Noninvasive and invasive testing after myocardial infarction

Robert A. O’Rourke, M.D., is the Charles Conrad Brown Distinguished Professor of Cardiovascular Disease at The University of Texas Health Science Center in San Antonio and Editor-in-Chief of Current Problems in Cardiology. He also is Chairman of the Council on Clinical Cardiology of the International Society and Federation of Cardiology. His research interests include analysis of the effects of cardiovascular drugs on myocardial &hernia and infarction and the assessment of ventricular systolic and diastolic finetion in normal and disease states. 726

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1991

NONINVASNE AND IN-VASRrE TESTING AFTER lMYOc=AEall)IAL INFARCTION

Despite a marked reduction in the age-adjusted incidence of coronary heart disease and myocardial infarction in the United States, more than 600,000 patients are hospitalized each year with acute myocardial infarcti0n.l The in-hospital mortality rate has declined steadily, which is in part related to the early use of thrombolytic therapy for patients who have an acute infarction. However, at the time of hospital discharge, surviving patients still have an increased risk of cardiovascular morbidity and mortality. Patients under 70 years of age who survive in the hospital after an acute myocardial infarction have a 5% to 10% mortality rate in the first year after discharge, with the highest proportion of deaths occurring in the first 3 months.’ In subsequent years there is a 3% to 5% annual mortality rate, which is six times higher than the expected death rate in an age-matched population without coronary disease? Over 80% of postinfarction deaths that occur after hospital discharge are related to complications resulting from coronary artery disease.’ There are three general approaches for making clinical decisions in patients who have recovered from acute myocardial infarction (Table 1). These include (1) risk stratification by noninvasive testing of patients who do not appear to be high risk before and during hospitalization; (2) coronary arteriography for virtually all patients in TABLE

1.

General Approaches After Infarction

to Patients

Risk stratification Clinical characteristics during the first days Noninvasive testing Cardiac catheterization and coronary arteriography Secondary prevention Coronary risk factor modification Dmg therapy (beta-blockers, aspirin1 Curr

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1991

4

727

whom it is not contraindicated; and (3) drug therapy for secondary prevention. The first two approaches will be discussed in this monograph. An excellent comprehensive discussion of medical therapy and secondary prevention after acute myocardial infarction was published by Jafri and associates in the September 1991 Current Problems in Cardiology3 Modification of risk factors for coronary artery disease, such as hypertension, hypercholesterolemia, and cigarette smoking, each of which is associated with greater morbidity and mortality after infarction, is recommended for all patients whether treatment includes medical management and/or myocardial revascularization.4 A recent report of the American College of Cardiology/American Heart Association (ACUAHA) Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedure, entitled “Guidelines for the Early Management of Patients with Acute Myocardial Infarction, ” is an excellent analysis of this subject.5 IDENTIFICATION

OF HIGIMUSK

SUBSETS

Certain clinical characteristics present at the onset of infarction indicate an unfavorable prognosis. Infarct-related mortality increases with age and reaches 50% in patients older than 80.6’ 7 The mortality rate in the first 2 years after myocardial infarction is increased twofold in patients with a prior acute infarction or chronic angina pectoris.5’ ’ A history of hypertension or diabetes mellitus increases the early and late postinfarction mortality.5’g Cigarette smoking is associated with increased risk for those who continue to smoke.5 The prognosis is poorer in women than men, which may be partially because coronary artery disease becomes clinically evident as women get older.“* I* b D. MCCALL: Dr. O’Rourke makes an important point here, that the prognosis in women, following a myocardial infarction is generally worse than that for men. Although this is generally accepted, some studies have shown that the short-term prognosis is better in women (Mayo Clinic Proceedings 60:305, 1985). In addition, the Framingham study also suggested that there may even be a better long-term prognosis in women than in men (Am J Epidemiol 1989; 130:469). Part of this confusion could be attributed to the fact that many of these studies were carried out in only small numbers of patients. A more definitive study (Circulation 1991; 8X4841, compared the in-hospital, and one year survival in 1,500 women, compared to that in over 4,000 men. They found that the cumulative, age adjusted one year mortality rate was 31.8% in women and only 23.1% in men, the difference being highly statistically significant. Further subgroup analysis of these patients indicated, as is suggested by Dr. O’Rourke, that the greater age in females may be a contributing factor. The multivariate analysis, however, of this large group of patients indicated that female gender was independently and significantly associated with the increased mortality, both during hospitalization and at one-year. Therefore, although the age difference may be impor-

72s

Curr

Probl

Cardiol,

November 1991

tant, it is still not certain tion than do men.

as to why females fare worse after a myocardial

infarc-

Certain clinical characteristics apparent during the early and late postinfarction periods indicate an increased risk for recurrent myocardial infarction, cardiac death, and sudden cardiac death (Fig 1). These include continuing or recurrent myocardial ischemia, moderate to severe reduction in left ventricular performance, and ventricular arrhythmias occurring late after infarction, while the patient is in the hospital. Each is an independent risk factor for morbidity and mortality, with myocardial ischemia and impaired left ventricular performance being stronger factors than ventricular arrhythmias.7J ‘, l2 Many patients will have two or three of these important risk factors, with frequent ventricular premature beats often occurring in-patients with markedly impaired left ventricular performance, and/or recurrent myocardial ischemia. Patients who present with an inferior wall myocardial infarction who have persistent ST segment depression in leads VI to V, have a worse prognosis than patients with inferior Q wave infarction who do not have precordial ST segment depression. Electrocardiograms

Continuing Myocardial lschemia

Ventricular Anhythmias FIG 1. Schematic representation of three factors identifying high risk patients after myocardial infarction and their interrelationships. (From O’Rourke RA: Clinical decisions for postmyocardial infarction patients. Mod Concepts Cardiovasc Dis 1986; 65:55-60. Used by permission.)

Cur-r Probl

Cardio& November 1991

72s

from patients in the two groups are shown in Figure 2. Forty-three consecutive patients with acute inferior Q wave myocardial infarction were prospectively evaluated to assess the clinical and prognostic importance of persistent precordial CV,-V,J ST segment depresTen of the 43 patients (group I) had persistent anterior presion.13 cordial ST segment depression of 1 mm or more in one or more precordial leads W1-V,J 24 hours after admission to the coronary care unit; 33 patients (group III did not. Group I patients were older, more frequently in Killip Class II to IV, and had higher peak creatine kinase concentrations (Fig 3). Hemodynamic differences between groups I and II included a higher pulmonary arterial wedge pres-

I

II

#t

##R

&I,

*w

VI

VP

V3

V4

VS

V6

FIG 2. Representative electrocardiograms (ECG) on admission and 24 hours later in a patient with an inferior Q wave infarction and persistent ST segment depression in leads V, to V, (Group I) and in a patient with an inferior wall infarction but no ST depression in the precordial leads (Group II). (From Lembo NJ, Starling MR, Dell’ltalia LJ, et al: Clinical and prognostic importance of persistent precordial (V,-V,) electrocardiographic ST segment depression in patients with inferior transmural myocardial infarction. Circulation 1986; 74:56-63. Used by permission.)

730

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1991

CLINICAL

VARIABLES

Age p c.01 -

65

I

Roles

s3

Killii Class ?lI

p<.o5 I

p<.oi

p<.OOl

loo

In E

I! 0 >

:

.9? z a

CK Peak p<.OOI 4000

60

60

55

0

J L GI

Gi

;

FIG 3. Differences between Group I and Group II inferior infarction patients were significant for age, presence of pulmonary rales, a third heart sound, Killip class of II-IV and the peak creatine kinase (CK) concentration. (From Lembo NJ, Starling MR, Dell’ltalia LJ, et al: Clinlcal and prognostic importance of persistent precordial (V,-V,) electrocardiographic ST segment depression in patients with inferior transmural myocardial infarction. Circulation 1986; 74:56-63. Used by permission.).

sure (19 If: 4 vs. 11 + 5 mm Hg; p < .OOl) and a lower cardiac index (2.0 ? 0.5 vs 2.6 2 0.7 < 1 min/m’; p < .05) in those with persistent precordial ST segment depression. Also, group I had a lower average left ventricular ejection fraction and a higher wall motion index than group II (Fig 4). Prognostically, group I had a higher incidence of recurrent myocardial infarction (30% vs. 0%; p<.Ol) and a higher l-year mortality (60% vs. 0%; p <.Ol)/ST segment depression in leads I and AVL did not have the same adverse prognosis and probably represents reciprocal ST segment changes in patients with inferior wall Q wave infarctions rather than “ischemia at a distance.” b D. MCCALL: The importance of the persistence of electrocardiographic abnormalities, other than the Q-wave of the index infarction, as a marker of prognosis, is highlighted by the ten year follow-up study of the Framingham cohort. (Circulation 1990; 81:780). This showed that the persistence of non-specific T-wave changes, ST segment changes, left ventricular and left ventricular hypertmphy, in addition to the Q-waves of the myocardial infarction, resulted in an almost three-fold excess risk, when compared to those who only had a Q-wave. It is

Curr

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1991

731

also of interest that this persistence of ST T changes and left ventricular hypertrophy continued to show a worse prognosis even in those patients in whom the initial index Q-wave had reverted to normal. It is presumed that the persistence of these other electrocardiographic abnormalities indicate either more extensive coronary disease, or greater degrees of left ventricular dysfunction, both of which contribute to a worsening mortality. Patients with new bundle branch block, particularly with an anteroseptal infarction, also have a worse prognosis than do those who do not develop this complication of infarction. The likelihood of sub-

RADIONUCLIDE ANGlOGRAPHlCVARIABLES: LVEF

LVWMI pe.05 -

ps.05 n

65

3.0

60

2.5

T

GI GII

RVEF p=NS 60

2x)

0

‘I O-’ GI GII

GI GII

FIG 4. Left ventricular ejection fraction (LVEF) was lower and left ventricular wall motion Index (LVWMI) was higher [more wall motion abnormalities] in Group I inferior wall myocardial patients than in Group II patients. The right ventricular ejection fraction (RVEF) was not statistically different. (From Lembo NJ, Starling MR, Dell’ltalia LJ, et al: Clinlcal and prognostic importance of persistent precordial (V,-V,) electrocardiographic ST segment depression in patients with inferior transmural myocardial infarction. Circulation 1986; 74:56-63. Used by permission.)

732

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Car-did,

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1991

sequent ventricular patients.14 MYOCARDL4L

tachyarrhythmias

is markedly

increased

in such

ISCHEMLA

For any severity of single or multivessel coronary artery disease and”for normal or any level of impaired left ventricular performance, the survival rate is related to the presence or absence of myocardial ischemia and, importantly, to its frequency and magnitude.15 Patients with recurrent episodes of myocardial ischemia while at rest or during moderate exertion differ prognostically from those with no evidence of myocardial ischemia or with myocardial ischemia occurring only during great exertion. Patients with severe myocardial ischemia at a low heart rate-blood pressure product involving large segments of the myocardium (>Z mm ST segment depression in several ECG leads and/or several new thallium 201 perfusion defects and/or several new wall motion abnormalities during exercise) have a high morbidity and mortality during the next year of follow-up.5,122 16,l7 The incidence of subsequent cardiac events in the postinfarction patient is increased considerably in those with exercise thallium 201 scintigraphy with thallium 201, which shows exercise perfusion defects with redistribution several hours later, multiple thallium perfusion defects, increased lung uptake of thallium or a combination of these findings16 (Fig 5). Thus, diagnostic workup and therapeutic management are likely to differ after infarction in patients who have evidence of spontaneous or exercise-induced myocardial ischemia compared with those who do not. LEFT

VENTRICULAR

DYSFUNCTION

There is a direct relationship between the extent of myocardial infarction (often, old plus recent) and the severity of left ventricular dysfunction. Also, the predischarge left ventricular ejection fraction correlates with subsequent survival after recovery from myocardial infarction.8 One-year cardiac mortality progressively increases as the ejection fraction declines below 40%, and a left ventricular ejection fraction of less than 30% is associated with a fivefold increased risk of death in the first year.8 Clinically, such patients often have cardiomegaly and/or left ventricular asynergy on cardiac palpation and auscultatory evidence of mitral valve regurgitation as well as cardiac enlargement on chest radiographs. A persistently elevated left heart filiing pressure, as manifested clinically by bibasilar rales, a third heart sound, and radiographic evidence of pulmonary venous hypertension also indicates moderate to severe risk.” Cum

hub1

Cardiol,

November

1991

733

8;% -

N=l40

*p~.OOOl

80

5’

60

9’%

S;% -

50 40 30 20 IO 0

-

6%.

sl 1 49

1TD;No Rd ort LU

42 f;

32 -52

Rd

MTD

LU

18 -21 MTD,t LU and Rd

FIG 5. Percentage of postinfarction patients after infarction who have subsequent cardiac events relative to results of predischarge thallium 201 exercise testing. Patients with redistribution (Rd) thallium defects, multiple thallium defects (MTD), increased lung uptake (LU) of thallium or a combination of the three had subsequently more events than patients with one fixed thallium defect only (1TD). (From Gibson RS, Watson DD, Craddock GE. et al: Prediction of cardiac events after uncomplicated myocardial infarction: A prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography. Circulation 1983; 68:321-336. Used by permission.)

734

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1991

VENTR1CULA.R ARRHYTHMIAS

Sudden death after myocardial infarction occurs in about 50% of cases and is not necessarily associated with myocardial ischemia or further infarction. Ventricular fibrillation appears to be the primary cause of sudden death. Frequent ventricular premature beats, presumably reflecting ventricular irritability, may identify patients at risk for ventricular tachyarrhythmias. Most studies have shown that frequent and/or complex ventricular premature beats occurring late during hospitalization for acute infarction or following hospital discharge are an independent risk factor for an increased first-year mortality. The Multicenter Post Infarction Research Group’ has established that 10 ventricular premature beats per hour indicate an increased risk after infarction, which is even greater in patients who also have depressed left ventricular function. However, there are no data yet to indicate that successful suppression of frequent ventricular premature beats is associated with a prolonged survival, and the proarrhythmic effects of antiarrhythmic therapy may worsen prognosis.” Nevertheless, patients with frequent and complex ventricular ectopy on electrocardiogram (ECG) or telemetry and those with welldocumented marked left ventricular dysfunction usually undergo a more detailed predischarge evaluation, including a 24- to 4%hour ambulatory electrocardiographic recording, a signal-averaged electrocardiogram, and/or electrophysiologic testing.5 In the patient with severe left ventricular dysfunction and/or frequent ventricular premature beats, the finding of “late potentials” on the signal-averaged ECG indicates a higher risk (Fig 6). In many institutions such patients often undergo electrophysiologic testing for inducible monomorphic ventricular tachycardia. b D. MCCALL: Since, as is pointed out by Dr. O’Rourke, at least half of the deaths in post-MI patients are sudden and presumably arrhythmic, it would be helpful to have a highly sensitive and specific indicator as to which patients would be most likely to suffer this fate. A recent large study (Circulation 1991; 83:756) evaluated the predictive accuracy of electrophysiologic studies, signal-averaged electrocardiogram, measurements of left ventricular function, and 24 hour holter monitoring, in 360 patients following a myocardial infarction. The patients were followed for one year, and the accuracy of each of the tests for predicting subsequent electrical events was evaluated. This particular study showed that inducible ventricular tachycardia on electrophysiologic testing was the single best predictor of sudden death in this group of patients. Although less sensitive, the signal-averaged electmcardiogram, when positive, was highly specific for predicting subsequent electrical events. It should not be taken from this study that all patients post-myocardial infarction should undergo electmphysiologic testing. It may be advisable, however, to suggest this in patients who are at high risk, i.e., those with very poor left ventricular function, and those who have shown persistent ventricular irritability throughout the hospitalization. Cur-r Probl

Cardiol,

November 1991

735

-I

D-2!ioKz Dowe . OoliIn(UV mctor 1 agnitu,de

’ I’

fhl’8tiOfk8

(nsl:

Std QRS Total QQS Under 4OuV

89 93 i%

” ‘I , ml% vo1trQer (UV) * Tot81 i3RS 55.2 ’ bet 4om 43.7 ’ Noiee 0.3

I&

Voltage9

WI

‘I -100

1 I

-100

U’

u

-

I -50

uv

.’ 1

-

--

‘I

FIG6. Left, a normal signal-averaged, high resolution ECG. Right, abnormal “late potentials” (shaded area). The total filtered right and contains a longer low frequency late component.

a signal-averaged ECG with QRS signal is longer on the

EARLYHOSPITAL COURSE Approximately half of the 15% to 30% of patients at high risk during the first year after myocardial infarction are identifiable on the basis of adverse clinical characteristics observed during the first 4 to 6 days of the hospital stay; specialized noninvasive testing has the greatest independent value for risk stratification in patients without these clinical features. In several studies the patients with the worst

736

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Pmbl

Candid.

November

1991

postinfarction prognosis were those who were unable to undergo further testing, particularly during exercise.lg Indicators of severe left ventricular dysfunction during early hospitalization include persistent sinus tachycardia, a systolic blood pressure 590 mm Hg, a persistent third heart sound, radiographic evidence of pulmonary venous congestion, and/or cardiomegaly.5, ‘OP‘* Electrical dysfunction because of myocardial infarction alone, recurrent myocardial ischemia, markedly impaired left ventricular function, or a combination of these factors also is associated with a high risk of early reinfarction or death. Arrhythmias associated with increased risk include ventricular fibrillation or asystole later than 24 hours after admission, new bundle branch block, second-degree or third-degree atrioventricular block, and atrial tachyarrhythmias.“’ ” Overt myocardial ischemia during hospitalization may be manifested as chest pain after the first 24 hours, new electrocardiographic ST-T wave changes, and a second elevation in cardiac serum enzyme levels .12+” In most patients with evidence of recurrent myocardial ischemia, early coronary arteriography is indicated to determine whether they are candidates for coronary angioplasty or coronary artery bypass graft surgery. In patients with manifestations of severe left ventricular failure, ambulatory electrocardiographic recordings may identify an especially high-risk subset of patients with frequent or complex ventricular premature beats. The prognosis is poorer and the incidence of subsequent ventricular tachycardia is greater in patients with severe left ventricular dysfunction or recurrent myocardial ischemia when the signal-averaged, high resolution electrocardiogram shows “late potentials.“22-24 Medical therapy appears warranted for patients without surgically correctable mechanical abnormalities such as papillary muscle dysfunction, left ventricular aneurysm, or ventricular septal defect unless there is evidence of ischemia producing bypass coronary artery stenoses.

RISK STRATIFICATION

By NONINVASIVE

TESTING

During the past 15 years there has been great interest and many clinical investigations regarding the usefulness of various noninvasive methods, when used at risk and during several types of stress, for separating high risk and low risk patients following an uncomplicated acute myocardial infarction.‘, 12,16,25-37 This approach to risk stratification expanded rapidly after the 1979 report of Theroux and associates38 of a much greater l-year mortality rate (27% vs. 2%) and reinfarction rate (7.8% vs. 0.7%) in patients with ST segment depression during a heart rate-limited, predischarge ECG exercise test. In this and other early clinical studies of predischarge ECG exercise

Curr

Probl

Cardiol,

November

1991

737

testing to detect ischemia,z6,28 cardiac mortality and recurrent myocardial infarction were used as hard end points and therapeutic decisions were not made solely on the basis of the exercise test that was performed. Also, patients included in early studies of postinfarction risk stratification did not undergo myocardial revascularization using either coronary artery bypass graft surgery or coronary angioplasty during the first year of follow-up as often in more recent reports on risk stratification. Most clinical studies have used a submaximal ECG exercise test in the predischarge evaluation of postinfarction. Five METsof exercise expenditure have been recommended as a useful end point in the absence of limiting symptoms such as angina, dyspnea, or fatigue. However, arbitrary limits of 130 beats/min or 70% of maximal predicted heart rate for age have been used to establish the safety of early exercise testing. In the author’s experience,36’ 37 a symptomlimited predischarge ECG exercise test using a low-level exercise protocol (Naughton) yields more information than a heart rate-limited protocol. More high risk patients are identified by the symptomlimited treadmill test. This is not surprising considering the greater duration of exercise, the higher maximum heart rate, and the greater heart rate pressure product attained with a symptom-limited exercise test (Fig 7). More recently, many centers have used a more strenuous (Bruce protocol) exercise protocol before hospital discharge with no increase in morbidity. In any case, safety is maximized when three or more consecutive ventricular premature complexes, ST segment depression >2 mm, or development of exertional hypotension (often indicating global left ventricular ischemia) are used as indicators for terminating exercise.26 Many patients do not exercise enough to be risk-stratified. In fact, the inability to obtain a treadmill workload of four METS on a symptom-limited exercise test 3 weeks after infarction indicates a sixfold increase in the likelihood of cardiac death, nonfatal ventricular fib& lation, or recurrent infarction during the first year after infarction. Failure to achieve a peak systolic pressure of 2110 mm Hg, or an increase in systolic blood pressure of less than 10 mm Hg over baseline values or the pressure of a decrease in systolic pressure during exercise to below baseline values imply a poor prognosis, particularly in active patients not being treated with beta blockers?, *’ Because of the suboptimal sensitivity and specificity of electrocardiographic recordings during exercise, other noninvasive techniques have detected myocardial ischemia and/or depressed left ventricular function at rest or with stress after infarction. Noninvasive tests added to the ECG exercise test that are most commonly used for risk stratification either detect abnormalities of global or segmental left ventricular systolic function during an ischemit episode (echocardiography, radionuclide ventriculography) or 738

Curr

Probl

Cardiol,

November

1991

n=29 *p 5 .Ol **pcOOl

160-

“0 s

a’

30 28

7-

* :i: T

**

* I

HRL SXL FIG 7.

A comparison of heart rate-limited (HRL) and symptom-limited (SXL) exercise tests prior to discharge is shown in 24 patients. The maximum (max) exercise duration, maximum heart rate (beats/mtn), maximum heart rate-pressure product, and METS obtained were all greater with the symptom-limited exercise tests. (From Starling MR, Crawford MH, O’Rourke RA: Superiority of selected treadmill exercise protocols predischarge and six weeks: Post infarction for detecting ischemia heart disease. Am Heart J 1982; 104: 1054- 1060. Used by permission.)

demonstrate reduced myocardial perfusion (thallium 201 imaging) during spontaneous or stress-induced myocardial ischemia. DETECTION

OF MYOCARDW

ISCHEMIA

Several clinical studies of patients who were able to perform sufficient exercise and had electrocardiograms interpretable for exerciseCurr

Probl

Car-dial,

November

1991

739

induced ischemia indicate a higher incidence of reinfarction and/or cardiac death in the first year after myocardial infarction in those with ST segment depression and/or angina during low-level ECG exercise testing prior to hospital discharge or 3 weeks after infarction.27-30 Predischarge ECG exercise testing is recommended because a cardiac event in unidentified high risk patients may recur prior to their postdischarge risk stratifying exercise test as indicated in a study of 89 patients who were scheduled to undergo both a prehospital discharge and an outpatient ECG exercise test 6 weeks after infarction.32 The second test was unobtainable in 19 patients, 9 of whom had a cardiac event prior to the scheduled 6 weeks postinfarction treadmill test, All nine had an abnormal predischarge exercise test and the cardiac events occurred despite restriction of their activity.32 The decision whether to perform a predischarge and subsequent 6-weeks postinfarction treadmill ECG tests for low risk patients or one test only 3 weeks after infarction will vary depending on the characteristics of a medical center’s infarction patient population and where they will receive their long term followup. b GA. BELLER: Our practice is also to perform exercise testing prior to hospital discharge for risk stratification in acute myocardial infarction. If one waits until 4-6

some tion. such nary lium

weeks postdischarge to perform a maximum symptom-limited

stress test,

high-risk patients will have already experienced cardiac death or reinfarcIf a patient is unable to exercise because of noncardiac limiting factors as arthritis, previous stroke, orthopedic abnormalities or chronic pulmodisease (without active bronchospasm), dipyridamole or adenosine thal201 imaging should be considered for assessing prognosis.

Other important factors to be assessed during the exercise test include the heart rate and blood pressure response to exercise and the development of new symptoms or physical findings during or after stress testing. An inadequate rise in blood pressure is common in patients with left main or severe three-vessel coronary artery disease, and new bibasilar rales, gallop rhythm, reversed splitting of S,, or a murmur of mitral regurgitation may be markers of exerciseinduced ischemia even when electrocardiographic findings are inconclusive. Because ST segment depression during exercise is a nonspecific response and both false-positive and false-negative ECG test results occur, thallium 201 myocardial perfusion imaging is a useful and more accurate method for detecting exercise-induced areas of myocardial ischemia after infarction. I6 It is not surprising that stressinduced thallium defects with subsequent redistribution 3 to 24 hours later occur during exercise in certain patients in the absence of either ECG, ST segment depression, or angina pectoris, the latter two frequently occurring as later manifestations of myocardial ischemia?‘!““ Figure 8 shows the sequence of events occurring during 740

Cut-r ProLd

Cardioi,

November 1991

FIG 8. Sequence of events during an episode of myocardial ischemia that may or may not result In ECG abnormalities and/or angina. The events are indicated in circles and test what mtght detect the presence of ischemia in rectangles. (From O’Rourke RA: The current and future usefulness of noninvasive techniques, in Knoebel SB, Daek S (eds): An ERA in Cardiovascular Medicine. New York, Elsevier, 1991, pp 16-24).

an episode of myocardial ischemia and the test commonly employed for their detection. Exercise stress-redistribution scintigraphy with thallium 201 has been used at 4 to 10 days after onset of infarction for predischarge risk stratification and the detection of residual ischemia because thallium imaging has been more sensitive and specific in detecting ischemia than exercise ECG testing alone. Gibson et al.16 reported on the accuracy of predischarge quantitative exercise thallium 201 scintigraphy for predicting future cardiac events in 140 asymptomatic patients recovering from acute uncomplicated infarction. The authors examined and compared the results of submaximal exercise treadmill testing, thallium 201 scintigraphy, and coronary arteriography. All patients were tested before hospital discharge, and each evaluation was carried out as part of a prospective research protocol rather than for specific clinical indications. During a mean follow-up of 16 months, 7 patients died of cardiac causes (5 suddenly), 9 had recurrent nonfatal myocardial infarction, and 34 patients experienced unstable angina pectoris requiring rehospitalization. Thallium scintigraphy was more sensitive than either treadmill exercise testing or coronary arteriography in identifying the 50 patients with subCurr

Pmbl

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1991

741

sequent clinical cardiac events (Fig 9). Indeed, the presence of defects caused by thallium involving different vascular beds, delayed redistribution in one or more scan segments showing an initial significant defect, and increased lung uptake (indicating pulmonary venous hypertension) detected all but three high risk patients, including 15 of 16 patients (94%) who either died or suffered reinfarction. By comparison, exercise ECG identified only 8 of 16 patients (50%) with “hard” events, including 3 of 9 (33%) who experienced reinfarction. In addition, 12 of 13 patients (92%) with single-vessel disease who had a cardiac event during follow-up demonstrated thallium 201 redistribution within the infarct region. Thallium 201 scintigraphy performed immediately after intravenous dipyridamole (0.56 mgkg over 4 min) and several hours later has been used to detect stress-induced myocardial ischemia in patients unable to perform an exercise test.41’ 42 Severe ischemia, bronchospasm, or hypotension can be reversed by intravenous aminophylline?l The results appear equivalent to thallium 201 exercise testing. Intravenous adenosine, which has a very short half-life and reportedly fewer side effects, is being evaluated as a substitute coronary artery dilator to dipyridamole for stress thallium imaging. The ACC/AHA recommendations for the noninvasive testing of low-risk patients by clinical indicators using ECG stress testing for risk stratification are shown in Table 2. Class I = usually indicated, always acceptable and considered usually effective. Class II = acceptable of uncertain efficiency and may be controversial (IIa = weight of evidence in favor of usefulness/efficiency; IIb = not well established by evidence, can be helpful and probably not harmful). Class III = not indicated, may be harmful. b D. McCall: There is no doubt, as is pointed out by the author, that exercise testing, with “‘Tl scintigraphy, is the most sensitive and most specific test for residual ischemia in the post-infarct patient. It clearly defines those with ischemia at a distance and accurately pinpoints those who require further investigation in the way of selective coronary arteriography and potential evaluation for PTCA and coronary artery bypass grafting. The question of the timing of this particular non-invasive evaluation may be critical and it is probably optimally carried out between day 7 and 10 post-infarction. One rather disconcerting report (Circulation 1991; 83:12781, showed that there were relatively frequent (49% 1 negative stress “*Tl tests when the test was carried out between 72 and 96 hours after thrombolytic therapy for an acute myocardial infarction. The interesting aspect in this study, was that it was the patients with the most extensive infarction, as measured by peak creatine kinase, who were most likely to show negative early stress -Tl scintigraphy. This was surprising in view of the fact that angiography had shown a residual 88% stenosis of the corresponding coronary arteries. It is possible that stunning with impaired membrane “‘Tl transport could have been responsible for this, and perhaps later rather than earlier application of zolTl sclntigraphy would be more valuable in detecting residual ischemia myocardium. 782

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Probl

Carciiol,

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1991

SMXT TEST

IO8 _ -*ST&ond/or ---‘NO

AP

ST & or AP

p~ooll

6-

TL-201 SCINTIGRAPHY ,8 _

=MTD and/or Rd/?LU --*IT&No Rd or? LU p
6-

CORONARY

IO i r;

8

0” a 5

6

u

---

=2or ~0.1

ANGIOGRAPHY

3VD VD

r-4

P*ooo?

~o~~~~~---y , r

24

Trme FIG

30

36

(months)

9.

Cumulative probability of cardiac events as a function of time for different subgroups formed by the exercise test response (top), scintigraphic findings (middle) or arteriographic findings (bottom) before hospital discharge. The solidlines and dashed lines represent the high risk and low risk cumulative probability, respectively. SMXT = ; AP = ; MTD = multiple thallium effects; Rd = redistribution; LU = lung uptake, VD = (From Gibson RS, Watson DD, Craddock GB, et al: Prediction of cardiac events after uncomplicated myocardial infarction: A prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography. Circulation 1983; 68:321-336. Used by permission.) Cum Probl

Cardiol,

November

1991

743

TABLE 2. Recommendations Clinical Indicators*

for Noninvasive

Evaluation

of Patients

at Low

Risk by

Class I 1. Stress ECG. (al Before discharge for prognostic assessment (submaximal at 6 to 10 days or symptom-linked at 10 to 14 days). (bJ Early after discharge for pmgnostic assessment and functional capacity t3 weeks) (cl Late after discharge (3 to 8 weeks) for functional capacity and prognosis if early stress was submaximal. 2. Exercise thallium 201 scintigraphy (whenever baseline abnormalities of the ECG compromise its interpretation). Class IIa 1. Exercise thallium 201 scintigraphy; before discharge for prognostic assessment with symptom-limited exercise at 10 to 14 days. 2. Dipyridamole thallium 201 scintigraphy (before discharge for prognostic assessment in patients judged to be unable to perform exercise) (pending expected Food and Drug Administration appmval). 3. Exercise radionuclide ventriculography predischarge at 10 to 14 days or early after discharge for prognostic assessment. 4. Exercise two-dimensional echocardiography (before discharge or early after discharge for prognostic assessment). Class IIB 1. Stress ECG. la) At any time to evaluate patients with a class I indication and baseline ECG abnormalities or coexisting medical problems that limit ability to achieve maximal exertion. In some of these patients, exercise testing may still yield clinically valuable information (duration of exercise, blood pwssure response, production of chest discomfort, etc). (b) Before discharge or early after discharge to evaluate patients who have sustained complicated myocardial infarction, but who have subsequently ‘stabilized” and for whom a decision for invasive evaluation has not been made. 2. Exercise thallium 201 myocardial scintigraphy (late after discharge at 6 to 8 weeks for prognostic assessment). 3. Dipyridamole thsllium or dobutamine thallium before discharge in patients judged unable to exercise (not appmved by the Food and Drug Administration for this indication). Class III 1. Stress ECG. (a) Within 72 hours of acute myocardial infarction. (b) At any time to evaluate patients having unstable postinfaxtion angina pectoris (cl At any time to evaluate patients with acute myocardial infarction who have uncompensated congestive heart failure, cardiac arrhythmia, or noncardiac conditions that severely limit their ability to exercise. Id) Before discharge to evaluate patients who have already been selected for cardiac catheterization. In this situation, an exercise test may be useful after catheterization to evaluate function or identify ischemia in distribution of a coronary lesion of borderline severity ‘Modified patients

744

from Gunner RM, Bourdillon PDV, Dixon DD, et al: Guidelines for the early management with acute myocardial infarction. JAm Co/l Candid 1990; 16249-292. Used by permission.

Cum- Prwbl

Cardiol,

November

of

1991

b GA. BELLER: Recently, repeat thallium 201 imaging after reinjection of a second dose of thallium following acquisition of the delayed 4-hour redistribution images has improved detection of myocardial viability (Dilsizian et al, N Engl J A4ed 1990; 323:141-146). Approximately 30% of persistent defects seen on postexercise and redistribution images show visually-enhanced thallium uptake on reinjection imagea, thereby increasing accuracy of distinguishing between ischemia and scar by myocardial perfusion imaging.

Ambulatory ECG recordings are useful for detecting episodes of ST segment depression or elevation in some patients after myocardial infarction who have symptomatic or “silent’ myocardial &hernia, but their sensitivity and specificity are still being defined and the majority of patients with true ischemic ST segment changes on ambulatory ECG recordings also will demonstrate ischemia during ECG exercise testing. In fact, the routine use of ambulatory ECG recordings to determine the presence of ischemic ST segment changes in patients after infarction is not recommended? 43 Rest and exercise measurements of the left ventricular ejection fraction help assess prognosis in patients after infarction; a suboptimal increase (<5 units) or an actual reduction in ejection fraction during exercise indicates an increased risk for subsequent cardiac events.35 However, the specificity of an abnormal response in the left ventricular ejection fraction during exercise for indicating myocardial ischemia, either measured by radionuclide angiography or twodimensional echocardiography, is relatively poor, particularly in women and the elderly. An abnormal exercise response is also frequent in patients with other forms of cardiac disease (e.g., aortic valve disease). Regional wall motion abnormalities usually develop during exercise-induced myocardial ischemia, often before abnormalities in global left ventricular systolic function and usually in the absence of diagnostic electrocardiographic changes and/or angina. Therefore, the detection of exercise-induced left ventricular wall motion abnormalities by two-dimensional echocardiography or radionuclide angiography has been used after infarction to detect atients who are at increased risk for subsequent cardiac events.3” r 4P35 Several clinical reports indicate that the assessment of left ventricular wall motion during or soon after exercise by two-dimensional echocardiography provides valuable information for the risk stratification of many patients after myocardial infarction.33’42 However, noninvasive imaging techniques for assessing regional wall motion have several limitations because of spatial resolution and the tethering of normal to abnormal myocardium. Furthermore, exercise echocardiography is not applicable to all patients and does not allow complete visualization of all myocardial segments in many others.40 In patients unable to exercise, stress-induced wall motion abnormalities appearing after intravenous administration of the coronary artery dilators dipyCurr

Probl

Car&l,

November

1fB1

746

ridamole or adenosine or of the positive inotropic agent dobutamine have been used to detect postinfarction myocardial ischemia.M An adequate prospective study comparing the usefulness of thallium myocardial perfusion imaging and exercise two-dimensional echocardiographic studies of regional wall motion for determining high risk in the same patients has not yet been reported. Also, the additional yield for detecting patients at increased risk for death or recurrent infarction by either of these two techniques has not been defined in patients with a negative optimal ECG exercise test in whom the duration and extent of exercise was sufficient, in whom abnormalities on the resting ECG did not preclude the interpretation of the results, and in whom no clinical evidence of increased risk during exercise was detectedPO Preliminary data from such a study currently underway at The University of Texas Health Science Center in San Antonio suggests enhanced sensitivity of both thallium 201 imaging and two-dimensional echocardiography during or after exercise when compared with ECG exercise testing; a higher percentage of patients and number of myocardial segments could be evaluated by thallium 201 imaging. Abnormalities in left ventricular diastolic function have been well documented during episodes of spontaneous or stress-induced myocardial ischemia. Both Doppler transmitral valve velocity recordings and radionuclide ventriculography time-activity curves have been used to assess left ventricular diastolic function.40 However, the accuracy, sensitivity, and specificity of these two noninvasive techniques for detecting left ventricular diastolic dysfunction during ischemic episodes compared with invasive hemodynamic measurements remain to be defined. Studies reported thus far have failed to show a favorable accuracy in these two noninvasive techniques when compared with the time constant of isovolumic relaxation or pressure-volume (dimension) relationships.“5 The prognosis after infarction in patients with angina associated with ischemia in the infarct zone (“per-i-infarct” ischemia) has been compared with that in patients who had postinfarction angina with coincident ECG ST-T wave changes outside the area of the prior infarction (“distant” or “remote” ischemia) in the study by Schuster and Bulkley.46 Untoward cardiac events occurred much more frequently in patients with ischemia at a distance than in those with ischemia in the infarct zone. Peri-infarct ischemia defined as thallium 201 redistribution in the area of a recent myocardial infarction is a common interpretation of postinfarction stress imaging studies, even in patients with neither chest pain nor ST segment changes during exercise. Whether or not this finding has the same prognostic significance as redistribution thallium defects in areas remote from the tied defect resulting from the prior infarction remains unanswered. The finding of peri-infarct 746

Curr

Probi

Cardiol,

November

1991

thallium redistribution defects without thallium uptake by the lung, systolic ventricular dilatation, or remote areas of reduced uptake, indicates little increase in risk. Resting wall motion abnormalities, as determined by echocardiography, radionuclide ventriculography, or contrast ventriculography, are commonly present in areas of previous myocardial infarction. The prognostic importance of worsening wall motion (e.g., from hypokinesis to akinesis) in the infarct area during exercise compared with new or worsening (e.g., hypokinesis to dyskinesis) wall motion abnormalities outside the area of infarction remains to be defined. In our prospective study in San Antonio, per&infarct ischemia by echocardiographic wall motion exercise studies is an even more common diagnosis than pee-infarct ischemia by exercise thallium imaging.

DETECTION

OF IMPAIRED

VENTRICULAR

PERFORMANCE

The predischarge resting global left ventricular ejection fraction correlates with subsequent survival after recovery from myocardial infarction. As previously indicated, a progressive increase in the l-year mortality rate after myocardial infarction occurs as the left ventricular ejection fraction, measured by radionuclide ventriculography, decreases to <40%.’ Several indirect indicators of left ventricular dysfunction in postinfarction patients exist, including symptoms of pulmonary venous hypertension or decreased cardiac output, and physical findings indicative of impaired left ventricular systolic an&or diastolic function. Exercise tolerance is another indirect indicator of left ventricular function. Most postinfarction patients with a left ventricular ejection fraction of less than 40% have either ST segment depression and/or angina during exercise tests and/or are unable to complete five or more METS of low-level ECG treadmill exercise testing without developing signs or symptoms of left ventricular decompensation.26 For the noninvasive quantitation of left ventricular systolic function, both radionuclide ventriculography and two-dimensional echocardiography are readily available (see Fig 8). Doppler echocardiography has also been used for this purpose but is less reliable. Radionuclide ventriculography can be applied to more patients for assessing segmental systolic wall motion but two-dimensional echocardiography is more sensitive for the detection of left ventricular thrombi, which are particularly common in patients with an anterior Q wave myocardial infarction. However, if one routinely prescribes three months of anticoagulation for patients with a recent anterior wall myocardial infarction,*z the need to determine whether or not an apical thrombus is present is debatable. Serial echocardiographic Curr

Probl

Cardiol,

November

1991

747

studies show a variable time of left ventricular thrombus formation, and a “negative” echocardiogram does not rule out the subsequent presence of ventricular clot.47 DETECTION

OF VENTRICULAR

ARRHYTHML4S

Twenty-four hour ambulatory ECG recordings before discharge detect less than one premature ventricular complex per hour in more than 50% of postinfarction patients, and their Z-year mortality rate is less than 5%.5 By contrast, the 15% to 25% of patients with 10 or more premature beats after infarction on ambulatory recordings have a &year mortality rate of greater than 20% .a Although frequent and complex ventricular premature beats at rest or with exercise are independent risk factors affecting prognosis, their impact on risk is greater when associated with either marked depression of left ventricular function or myocardial ischemia. Furthermore, there is no proven benefit of successful suppression of nonsustained ventricular arrhythmias after myocardial infarction, and the proarrhythmic effects of currently available antiarrhythmic drugs may be lethal. Therefore, the routine use of continuous ambulatory ECG recordings after infarction is not indicated. The signal-averaged electrocardiogram assesses chronic cardiac electrical instability; its clinical role is not yet fully defined. In several studies, the presence of “late potentials” on the signal-averaged ECG correlates with late ventricular tachycardia after myocardial infarction, independent of the frequency of spontaneous ectopy and the presence of left ventricular aneurysm.22-24~ 4s These studies suggest that the signal-averaging ECG provides a useful index for electrical myocardial instability, particularly in patients with severely depressed left ventricular systolic function, which often is associated with sudden death and sustained ventricular tachycardia. Many clinical investigations are being performed to assess the sensitivity, specificity, and reliability of signal-averaged ECG in various subgroups of patients with recent myocardial infarction. Whether or not all patients who have had myocardial infarction with late potentials on the signal-averaged ECG should undergo electrophysiologic testing is debatable. In a recent report by Kuchar et a15’ late potentials on the signal-averaged ECG in a canine model of infarction were correlated with inducible ventricular tachycardia on electrophysiologic testing. Recently, it has been shown that an abnormal signal-averaged ECG with late potentials is most likely to be detected 7 to 10 days after an acute myocardial infarction and tends to correlate with a “closed” infarct-related coronary artery by arteriography.51 However, the relatively low positive predictive accuracy of the high resolution ECG in 748

Curr

Probl

Cardiol,

November

1991

patients after myocardial infarction emphasizes the need for continued methodologic refinements that will increase its diagnostic its use for the risk stratification of patients power.24 Nevertheless, with remote infarction having nonsustained ventricular tachycardia appears promising. Those patients with abnormal signal-averaged ECG are more prone to inducible sustained monomorphic ventricular tachycardia. In many centers such patients with “late potentials” on the high resolution ECG will undergo electrophysiologic testing with subsequent decisions based partly on the presence or absence of inducible ventricular tachyarrhythmia. Electrophysiologic testing has been used to risk stratify many patients with coronary artery disease and ventricular ectopic activity. When sustained ventricular tachyarrhythmia is inducible, the l-year mortality, even on antiarrhythmic drugs, exceeded 30% vs. 2% in those without inducible arrhythmias.5 Because of no randomized trials, the application of electrophysiologic studies to evaluate ventricular ectopic activity occurring late after acute myocardial infarction remains controversial.4s PRACTICAL

APPROACH

TO RISK

STRATZFZCATZON

Several important factors should be considered when ordering noninvasive diagnostic tests for patients recovering from acute myocardial infarction. These include the quality of the available laboratory for performing the specific test(s), and the sensitivity, specificity, and accuracy of the test(s) and their cost and accuracy compared with alternative methods. How a positive or negative result will affect subsequent clinical decisions is an important factor. As might be expected, the better approach at one medical center may differ from that at another. Different laboratories for performing echocardiographic or nuclear cardiac imaging studies vary in the equipment available and the expertise of specially trained staff. Clinical decision-making, in patients with recent myocardial infarction, focuses on the patients’ preinfarction indicators of high risk; the clinical evidence of recurrent myocardial ischemia, persistent left ventricular decompensation or recurrent cardiac arrhythmias during the initial 4 days of hospitalization; and on risk stratification of patients to low or high risk groups using noninvasive methods that detect evidence of myocardial ischemia, severely depressed left ventricular performance, and/or frequent ventricular ectopy (Fig 10). Patients with myocardial infarction complicated by persistent congestive failure, persistent or recurrent myocardial ischemia, or recurrent cardiac arrhythmias are usually referred for coronary arteriography unless a contraindication to further intervention is present.5’ I2 Cur-r Probl

Cardiol,

November

1991

749

PROGNOSTIC STRATIFICATION HYOCARDIAL INFARCTION

r

Days

1-4:

CLINICAL (Ischemia,

ASSESSMENT LV function,

t Days

4-10:

IN POST PATIENTS

Arrhythmias?) No High Risk Characteristics

PRE-DISCHARGE EVALUATION Symptom-Limited ETT (Thallium or Wall Motion

Study)

No Ischemia or LV Dysfunction Days

40-60:

POST-DISCHARGE EVALUATION ETT (Thallium or Wall Motion

Maximum

Study)

No Ischemia or LV Dysfunction LOW RISK 1st year

CATEGORY mortality

< 2%

FIG 10. Schematic representation of an approach to predischarge and subsequent postdischarge risk stratification of postinfarction patients. ETT = exercise treadmill testing; LV = left ventricular. (From O’Rourke RA: Post myocardial infarction risk stratification: Clinical overview. Circulation (in press). Used by permission.)

For effective risk stratification of the large group of patients with uncomplicated myocardial infarction, an exercise test with electrocardiographic monitoring is a minimum requirement for patients who are able to exercise.” In the author’s opinion, risk stratification should be performed prior to discharge. Others believe it should be initiated 3 weeks after infarction.12 A low-level, symptom-limited electrocardiographic treadmill exercise test should be done between the fourth and tenth day after infarction to determine the presence of exercise-induced myocardial ischemia. As indicated previously, a symptom-limited rather than heart rate-limited ECG exercise test identifies more high-risk patients.37 A more strenuous exercise protocol, which is used at many institutions is associated with low morbidity. Coincident thallium myocardial imaging currently is sug750

Curr

Probl

Cardiol,

November

1991

gested for many patients, and definitely for patients with electrocardiographic abnormalities that make the interpretation of the ECG response to exercise difficult. An alternative approach is to record exercise-induced wall motion abnormalities, in addition to the electrocardiogram, during exercise or immediately after exercise using two-dimensional echocardiography or radionuclide ventriculography. b GA. BELLER: It should be emphasized that exercise myocardial perfusion imaging with thallium 201 or one of the newer technetium S9m imaging agents (Sestamibi; Tebomxime) requires meticulous attention to quality control in imaging technique and well-experienced and trained interpreters to obtain the maximum benefit for clinical decision making. If image artifacts are mistakenly interpreted as representing perfusion defects, some patients will be referred for unnecessary coronary angiography. When used optimally, radionuclide imaging of perfusion and viability can add significantly to the risk stratification process by sparing patients with low-risk scan findings premature catheterization and by identifying high-risk patients that will benefit from early angiography with a view toward revascularization even in absence of symptoms.

To detect additional negative predischarge

cases of exercise-inducible ischemia despite a low-level exercise test in patients after myo-

cardial infarction, a repeat high-level near maximum heart rate With thallium

exercise test 201 imaging

to maximum or and/or echocar-

diographic determination of wall motion abnormalities is recommended 6 to 8 weeks after myocardial infarction.36’ 37 More patients at risk will be identified with a Bruce exercise ECG protocol at this time than with low-level symptom-limited exercise testing (Naughton protocol) because of a greater maximum heart rate and heart rate blood pressure produced With the Bruce protoco13’ (Fig 11). Patients with a negative ECG and thallium treadmill exercise test have a very low incidence of cardiac events during the next year, with a mortality rate of less than 2% .I2 However, patients with a negative test who are unable to perform at least 5 METS of activity during exercise testing have not been adequately stratified, and often require additional noninvasive tests (e.g., radionuclide ventriculography) or cardiac catheterization. Three different strategies for the predischarge or early postdischarge exercise evaluation of patients with a recent myocardial infarction are included in a recent report by the ACCAHA Subcommittee on Guidelines for the Early Management of Acute Myocardial Infarction7 (Fig 12). The workup of patients with spontaneous myocardial ischemia and/or persistent depression of left ventricular systolic function usually is more extensive and usually includes cardiac catheterization and coronary arteriography. b R.C. SCHLANT: We also generally prefer to perform both a pm-discharge test and a post-discharge ECG exercise test 4 to 8 weeks post-myocardial infarction. Cum Probl

Cardiol,

November 1991

751

n= 31 tp<.02 *sp< .OOl .-5 ‘J

16-

.- _;A Lz x 5

864-

5 I+- T n l2- 1 $7 IO2-

-I-

2 B

h P

30 28 26

l60Q, l50E l40lx t z l30XQ l2015 I IO:: IOO2 go-

**: 6 t $ 2

l4l2IO8642-

I

0’ L

SXL B

FIG 11. Comparative effects of symptom-limited, low-level (SXL) treadmill testing and a Bruce (B) protocol stress test on maximum exercise duration, maximum heart rate (beats/min), heart rate-blood pressure product and METS achieved in 31 patients studied 6 weeks after infarction. (From Starling MR, Crawford MH, O’Rourke RA: Superiority of selected treadmill exercise protocols predischarge and 6 weeks: Post infarction for detecting ischemia heart disease. Am HeartJ 1982; 104:1054-1060. Used by permrssion.)

For the test prior to discharge we individualize and usually use a Bruce protocol or, for older patients or patients with clinical evidence of significant left ventricular dysfunction, a modified Bruce or Naughton protocol. Often we use a submaximal test when it is performed 5 to 10 days after the infarct and a symptom-limited test when it is performed 10 or more days after the infarct. We also 752

Curr

Probl

Cardiol,

November

1991

FIG 12. Strategies Bourdillon management 16:249-292.

use with that

for predischarge or early post discharge exercise evaluation. PVD, Dixon DW, et al: ACC/AHA Task Force Report: Guidelines of patients with acute myocardial infarction. J Am Co/l Used by permission.)

concurrent thallium electrocardiographic may occur.

ROUTINE

CARDIAC

myocardial abnormalities

imaging that

in many limit the

(Gunnar RM, for the early Cardiol 1990;

patients, especially value of any ECG

those changes

CATHETERIZATION

Although some clinicians recommend cardiac catheterization and coronary arteriography for the majority of patients who survive an acute myocardial infarction,52 the indications for cardiac catheterization, left ventricular cineangiography, and selected coronary arteriography in patients with a recent myocardial infarction remain controversial.53 The recent report of the ACCIAHA Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures5 provides guidelines for recommending or not recommending coronary arteriography: (1) during the initial 6 hours of myocardial infarction; (21 after the initial 6 hours, up to but not including predischarge evaluation; and (3) from immediate predischarge up to 8 weeks after discharge. The desirability for accurately identifying patients who are at high risk for recurrent cardiac events (sudden and nonsudden cardiac Cum

Probl

Cardiol,

November

1991

753

death, myocardial infarction, and unstable angina) during the first year and subsequent years of follow-up and for defining patients who are likely to live longer after coronary artery bypass graft operation or percutaneous transluminal coronary angioplasty PICA) must be balanced against the financial cost and cardiac catheterization facilities necessary for the invasive study of most postinfarction patients.53 These considerations would include patients who can be identified as being at low risk for subsequent cardiac events and those who are not suitable for invasive interventions. As previously indicated, a low risk subgroup of patients can be confidently defined with a careful clinical evaluation prior to hospital discharge that considers preinfarction clinical characteristics, the hospital course after myocardial infarction, and the patient’s predischarge clinical status. The addition of low-level to maximum electrocardiographic exercise testing and of rest and exercise radionuclide or echocardiographic studies to the assessment of patients with a recent uncomplicated myocardial infarction permits further stratification of risk, with high risk patients usually being referred for early cardiac catheterization and coronary arteriography.8-12’ 52--54 As discussed earlier, other techniques such as ambulatory ECG recordings, the signal-averaged thigh resolution) ECG, and electrophysiologic testing may provide more prognostic information but does not yet improve survival in appropriate patients with antiarrhythmic therapy.lg Ischemia-induced arrhythmias often are impaired by coronary artery bypass surgery and patients with ventricular aneurysms often are arrhythmia-free after aneurysm resection. Definite clinical indications for cardiac catheterization and coronary arteriography soon after infarction include recurrent angina or ECG changes of myocardial ischemia, persistent moderate to severe left ventricular dysfunction, and uncontrollable ventricular tachyarrhythmias.l” 52, 53 The most important use of cardiac catheterization continues to be the diagnosis of cardiac disease. In the group of patients who have had a well-documented myocardial infarction, the arteriographic presence of a 270% coronary artery stenosis of one or more arteries is highly likely (>90% of cases), except in unusual circumstances in which myocardial infarction is caused by coronary artery spasm or embolization of thrombus from the heart to the coronary arteries.53 Occasionally, an anomalous coronary artery may be the only abnormality present in a patient with myocardial infarction, particularly in those under 30 years of age. Thus, except in rare instances, cardiac catheterization usually is not used after infarction to document the presence of coronary artery disease.53 It is well known that the extent of coronary artery occlusive disease is a major prognostic factor for patients who survive acute myocardial infarction. Also, there is a general consensus that selected 764

Cum

Probl

Cardiol,

November

19%

patients with left main coronary artery disease or three-vessel disease have improved longevity after coronary artery bypass graft surgery in contrast to medical therapy.15 In addition, the availability of coronary angioplasty for patients with appropriate coronary artery lesions and the sometime occurrence of unusual forms of coronary artery disease are positive arguments for obtaining knowledge of the coronary artery anatomy in all patients after myocardial infarction. Because there are currently no noninvasive techniques that permit visualization of the complete coronary artery circulation, each patient after acute myocardial infarction ideally should undergo selective coronary arteriography. Although desirable for prognostic and therapeutic considerations, it is not practical to apply coronary arteriography to every postinfarction patient in the United States today. Importantly, the routine performance of cardiac catheterization and coronary arteriography in these patients will lead to a greater number of interventional procedures, particularly coronary angioplasty, in a group of patients without evidence of myocardial ischemia who are at low risk of recurrent cardiac events, even with no therapy. Again, it must be emphasized that for any amount of one, two, or three-vessel coronary artery disease and for any degree of normal or reduced left ventricular systolic function, the patients’ survival curve varies greatly, with early mortality being related to the severity and frequency of myocardial ischemia.15 In the study by Gibson et al., the detection of exercise-induced myocardial ischemia was more accurate than coronary arteriography in predicting subsequent prognosis in patients after infarction.‘” Currently, the most common reason for performing cardiac catheterization soon after acute myocardial infarction is to obtain an anatomical assessment of cardiac structural lesions (coronary arteries, left ventricle, mitral valve) when an invasive intervention is being considered. There is a consensus for recommending coronary arteriography in patients with early evolving myocardial infarction who develop clinical evidence of pump failure (shock), have auscultatory or echocardiographic evidence of acute interventricular septal rupture, or in whom persistent or recurrent myocardial ischemia is indicated despite thrombolytic therapy.5 It is also recommended by many clinicians for patients who, within the first 6 hours of infarction, have contraindications to thrombolytic therapy but not to FICA or surgery, and for patients who have had bypass graft surgery where the infarct-related artery is a previously bypassed vessel.5 Some physicians recommend coronary arteriography for patients who can be taken quickly to an appropriate facility where emergency catheterization, PICA, and bypass graft surgery are readily available. This is particularly relevant to patients with an acute Q wave anterocostal wall myocardial infarction. Very early coronary arteriography is not recommended as a routine procedure for patients Curr

Probl

Cardiol,

November

1991

755

receiving thrombolytic therapy or for other patients with an uncomplicated myocardial infarction who have no evidence of recurrent or persistent &hernia. The ACC/AHA Task Force5 report recommendations for coronary arteriography in patients with early evolving myocardial infarction are shown in Table 3. In patients in the first 6 hours after the onset of myocardial infarction, the most accepted criteria for recommending coronary arteriography are similar and include episodes of ischemic chest pain, particularly if associated with ECG or other noninvasive indicators of an ischemic etiology; acute mitral regurgitation or ventricular septal defect as suspected causes of heart failure or shock; the presence of a pseudoaneurysm as evidenced by noninvasive testing; and cardiogenie shock or severe heart failure5 Coronary arteriography also is recommended by many physicians for patients with congestive heart failure during intensive medical therapy and for those with recurrent ventricular tachycardia or ventricular fibrillation despite rigorous antiarrhythmic therapy. Coronary arteriography is an alternative approach used by many physicians to evaluate asymptomatic patients who received antithrombolytic therapy earlier during the evolving phase of infarction. Many of the patients, who were initially risk-stratified, will subsequently be referred for cardiac catheterization. Late inhospital coronary arteriography is definitely not indicated for patients with uncomplicated completed myocardial infarcTABLE

Early

3.

Evolving

Myocardial

Infarction

(Initial

Hours

of Myocardial

Infarction)

Class I 1. All patients developing pump failure/shock syndrome. 2. All patients suspected of developing an acute ventricular septal defect 3. Persistent or recurrent &hernia, or both, despite thrombolytic therapy. Class Da 1. When coronary angiography can be performed within the first 6 hours after the onset of chest pain in patients who are candidates for revascularization therapy using percutaneous transluminaI coronary angioplasty or comnary artery bypass surgery (but who are not candidates for thrombolytic therapy). 2. Patients who have had a previous aortocomnaty vein graft if the graft is to the suspected infarct-related vessel. Class IIb 1. Patients who can be taken quickly for angioplasty or bypass surgery in a facility designed for these emergency procedures. Class IIi 1. As a mutine after early intravenous thmmbolytic therapy. 2. Patients with uncomplicated myocarclial infarction having no evidence of ongoing ischemia. Fmm Gunner Rhf, Bouniilloo PDV, Dinon DD, et al: Guidelines for the eariy management with acute mpxardial infarction. J Am Cdl Cardiol 1990; 16249-292. Used by permission.

766

Curr

Probl

Cardioi,

of patients

November

1fIBl

tion in whom no acute mechanical or surgical intervention is contemplated. The ACUAHA Task Force report5 recommends coronary arteriography for appropriate convalescent myocardial infarction patients (immediate predischarge to 8 weeks after discharge) who have postinfarction angina or evidence of myocardial ischemia on laboratory testing. Coronary arteriography tends to be recommended by many clinicians for patients returning to a physically or emotionally demanding employment and for those with a less than 40% left ventricular ejection fraction.5’ 12,53 There is less supporting evidence for routine coronary arteriography in all patients who have had thrombolytic therapy, uncomplicated and asymptomatic patients under age 45, and patients with non-Q wave infarction but no inducible ischemia by noninvasive testing.5 The ACUAHA Task Force recommendations for coronary arteriographic evaluation are indicated in Table 4. Coronary arteriography in the convalescent stage of infarction is not indicated in patients who, for various reasons, are not candidates for mechanical or surgical myocardial revascularization. It is usually not useful in patients with left ventricular ejection fraction of less than 20% when neither angina nor other evidence of ischemia is present. Positron emission tomography may provide evidence of underpeffused yet viable myocardium in some of these patients” and revascularization may improve ventricular function. Additional exceptions include patients with potentially resectable ventricular aneurysms and those who are candidates for cardiac transplantation. Arteriography is not indicated in patients with ventricular arrhythmias, but no symptomatic or inducible ischemia and preserved exercise tolerance, unless an aneurysm is suspected, or sustained ventricular tachycardia is inducible. b CA. BELLER: Some postinfarction patients with severe multivessel coronary artery disease and an left ventricular ejection traction SO%persistent defect) rarely show improved wall motion after revascularization.

It is medically sound and cost effective to identity high and low risk subgroups of patients when considering the need for cardiac catheterization and for aggressive medical or surgical management in relation to the risk of subsequent cardiac morbidity and mortality.78 12,53 Cur-r Probl

Cardid,

November

1991

757

TABLE

4.

Convalescent Myocardial After Discharge)

Infarction

(Immediate

Predischarge

up to 8 Weeks

Class I 1. Patients with postinfarction angina pectoris. 2. Patients with evidence of myocatdial ischemia on laboratory testing: exercise-induced ischemia (with or without exercise-induced angina pectoris), manifested by 21 mm of ST segment depression or exercise-induced reversible thallium perhision defect or defects, increased lung thallium uptake or exercise-induced ejection fraction or wall motion abnormalities on radionuclide ventriculography or two-dimensional echocardiography. Class IIa 1. Patients with the need to return to unusually active and vigorous physical employment. 2. Patients with a left ventricular ejection fraction <40%. Class IIb 1. As a routine in patients receiving thmmbolytic therapy during the evolving phase of infarction. 2. Othenvise uncomplicated and asymptomatic patients who are 45 years of age or younger. 3. Patients with uncomplicated non-Q wave myocardial infarction with no evidence of myocardial ischemia on noninvasive laboratory testing. Class III 1. Patients with a debilitating disease or condition that will interfere with invasive intervention. 2. Patients with coexisting disease that is primarily responsible for the patients’ prognosis, and a greatly shortened life expectancy, unless mvascularization is deemed necessary to facilitate treatment of the underlying disease. 3. Patients with very advanced left ventricular dysfunction (ejection fraction <20%) in the absence of angina pectoris or evidence of ischemia. An exception is the patient who is a candidate for aneurysmectomy or cardiac transplantation. 4. Patients with ventricular arrhythmias who have no evidence of ischemia symptomatically or during exercise testing, well preserved exercise tolerance, and no suggestion of aneurysm formation. An exception may be the patient with inducible sustained ventricular tachycardia. Modied patients

from Gunner RM, Bourdillon PDV, Dixon DD, et al: Guidelines for the early management with acute myocardial infarction. J Am Co/l Cardiol1990; 16249-292. Used by permission.

of

SUMMARY

Recurrent myocardial ischemia, moderate to marked depression of left ventricular systolic function, and late-occurring or recurrent cardiac arrhythmia indicate increased risk for patients with acute myocardial infarction. Some patients, on the basis of high risk and/or unsuccessful response, will be early candidates for early aggressive diagnostic and therapeutic procedures. Others will have clinical indicators of increased risk during hospitalization that warrant diagnostic coronary arteriographic assessment before discharge. Still other patients with low risk clinical characteristics can be further stratified by predischarge or early postdischarge stress testing for 758

Cur-r

Probl

Cardiol,

November

1991

myocardial occurrence be treated higher risk medical or

ischemia, left ventricular functional reserve, and/or likely of arrhythmias. Some stratified to low risk patients will only with secondary prevention measures. Others at will undergo more aggressive evaluation and subsequent surgical therapy.

b GA. BELLER: Dr. O’Rourke has written an erudite and comprehensive review of the noninvasive and invasive approaches to risk stratification after acute myocar-dial infarction, drawing upon the most current published data on the subject. He presents a very balanced view on a somewhat controversial topic, providing evidence that “routine” cardiac catheterization in infarct sutvivors is unnecessary and that functional evaluation under resting and stress conditions provides a useful initial step in prognostication. b R.C. SCHLWT: Dr. O’Rourke-has pmvided a thorough but concise statement of non-invasive and invasive testing of patients after myocardial infarction. It is important to emphasize that the proper testing of an individual patient must be determined by the responsible physician who is familiar with the local facilities available. The appropriate management algorithm for a patient in a given hospital may be quite ditferent if the same patient were in a different hospital. An additional risk factor for recurrent cardiac events is the level of serum cholesterol. This was clearly identified as a potent continuing factor in the Coronary Drug Project”’ although it is not as strong an indicator as left ventricular dysfunction, evidence of myocardial ischemia or ventricular ectopy. Recent studies have provided strong evidence that aggressive therapy to lower elevated levels of total cholesterol and low density lipoprotein (LDL) cholesterol can significantly decrease the incidence of cardiac events and even the angiographic progression of coronary artery disease?-*’ Such data makes it even mom important for the responsible physician to diagnose and treat hyperlipidemia. It may well be that we should try to lower the LDL cholesterol to levels below 100 mgdl in order to produce an early and significant effect. Even if there is no detectable regression of the size of coronary athemmata, the lowering of abnormally high concentrations of LDL cholesterol and total cholesterol may be associated with a significant improvement in the “activity’ and the tendency of the athemma to fissure, in the thmmbogenic activity of its contents, and in the thmmbogenic factors in blood. The continuation of cigarette smoking is also a strong risk factor in patients following a myocardial infarction.” This excellent review by Dr. O’Rourke should be of great value to all physicians who help care for patients with acute myocardial infarction. b D. MCCALL: In this review, the author has provided the reader with an excellent overview of a very important facet of care for the patient with an acute myocardial infarction. This review is an invaluable resource for cardiologists and internists who have to be concerned for the appropriate follow-up care to improve the ultimate survival of the patient with coronary disease. Dr. O’Rourke has given an excellent review of all non-invasive and invasive tests designed to select the high-risk from the low-risk patient. The “take home” message is that risk stratification, as indeed all other aspects of the care of the infarct patient, should be individualized. Performing standard tests, by mte, may on the one hand miss some aspects that are important to risk stratification or on the other hand prove to be very cost inefficient. Only by individualizing the tests based on Curr

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careful clinical observation of the patient effective manner, be carried out.

will optimal

risk stratification,

in a cost

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