DIAGNOSTIC METHODSCORONARY ARTERY DISEASE

Noninvasive prediction of the angiographicextent of coronary artery disease aftermyocardial infarction: comparison of clinical,bicycle exercise electrocardiographic, andventriculographic parametersDENISE D. MORRIS, B.S. _ ALAN ROZANSKI. M.D., DANIEL S. BERMAN. M.D.,GEORGE A. DIAMOND, M.D.. AND H. J. C. SWAN. M.D., PH.D.

ABSTRACT To assess alternative criteria for the prediction of multivessel coronary artery diseaseafter myocardial infarction, we compared the clinical, bicycle electrocardiographic, and radionuclideventriculographic (ejection fraction and wall motion) responses in 110 patients undergoing coronaryangiography after myocardial infarction. Ninety-seven of the 1 10 patients had multivessel coronaryartery disease (two or more diseased vessels). Clinical or electrocardiographic abnormalities wereobserved in 41 of 97 (sensitivity = 43%) patients with multivessel disease, and in only two of 13(specificity = 85%) patients without multivessel disease. The average information content of thesecombined clinical and electrocardiographic variables relative to perfect discrimination was 5%. Amongthe scintigraphic parameters, the conventional criterion for ejection fraction abnormality, a rise of lessthan 5% had a sensitivity of 72% and a specificity of 62% for multivessel coronary artery disease, whilea fall in ejection fraction of 5% or more had a sensitivity of 39% and specificity of 92% for multivesselcoronary artery disease. The presence of an exercise wall motion abnormality in the nonadjacentnoninfarcted (remote) region had a sensitivity of 82% and specificity of 55% for multivessel coronaryartery disease. A more stringent criterion, worsening of remote wall motion with exercise, had asensitivity of 52% and specificity of 75%. When this latter criterion was combined with a fall inejection fraction, the sensitivity for multivessel coronary artery disease increased to 62%, specificityremained 75%, and information content increased from 5% to 10%. We conclude that conventionaldiagnostic criteria for abnormal clinical, bicycle electrocardiographic, or scintigraphic results do notidentify patients with additional coronary artery disease after infarction with high accuracy. Twoalternative ventriculographic parameters a fall in ejection fraction and wall motion worsening -aresimilar to clinical parameters in specificity, but have a higher sensitivity and information content.Circulation 70, No. 2, 192-201, 1984.

IN MOST exercise radionuclide laboratories the samecriteria for abnormality appear to be used in patientsreferred for diagnosis of coronary artery disease as inthose with previous myocardial infarction referred forfunctional evaluation. Thus, 32 of 41 studies `l either

From the Division of Cardiology. Department of Medicine, and theDepartment of Nuclear Medicine. Cedars-Sinai Medical Center. and theDepartment of Medicine UCLA School of Medicine. Los Angeles.

Supported in part by NIH SCOR grant No. 17651.Dr. Rozanski is supported by a grant-in-aid from the American Heart

Association. Greater Los Angeles Affiliate.Address for correspondence: Alan Rozanski, M.D.. Division of Car-

diology, Cedars-Sinai Medical Center, 8700 Beverly Blvd.. Los Ange-les, CA 90048.

Received Oct. 21. 1983: revision accepted April 26, 1984.*Current address: c/o Office of Student Affairs. School of Medicine,

University of California. San Diego, LaJolla, CA 92093.

192

pooled patients referred for diagnosis and postinfarc-tion patients in determining the sensitivity and speci-ficity of exercise radionuclide ventriculography or ap-plied the same criterion of abnormality to the separatepopulations. 1-19

The question asked of the test in a patient beingdiagnosed ("Is disease present?") differs from that in apostinfarction patient ("Is additional disease pres-ent?"). For the postinfarction patient, in whom diseaseis almost always present, the goal of testing is to pre-dict prognosis. However, in the absence of a largebody of data regarding prognosis, a decision to per-form angiography often follows from noninvasive teststhat indicate disease is present in more than one vascu-

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lar territory. However, conventional criteria for diag-nosis may not optimize the identification of postinfarc-tion patients with multivessel disease. The purpose ofour study, then, was to evaluate alternative criteria forexercise ejection fraction and segmental wall motion inpredicting the extent of angiographic coronary arterydisease in postinfarction patients and to compare theaccuracy of these predictions to those based on clinicalevaluation and bicycle stress electrocardiography.

MethodsPatient selection criteria. The study population consisted of

patients meeting the following selection criteria. Each patienthad a history of a single prior transmural myocardial infarctionas confirmed by resting electrocardiographic examination andangiographic evidence of coronary artery disease. Infarct loca-tion was anterior (anterior, anterolateral, anteroseptal) in 58patients and posterior (posterior, posterolateral, inferior, infero-lateral) in 52.42 Patients with electrocardiographic evidence ofboth anterior and posterior infarction were excluded, as werepatients with normal coronary arteriograms, valvular disease, orprevious coronary bypass surgery. All patients underwent bothexercise radionuclide ventriculography and coronary angiog-raphy within 3 months of infarction and there were no interven-ing cardiac events. Testing was performed 6 weeks or longerafter infarction. One hundred and ten patients met these criteria,including 97 men and 13 women ranging in age from 26 to 83years (mean 56 + 1 1).

Assessment of chest pain. Seventy patients had a history ofchest pain. Before testing, an examining cardiologist assignedone of four chest pain symptom classifications to each patient,according to the characteristics of the pain (substernal location,exertional precipitation, and prompt relief by rest or nitroglycer-in).43 If all three characteristics were present, pain was classi-fied as typical angina (34 patients), if two were present, it wasclassified as atypical angina (13 patients), and if less than twocharacteristics were present, pain was considered nonanginal(23 patients). The 40 remaining patients were asymptomatic.

Exercise protocol. Exercise was performed on an uprightbicycle ergometer in conjunction with radionuclide ventriculog-raphy. /3-Blocking drugs were withheld for at least 24 hr beforetesting; long-acting nitrates were withheld for the day of testing.Before imaging each patient was injected with 25 mCi of redblood cells labeled with technetium-99m in vitro. Patients per-formed graded stress tests beginning at a workload of 200 kilo-pond-meters (kpm) per minute and increasing by 200 kpm every3 min of exercise. Exercise was maximal, and was terminatedby the physician only for severe chest pain, serious arrhythmia,or exertional hypotension (>10 mm Hg fall in systolic bloodpressure from any previous recorded level during stress). Cardi-ac rhythm, ST segments, and heart rate were continuously mon-itored during and after exercise, and blood pressure was record-ed at rest, during the third minute of each exercise level, andafter exercise.

Exercise electrocardiography. The electrocardiographic re-sponse to exercise was not evaluated in patients with electrocar-diographic evidence of left ventricular hypertrophy, left bundlebranch block, or in patients taking digitalis (18 patients). Thedepth of ST segment depression was measured at 0.08 sec afterthe J point relative to the PR segment. The stress test wasconsidered positive if horizontal or downsloping ST segmentdepression of 1.0 mm or more was noted during exercise orrecovery. If ST segment depression was present at rest, anadditional 1.0 mm was required for abnormality.

Imaging protocol. With a mobile scintillation camera/com-puter system equipped with an all-purpose collimator, multiple-gated imaging was performed immediately before stress testingand during the last 2 min of each exercise stage. Images wereobtained in the 40 to 50 degree left anterior oblique view, withthe exact angle of obliquity determined by that which best sepa-rated the left and right ventricles. Acquisition was obtained over20 frames of equal duration distributed uniformly over the cardi-ac cycle (approximately 100,000 counts per frame).Image analysis. Left ventricular end-diastolic, end-systolic,

and background regions of interest were manually assigned, andrest and exercise left ventricular ejection fractions were calcu-lated as the number of stroke counts divided by the background-corrected end-diastolic counts.44 The exercise ejection fractionresponse was characterized as a "rise" if it increased by at least0.05 from that at rest,22 27 as "flat" if it changed less than 0.05from that at rest, and as a "fall" if it decreased by 0.05 or morefrom that at rest.

Left ventricular images were evaluated in a closed-loop com-puter video display after spatial and temporal smoothing forimage enhancement.44 Segmental wall motion was assessed byat least two experienced observers without knowledge of clini-cal data on the patients. For each image, the left ventricle wasdivided into five segments, and segmental wall motion wasscored on a five-point scale as follows: 3 = normal wall motion;2 = mild hypokinesis; 1 = moderate hypokinesis; 0 = akine-sis; -1 = dyskinesis.45 Differences in determinations weremediated by joint interpretation.The two following criteria for wall motion abnormality were

compared: (1) any peak exercise abnormality (score < 3),which is the conventional diagnostic criterion,7-21 and (2) anyexercise-induced "worsening" of normal or resting hypokineticsegments, defined as a decrease of at least one grade from rest topeak exercise. A change from akinesis to dyskinesis, however,was not considered worsening.Coronary angiography. Coronary angiography was per-

formed in multiple projections by the Judkins technique. Theextent of narrowing of luminal diameter was determined by aconsensus reading of at least two experienced angiographers.Coronary artery disease was defined as 50% or more narrowingof luminal diameter of a major branch of any coronary vessel.Multivessel disease was defined as coronary artery disease of atleast two of the three major coronary arteries (left anterior de-scending, left circumflex, and right). According to this defini-tion, isolated left main disease was considered to be a form ofmultivessel disease. Regional wall motion abnormalities wereattributed to specific coronary vascular distributions; the leftanterior descending coronary artery was considered to supplythe anterior circulation, while the left circumflex and right coro-

nary arteries were considered to supply the posterior circulation.The two septal segments were assigned to the distribution of theanterior circulation, and the two posterolateral segments to thedistribution of the posterior circulation. The segment betweenthese regions, representing the inferior wall or apex or both,depending on the orientation of the heart, was termed the infero-apex and was analyzed separately. For the prediction of mul-tivessel disease, wall motion parameters were evaluated in thenonadjacent, noninfarcted myocardial region, termed the re-

mote region. Specifically, the posterolateral segments were

evaluated in the patients with prior anterior infarction and theseptal segments were evaluated in the patients with prior poste-rior infarction.Data analysis. Age, exercise duration, rest and peak exercise

heart rate, systolic blood pressure, and ejection fraction valueswere compared as continuous variables with an unpaired t testfor multivessel vs single-vessel disease patient groups. Theremaining clinical, electrocardiographic, and scintigraphic pa-

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rameters were analyzed as dichotomous variables with the chi-square test or Fisher's exact test. A p value of .05 or less wasconsidered significant. The accuracy of a given sensitivity/specificity combination was defined by its average informationcontent, 1, expressed as a percentage relative to the informationprovided by coronary angiography46:

1 [ap log, (ap) + bq 1og2 (bq) -

j

(ap + bq) log2 (ap + bq)] p log2 Pi

where a = true positive rate; b false-positive rate; pprevalence (from 0 to 1); q = 1 p.

ResultsAngiographic findings. The 110 patients were divided

into four subgroups based on angiographic findings.Thirteen patients had single-vessel and 97 patients hadmultivessel disease, including 32 with double-vesseland 52 with triple-vessel coronary artery disease (andno left main coronary artery stenosis). The 13 otherpatients with multivessel disease had left main coro-nary artery disease; all had concomitant left anteriordescending and left circumflex coronary artery dis-ease, and 10 had additional right coronary artery dis-ease. In each patient with single-vessel disease, theangiographically determined location of disease corre-sponded to the location of infarction as determined byresting electrocardiography. Of 58 patients with ante-rior infarction, 50 (86%) had additional disease of theposterior circulation, and of 52 patients with posteriorinfarction, 40 (78%) had additional disease of the ante-rior circulation.

Clinical and electrocardiographic response. The clinicalprofiles of the patients and rest/exercise hemodynamicfindings according to the extent of coronary arterydisease are summarized in table 1. A history of typicalangina was twice as common in patients with multives-sel disease as in patients with single-vessel disease (p< .01), but most clinical and hemodynamic findingsdid not vary significantly.The frequency of clinical and electrocardiographic

abnormalities induced by graded bicycle exercise foreach angiographic subgroup is illustrated in figure 1.Fifty-six patients experienced chest pain, ST depres-sion, or hypotension during exercise, while the other54 stopped exercise only because of fatigue. Exercise-induced chest pain and ST depression each occurredwith low frequency in all patient subgroups, exceptamong patients with left main coronary artery disease.Exertional hypotension was uncommon in all sub-groups, occurring in only six patients in this study.Although clinical and electrocardiographic abnormali-

TABLE 1Clinical and hemodynamic profiles of patients

Extent of coronary artery disease

SVD DVD TVD Left main

n 13 32 52 13Age (years) 49 - 13A 54 ± 10 59 ± 11 64 ± 09% Male 88 81 88 78Chest pain (t7c)

Asymptomatic 38 41 35 3 1Nonanginal 38 22 17 15Atypical 8 6 15 15Typical 16A 31 33 38

Rest HR 75±12 74-12 75±12 73±18Rest BP 128±18 131 +23 130±16 137+30Peak HR 134 22 141 23 130 ± 16 130 24Peak BP 176+35 183+34 172+29 176+36Min ex 10±4 10±4 9+3 8±3B

SVD = single-vessel disease; DVD = double-vessel disease; TVDtriple-vessel disease; HR = heart rate: BP = systolic blood pressure;

Min ex = minutes of exercise.Ap < .01 vs multivessel disease; Bp < .05 vs single-vessel disease.

ties were associated with multivessel disease - 22 of23 (96%) patients with exercise chest pain, 22 of 25(88%) patients with ST depression, and all six patientswith exertional hypotension had multivessel diseasethe relatively low sensitivities of these variables madethem poor predictors of extent of disease. Even whenthese variables were analyzed in combination, the abil-ity to predict multivessel disease was poor. Only 42(43%) of the 97 patients with multivessel disease hadany clinical abnormality (i.e., chest pain, ST depres-sion, or hypotension), while two (15%) of the 13 pa-tients with single-vessel disease also had one abnor-mality or more; information content was only 5%.There were no significant differences in clinical orexercise electrocardiographic parameters among pa-tients with single-vessel or multivessel disease.Response of ejection fraction. Figure 2 illustrates the

magnitude of change in ejection fraction from rest topeak exercise, characterized as a rise, flat, or a fall.Although the mean value of change in ejection fractionwas significantly lower in patients with multivesseldisease (-0.05 ± 0.08) compared with in patientswith single-vessel disease (+0.02 ± 0.09; p < .05),there was a wide overlap of functional responses. Thechange in ejection fraction during exercise rangedfrom -0.27 to + 0. 19 in patients with multivesseldisease, and from -0.13 to +0.18 in patients withsingle-vessel disease. The conventional diagnostic cri-terion for an abnormal ejection fraction response (lessthan 0.05 rise) did not accurately distinguish patientswith from those without multivessel disease. An ab-

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100

50

CHEST PAIN

OLi100 _

$oe50

oLJ100 _

+ ECG

HYPOTENSION

ae 501-

OSVD DVD TVD L MAIN

CAD EXTENTFIGURE 1. The frequency of clinical and electrocardiographic abnor-

malities induced by graded bicycle stress in each angiographic subgroupof patients with prior infarction. A stepwise increase in the frequency of

abnormality with increasing extent of coronary artery disease (CAD) is

observed. SVD = single-vessel disease; DVD = double-vessel dis-ease; TVD = triple-vessel disease; LMain = left main disease.

normal response was observed in 70 of 97 multivesseldisease patients (sensitivity = 72%), but was alsonoted in five of 13 single-vessel disease patients(specificity = 62%). A flat response was observed in33% (32 of 97) of patients with multivessel disease andin 31% (four of 13) of patients with single-vessel dis-ease. A fall in ejection fraction, on the other hand, was

observed in 38 patients with multivessel disease (sensi-tivity = 39%), and in just one patient with single-vessel disease (specificity 92%). Thus, a fall inejection fraction was a specific but relatively insensi-tive predictor of multivessel disease in this population.As a group, the patients with left main disease had thepoorest responses, and no patient in this group had a

greater than 5% increase in exercise ejection fraction.Response of wall motion. Since the assessment of exer-

cise wall motion was limited to a single view, wallmotion analysis was confined to the region remote

from that of infarction (figure 3). A remote wall mo-

tion abnormality was noted in 74 of 90 postinfarctionpatients with multivessel disease (sensitivity = 82%):37 of 50 (74%) with posterior circulation disease andanterior infarction had posterolateral wall motion

Vol. 70, No. 2, August 1984

abnormalities, and 37 of 40 (93%) with anterior circu-lation disease and posterior infarction had septalabnormalities (p < .05). However, only nine of 20patients without multivessel disease had completelynormal wall motion in the remote region at peak exer-

cise (specificity = 45%). When wall motion worsen-

ing in the remote region was used to predict multives-sel disease, sensitivity decreased to 52% andspecificity increased to 75%. Seven patients had thecombination of disease of the posterior circulation in-volving both the left circumflex and right coronary

arteries and no disease of the anterior circulation. Fourof these patients had a septal wall motion abnormalityat peak exercise, but only one patient had worsening ofwall motion in the septum with exercise, again reflect-ing the greater specificity of this criterion. Two ofthese patients also had worsening of wall motion in theposterior circulation.When worsening of wall motion was analyzed in

combination with a fall in ejection fraction, the sensi-tivity for predicting multivessel disease increased to

+0.25

+0.15

+0.05LLW

-0.05

-0.151

-0.25

SVD DVD TVD L MAINCAD EXTENT

FIGURE 2. The ejection fraction response to exercise, shown as the

change from rest to peak exercise (AEF), with reference to extent of

coronary artery disease (CAD) and infarct location (anterior infarction= closed circles; posterior infarction = open circles). The area above

and including the upper dashed line represents a rise in EF, the area

between the dashed lines represents a flat EF response, and the area

below and including the lower dashed line represents a fall in EF. MI

myocardial infarction; other abbreviations as in figure 1.

195

INFARCT LOCATION* Anterioro Inferior

* 0

00 000

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100 REMOTE ABNORMALITYO Anterior

Inferior

8e 50 _

°°r REMOTE WORSENING

50j-

0 L-

FIGURE 3. Sensitivities and specificities of wall motion parameters fo

predicting disease of the remote coronary circulation after infarctionTwo criteria were examined: any remote abnormality at peak exercis(top) and remote exercise-induced worsening (bottom). Striped barsummarize results in patients with anterior infarction, solid bars those i]patients with posterior infarction. MI = myocardial infarction.

62% and specificity remained 75%. This combinatioiwas more sensitive, although slightly less specificthan the combined clinical and exercise electrocardiographic variables (table 2). The average informatiorcontent of ventriculographic parameters was twice thaof the combined clinical and exercise electrocardiographic parameters, but this difference was not statistically significant.

Analysis of the inferoapex. Since 93 (85%) of the 1 1(

patients had resting inferoapical wall motion abnormalities, we analyzed only exercise-induced worsen

ing in this region with respect to the prediction o

multivessel disease. In patients with prior anterior infarction, worsening in the inferoapical region was no

associated with disease of the posterior circulation (j= .697). In patients with prior posterior infarctionhowever, inferoapical worsening was associated wit}disease of the anterior circulation (p = .017). Therefore, in patients with prior posterior infarction, inclusion of the inferoapical region as part of the remote(noninfarct) region increased sensitivity for multivessel disease from 60% to 73%, while specificity re

mained 75%.

196

Discussion

Ml Our results indicate that no single clinical, electro-Ml cardiographic, or scintigraphic abnormality is both

highly sensitive and specific for the prediction of mul-tivessel disease in patients with prior infarction. Thenonscintigraphic variables we evaluated were all in-sensitive as predictors of multivessel disease. For ex-

ample, exercise-induced chest pain and ST depressionwere each noted in less than 25% of the patients withmultivessel disease, while exercise-induced hypoten-sion was observed in only 6%. Even the combinedanalysis of these parameters the presence of anyabnormality was insensitive in identifying the pres-

ence of multivessel disease; abnormalities were detect-ed in less than half of such patients.The ejection fraction response to exercise showed

considerable overlap among angiographic subgroups.The conventional definition of an abnormal rest/exer-cise ejection fraction response in patients without in-farction (less than 0.05 rise), was not effective in sepa-

rating the subgroups of patients with prior infarctionbecause it was nonspecific. Nevertheless, no patient

)r with left main disease had a greater than 0.05 rise in1. exercise ejection fraction. In contrast, an ejection frac-e tion fall during exercise was much more specific, but.s much less sensitive, for detecting multivessel disease.n We examined two criteria for interpretation of re-

gional wall motion relative to the prediction of addi-tional disease the presence of any exercise abnor-

n mality in the myocardial region remote from the site of

TABLE 2

n Comparison of variables in the prediction of multivessel diseaseafter infarction

it

f

~t

p

Sensi- Speci- Infor.. ~~~mation

tivity ficity concontent

n/total % n/total % (%)

Clinical responseAExercise chest pain 22/90 44 19/20 95 6Exercise ST depressionC 22/73 30 16/19 84 2Exercise hypotension 6/90 7 20/20 100 3Any abnormality 40/90 44 16/20 80 5

EF responseAFlat or fall (<0.05 rise) 68/90 76 13/20 65 12Fall (-0.05) 39/90 43 19/20 95 15

Wall motion responseRemote region abnormality 74/90 82B 11/20 55 10Remote region worsening 47/90 52 15/20 75 5Worsening or EF fall 56/90 62 15120 75 10

EF = ejection fraction.AData reanalyzed to correspond to wall motion analysis.Bp < .05 for anterior vs posterior infarction.CExcludes 18 patients. as described in text.

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infarction, and the presence of exercise-induced wors-

ening in these regions. The former, more liberal, crite-rion proved to be relatively sensitive, but nonspecific,while the latter was less sensitive but more specific forthe presence of multivessel disease. As with other car-

diac tests,46 then, a predictable tradeoff in sensitivityand specificity for the detection of multivessel diseaseresults from revising the criteria for abnormality.

In our study, the development of worsening wallmotion was more sensitive than clinical or electrocar-diographic abnormalities in detecting multivessel dis-ease after infarction. These data correlate with the em-piric observations of others. Various investigatorshave reported that chest pain is a late manifestation ofmyocardial ischemia, and that it is commonly preced-ed by the development of hemodynamic and electro-cardiographic abnormalities.47 50 Upton et al.',4 for ex-

ample, demonstrated that abnormalities in leftventricular function were present at the first level ofexercise in 22 of 25 patients with coronary artery dis-ease before angina pectoris or electrocardiographic ab-normalities developed. Similarly, Kimchi et al.5" ob-served that wall motion abnormalities during the firststage of exercise occurred twice as frequently as STdepression. The higher sensitivity that we observed forexercise wall motion abnormalities in this study, there-fore, is not surprising. Our ability to identify multives-sel disease in patients with prior anterior infarction,however, may be limited by our use of a single 45degree left anterior oblique view, since the myocardialregion supplied by the right coronary artery is not

visualized. For example, in a patient with anterior in-farction, left anterior descending coronary artery dis-ease, and additional right coronary artery disease, one

would not expect to see a posterolateral wall motionabnormality with exercise. In this regard it is not sur-

prising that our results in predicting additional diseasein patients with inferior infarction were superior tothose in patients with anterior infarction. We havenoted that the addition of a second, anterior view exer-

cise study aids in the evaluation of the extent andlocation of coronary artery disease.52 53

Comparison to previous studies. Although few reportson exercise radionuclide ventriculography were spe-

cifically designed to assess its ability to predict extentof disease after infarction,40 41 we were able to extractthe combined experience with 963 such patients from a

total of 21 studies31' 33-35, 3740, 5t66 (table 3). A numberof trends are evident. First, as in our study, no nonscin-tigraphic parameter is both highly sensitive and specif-ic in predicting the presence of multivessel disease.Results of the few studies reporting the frequency ofexercise-induced chest pain or ST segment depressionduring bicycle exercise are in accord with those of our

study.40 54 Second, both exercise-induced chest pain

and ST depression occurred almost twice as frequentlywith treadmill exercise as with bicycle exercise. This isalso consistent with our experience. In a previousstudy we evaluated 36 patients undergoing treadmilland bicycle exercise within 2 weeks of each other andfound the frequencies of chest pain and ST depressionto be 17% and 28%, respectively, during bicycle exer-

TABLE 3Summary of the pooled medical literature: prediction of multivessel disease

Sensitivity Specificity Information

n/total % n/total % content (%)

Bicycle stressChest pain40 54 36/96 38 29/40 73ST depression54 16/47 34 18/22 82 2

Treadmill stressChest pain55, 56 76/133 57 56/65 86 15ST depression34 55 61 217/365 59 107/145 74 8Hypotension62 3/17 18 23/23 100 9

Stress-redistribution thallium scintigraphyMultiple visual defects35' 63, 64 41/73 56 23/25 92 20Multiple quantitative defects65 24/36 67 20/24 83 18

Exercise radionuclide ventriculographyAbnormal EF response31' 33, 34, 37-40, 66, A 115/139 83 39/71 55 11EF faII31, 33, 34, 37-40 71/138 51 43/61 70 3Remote wall motion worsening40 19/51 37 23/23 100 22EF fall or remote wall motion worsening40 38/51 75 18/23 78 20

EF = ejection fraction.ALess than 0.05 rise with exercise.

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cise, but 50% and 70%, respectively, during treadmillexercise.67 Thus, had we used treadmill rather thanbicycle exercise the accuracy of predicting multivesseldisease by electrocardiography may have improved.Third, scintigraphic parameters appear to be more sen-

sitive than clinical parameters in predicting the pres-

ence of multivessel disease. 3 1.3-35, 37-40. 63-66 This highersensitivity, however, was dependent on the criterionemployed. Wasserman et al.40 observed a lower sensi-tivity and higher specificity for exercise-induced wors-

ening of wall motion than that in this study, but theyapplied a more stringent definition of worsening a

score that decreased by at least two grades in the re-

mote region.With an experimental design parallel to that of this

study, Wasserman et al.40 reported a somewhat highersensitivity and correspondingly lower specificity foran ejection fraction fall of 0.05 or more. This differ-ence may represent the effect of the exercise protocolon the ejection fraction response,68 or may represent a

difference in patient populations.69 7( With respect tothe former possibility, our patients performed uprightexercise, while their's performed supine exercise.Most studies comparing upright and supine exercise,

however, indicate a similar ejection fraction response

in the two positions.7' 7 With respect to the latter pos-

sibility, our study population had a significantly higherprevalence of multivessel disease (88% vs 69%, p-.002) and a higher proportion of females (15% vs 5%,p = .062).

Several studies have used submaximal exercise test-ing early after infarction (before hospital discharge)(table 4).65- 73-79 These studies suggest that the sensitiv-

ity of scintigraphy for detection of multivessel diseasemight be somewhat higher (and specificity somewhatlower) than that of conventional "late" (postdis-charge) evaluation. Results were similar, however, inthe two studies in which the same patients were exam-

ined both early and late. One study compared the ven-triculographic response to exercise at 3 and 8 weeksafter infarction,4` while the other compared the resultsof thallium stress testing at 2 weeks and 3 months afterinfarction.6` These results imply that the same radionu-clide test criteria might be useful for both periods.

Limitations of the present study. In assessing the non-

invasive test parameters we used a highly conventionalmethod of classification of the coronary anatomybased on the presence or absence of multivessel dis-ease. This classification is justified by a clinical fact oflife: the physician often decides to catheterize a patienton the basis of noninvasive test results indicating dis-ease in at least one vessel outside the infarct zone.

Second, since we sought to compare our results tothose of previous investigations, we adopted the classi-fication most often used in these studies. We recog-

nize, however, that this classification is both arbitraryand simplistic. There is a continuum of the extent andseverity of coronary artery disease that is not represent-ed by single vs multivessel disease assignments be-cause of such factors as degree of stenosis, proximityof stenosis to the coronary orifice, length and numberof stenoses, and the adequacy of collateral circula-tion."3' Newer methods for expressing the degree ofcoronary artery disease are being devised8' and thesemay ultimately provide better correlation between an-

giographic data and noninvasive test results.

TABLE 4Summary of the pooled medical literature: prediction of multivessel disease before hospital discharge

Sensitiv ity SpeciftcityInf'ormaltion

n/total % n/total % content (%)

Bicycle stressChest pain73 74 40i66 61 30/41 73 6ST depression73. 74 39/66 59 28/41 68 J

Treadmill stressChest pain75-77 43/77 56 47/50 94 22ST depression73-7 41 77 53 39/48 81 9

Stress-redistribution thallium scintigraphyMultiple visual defects74 78 36/50 72 34/47 72 14Increased lung uptake79 15/32 47 21/27 78 5Multiple quantitative defects65 75 45/64 70 46/48 96 37

Exercise radionuclide ventriculographyAbnormal EF73 A25 256 96 6/16 38 13EF fall73 16!26 62 3i16 19 3

EF = ejection fraction.ALess than 0.05 rise with exercise.

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A second limitation of this study derives from theassumption that knowledge of coronary anatomy accu-rately predicts cardiac prognosis. Thus, while cardiacevents occur more often in patients with angiographi-cally more severe disease, resting left ventricular func-tion remains a potent predictor of prognosis inde-pendent of anatomy.82 Our current experience withthallium-201 and exercise blood pool scintigraphysuggest that these studies may provide independentpredictors of prognosis. Jones et al.,13 for example,recently reported that combined knowledge of exerciseejection fraction and coronary anatomy better predict-ed benefit from coronary bypass surgery than knowl-edge of anatomy alone. Patients with coronary arterydisease and normal exercise ejection fraction re-sponses fared no better after surgery than their medicalcohorts without surgery. Furthermore, Gibson et al.84demonstrated that low-level stress-redistribution thal-lium scintigraphy is more accurate than coronary an-giography in predicting subsequent cardiac events overa 36 month period. Of note is the fact that, in theirstudy, new events occurred in 13 of 58 (22%) postin-farction patients with single-vessel coronary artery dis-ease and 12 of these had a high-risk thallium pattern.Similarly, with the use of exercise radionuclide ventri-culography, Nicod et al.73 found that 11 of 16 postin-farction patients with single-vessel disease had a majorcardiac event within a follow-up period of 8 months,and the prognostic outcome was correctly predicted in13 of these patients by the change in ejection fraction.73In the present study, such single-vessel disease pa-tients with exercise-induced ischemia after infarctionwould have been classified as "false positive" foradditional disease. Additional work is needed to clari-fy whether consideration of the more relevant clinicalquestion regarding prognosis obviates the limitationsof this technique in predicting multivessel coronaryartery disease.We conclude that abnormal clinical responses, in-

cluding chest pain, ST depression, and hypotensionduring bicycle exercise yield high specificity but lowsensitivity for detection of multivessel coronary arterydisease in patients with prior myocardial infarction. Incontrast, the conventional diagnostic criteria for radio-nuclide ventriculography are relatively sensitive butnonspecific for identifying additional disease in pa-tients with prior infarction. Two alternative scinti-graphic criteria, however, appear to be more specificpredictors of remote disease in patients with myocardi-al infarction: worsening of wall motion in the distribu-tion of the remote circulation and an ejection fractionfall during exercise. These data imply that the interpre-Vol. 70, No. 2, August 1984

tation of scintigraphic (and probably other) tests can beimproved by independent optimization of criteria indiagnostic and postinfarction populations.

We thank Patricia Allen, Joye Nunn, Jurate Sutor, and Bar-bara Voigt for their technical assistance, Lance Laforteza forillustrations, and JoAnn Prause, M.S., for statistical advice.

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