walking from 20 min once per day at a slightly faster pace to 30 min once ortwice per day

Some specific advice: Table 16.1 lists the approximate energy requirements of each activity You may gradually increase your activities by

Recognizing heart symptoms

Your heart will give you warning signs if it is not ready for increased activity Here are some guidelines to use:

Pulse: Locate your pulse and count the number of times it beats for 15 s and multiply that number by 4 This is your heart rate for 1 min

Take your pulse before you begin your walk or any new activity and at the end of the activity Contact your health care provider beforeresuming exercise if:

You detect abnormal heart action: pulse becomes irregular, fluttering or jumping in chest or throat, very slow pulse rate, sudden burst

of rapid heartbeatsChest pain: Contact your health care provider before resuming exercise if you experience pain or pressure in the chest, arm, or throatprecipitated by exercise or following exercise Remember to take your nitroglycerin and rest if you do experience pain

Dizziness: Contact your health care provider before resuming exercise if you become dizzy, light-headed, or faint during exercise

Breathing difficulty: Contact your health care provider before resuming exercise if you become short of breath during or after a newexercise, or if you awaken from sleep short of breath

aInformation in Chapter 16, Table 16.1 should be given to patients who receive the instructions in this table.

bPace of these activities may be scaled up or down by results of early post-MI stress test when available.

cThese figures may be markedly modified by results of early stress test or medication.

MI, myocardial infarction.

977

In Chapter 16, Table 16.1 lists a broad array of activities

corresponding to the recommended energy levels during

and after the recuperation period Resumption of

activi-ties with increasing energy requirements should be

grad-ual; in particular, the duration of new activities should be

brief at first, with gradual increase, according to how the

patient feels The schedule given in Table 63.4 can be given

to most patients A more aggressive plan can be tailored

for the patient if an early physical conditioning program,

guided by early stress testing, is available Similarly, stress

test-guided conditioning also can be planned for patients

after the first 1 to 2 weeks of convalescence from an MI

Supervised programs that enroll patients soon after MI

are widely available In addition to the American

Associa-tion of Cardiovascular and Pulmonary RehabilitaAssocia-tion,

affil-iates of the AHA commonly maintain lists of local exercise

programs A comprehensive discussion of exercise

condi-tioning is found below (see Physical Condicondi-tioning After

Myocardial Infarction)

Return to Work

Because many patients will have their first MI during their

active working years, they are commonly concerned about

returning to work After an MI, 10% to 20% of patients are

unable to return to their former occupational and

recre-ational activities Fortunately, the remaining 80% to 90%

of patients are able to do so within 2 to 6 months In fact,

88% of those younger than 65 years are able to return to

their usual work after an MI (1) Patients who do not return

to work within 6 months of MI are unlikely ever to return to

work (32), and this often is caused by psychological rather

than physical factors (see Psychological Problems)

Psy-chological distress is common even in individuals who are

able to return to work after an MI (33)

Many factors determine whether an individual returns

to work after an MI Health care providers should be aware

that only some of these factors are related to the patient’s

cardiac or medical condition An individual’s employment

history and societal factors are important determinants of

the likelihood of returning to work Local unemployment

rates, working conditions, employer attitudes about

ad-justing workloads, employer return-to-work policies, and

medical care benefits are all important determinants (34)

Obviously, the type of work is also an essential

consider-ation Patients whose occupations involve mental stress

and hectic schedules should be advised to return to work

on a part-time basis at first, leaving plenty of time for rest

and relaxation For patients whose work involves

signifi-cant physical exertion, the timing of return to work can be

based on the information given in Tables 16.1 and 63.4 and

guided by the results of exercise stress testing and

mon-itored responses during a supervised rehabilitation

pro-gram It is evident from Table 16.1 that most occupations

require an energy level of≤6 METs Occupational ities classified as heavy work require energy expenditure

activ-of≤7 METs Certain activities may produce an increasedworkload on the heart because of psychological stress(e.g., driving a vehicle in heavy traffic) or because they en-tail significant resistive exercise (e.g., carpentry, plumbing,shoveling, operating pneumatic tools, or carrying objectsheavier than 30 lb)

Patients with MIs complicated by poorly controlledangina, CHF, or arrhythmias should be evaluated in con-junction with a consulting cardiologist (see Medical Com-plications) before a plan for returning to work and otheractivities is formulated Some of these patients may qualify

for permanent medical disability (see Chapter 9) or for job retraining through vocational rehabilitation The funda- mental difference between impairment and disability caused

by CAD was underscored in the report of the 1989 BethesdaConference on Insurability and Employability of the Pa-tient with Ischemic Heart Disease (35) Impairment is amedically defined disorder and is a key component of dis-ability, but it is just one of several factors that determine theoverall ability of a person to perform meaningful work Ad-ditional factors that affect disability include other medicaldisorders, age, sex, education, training, and psychosocialsupport The main points in the report state that most MIpatients can return to work; prognosis can be estimated byclinical examination and noninvasive studies that evaluate

LV function (echocardiogram), myocardial jeopardy lium stress test), and electrical instability (Holter monitor);

(thal-cardiac catheterization is not routinely required; specialassessment may be needed for jobs requiring sudden orsustained high effort or heat exposure (e.g., firefighters) orfor those in whom sudden disability may endanger others(e.g., airline pilots); a trial period of progressively increas-ing part-time work may be necessary for smooth transitionfrom total disability to full-time work; and maximal func-tional capacity should be evaluated as soon as the clinicalstatus is stable, usually 3 to 5 weeks after uncomplicated

MI, 7 weeks after coronary bypass surgery, and 1 weekafter coronary angioplasty in patients who have not had

an MI

Although cardiac rehabilitation, including education,counseling, and behavioral intervention, has many ben-efits, it has not been shown to alter the rates of return

to work This was the conclusion of the 1995 Cardiac habilitation Clinical Guideline No 17 of the Agency for

Re-Health Care Policy and Research (see Wenger et al., www

hopkinsbayview.org/PAMreferences) The expert panel ported that although education and counseling may im-prove a patient’s potential for return to work, many otherfactors play a role in return to work, including willingness

re-of the employer to rehire the patient, the patient’s level re-ofjob satisfaction, economic incentives, and perceived stress

of the job

Sexual Activity

It is safe for patients who are symptom-free during usual

activities of daily living to resume sexual intercourse

within 4 to 6 weeks of MI Available data suggest that the

energy requirement approximates 3 METs during foreplay

and afterplay and 5 METs at climax (36) These are

equiv-alent to the oxygen demands of a brisk walk around the

block or climbing one flight of stairs

The Myocardial Infarction Onset Study provides mation about the risk of sexual activity in patients with

infor-cardiac disease and is of particular benefit to those

coun-seling individuals about sexual activity after an MI (37)

Although this study confirmed that sexual activity can

trig-ger MI, the risk appears to be small and transient

No-tably, the relative risk of triggering an MI in individuals

with a history of angina or previous MI is not greater

than the relative risk in individuals without prior cardiac

disease

The same study indicated that regular exercise appears

to reduce, and possibly to eliminate, the small increased

risk of MI associated with sexual activity Thus, health care

providers who counsel patients after an MI can reassure

them that the risk of triggering an MI during sexual activity

is particularly low for those who exercise regularly When

counseling patients about resumption of sexual activity,

the health cared provider should give specific advice and

encourage questions The pamphlet Sex and Heart Disease,

available from the AHA (http://www.americanheart.org), is

a helpful adjunct to counseling Frequency of sexual

inter-course can be similar to the frequency before the patient’s

MI Sexual foreplay without completion of intercourse can

be recommended to patients who wish to resume sex

cau-tiously In general, sexual activity can be resumed in the

position that was most gratifying before the MI; however,

patients should avoid positions in which they support their

weight on their arms because this requires sustained static

type of work (see Physical Conditioning After Myocardial

Infarction) and may put extra stress on the heart by

in-creasing the blood pressure Sexual activity should be

en-gaged in when both partners are relaxed It is best to

ab-stain from intercourse for 2 or 3 hours after eating a large

meal because eating increases the work of the heart

Inability to return to a previous pattern of sexual ity may be caused by angina (precipitated by intercourse),

activ-new medications, or psychological stress associated with

the recent MI If an otherwise stable patient develops

angina during intercourse, sublingual nitroglycerin can be

taken just before sexual activity

Erectile dysfunction may be particularly common inmen with CAD because the two conditions share common

risk factors For this reason, patients recovering from an

MI may ask their practitioner about the use of

medica-tions to treat erectile dysfunction Three drugs approved

for erectile dysfunction are sildenafil (Viagra), tadalafil

(Cialis), and vardenafil (Levitra) These drugs work by hibiting the action of cyclic guanosine monophosphate(cGMP)-specific phosphodiesterase type 5, thereby block-ing the breakdown of cGMP and allowing it to accumulate

in-in the corpus cavernosum of the penis A study in-in men withsevere coronary stenosis showed that oral sildenafil did notproduce any adverse cardiovascular effects, even in coro-nary flow (38) When patients with CAD were given silde-nafil, vardenafil, or tadalafil before exercise stress testing

to a level of cardiac work at least as great as that enced during sexual intercourse, no significant cardiovas-cular problems were encountered (39–42) Although cau-tion should be used when prescribing sildenafil, tadalafil,and vardenafil to patients with CAD, particularly if the in-dividual is not physically active on a regular basis, thesedrugs appear safe in the absence of low blood pressure oraortic stenosis It must be emphasized, however, that thesedrugs should be used cautiously by men who are takingmedicines that contain organic nitrates of any kind, includ-ing nitroglycerin Because nitrates increase cGMP, the con-comitant use of an organic nitrate and sildenafil, tadalafil,

experi-or vardenafil may result in dramatic, and potentially gerous, reductions in arterial blood pressure Chapter 6discusses the evaluation and management of drug-inducedand psychological sexual dysfunction, both of which mayoccur after MI

A small supply of a minor tranquilizer (see Chapter 22) or ashort-acting hypnotic (see Chapter 7) can be prescribed ifneeded Participation in group classes and group exerciseprograms can help patients adjust to changes in their livesafter MI (see Patient Education)

Another common psychological complication of MI is

an inappropriate fear of physical activity of any kind (i.e., the so-called cardiac cripple or ergophobic) Early partic-

ipation in supervised physical activity, including the ercise stress test, and exercise conditioning have beenshown to enhance the patient’s self-confidence and abil-ity to perform physical tasks (43) Having the partner orfamily member observe an exercise test may help to es-tablish confidence that the patient is not a cardiac crip-ple In some medical centers, partners or family mem-bers are offered an opportunity to walk on the treadmill

ex-This serves to establish a reference point for estimatingability to engage in activity Engaging in a wide range of

activities in the months after an MI is important because

self-confidence is task specific (43,44) Most cardiac

ex-ercise programs (see below) initially emphasize activities

using the legs, such as walking and jogging Although these

activities increase self-confidence in tasks requiring leg

work, they do little for arm self-confidence To increase

arm self-confidence, patients must practice separate arm

exercises (44,45) This is especially important for patients

who plan to return to work that may require upper-body

and arm efforts The use of resistance training in cardiac

rehabilitation now is routinely recommended for

physi-ologic benefits and may help to increase self-confidence

(46,47)

Another common problem is denial of illness persisting

beyond the first few days in the hospital The behavior

asso-ciated with persistent denial may create substantial risks

This is especially true of patients who are extremely

com-petitive and are used to controlling most of the

circum-stances of their lives (48) Typically they are determined

to return to work as soon as possible and will refuse

car-diac rehabilitation on the basis that they can do it better

on their own This behavior arouses anxiety, fear, and

con-cern in the family and may lead to significant interpersonal

conflict An open discussion with patient and partner, with

each acknowledging the other’s concerns, often can lead to

resolution of these conflicts and more appropriate

behav-ior from each of them

At times it is useful to teach patients to use various

forms of feedback to guide their activities Specifically,

pa-tients are taught to use a target heart rate based on an

exercise stress test; to observe themselves and how they

feel, with the basic instruction to rest if fatigue or any

car-diac symptoms occur during exercise; to call their primary

care provider or cardiologist if symptoms persist after

us-ing nitroglycerin; and to view family members as a source

of feedback In most cases, family members’ observation

on how the patient looks is remarkably accurate If a

part-ner says his or her partpart-ner looks tired or does not look

right, he or she probably is correct (and vice versa) By

hav-ing the patient agree to consider these comments as

well-meaning, the patient usually will comply with the partner’s

advice Thereafter, the number of reminding behaviors is

reduced progressively, and the rehabilitation process can

proceed with greater enthusiasm from both partners With

more difficult patients or with partners having pre-existing

interpersonal strife, the consultation of a psychiatrist or

psychologist may be helpful in managing adjustment

prob-lems

Some patients have severe psychological and behavioral

problems after MI that may interfere with their

rehabil-itation The most common problem is persistent

depres-sion, which may have characteristics of a major or

mi-nor depressive illness or may present as an adjustment

disorder characterized by anxiety, depression,

somatiza-tion, or a mixture of these responses (49) Chapters 21,

22, and 24 discuss the diagnosis and management of theseproblems

Approximately 40% of patients have either minor or

major depression soon after an MI (49) Major depression

occurs in 15% to 20% of patients and is associated with

a threefold to fourfold increased cardiovascular ity at 6 months (13) Individuals with major depressionsoon after an MI are likely to remain depressed for atleast several months and possibly longer (49) Thus, thepractitioner who views depression as an expected reac-tion that is likely to improve and not likely to influencerecovery may be missing an opportunity to improve thepatient’s quality of life and health Because major depres-sion typically does not resolve spontaneously, the patientwho leaves the hospital depressed may continue to expe-rience mood disturbance at the very time when participa-tion in risk-reducing behaviors is critical It is importantfor health care providers to recognize that patients withdepression after an MI are less likely to adhere to recom-mended behavior and lifestyle changes intended to reducethe risk of subsequent cardiac events (50)

mortal-These findings highlight the importance of recognizingsymptoms of depression and offering patients appropriatetreatment, which should include a program of cardiac re-habilitation A study in which depressive symptoms werepresent in 20% of patients after a major coronary eventshowed that symptoms resolved in two thirds of these pa-tients after a program of cardiac rehabilitation (51) Un-fortunately, patients with depression are more difficult torecruit and retain in these programs than are individualswithout depression (52,53) When depression is identified

in a patient recovering from an MI, the practitioner shouldencourage the individual to socialize and to increase inter-actions with friends and family Depression resolves morerapidly after an MI when patients have good social support(54) Social support may even buffer the adverse effects ofdepression on prognosis The 1-year cardiac mortality ofdepressed patients with the lowest levels of perceived so-cial support has been observed to be more than five timesthat of depressed patients with the highest levels of per-ceived social support (54)

The selective serotonin reuptake inhibitors (SSRIs) can

be used safely by patients with ischemic heart disease(55–58) In light of these studies and the general absence ofsignificant cardiovascular side effects of the SSRIs, antide-pressants in this class are preferable to tricyclic antidepres-sants (TCAs) in patients with depression after an MI whorequire antidepressant therapy TCAs may increase restingheart rate, produce orthostatic hypotension, and adverselyaffect intracardiac conduction and, possibly, the suscepti-bility to ventricular arrhythmias (59) In a study that com-pared the effects of the SSRI paroxetine to the effects ofthe TCA nortriptyline in patients with ischemic heart dis-ease and major depression, patients treated with the TCAexperienced significantly more adverse cardiac events than

patients treated with paroxetine (56) Although concerns

about the safety of SSRIs in patients with ischemic heart

disease have been allayed, no trial to date has shown that

treatment of depression with either an SSRI (58) or with

cognitive behavior therapy (60) improves survival

Chap-ter 24 discusses in detail the treatment of depression

Medical Therapy

Overview

There is evidence that β-blockers and aspirin reduce

the risk of morbidity and mortality after MI For

cer-tain subgroups of patients, long-term treatment with

angiotensin-converting enzyme (ACE) inhibitors also

im-proves prognosis Despite the widespread use of calcium

channel blockers after MI, there is no evidence that this

class of drug improves prognosis The evidence for

cur-rent recommendations regarding each of these classes of

drugs is thoroughly reviewed by Hennekens et al (see

www.hopkinsbayview.org/PAMreferences)

β-Adrenoreceptor Blockers

β-Blocker therapy is recommended for all patients who

have had an MI Treatment should begin during the

ini-tial hospitalization and should be continued indefinitely

Although the benefits ofβ-blocker therapy are modest in

low-risk patients (i.e., younger patients without a prior MI,

those who have not had an anterior MI, or those who do

not now have complex ventricular ectopy or significant

LV dysfunction) (61), it is generally recommended that

unless a clear contraindication exists, even low-risk

pa-tients should receive β-blockers indefinitely When

initi-ated early in the course of an infarction (within 6 hours),

β-blockers may limit or reduce infarct size Later in the

postinfarct time period, the mechanism for reduction in

mortality is prevention of reinfarction and the

antiarrhyth-mic property ofβ-blockers The overall magnitude of benefit

from the use ofβ-blockers seems to be an approximately

one-third reduction in first-year mortality and about the

same magnitude of reduction in reinfarction during the

first post-MI year These benefits may extend beyond

1 year in some subgroups Contraindications or relative

contraindications to the use ofβ-blockers include asthma,

bradycardia, and insulin-treated diabetes mellitus The

produce attenuation of heart rate and blood pressure

re-sponse to exercise without producing side effects

Chap-ter 67 summarizes the characChap-teristics of the available

β-blocking drugs.

Antiplatelet Therapy

Daily aspirin (75–325 mg) is recommended for all patients

who have had an MI Although the efficacy of other types

of antiplatelet therapy is less well established, clopidogrel

(75 mg/day) may be substituted for aspirin if the patienthas an aspirin allergy or aspirin intolerance Clopidogreloften is recommended in addition to aspirin for patientswho have had an MI, particularly if they have been treatedwith percutaneous coronary intervention (PCI) Clopido-grel is usually given for at least one month, althoughthe optimal duration of clopidogrel therapy is debated

Because many patients have drug-eluting stents placedduring PCI, which often require prolonged use of clopi-dogrel and aspirin, the decision about how long to con-tinue this drug should be made in conjunction with theconsulting cardiologist If the risk is acceptable, warfarinanticoagulation is a reasonable alternative for secondaryprevention of MI in patients unable to take aspirin or forthose with atrial fibrillation, LV thrombus, or extensivewall-motion abnormality Multiple randomized trials ofantiplatelet therapy for secondary prevention of vasculardisease show that prolonged treatment with aspirin has

no effect on nonvascular mortality but reduces vascular

mortality by approximately 15% and nonfatal vascular events (stroke or MI) by approximately 30% in patients

with pre-existing cardiac or cerebral vascular diseases (62)

Post-MI benefits are similar to the benefits in patients after

stroke and transient ischemic attack In absolute terms, the

benefits of antiplatelet therapy accrued to approximately

40 per 1,000 treated patients during the first month oftreatment after an acute MI and to approximately 40 per1,000 patients with a history of MI who were treated for

3 years There is no difference in the degree of tion afforded by aspirin alone at a dosage of 325 mg/dayand that afforded by higher aspirin dosages or other an-tiplatelet agents Aspirin 100 mg/day has been shown toimprove coronary artery bypass graft patency at 4 months(90% of grafts patent vs 68% in the placebo group) (63) and

protec-to decrease significantly the frequency of restenosis afterpercutaneous transluminal coronary angioplasty (64) andthrombolysis (65) Chapter 57 provides additional details

on antiplatelet agents

Angiotensin-Converting Enzyme Inhibitors

All patients who have had an MI and whose LV tion fraction is<40% should receive an ACE inhibitor in

ejec-the absence of specific contraindications (see Hennekens,

et al., MI management guidelines, www.hopkinsbayview

org/PAMreferences) Although the benefit of ACE hibitors may be less in those with normal or mildly reduced

in-LV function, even these patients should be considered fortreatment with ACE inhibitors, in addition to aspirin andbeta blockers The purpose of using these agents after

an MI is to prevent adverse LV remodeling and recurrentischemic events

Long-term use of ACE inhibitors by patients with

chronic ischemic congestive cardiomyopathy is associated

with significant improvement in morbidity and mortality

irrespective of severity and symptoms of failure A large

placebo-controlled study showed that patients with

re-cent MI and LV dysfunction (ejection fraction ≤40%

by radionuclide ventriculography) who were

random-ized to captopril experienced a modest reduction in

car-diovascular and overall mortality, progression to severe

heart failure, and recurrent MI during 3 years of

treat-ment (66) Another large study showed that asymptomatic

patients with LV ejection fraction ≤35% who were

ran-domized to enalapril also experienced a reduction in

mor-tality or progression to heart failure during 3 years of

treat-ment (67) The benefits accrued chiefly to patients with

the lowest ejection fractions In asymptomatic patients

with reduced ejection fractions, ACE inhibitors should be

started at low dosages (e.g., enalapril 2.5 mg/day; captopril

6.25 mg three times daily) with gradual increases (e.g.,

enalapril up to 10 mg/day; captopril up to 25 or 50 mg three

times daily) guided by blood pressure response and renal

function An angiotensin II receptor blocker (ARB) is an

ac-ceptable alternative for patients who have sustained an MI

or who have CHF and who are intolerant of ACE inhibitors

Chapter 67 summarizes the characteristics of ACE

inhi-bitors

Calcium Channel Blockers

Calcium channel blockers are not recommended for

sec-ondary prevention after an MI Because calcium channel

blockers have not been demonstrated to significantly

re-duce mortality in MI survivors, they should be used only in

patients with symptomatic ischemia or hypertension that

is not controlled despite treatment with β-blockers and

ACE inhibitors or ARBs Calcium channel blockers may be

appropriate for patients with good LV function who have

specific contraindications to beta blockers or who tolerate

them poorly

Smoking, Hyperlipidemia,

Hypertension, and Exercise

Smoking

All patients who smoke after an MI should be counseled to

stop Post-MI morbidity and mortality are significantly

re-duced in patients who discontinue smoking Smokers who

have survived an MI usually are motivated to stop

Chap-ter 27 describes practical ways to assist patients who

de-sire to stop smoking, including the prescription of nicotine

substitution products

Lipid-Lowering Diet and Drugs

A diet low in saturated fat and cholesterol (the AHA Step

II diet) should be recommended to all patients after an MI

As noted in the Third Report of the National Cholesterol

Education Program (NCEP) Expert Panel on Detection,Evaluation, and Treatment of High Blood Cholesterol inAdults (Adult Treatment Panel III) (see Expert Panel on De-tection, Evaluation, and Treatment of High Blood Choles-terol in Adults, www.hopkinsbayview.org/PAMreferences),most patients with CAD require drug therapy to reducelow-density-lipoprotein (LDL) cholesterol Lipid-loweringtherapy should be recommended to reduce LDL choles-terol to<100 mg/dL In general, treatment should begin

with a statin, although whether reducing LDL cholesterol

lipid-lowering drugs, produces similar reductions in nary events in patients who have sustained an MI is notclear Whereas a target LDL cholesterol of<100 mg/dL

coro-has been established by the expert panel, later data gest that the optimal LDL level may be even lower, perhaps

sug-in the 75 to 80 mg/dL range (68) For patients who havenormal total and LDL cholesterol levels but whose high-density lipoprotein (HDL) cholesterol is<35 mg/dL, an

exercise program should be recommended in an attempt

to raise HDL cholesterol Drug therapy (e.g., with niacin

or a fibrate) also may be considered for this purpose

As pointed out in the American College of Physicians’

risk stratification report (see American College of cians, www.hopkinsbayview.org/PAMreferences), lipid lev-els measured within 24 to 48 hours of an MI are accurateand can guide post-MI secondary prevention decisions

Physi-Chapter 82 provides detailed information on cholesteroland atherosclerotic disease

Exercise

The role of formal exercise programs in rehabilitation after

MI is described in detail in Physical Conditioning afterMyocardial Infarction

Medical Complications

Table 63.5 lists the principal medical complications of MI,the procedures that may be useful in diagnosing or evalu-ating them, and potential therapies As noted earlier (seeRisk Stratification Before Hospital Discharge), complica-tions identified early are addressed very aggressively be-fore or shortly after discharge In general, use of advancedand costly procedures to evaluate the complications listed

in Table 63.5 should be coordinated with a consulting diologist

car-Postinfarction Angina

As discussed in the prognosis, angina is common in vivors of MI Chapter 62 describes in detail the evaluationand medical management of angina Because protection

sur-of the heart from transient ischemia may be especiallyimportant during recovery from an MI, it is advisable to

◗TABLE 63.5 Medical Complications of MI

Angina or other evidence of

reversible ischemia

ECG stress testing, echocardiographic or radionuclidestress testing, Holter monitor for silent ischemia,coronary arteriography

Standard antianginal therapy (see Chapter62), coronary artery bypass or PTCA forselected patients, physical conditioning

(reduced ejection fraction, segmental dysfunction,rupture, ventricular aneurysm)

?anticoagulants (see Chapter 66 fortreatment of heart failure), surgery in a fewselected patients

study in selected patients

β-Blockers, other antiarrhythmics (see

Chapter 64), surgery or implantabledefibrillator in selected patientsPost-MI syndrome

(Dressler syndrome)

(see text)

surgery in selected patients

aShould be coordinated with and interpreted by consulting cardiologist.

CHF, congestive heart failure; ECG, electrocardiogram; MI, myocardial infarction; PTCA, percutaneous transluminal

coronary angioplasty.

prescribeβ-blockers in most patients (see above) and to

undertake aggressive evaluation and management of

pa-tients who develop angina within the first 3 months after

MI Because of the poor prognosis associated with angina

that occurs very early after an MI, patients with this

prob-lem after hospital discharge should be referred to a

cardi-ologist for consideration of coronary catheterization and

possible coronary revascularization

Postinfarction Symptomatic Congestive

Heart Failure

Postinfarction symptomatic CHF usually develops before

hospital discharge Currently, most patients undergo

mea-surement of LV ejection fraction as part of their

evalua-tion before discharge so that those at increased risk for

developing symptomatic CHF after discharge are known

As noted above, ACE inhibitors delay deterioration in

func-tional capacity and improve survival in patients with CHF

after MI (66) Chapter 66 describes in detail the use of ACE

inhibitors and other agents for CHF Selected patients with

persistent CHF may have segmental or global LV

dysfunc-tion or mitral regurgitadysfunc-tion that may improve after

car-diac surgery and may benefit from referral to a

cardio-logist

Postinfarction Arrhythmias

A substantial proportion of MI survivors have complex

ventricular arrhythmias (see criteria in Table 63.1) on

24-hour ambulatory ECG monitoring after the first week

of hospitalization Controlled trials do not show that

sup-pression of ventricular ectopy with drug therapy improves

mortality Therefore, routine testing to determine whetherventricular arrhythmia is present after an MI is not rec-ommended Studies evaluating the benefits of implantabledefibrillators in specific high-risk populations have shownthat defibrillators prolong life compared with use of an-tiarrhythmic drugs (69,70) Chapter 64 provides a com-prehensive discussion of the management of symptomaticarrhythmias

Postmyocardial Infarction (Dressler) Syndrome

An estimated 3% to 4% of patients develop this tion, usually within 1 to 8 weeks after an MI The syndrome

complica-is characterized by the pain of pericarditcomplica-is (substernalpain relieved by leaning forward and increased with in-spiration), presence of a friction rub, pericardial effusion(which can best be demonstrated by echocardiography),malaise, fever, leukocytosis, and often unilateral or bilat-eral pleural effusion The principal considerations in thedifferential diagnosis are pulmonary embolism and recur-rence or extension of the recent MI

A patient with suspected Dressler syndrome should beconsidered for hospitalization A possible recurrent MIshould be addressed by monitoring, serial ECGs, and mea-surement of cardiac enzymes Evaluation for pulmonaryembolization requires ventilation–perfusion lung scanning

or spiral computed tomography If these tests do not plain the patient’s symptoms, the clinical diagnosis ofDressler syndrome can be made with reasonable assur-ance Echocardiographic evidence of a pericardial effu-sion and an elevated erythrocyte sedimentation rate may

ex-be present

Dressler syndrome usually responds to salicylates or

in-domethacin In patients who do not respond to these drugs,

prednisone provides prompt relief of symptoms However,

use of steroids within 4 weeks of an MI may interfere

with postinfarction healing and may increase the risk of

myocardial rupture; therefore, use of steroids should be

limited to patients who are>4 weeks postinfarction Once

the diagnosis is secure and symptoms are controlled, the

patient can be discharged The anti-inflammatory drug

chosen in the hospital should be administered for a few

weeks after discharge Patients who have recurrent

symp-toms when anti-inflammatory treatment is discontinued

should resume treatment for another month or longer

Arterial Embolization

Arterial embolization occurs after hospitalization in 5% to

10% of MI survivors The emboli seem to originate from

mural thrombi that typically are seen in the LV apex

ad-jacent to akinetic or dyskinetic wall segments

Approxi-mately 30% to 40% of hearts with akinetic or dyskinetic LV

apices show mural thrombi on the echocardiogram Thus,

anticoagulation (see Chapter 57) in patients with mural

thrombi is generally recommended, although the impact

and appropriate duration of anticoagulation have not been

assessed in a prospective trial However, most cardiologists

recommend anticoagulation therapy for 3 to 6 months for

MI survivors who have mural thrombi In patients with

LV systolic dysfunction, warfarin use is associated with

improved survival and reduced morbidity (71) Patients

with atrial fibrillation or a history of embolic events also

should be considered for systemic anticoagulation with

warfarin

Referral for Cardiology Consultation

Selected MI survivors may benefit from coronary

angio-plasty or cardiac surgery by symptom reduction or

im-proved prognosis Patients in the following groups should

be referred promptly to a cardiologist to ensure optimal

medical therapy and to obtain an opinion about the

advis-ability and the timing of invasive procedures:

■ Patients with uncontrolled angina refractory to medical

therapy, with a markedly positive exercise stress test at

low workload or with evidence of LV dysfunction during

exercise (e.g., increased lung uptake of thallium during

exercise)

■ Patients with a ventricular aneurysm

■ Patients with CHF refractory to medical therapy (ACE

inhibitors, digitalis, and diuretics)

■ Patients with structural complications, such as

ventric-ular septal defect (suggested by holosystolic murmur

and thrill at the left sternal border), papillary

mus-cle rupture (suggested by refractory CHF and tolic apical murmur), segmental akinesis, or ventricularaneurysm

holosys-■ Patients with electrical instability (e.g., symptomatic

bradycardia, high-grade atrioventricular blocks, tricular tachycardia, or other arrhythmias)

ven-Home Care for Acute Myocardial Infarction

Although not generally advisable, management at homemay be appropriate for an occasional patient who has astable acute MI and objects to hospitalization, a patientwho is predicted to have a high likelihood of becomingvery disoriented and agitated in a cardiac care unit, or apatient who consults a health care provider several daysafter the onset of symptoms of infarction The scheme forrehabilitation after MI described in this chapter can beadapted to these situations

MANAGEMENT OF UNSTABLE ANGINA AFTER DISCHARGE FROM HOSPITAL

Of patients admitted to a hospital with unstable anginabut without MI, 15% to 30% continue to have pain de-spite vigorous medical management Patients in this grouphave an estimated 1-year mortality rate of 25% Therefore,most are evaluated and referred for coronary angioplasty

or coronary artery bypass surgery These interventions lieve or eliminate symptoms in most cases and improvesurvival for those with left main CAD, three-vessel disease,and two-vessel disease with LV dysfunction

re-To date, the rehabilitation of the medically managedpatient with unstable angina has not been studied as sys-tematically as the rehabilitation of the patient after MI

These patients should receive education similar to thatrecommended for patients after MI regarding the nature

of CAD, the recognition of symptoms, and the control ofrisk factors (see above) Because these patients have notsustained an ischemic injury that typically would require

≥2 months to heal, they often return to their usual ties more rapidly than patients who have had an MI This

activi-is true particularly if the angina activi-is well controlled and astress test shows good effort tolerance (≥9 METs) and min-imal or no changes caused by ischemia or LV dysfunction

Chapter 62 provides additional information regarding themanagement of unstable angina

PHYSICAL CONDITIONING AFTER MYOCARDIAL INFARCTION

Regular exercise, with the goal of attaining the physiologic

adaptation known as the conditioning effect, is safe and

beneficial for almost all patients after MI (46), just as it is

for healthy people and patients with most chronic diseases

The basic principles of exercise training are applicable to

people with and without heart disease Low-intensity

ex-ercise that does not produce a conditioning effect may be

associated with health benefits (see Chapter 16) Cardiac

rehabilitation programs are excellent resources to which

patients can be referred for a supervised exercise program

Contemporary programs also are experienced in

address-ing the individualized exercise and learnaddress-ing needs of each

patient in the rehabilitation setting

Chapter 16 describes in considerable details the diovascular principles related to exercise; Chapter 68 de-

car-scribes important principles regarding the

musculoskele-tal system A brief summary of these principles is provided

here

The body adapts to the kind and amount of physical

demands placed on it The response is specific, with the

greatest changes observed only in those parts of the body

on which demands are placed For exercise to improve

fit-ness, it must overload the muscles or organ system involved

in the exercise To overload is to exercise at a greater

in-tensity than the inin-tensity to which a person is accustomed

Threshold of training is the amount of exercise that must be

done to produce fitness improvements Because the effects

of exercise are specific to the type of activity engaged, an

optimal exercise program should include a variety of

activ-ities designed to improve each of the major components of

fitness: cardiovascular endurance, muscle strength,

mus-cle endurance, and flexibility

The principal hemodynamic adaptation to cular or aerobic exercise in patients with heart disease

cardiovas-takes place in the peripheral vascular and muscular

sys-tems Trained muscles can extract more oxygen from a

given blood flow, and there is a better distribution of the

cardiac output Heart rate and blood pressure are lower at

rest and at a given submaximal workload As a result, the

patient can do more work with less cardiac effort (i.e., less

myocardial oxygen demand) This is extremely beneficial

to cardiac patients who have limited coronary artery blood

supply or poor LV function Angina may occur at the same

threshold, that is, the same double product (heart rate

× systolic blood pressure), but this threshold is reached

at a higher level of body work or MET level METs are

used to rate the energy requirement of different

physi-cal activities, as indicated by the amount of oxygen

ex-tracted during those activities One MET is 3.5 mL O2/kg

body weight per minute and is equivalent to oxygen

re-quirement at rest, 2 METs are twice the resting

require-ments, and so on (METs required for a broad range of

activities are given in Table 16.1) In patients with CAD,

the increase in angina-free exercise capacity with

regu-lar exercise is achieved through some of the same

mech-anisms by which β-blockers and nitrates increase work

capacity Similar to the effect of these drugs, the effect ofexercise training is to reduce heart rate and blood pres-sure at rest and during work In healthy people who per-form aerobic exercise, changes occur in the heart itself,including increased diastolic volume, increased ejectionfraction at rest and to a greater extent during exercise, andenhanced contractility Few studies show any of this cen-tral effect in cardiac patients However, there is evidencethat cardiac patients may achieve central changes if theytrain hard and long enough (72) Improvement in coronarycollateral circulation or myocardial perfusion has beenshown in patients who participate in regular physical ex-ercise and adhere to a low-fat diet (73) However, the in-dependent effect of exercise on CAD progression is not yetknown

In recent years, there is increased recognition of theimportance of resistive training for individuals with andwithout cardiovascular disease The AHA issued a Sci-entific Advisory on “Resistance Exercise in IndividualsWith and Without Cardiovascular Disease” (see www

hopkinsbayview.org/PAMreferences) This advisory, whichhas been endorsed by the American College of SportsMedicine, notes that after careful screening and risk strat-ification, and when appropriately prescribed, resistancetraining is an effective method for improving muscularstrength and endurance, preventing and managing a vari-ety of chronic medical conditions, modifying cardiac riskfactors, and enhancing psychosocial well-being Examples

of resistance training are weight lifting, pushups, situps,isometrics, and use of elastic stretch bands Most activi-ties requiring lifting and straining, such as weight training,have a large static component In such activities there isincreased peripheral vascular resistance, with subsequentincrease in blood pressure but little increase in heart rate

or cardiac output Such exercises do not bring about hancement in oxygen extraction, so they are generally notaerobic Brief periods of moderate resistive exercise ap-pear safe In fact, studies show that cardiac patients whowere required to carry or lift weights or to perform iso-metric exercise after MI had fewer ischemic electrocardio-graphic changes and arrhythmias during resistive exercisethan during aerobic exercises (74) Therefore, gradual in-volvement in resistive training may be beneficial and de-sirable, especially for patients whose jobs or recreationalactivities require static efforts

life and psychosocial outcomes, and promote compliance.

Cardiac Rehabilitation Clinical Guideline No 17 (see

Wenger et al., www.hopkinsbayview.org/PAMreferences)

from the Agency for Health Care Policy and Research

de-fined the scientific basis for recommendations for

multi-factorial cardiac rehabilitation services that include

med-ical evaluation, prescribed exercise, cardiac risk factor

modification, and education, counseling, and behavioral

interventions Provision of these services is physician

di-rected and typically is implemented by a team of health

care professionals that may include nurses, clinical

exer-cise physiologists, and physical therapists Unfortunately,

despite the scientific evidence demonstrating the benefits

of cardiac rehabilitation, the report points out that only

11% to 20% of the several millions of patients with

coro-nary heart disease participate in cardiac rehabilitation

pro-grams

Benefits of Conditioning

Cardiac patients who exercise regularly and have become

conditioned show better control of angina and

enhance-ment of physical working capacity Because of the

periph-eral cardiovascular adaptations described earlier, angina

pectoris occurs at higher exercise levels This increased

anginal threshold allows the patient to do more work, and

at any given level of work the patient feels more

comfort-able because the work represents a lower percentage of

a now higher maximal capacity Similar benefits for

pa-tients with LV dysfunction and chronic heart failure also

have been demonstrated (75,76) Rating of perceived

exer-tion (RPE) is a scale that measures how hard any given

level of work feels (Table 63.6) The RPE is administered

6

7 Very, very light8

9 Very light10

11 Fairly light12

13 Somewhat hard14

15 Hard16

17 Very hard18

19 Very, very hard20

From Borg G Subjective effort in relation to physical performance and

working capacity In: Pick HL, ed Psychology: from research to practice.

New York: Plenum, 1978:333, with permission.

during exercise testing The patient is asked to rate thework at each stage of the test After conditioning, the RPE

is lower at any given stage and is associated with a lowerheart rate and blood pressure (77) RPE is also a usefulway to prescribe exercise This approach focuses on howthe patient actually feels and correlates closely with thetarget heart rate and desired MET level For most cardiacpatients, a prescription at 13 to 14 (“somewhat hard” to

“hard”) on the RPE scale is both safe and effective for diovascular conditioning

car-The effect of exercise training on longevity in patients ter MI has been established Meta-analysis of the combined

af-results of 10 randomized clinical trials demonstrates a 25%

reduction in cardiovascular mortality, although not in fatal reinfarction, for patients in rehabilitation programs(78) Benefits of exercise conditioning on the psychometricprofile are not firmly established (78)

non-Risks of Conditioning

With proper selection, supervision, monitoring, and cautions, physical conditioning for cardiac patients isremarkably safe Cumulative data from >1.5 million

pre-person-hours of exercise, done predominantly 3 monthsafter MI, show that the risks of ventricular fibrillation,acute MI, and death are one in 10,000 to one in 32,000, one

in 253,000, and one in 100,000 to one in 212,000 hours of exercise, respectively (79) There is no compa-rable large series on exercise conditioning earlier than

person-3 months after MI In the authors’ experience with cise programs beginning an average of 7 to 10 days afterhospital discharge, there have been few serious compli-cations during exercise over a 30-year period These pa-tients exercise under supervision three times per week,for up to 12 weeks, at a conditioning heart rate of ap-proximately 80% of what they safely achieved on a post-

exer-MI stress test, performed before starting the exerciseprogram

Cardiovascular Medications and Conditioning

Many patients who enroll in exercise programs are ing multiple medications Many of these medications alterthe cardiovascular response to exercise Patients enrolled

tak-in a conditiontak-ing program should ideally undergo stresstesting (see below) while taking their regular medications,and the effects of their drugs should be considered in in-terpreting test results For example,β-blockers attenuate

the heart rate response to exercise Thus, heart rate is notuseful as an end point for stress testing or as a parameterfor the patient to monitor during exercise conditioning In

a patient taking aβ-blocker, symptoms, ECG changes,

fa-tigue, and RPE (Table 63.6) are used as end points during