Acute Coronary Syndromes: Unstable Angina Pectoris and Acute Myocardial Infarction

More and better prospectively collected data are needed to understand acute coronary
syndromes in the elderly (see Chapters 17, 18, 19, and 20). Data from randomized,
controlled trials usually involve relatively small numbers of the elderly, and those
participating tend to represent healthy older persons. Diagnostic problems arise, as
alluded to in the earlier section, because clinical presentations are atypical, the ECG is
much less likely to show an elevated ST segment in AMI (and a variety of ECG changes
related to past coronary and other cardiovascular disease may be present), and only
minimal enzyme elevations may occur. Hence, differentiating unstable angina pectoris
(UAP) from AMI is difficult. Management is often similar in patients who present this
diagnostic dilemma. Definite AMI carries a higher mortality and greater risk of
complications, but with UAP, advanced age is an independent risk factor for complication
and death. Elderly patients who present with acute coronary syndromes are more likely to
be female and to have a history of hypertension, diabetes, previous MI, angina pectoris,
or CHF than their younger counterparts. Delay in presenting to the hospital is a feature of
acute coronary syndromes in the elderly. Forty percent of patients older than age 75 may
die before arrival at the hospital, in part due to a delayed response to symptoms and
psychosocial factors (181185).
Clinical Presentation
Clinical presentation in AMI can be classified as typical, painless or atypical, or silent.
Silent MI (absolutely no symptoms and detection exclusively by serial ECG changes or
unmistakable evidence of myocardial scar or both) occurs in 40% of elderly patients
(186189). Complaints other than pain, particularly dyspnea (30% to 50% of patients) but
also syncope, acute confusion, vague constitutional symptoms, or signs and symptoms of
stroke or peripheral embolism, are as common as typical ischemic discomfort,
particularly in the over-80 age group (190,191).
Dyspnea in the elderly MI patient may be more common due partly to age-related
diastolic dysfunction, age-related lung changes, or associated independent pulmonary
disease (145,192). Neurologic symptoms, syncope, stroke, and acute confusion are
related to an acute reduction in cardiac output and age-related central nervous system
(CNS) changes or independent cerebrovascular disease. Concurrent hypoxemia, changes
in glucose tolerance, or delayed medication clearance may be contributors. Delirium may
accompany any illness in the elderly and may be the presenting complaint in the very
elderly with AMI.
When pain is the principal presenting complaint, it may be atypical in character and
location, and sometimes appears as an upper abdomen pain rather than a crushing or
squeezing substernal sensation. Elderly patients have changes in opiate receptor affinity
and an altered pain threshold, but the explanation for frequent atypical and confusing pain
syndromes is not known.
Diagnosis and Clinical Course

The elderly have a higher rate of nonQ-wave MI (184,192) and much higher mortality.
Complications are more frequent among the elderly despite their having lower total
creatine kinase levels. This paradox cannot be explained on the basis of past disease,
because patients with their first MI (with or without ST-segment elevation) also show
these phenomena (193,194). Their occurrence may be related to a different
pathophysiology with less frequent total coronary artery obstruction.
Age is by far the single strongest predictor of 30-day mortality in many different models
and for study sample sizes varying from a few hundred to 41,000 patients (146,193
195,242) (eFig. 33.0.6). This extraordinarily high mortality with increasing age must be
related in large part to changes of aging per se (which reduce the elderly patients
physiologic reserve and ability to respond to the stress of AMI); these include diastolic
dysfunction, altered baroreceptor and beta-receptor responses (diminishing heart rate and
increasing blood pressure), and reduced lung compliance and renal function (which make
these organs prone to complications due to reduced cardiac output and pressure changes).
Electrocardiographically determined infarct location does not predict risk in the elderly
as well as in the young. Inferior infarcts carry risks similar to anterior ones, which is
probably related to a high incidence of right ventricular infarction or age-related changes
or both.
A single-institution study of 198 patients with inferior MI who were older than 75 years
(195) found an overall mortality of 23%. In patients who had right ventricular MI (41%
of the sample), mortality was 47%. A graded mortality from 5% to 30% was seen in
patients without right ventricular MI related to the degree of reduction in left ventricular
ejection fraction. No relationship was seen between left ventricular ejection fraction and
mortality in patients with right ventricular MI. Death was primarily related to cardiogenic
shock. A higher incidence of complete atrioventricular block (33% vs. 9%) and
interventricular septal rupture (9% vs. 0%) was present in the patients with right
ventricular MI. This was the first MI for all patients studied.
The nonspecific ECG changes that are often present with AMI and bundle branch block
deserve special comment. Right or left bundle branch block occurs in 5% to 10% of AMI
cases. In an extraordinary sample of 29,585 patients with AMI and left bundle branch
block in the Second National Registry of Myocardial Infarction, the mean age was 76.4
years and mortality was 22% (145). Only 8.4% of this sample had any form of
reperfusion therapy. This low use of a powerfully effective therapy in such a high-risk
group of AMI patients must be related to the lack of typical symptoms (only 50% of this
sample had chest pain) and nonspecific ECG (left bundle branch block) abnormalities.
The risk of cardiac rupture greatly increases in the elderly, reflecting age-related
fundamental changes in cardiac anatomy (193). Thrombolytic therapy increases the risk
of cardiac rupture (197), adding to the age-related hazard of rupture.
Management and Reperfusion Therapy

Management decisions during the first several hours have the greatest effect on survival
in the elderly (147,196199), as is true for all age groups. The pivotal decision is whether
to proceed to reperfusion therapy (thrombolytic therapy or percutaneous catheter-based
intervention). The overall care available and the expertise and experience of the hospital
and its staff may be the most important factors determining outcome for the majority of
elderly AMI patients (148,149). Therapeutic interventions carry added risks in the elderly,
so the potential benefits must be carefully considered and judged to be clearly present. In
younger patients, the prevailing philosophy in the United States is to undertake many
therapies and interventions in AMI almost as a routine despite the lack of convincing
evidence of benefit with regard to mortality and recurrence of MI in some subsets (200).
This approach is clearly not justified in the elderly. An additional important factor in
treating the elderly, particularly those older than 80 years of age or those who are frail, is
the need to consider the patients values and wishesa matter that is extremely difficult
to address in view of the drama and urgency that surround AMI and often include transfer
to physicians at facilities with no background information concerning the patient. For
many elderly patients, life will not be prolonged (or quality of life improved) despite
effective therapy for their acute coronary syndromes (160). Thoughtful, refined clinical
judgment with a highly individualized approach to each patient is the key to optimal
management with emphasis on the use of treatments that are known to be helpful and
have a low propensity for major complications.
Thrombolytic Therapy
Elderly patients are underrepresented in all thrombolytic trials (147,196199) because of
concern about the risk of complications, particularly cerebral hemorrhage. Although most
major hemorrhages occur at vascular puncture sites, intracranial hemorrhage rates are
increased in the elderly. Spontaneous ischemic strokes related to AMI increase in
frequency with age.
The increased risk of stroke in patients older than age 70 is thought to result from the
reduced integrity of the cerebrovascular system, previous silent cerebral ischemic events,
or cerebral amyloid angiopathy. Large randomized, controlled trials and case-control
studies all demonstrate a higher risk of cerebral hemorrhage in the elderly with tissuetype plasminogen activator (t-PA) than with streptokinase treatment (201203). An
algorithm to estimate the probability of hemorrhagic stroke after thrombolysis indicated
that age and the use of t-PA are two of the most important variables, along with female
gender, low body weight, and hypertension (33,33a).
Heparin sodium use requires special attention in the elderly. In addition to age, small
body size and female gender alter metabolism and dosing requirements. Lower dosages, a
3,000-U bolus (instead of 5,000) and 500 U per hour rather than 1,000 should be
considered for 50-kg elderly patients, and partial thromboplastin time should be followed
fastidiously. Low-molecular-weight heparin is increasingly popular and does not require
monitoring. Comparative safety data for the elderly are not available.

Given the profound effect of age on mortality, the increased rate of hemorrhagic events
must be weighed against the substantial mortality reduction that is felt possible with
thrombolytic therapy. Efficacy was demonstrated in multiple randomized, controlled
trials. In the Fibrinolytic Therapy Trialists overview, the greatest absolute benefit of
thrombolytic therapy was seen in patients older than age 75 (147), but the number of
elderly in randomized, controlled trials is relatively small. Studies of effectiveness now
question this finding. The data compiled by the Health Care Financing Administration for
its Cooperative Cardiovascular Project during the years 1994 to 1995 have been studied
by two different groups of investigators in retrospective studies. Patient selection was
different and methodologies were not identical. In the study by Berger et al., 15,940
patients older than the age of 65 had thrombolytic therapy or primary angioplasty (1,599)
(204). They concluded that patients who underwent reperfusion had a lower mortality at 1
year than those who did not undergo reperfusion. Interestingly, only primary angioplasty
was associated with a better survival at 30 days (see subsequent paragraph). Using the
same database, Thiemann et al. evaluated 7,864 Medicare patients who had fee-forservice treatment (205). In evaluating thrombolytic therapy in this group, they concluded
that a survival benefit was seen in patients 65 to 75 years old, but in the group aged 76 to
86 years, thrombolytic therapy was associated with survival disadvantage. Hence, data
are conflicting, and a serious concern exists that patients older than the age of 75 may not
benefit from thrombolytic therapy. If adverse outcomes in the over-75 group are
confirmed, pharmacologic differences in the handling of drugs (and the interaction
among drugs) as well as changes related to the aging process per se may explain the lack
of benefit.
These confusing and inconsistent findings coupled with the atypical clinical presentations
and ECG findings, as well as the delay in seeking care, make the use of thrombolytic
therapy problematic in older patients, especially those older than the age of 75. In
addition, a disappointingly small number of elderly patients meet conventional eligibility
criteria for thrombolytic therapy: ST-segment elevation, arrival within 6 hours of the
event, and no contraindication. In one study, only approximately 10% of patients older
than age 75 met eligibility criteria because of the absence of ST-segment elevation, late
arrival, and comorbidity (184).
Primary Percutaneous Catheter-Based Interventions
Issues related to logistics and the treatment of low-risk patients are still debated, but the
extremely high mortality and features discussed earlier make PCI particularly appealing
for the elderly because it can be used in patients without ST-segment elevation and the
major CNS morbidity risks of thrombolytic therapy can be largely avoided.
Some of the issues related to the use of PCI have been discussed under thrombolysis
(see also Chapter 18). Pooled analyses of the results of randomized, controlled trials of
PTCA versus thrombolytic therapy (primarily in younger patients) found a mortality
advantage and reduced in-hospital reinfarction rates in patients randomly assigned to
undergo to angioplasty (206,207). These results were not confirmed in an important
observational study of patients of all ages (more than 3,000 patients) performed in

Seattle, Washington, and in a French study, which showed no benefit for angioplasty
(208,209).
Another observational trial of the Second National Registry of Myocardial Infarction
suggests that primary PTCA and fibrinolytic therapy result in similar outcomes (154).
Patients with ST-segment elevation underwent primary PTCA (4,939) or were given t-PA
(24,705). Fifteen percent of the patients in both groups were older than 75 years of age,
and mortality among these patients was 16.5% in the group receiving t-PA and 14.4% in
those undergoing PTCA. For total mortality and disabling strokes, the rates were 18.4%
for those given t-PA and 14.6% for those undergoing PTCA.
Two registry studies add substantial observational data but do not resolve some of the
major issues. Berger et al. (204) studied the Health Care Financing Administrations
Cooperative Cardiovascular Project database, which contains information on 140 clinical
variables collected prospectively. They studied the 20,683 patients who received
reperfusion therapy out of 80,356 who were judged eligible for reperfusion. The total
cohort contained 234,769 patients older than 65 years. The data analyses are extensive,
complex, and sophisticated, and incorporated baseline patient cardiac risk factors,
hospital characteristics, and (to a limited degree) qualitative general patient
characteristics, including presence of chronic obstructive pulmonary disease or dementia,
and degree of mobility limitation. The conclusion from this study is that primary PTCA is
associated with a modest short-term and long-term mortality benefit compared to
fibrinolytic therapy. Thirty-day mortality was 8.7% versus 11.9% and 1-year mortality
was 14.4% versus 17.6%. In the smaller subgroup of patients who were classified as ideal
for reperfusion therapy, the observed benefit of primary PTCA was not seen. The
relatively low mortalities indicate considerable bias in case selection in favor of healthier
old people.
In summary, the precise role of PCI in elderly patients with AMI remains to be defined.
Additional registry data will be useful, but the decision to use PCI, fibrinolytic therapy, or
neitherparticularly in patients older than the age of 75is likely to remain inherently a
highly individualized clinical decision. In addition, the logistics and expertise required
for timely catheter-based interventions provide major obstacles to the widespread and
routine use of this approach. The presence of multivessel disease, which is regularly
found in the elderly, makes it imperative to identify the infarct-related vessels in these
patients, most of whom have ST-segment depression.
Adjunctive Therapy
Adjunctive therapy has not been evaluated as intensely in the elderly as in the young, but
clearly several adjunctive agents are very effective in the elderly and tend to be
underused.
Aspirin use was investigated in the Second International Study of Infarct Survival (198).
Patients older than age 70 achieved particular benefit, with a 21% relative reduction in
mortality (from 22.3% to 17.6%). As doses increased from 80 mg to 325 mg in this study,

the rate of gastrointestinal complications increased twofold, particularly in the elderly. No

data are available on gastrointestinal bleeding in the elderly with the use of
cyclooxygenase-2 inhibitors. Aspirin is underused in treating acute MI in the elderly, with
reported usage rates of 55% in patients older than age 75 versus 65% in those younger
than age 75 (210213).
Early studies of intravenous glycoprotein IIb/IIIa receptor blockers have shown promise in
treating acute coronary syndromes but primarily in patients undergoing PCI. Data
specifically pertinent to older patients are fragmentary. If PCI is not performed, no
mortality benefit has been seen in randomized, controlled trials. Trials combining II b/IIIa
agents and thrombolytic agents for reperfusion are under way (see Chapters 17 and 18).
Beta-blocker therapy has a greater effect on survival after MI in the elderly than in
younger patients (214,215), with a 34% reduction in mortality in patients between the
ages of 60 and 69 but only a 19% reduction in patients aged 30 to 59 years who received
propranolol 5 to 21 days after MI. Early intravenous administration has been studied in
three randomized, controlled trials (216219). In 8,513 patients older than 60 (the
majority was older than 65), mortality was reduced from 8.9% to 6.9%, so that 20 lives
were saved per 1,000 patients treated. In the 14,687 patients younger than age 65, the
mortality reduction, from 2.6% to 2.5%, was insignificant. These studies were performed
before the fibrinolysis era, but the use of early intravenous beta-blockade as an adjunct to
thrombolysis suggests that the agent is useful in that setting.
The use of long-term beta-blocker therapy for secondary prevention after AMI is of value
in elderly patients. Three large randomized, controlled trials using propranolol
hydrochloride, atenolol, or metoprolol show convincing reduction in mortality in both
young and old patients after MI (217,220,221). Mortality reduction was much greater in
the 2,462 older patients (14.9% to 8.9%) than in the 4,654 younger patients (7.6% to
5.5%). For every 1,000 patients treated, 60 lives were saved among the older patients
compared with 21 lives among the younger patients. Despite these clear benefits,
clinicians underprescribe beta-blockers in elderly patients (212,213), perhaps because
they fear the side effects that are more frequent in the elderly, including heart block, CHF,
bronchospasm, depression, and impaired glucose metabolism. Beta-blocker therapy can
benefit even those with mild CHF, diabetes, or both. The substantial benefit of these
drugs makes it important that they be used liberally, with careful observation for adverse
effects in patients who have relative contraindications, such as bradycardia, low systolic
blood pressure, and propensity to heart block.
The survival benefit of treatment with ACE inhibitors after AMI is greater in the elderly
than in younger groups. In one trial, the reduction in the risk of death was greatest (25%)
in patients older than 65 years who received captopril, whereas it was lower in those
younger than 55 years (8%); the reduction in recurrent, fatal, or nonfatal MI was also
greater in those older than 65 years (213). Among patients older than 70 in the third
Gruppo Italiano per lo Studio della Sopravvivenza nellInfarto Miocardio study (GISSI3), a 12% reduction was seen in the combined end point of mortality and severe

ventricular dysfunction (222,223). Details concerning the timing of initiation of therapy

and implications of left ventricular dysfunction are discussed in Chapter 18.
The role of intravenous antithrombin agents in the elderly is complicated. Intensive
anticoagulation poses particular bleeding risks in the elderly. The use of low-molecularweight heparin has not been compared with the use of fractionated heparin in the elderly.
Combinations of fibrinolytic, antiplatelet (glycoprotein IIb/IIIc), and antithrombin agents
are being evaluated, which adds to the uncertainty. Heparin is required with t-PA therapy
but offers no advantage with streptokinase treatment (224). The use of heparin is always
associated with increased bleeding risks.
Calcium channel blockers are favored in many situations when beta-blockers are
contraindicated, but multiple clinical studies have shown no benefit of this treatment for
AMI (225,226). Although their use remains popular, the lack of efficacy of these agents
appears to be a class effect, and independent of age, at least for the first-generation
calcium channel blockers. Second-generation agents may have a role in certain subsets
(see Chapters 18 and 20).
Glucose-Insulin Infusions
Diabetes is commonly present in elderly MI patients and is a predictor of adverse
outcomes. The hypothesis that glucose-insulin-potassium infusions can alter the
metabolic substrate and improve the outcome of AMI has been evaluated for 40 years
(227,228). Swedish investigators (229,230) have used insulin-glucose infusions to treat
diabetic patients. The short-term and long-term outcomes obtained in a well-designed
randomized, controlled trial involving 600 patients (mean age, 68 years) demonstrated
convincing benefit. After a 24-hour infusion, subcutaneous insulin was given four times
daily for at least 3 months in the treatment group. Mortality was lower in the treatment
group than in the control group (9.1% vs. 11.2%). By the end of 1 year, the reduction in
mortality was 18.6% versus 26.1%. This mortality benefit was still present 3.5 years after
infarction. Of particular importance is the fact that the mortality reduction was most
evident in patients who had a low cardiovascular risk profile and who had received no
insulin treatment before the AMI. Among this subset of patients, the 3-year mortality was
6.5% in the infusion group and 13.5% in the control group. Fastidious control of
hyperglycemia during the course of AMI should be seriously considered in all elderly
patients.
Complications and Cardiogenic Shock
The complications of AMI are, overall, more frequent and the consequences of the
complications more catastrophic in the elderly. Primary ventricular fibrillation is the
probable exception to that rule because it is less frequent with increasing age.
Complications are discussed in detail in Chapters 18, 19, and 20. The approach to
complications is no different in the elderly than in younger cohorts, when allowances are
made for comorbidity and the implications of competing risks.

Cardiogenic shock (see Chapter 19) deserves special comment because it is relatively
common (7% to 10% of all AMI cases), is the leading cause of death in AMI, occurs
overwhelmingly in the elderly, and continues to carry a high mortality. The studies of
Hochman and her colleagues (231233) have provided important insight into the issues
involved, including the problems in establishing the diagnosis, that is, verifying that the
shock is related to myocardial dysfunction. In addition to confirming that the patients
hypotension and hypoperfusion are not related to decreased left ventricular filling
pressure or arrhythmias, one must look for mechanical complications (ruptured
ventricular septum, ruptured papillary muscle with mitral regurgitation, and free wall
ventricular rupture) (233236). All of these complications are more frequent in the
elderly and, of course, require a different management approach. Hochman and her
colleagues have studied cardiogenic shock in a sample of 302 patients in a randomized,
controlled trial and have extensive data on a registry of an additional 1,109 patients.
These studies provide an extraordinary body of data, but problems related to transfer bias
and the fact that these studies were performed at highly experienced centers that can
provide optimum care for complicated cases make it probable that their results cannot be
directly transferred to the usual practice setting. The outcome for patients age 75 or older,
however, is probably correct. In that subset of patients, revascularization had an adverse
effect compared to optimum medical therapy. Of the many subsets analyzed, this was the
only subset in which an adverse outcome occurred with revascularization. In multiple
subsets, the benefit of revascularization was small and often statistically insignificant (see
Chapter 19 for further information). The complexities of cardiogenic shock, including the
use of intraaortic balloon pumping, revascularization therapies, and a variety of
pharmacologic agents, require the ultimate in clinical judgment in treating the elderly and
especially patients older than age 75 (237). A highly individualized, thoughtful approach
will provide the optimum outcome and most humanistic alternative in treating this
relatively common and extremely lethal complication, which probably carries a mortality
of at least 50% despite optimum therapy (231237).
Risk Stratification after Myocardial Infarction
Elderly hospital survivors of AMI have an extremely high overall 1-year mortality, in the
range of 30% to 40%, including hospital mortality. This rate is highly variable depending
on a number of factors, particularly left ventricular dysfunction, residual myocardial
ischemia, and major ventricular arrhythmias (eFig. 33.0.7). Half of these deaths occur
within the first 3 months (238,239). (See also Chapter 20.)
A useful approach is to divide the survivors of AMI into high- and low-risk groups and
use revascularization procedures in the high-risk groups (240,241). Intensive medical
therapy for left ventricular dysfunction and prevention of progression of atherosclerosis is
indicated in all survivors, as discussed in the section Cardiovascular Risk Factors in the
Elderly. Very high 1-year mortality (up to 50%) is seen for some elderly AMI survivors
who have significant ventricular dysfunction, major comorbidities, and limited ability to
ambulate. The inability to perform an exercise test, regardless of the reason, is associated
with a high short-term mortality (171,172). However, this group also has a high rate of

mortality and complications after interventions. Again, a highly individualized approach

must be taken through risk stratification after AMI in the elderly, with emphasis on
noncardiac disease featuresevidence of aging and comorbidity. Overall exercise
tolerance is the single most predictive feature.
Clinical exercise test variables that correlate with adverse long-term outcome in the
elderly include an inability to increase systolic blood pressure by more than 30 mm Hg,
an exercise duration of less than 5 minutes, and poor increase in the rate pressure product.
In one study, the prediction of 1-year outcome for older patients after MI on clinical
grounds only (by experienced clinicians) was not improved by knowledge of the results
of exercise testing, radionuclide angiography, or 24-hour Holter ECG recording (241)
(eFig. 33.0.8). All these studies emphasize the importance of the overall evaluation of the
elderly patient after MI, not only the assessment of CHD severity.
Because many elderly patients cannot exercise (40% in some studies), stress has been
induced pharmacologically to assess perfusion and ventricular performance.
Dipyridamole, adenosine or dobutamine in conjunction with thallium or
echocardiography can be used; dobutamine is particularly useful in older patients with
obstructive lung disease for whom dipyridamole and adenosine are relatively
contraindicated. Although these approaches are appealing, reports ordinarily do not give
information about the incremental value of these approaches. An urgent need exists to
determine the incremental value of post-MI testing in the elderly.
The use of coronary arteriography is another debated issue. Valuable information can be
obtained, including information on systolic and diastolic function, cardiac
hemodynamics, and extent, severity, location, and characteristics of lesions (including
residual thrombosis of coronary lesions). In addition, valvular disease, particularly
calcific aortic stenosis, is frequently present and can be evaluated.
For these
reasons, some argue that angiography should be a routine part of risk stratification
(240,241) in the elderly. Multivessel disease is present in a high percentage of elderly
patients, however, and the incremental value of coronary arteriography for assessing
prognosis (in contrast to planning treatment) is problematic. In a large observational
study of post-MI angiography in the United States and Canada, the greater use of
angiography in the United States (35% vs. 10%) was not associated with a reduction in 1year mortality (35% in both cohorts) (150).
In the absence of outcome data, highly individualized decisions are required with regard
to the use of post-MI arteriography in the heterogeneous population of elderly post-MI
patients.
Cardiac Rehabilitation
Normal aging is accompanied by reduced exercise capacity or alterations in lifestyle, or
both, which reduce physiologic reserve. Hence, rehabilitation involving exercise is
particularly important in the elderly (243247). Healthy elderly patients can significantly
increase their exercise capacity through exercise training, which need not occur within a

structured group program but is feasible at home (although fewer outcome data are
available using this design). An important component of cardiac rehabilitation programs
is individual and group counseling, including focused diet, risk-factor modification, and
social adjustment interventions. A British study of 166 consecutively treated patients aged
70 to 97 years randomly assigned to attendance at a special outpatient counseling clinic
or to the usual medical follow-up showed reduced hospital readmissions, less depression
and anxiety, and increased mobility and physical function with outpatient counseling
(244). Comprehensive cardiac rehabilitation in some form should be strongly considered
after MI in elderly patients.

ECG during Acute> MI

The diagnostic accuracy of the ECG depends on the extent and location of transmural
injury or necrosis. In general, the 12-lead ECG is specific but only moderately sensitive
for detection of <acute> myocardial injury (187,188). Systematically recording leads V4R,
V8, and V9 (i.e., a 15-lead ECG) increases the probability of detecting ST elevation from
47% to 59%, with no decrease in specificity (22).
The infarction descriptors
anterior, inferior, and lateral have classically been attributed to occlusions of the LAD,
right <coronary> artery (RCA), and circumflex artery (LCX), respectively. Other terms
such as apical, septal, high lateral, and posterior are also in use. The 12-lead ECG is
only moderately accurate in determining the anatomic location of <acute> infarction,
however, and the correspondence of some ECG terms with the pertinent site of infarction
is rather poor (189). The ECG is most sensitive for detecting <acute> occlusion of the
LAD and least sensitive for detecting involvement of the circumflex artery. Automated
diagnoses of infarction (i.e., provided by the electrocardiographer) are specific but not
sensitive; their most promising application is in the prehospital setting (190192).
Acute> Anterior/Anteroseptal/Anterolateral Infarction (Left Anterior Descending Artery
Occlusion)
<

During <acute> anterior injury, V2 is the most sensitive lead for recording ST elevation
(sensitivity, 99%) and for identifying the culprit lesion in the LAD. Other powerful
predictors of proximal LAD occlusion include ST elevation in aVL and concomitant ST
depression in inferior leads (193,194) (Fig. 59.11A, Fig. 59.11B). ST elevation that
extends to leads I and aVL often coexists with inferior ST depression. The magnitude of
ST depression in inferior leads correlates better with that of ST elevation in leads I and
aVL than with the ST elevation of precordial leads.
The maximal ST elevation is
best recorded in V2 as well as V3 (195) (eFig. 59.10.5; Fig. 59.11A, Fig. 59.11B). Highly
specific signs for occlusions at the level of the first septal perforator include ST elevation
in aVR (196), disappearance of preexistent septal Q waves in lateral leads (197,198), and
ST depression in V5 (196).

Occasionally, ST elevation is also present in lead V 1. Lead V1 captures electrical

phenomena from the right paraseptal area, which is supplied by the septal branches of the
LAD. In most patients the septum is additionally protected by a conal branch of the RCA
(double circulation), and this explains why patients with anterior myocardial infarction
usually have no ST elevation in V1 (196). The presence of ST elevation in V1 (eFig.
59.10.5) correlates strongly with ST elevation in V 3R and predicts the less common
anatomical scenario in which a small conal branch of the RCA does not reach the
interventricular septum (199).
<

Acute> Inferior Infarction (Right <Coronary> or Circumflex Artery Occlusion)

The typical ECG pattern of inferior infarction consists of ST-segment elevation in leads
II, III, and aVF (Fig. 59.12).
In 80% to 90% of cases the culprit lesion is in the
RCA (200); the remainder of the patients have LCX occlusion. Higher ST elevation in
lead III than in lead II strongly suggests RCA occlusion (201,202). Because lead aVL
faces the superior part of the left ventricle and directly opposes the inferior wall, STsegment depression in aVL usually indicates RCA occlusion (sensitivity, 94%; specificity,
71%) (203). Precordial ST depression accompanying inferior injury is more likely to
develop from LCX than from RCA occlusion (Fig. 59.13). Horizontal ST depression with
initially negative then upright T waves in leads V1 to V3 or V4 (Fig. 59.13) is associated
with posterior wall motion abnormalities (204). Concomitant ST elevation in leads V5 and
V6 also indicates posterolateral ischemiatriggered by either RCA or LCX occlusion
(205). When this ST elevation is significant (more than 0.2 mV), it is likely a sign of
infarction related to a megaartery (RCA or LCX), with a large ischemic burden (205).
<

Acute> Lateral and Posterior Infarctions (Circumflex Artery Occlusion)

The vascular beds of the LCX show broad anatomic variability and supply a rather small
ventricular area. This is why the standard 12-lead ECG displays ST-segment elevation in
less than half of cases of LCX occlusion. When present, ST elevation is more often seen
in leads II, III, and aVF, followed by leads V5, V6, and aVL (206). In some cases, a
concomitant ST depression is seen in leads V1 to V3 (Fig. 59.13).
One-third of patients with chest pain secondary to spontaneous LCX occlusion present
with isolated ST depression. ST depression in V 1 and V2 is a sensitive sign (203,206).
Another one-third of patients present without any changes in the 12-lead ECG. In a study
of 33 consecutively treated patients with LCX occlusion, however, ST elevation in V 7
through V9 was always detected and was associated with posterior wall motion
abnormalities (207). Leads V7 to V9 are more specific than precordial leads for detection
of posterior infarction (84% vs. 57%), with similar sensitivity (approximately 80%)
(208).
<

Acute> Right Ventricular Infarction

Transmural injury of the right ventricle translates into ST-segment elevation of 0.1 mV or
more in precordial leads. ST elevation in V1 is highly specific for proximal RCA
occlusion (202). In approximately 7% of patients, ST elevation extends to lead V 5, which
suggests anterior infarction. This ST elevation decreases toward V 4, however, whereas in
anterior injury from LAD occlusion, the ST segment is more elevated in V 2 and V3 than
in V1 (209).
Right ventricular infarction is usually concurrent with infarcts of the inferior wall (eFig.
59.13.1). Half of patients with inferior injury have ST elevation in V4R (sensitivity and
predictive accuracy for right ventricular infarction are both 93%) (210). Isolated right
ventricular infarction is rare and occurs mainly in patients with right ventricular
hypertrophy (211).
ST-Segment Depression in Patients with <Acute> <Coronary> <Syndromes>
Isolated ST-Segment Depression
In a study of 136 patients presenting with isolated ST-segment depression in the 12-lead
ECG, <evolution> to infarction was observed in 54% of cases. One-year mortality was
high for patients both with and without infarction (212). In general, ST depression is
associated with older age, multivessel or left main <coronary> artery disease, multiple
infarctions, or poor left ventricular function (213,214). A common cause of primary ST
depression is the subocclusion of the left main <coronary> artery, and the ECG frequently
shows a combination of ST depression in leads I, II, and V4 to V6 with ST elevation in
aVR. A sum of ST changes of 18 mm is 90% sensitive for left main artery disease (215).
A maximum ST depression in leads V2 and V3, on the other hand, indicates LCX
occlusion (specificity, 96%; sensitivity, 70%). Recognizing this is important, because
patients with isolated ST depression from LCX occlusion benefit from thrombolysis
(216). Isolated ST depression in inferior leads may be caused by either inferior
subendocardial ischemia or by a prominent atrial repolarization (Ta) wave during right
atrial enlargement (100).
ST-Segment Depression Concomitant with ST Elevation
Many patients with <acute> chest pain present with reciprocal ST-segment depression,
that is, ST depression concomitant with ST elevation in a different lead group. The
mechanism underlying such ST depression is assumed to be mirroring, a phenomenon of
electrical reflection of the transmural injury onto the opposite ventricular wall. The ST
depression is captured by a lead placed at 180 degrees to the lead recording ST elevation,
but the terms reciprocal and mirror are loosely applied to other recording points as well
(217). For example, ST depression that is maximal in leads V 5 and V6 may be related to
<acute> ischemia of the right ventricle; it is the reciprocal of ST elevation in V3R (181).
Another possible mechanism for ST depression is regional subendocardial ischemia or
infarction. Although strictly speaking mirroring is also involved in the ST depression of
subendocardial ischemia (because the ST elevation in the subendocardial layer is

reflected onto the epicardial layer), most clinicians consider this ST depression
nonmirror because it is a primary manifestation of artery occlusion, not secondary to
ST elevation in a different territory (218). In patients with chest pain and predominant ST
depression in any lead except aVR, ST depression of at least 0.4 mV is 97% specific (and
20% sensitive) for <acute> infarction (212). Several investigators have found that inferior
ST depression during anterior injury is not accompanied by inferior ischemia (as assessed
by perfusion imaging), which suggests that mirroringrather than inferior
subendocardial ischemiais responsible for the ST depression (217,218). Over 85% of
patients with ST depression in lead aVF have a culprit lesion in the proximal LAD. On
the other hand, the significance of anterior ST depression accompanying inferior injury
may depend on the leads involved. ST depression in leads V 1 through V3 or I through aVL
seems to correspond to mere mirroring, often from LCX occlusion. On the other hand, ST
depression deeper in V4 through V6 than in V1 through V3 is associated with anterolateral
or septal subendocardial injury from a severe lesion in the LAD or in the left main
<coronary> artery (219) (Fig. 59.14).
Nonischemic ST Depression
The most important differential diagnosis in patients with ST depression and chest pain
(with or without abnormal levels of creatine kinase) (220) is aortic dissection. As many as
50% of patients with dissection of the thoracic aorta may present with ECG
abnormalities, mainly ST-segment depression (221), unless the origin of a <coronary>
artery is involved in the dissection and signs of transmural injury develop.
Diagnosis of <Acute> Myocardial Infarction in the Presence of Confounding Factors
Right Bundle Branch Block
The diagnosis of evolving <acute> anterior infarction in patients with RBBB can be
suspected when secondary T waves (opposite to the QRS complex) in leads V1 to V3 or
V4 are replaced by T waves of concordant polarity with the QRS
(pseudonormalization). ST elevation is often easily detected (Fig. 59.15).
Left Bundle Branch Block
In patients who present with <acute> chest pain and LBBB, ECG interpretation is difficult
because the normal sequence of ventricular activation can be altered by both LBBB and
<acute> myocardial injury. During either occlusion of a <coronary> artery by an
angioplasty balloon or <acute> infarction, however, further ST-segment elevation does
occur in LBBB (222224). In a study that analyzed all published criteria for the diagnosis
of <acute> infarction in the presence of LBBB, the ECGs of 131 patients who had LBBB
and enzyme-confirmed <acute> infarction were compared with 131 ECGs of external
controls who had chronic <coronary> artery disease and LBBB (eTable 59.0.6, Fig.
59.16). Criteria were validated in an independent sample of patients with <acute>
<coronary> <syndromes> and LBBB. A scoring system suggested that a highly specific
diagnosis of <acute> infarction could be made with a total score index of 3 points or

higher (eTable 59.0.6). This score was associated with specificities of 90% or higher in
both the derivation and the validation samples (225,226).
Ventricular Pacing
In patients with permanent pacemakers and chest pain, the presence of ST elevation of
0.5 mV or more in leads with a negative QRS complex has a specificity of 88% and a
sensitivity of 53% for the diagnosis of <acute> infarction. Two other criteria with high
specificity but low sensitivity are ST elevation of 0.1 mV in leads with concordant QRS
polarity and ST depression of 0.1 mV or more in lead V 1, V2, or V3. No criteria involving
the QRS complex or isolated T waves is highly specific (227).
Nondiagnostic Electrocardiograms
As many as 15% to 18% of <acute> myocardial infarctions do not produce changes in the
initial ECG, and an additional 25% produce nonspecific changes (228). Recording serial
ECGs increases the probability of detecting <acute> infarction (229). Maximizing the
information provided by the admission ECG is ideal, however, because reperfusion
therapies are more effective when administered early. A 15-lead ECG that includes leads
V4R, V8, and V9 should be obtained in all patients without ST elevation in the 12 standard
leads; this increases the detection rate of ST elevation from 47% to 59% with no decrease
in specificity (22). In patients with nondiagnostic ECGs at admission, the most frequent
culprit artery is the circumflex (230). Once patients with <acute> infarction and normal
admission ECGs have undergone angiographic evaluation and survived hospitalization,
the frequency of involvement of the infarct-related artery is similar for the three major
arteries. Patients who never develop ECG changes have lesions in branch vessels (231).
In the absence of confounding factors, nondiagnostic ECGs in patients with suspected
<acute> infarction are associated with a low incidence of in-hospital events and mortality
(232).
Individuals who present to the emergency department with chest pain and signs of left
ventricular hypertrophy in the ECG may pose a particular diagnostic challenge because
secondary T waves and ST-segment changes act as confounders. Remarkably, a
multicenter study concluded that patients with both <acute> chest pain and
electrocardiographic signs of left ventricular hypertrophy are four times less likely to
have <acute myocardial infarction and one-third less likely to have ischemia than patients
who do not show ECG signs of left ventricular hypertrophy (233).

ECG during Acute MI

The diagnostic accuracy of the ECG depends on the extent and location of transmural
injury or necrosis. In general, the 12-lead ECG is specific but only moderately sensitive
for detection of acute myocardial injury (187,188). Systematically recording leads V4R,

V8, and V9 (i.e., a 15-lead ECG) increases the probability of detecting ST elevation from
47% to 59%, with no decrease in specificity (22).
The infarction descriptors
anterior, inferior, and lateral have classically been attributed to occlusions of the LAD,
right coronary artery (RCA), and circumflex artery (LCX), respectively. Other terms such
as apical, septal, high lateral, and posterior are also in use. The 12-lead ECG is only
moderately accurate in determining the anatomic location of acute infarction, however,
and the correspondence of some ECG terms with the pertinent site of infarction is rather
poor (189). The ECG is most sensitive for detecting acute occlusion of the LAD and least
sensitive for detecting involvement of the circumflex artery. Automated diagnoses of
infarction (i.e., provided by the electrocardiographer) are specific but not sensitive; their
most promising application is in the prehospital setting (190192).
Acute Anterior/Anteroseptal/Anterolateral Infarction (Left Anterior Descending Artery
Occlusion)
During acute anterior injury, V2 is the most sensitive lead for recording ST elevation
(sensitivity, 99%) and for identifying the culprit lesion in the LAD. Other powerful
predictors of proximal LAD occlusion include ST elevation in aVL and concomitant ST
depression in inferior leads (193,194) (Fig. 59.11A, Fig. 59.11B). ST elevation that
extends to leads I and aVL often coexists with inferior ST depression. The magnitude of
ST depression in inferior leads correlates better with that of ST elevation in leads I and
aVL than with the ST elevation of precordial leads.
The maximal ST elevation is
best recorded in V2 as well as V3 (195) (eFig. 59.10.5; Fig. 59.11A, Fig. 59.11B). Highly
specific signs for occlusions at the level of the first septal perforator include ST elevation
in aVR (196), disappearance of preexistent septal Q waves in lateral leads (197,198), and
ST depression in V5 (196).
Occasionally, ST elevation is also present in lead V1. Lead V1 captures electrical
phenomena from the right paraseptal area, which is supplied by the septal branches of the
LAD. In most patients the septum is additionally protected by a conal branch of the RCA
(double circulation), and this explains why patients with anterior myocardial infarction
usually have no ST elevation in V1 (196). The presence of ST elevation in V1 (eFig.
59.10.5) correlates strongly with ST elevation in V3R and predicts the less common
anatomical scenario in which a small conal branch of the RCA does not reach the
interventricular septum (199).
Acute Inferior Infarction (Right Coronary or Circumflex Artery Occlusion)
The typical ECG pattern of inferior infarction consists of ST-segment elevation in leads
II, III, and aVF (Fig. 59.12).
In 80% to 90% of cases the culprit lesion is in the
RCA (200); the remainder of the patients have LCX occlusion. Higher ST elevation in
lead III than in lead II strongly suggests RCA occlusion (201,202). Because lead aVL
faces the superior part of the left ventricle and directly opposes the inferior wall, STsegment depression in aVL usually indicates RCA occlusion (sensitivity, 94%; specificity,
71%) (203). Precordial ST depression accompanying inferior injury is more likely to
develop from LCX than from RCA occlusion (Fig. 59.13). Horizontal ST depression with

initially negative then upright T waves in leads V1 to V3 or V4 (Fig. 59.13) is associated

with posterior wall motion abnormalities (204). Concomitant ST elevation in leads V5 and
V6 also indicates posterolateral ischemiatriggered by either RCA or LCX occlusion
(205). When this ST elevation is significant (more than 0.2 mV), it is likely a sign of
infarction related to a megaartery (RCA or LCX), with a large ischemic burden (205).
Acute Lateral and Posterior Infarctions (Circumflex Artery Occlusion)
The vascular beds of the LCX show broad anatomic variability and supply a rather small
ventricular area. This is why the standard 12-lead ECG displays ST-segment elevation in
less than half of cases of LCX occlusion. When present, ST elevation is more often seen
in leads II, III, and aVF, followed by leads V5, V6, and aVL (206). In some cases, a
concomitant ST depression is seen in leads V1 to V3 (Fig. 59.13).
One-third of patients with chest pain secondary to spontaneous LCX occlusion present
with isolated ST depression. ST depression in V1 and V2 is a sensitive sign (203,206).
Another one-third of patients present without any changes in the 12-lead ECG. In a study
of 33 consecutively treated patients with LCX occlusion, however, ST elevation in V7
through V9 was always detected and was associated with posterior wall motion
abnormalities (207). Leads V7 to V9 are more specific than precordial leads for detection
of posterior infarction (84% vs. 57%), with similar sensitivity (approximately 80%)
(208).
Acute Right Ventricular Infarction
Transmural injury of the right ventricle translates into ST-segment elevation of 0.1 mV or
more in precordial leads. ST elevation in V1 is highly specific for proximal RCA
occlusion (202). In approximately 7% of patients, ST elevation extends to lead V5, which
suggests anterior infarction. This ST elevation decreases toward V4, however, whereas in
anterior injury from LAD occlusion, the ST segment is more elevated in V2 and V3 than
in V1 (209).
Right ventricular infarction is usually concurrent with infarcts of the inferior wall (eFig.
59.13.1). Half of patients with inferior injury have ST elevation in V4R (sensitivity and
predictive accuracy for right ventricular infarction are both 93%) (210). Isolated right
ventricular infarction is rare and occurs mainly in patients with right ventricular
hypertrophy (211).
ST-Segment Depression in Patients with Acute Coronary Syndromes
Isolated ST-Segment Depression
In a study of 136 patients presenting with isolated ST-segment depression in the 12-lead
ECG, evolution to infarction was observed in 54% of cases. One-year mortality was high
for patients both with and without infarction (212). In general, ST depression is

associated with older age, multivessel or left main coronary artery disease, multiple
infarctions, or poor left ventricular function (213,214). A common cause of primary ST
depression is the subocclusion of the left main coronary artery, and the ECG frequently
shows a combination of ST depression in leads I, II, and V4 to V6 with ST elevation in
aVR. A sum of ST changes of 18 mm is 90% sensitive for left main artery disease (215).
A maximum ST depression in leads V2 and V3, on the other hand, indicates LCX
occlusion (specificity, 96%; sensitivity, 70%). Recognizing this is important, because
patients with isolated ST depression from LCX occlusion benefit from thrombolysis
(216). Isolated ST depression in inferior leads may be caused by either inferior
subendocardial ischemia or by a prominent atrial repolarization (Ta) wave during right
atrial enlargement (100).
ST-Segment Depression Concomitant with ST Elevation
Many patients with acute chest pain present with reciprocal ST-segment depression,
that is, ST depression concomitant with ST elevation in a different lead group. The
mechanism underlying such ST depression is assumed to be mirroring, a phenomenon of
electrical reflection of the transmural injury onto the opposite ventricular wall. The ST
depression is captured by a lead placed at 180 degrees to the lead recording ST elevation,
but the terms reciprocal and mirror are loosely applied to other recording points as well
(217). For example, ST depression that is maximal in leads V5 and V6 may be related to
acute ischemia of the right ventricle; it is the reciprocal of ST elevation in V3R (181).
Another possible mechanism for ST depression is regional subendocardial ischemia or
infarction. Although strictly speaking mirroring is also involved in the ST depression of
subendocardial ischemia (because the ST elevation in the subendocardial layer is
reflected onto the epicardial layer), most clinicians consider this ST depression
nonmirror because it is a primary manifestation of artery occlusion, not secondary to
ST elevation in a different territory (218). In patients with chest pain and predominant ST
depression in any lead except aVR, ST depression of at least 0.4 mV is 97% specific (and
20% sensitive) for acute infarction (212). Several investigators have found that inferior
ST depression during anterior injury is not accompanied by inferior ischemia (as assessed
by perfusion imaging), which suggests that mirroringrather than inferior
subendocardial ischemiais responsible for the ST depression (217,218). Over 85% of
patients with ST depression in lead aVF have a culprit lesion in the proximal LAD. On
the other hand, the significance of anterior ST depression accompanying inferior injury
may depend on the leads involved. ST depression in leads V1 through V3 or I through aVL
seems to correspond to mere mirroring, often from LCX occlusion. On the other hand, ST
depression deeper in V4 through V6 than in V1 through V3 is associated with anterolateral
or septal subendocardial injury from a severe lesion in the LAD or in the left main
coronary artery (219) (Fig. 59.14).
Nonischemic ST Depression
The most important differential diagnosis in patients with ST depression and chest pain
(with or without abnormal levels of creatine kinase) (220) is aortic dissection. As many as

50% of patients with dissection of the thoracic aorta may present with ECG
abnormalities, mainly ST-segment depression (221), unless the origin of a coronary artery
is involved in the dissection and signs of transmural injury develop.
Diagnosis of Acute Myocardial Infarction in the Presence of Confounding Factors
Right Bundle Branch Block
The diagnosis of evolving acute anterior infarction in patients with RBBB can be
suspected when secondary T waves (opposite to the QRS complex) in leads V1 to V3 or
V4 are replaced by T waves of concordant polarity with the QRS
(pseudonormalization). ST elevation is often easily detected (Fig. 59.15).
Left Bundle Branch Block
In patients who present with acute chest pain and LBBB, ECG interpretation is difficult
because the normal sequence of ventricular activation can be altered by both LBBB and
acute myocardial injury. During either occlusion of a coronary artery by an angioplasty
balloon or acute infarction, however, further ST-segment elevation does occur in LBBB
(222224). In a study that analyzed all published criteria for the diagnosis of acute
infarction in the presence of LBBB, the ECGs of 131 patients who had LBBB and
enzyme-confirmed acute infarction were compared with 131 ECGs of external controls
who had chronic coronary artery disease and LBBB (eTable 59.0.6, Fig. 59.16). Criteria
were validated in an independent sample of patients with acute coronary syndromes and
LBBB. A scoring system suggested that a highly specific diagnosis of acute infarction
could be made with a total score index of 3 points or higher (eTable 59.0.6). This score
was associated with specificities of 90% or higher in both the derivation and the
validation samples (225,226).
Ventricular Pacing
In patients with permanent pacemakers and chest pain, the presence of ST elevation of
0.5 mV or more in leads with a negative QRS complex has a specificity of 88% and a
sensitivity of 53% for the diagnosis of acute infarction. Two other criteria with high
specificity but low sensitivity are ST elevation of 0.1 mV in leads with concordant QRS
polarity and ST depression of 0.1 mV or more in lead V1, V2, or V3. No criteria involving
the QRS complex or isolated T waves is highly specific (227).
Nondiagnostic Electrocardiograms
As many as 15% to 18% of acute myocardial infarctions do not produce changes in the
initial ECG, and an additional 25% produce nonspecific changes (228). Recording serial
ECGs increases the probability of detecting acute infarction (229). Maximizing the
information provided by the admission ECG is ideal, however, because reperfusion
therapies are more effective when administered early. A 15-lead ECG that includes leads
V4R, V8, and V9 should be obtained in all patients without ST elevation in the 12 standard

leads; this increases the detection rate of ST elevation from 47% to 59% with no decrease
in specificity (22). In patients with nondiagnostic ECGs at admission, the most frequent
culprit artery is the circumflex (230). Once patients with acute infarction and normal
admission ECGs have undergone angiographic evaluation and survived hospitalization,
the frequency of involvement of the infarct-related artery is similar for the three major
arteries. Patients who never develop ECG changes have lesions in branch vessels (231).
In the absence of confounding factors, nondiagnostic ECGs in patients with suspected
acute infarction are associated with a low incidence of in-hospital events and mortality
(232).
Individuals who present to the emergency department with chest pain and signs of left
ventricular hypertrophy in the ECG may pose a particular diagnostic challenge because
secondary T waves and ST-segment changes act as confounders. Remarkably, a
multicenter study concluded that patients with both acute chest pain and
electrocardiographic signs of left ventricular hypertrophy are four times less likely to
have acute myocardial infarction and one-third less likely to have ischemia than patients
who do not show ECG signs of left ventricular hypertrophy (233).