Thorax, 1981, 36, 428-434 Use of exercise tests in assessment of the functional result of aortocoronary bypass surgery I Y LUKSIC, J A RAFFO, DA S G MARY, D A WATSON, P B DEVERALL, AND R J LINDEN From the Department of Cardiovascular Studies, University of Leeds, and Department of Medical Cardiology, Eastern and Western Districts, Leeds Area Health Authority, Leeds ABSTRACT The value of an objective exercise test for the assessment of the functional results of aortocoronary bypass was investigated in 19 patients who were studied before and six months after the operation. For positive tests the end point was defined as a net ST segment depression of 0-1 mv 80 ms after the J point of the ECG. For negative tests the end point was 85% of the age-predicted maximal heart rate response. One patient who was not able to attain either of these points after the operation was excluded. In the remaining 18 patients three indices were used in the analysis. First, the heart rate (HR) and the product of heart rate and systolic blood pressure (RPP) were measured at the defined level of ST segment depression during positive exercise tests to yield HR/ST and RPP/ST threshold respectively. Second, the HR and RPP were measured at the end point of the negative tests. Third, the duration of exercise till the end point of the tests was measured. In each patient the duration of the postoperative test was longer than that of the preoperative test. While all the patients had a positive exercise test before the operation, the test was negative in 11 after it. In 10 of these 11 patients the HR and RPP at- tained at the end point of the postoperative test had increased; the HR and RPP remained unchanged in one patient. Positive tests were still present in seven of the 18 patients. In five of these the HR/ST threshold and RPP/ST threshold were greater after than before operation, and they remained unchanged in two. An improvement in myocardial blood supply after aorto- coronary bypass was suggested indirectly by the ability to attain, during exercise, a higher HR and RPP at the end point of the test. The test proved especially valuable in patients who re- tained a positive exercise test after the operation. Aortocoronary bypass is widely used in the treat- ment of coronary artery disease. While it has been shown that the operation is associated with an acceptable rate of graft patency, evidence that it leads consistently to reversal of regional myo- cardial ischaemia especially in patients with more than one bypass graft has been scarce.' 2 Recently a non-invasive exercise test with an objective end point was used to study the effects of physical training in patients with angina pectoris caused by coronary artery disease.3 It was shown that the ability to attain during exercise a greater heart rate and systolic blood pressure at a predetermined level of ischaemic ST segment depression, could Address for reprint requests: Professor RJ Linden, Department of Cardiovascular Studies, The University of Leeds, Leeds LS2 9JT. be attributed to an improvement in myocardial blood supply.3 The present study was planned prospectively to investigate whether, using this method in patients in whom a bypass operation had been performed, there was an improvement in myocardial blood supply. Subjects and methods Nineteen consecutive patients, in whom the diag- nosis of angina pectoris caused by coronary artery disease was established by the ischaemic response during exercise electrocardiography and by sel- ective coronary arteriography, were investigated before and after aortocoronary bypass. Patients 428 on 21 March 2019 by guest. Protected by copyright. http://thorax.bmj.com/ Thorax: first published as 10.1136/thx.36.6.428 on 1 June 1981. Downloaded from
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Thorax, 1981, 36, 428-434
Use of exercise tests in assessment of thefunctional result of aortocoronary bypass surgery
I Y LUKSIC, J A RAFFO, D A S G MARY, D A WATSON, P B DEVERALL,
AND R J LINDEN
From the Department of Cardiovascular Studies, University of Leeds, and Department ofMedical Cardiology, Eastern and Western Districts, Leeds Area Health Authority, Leeds
ABSTRACT The value of an objective exercise test for the assessment of the functional results ofaortocoronary bypass was investigated in 19 patients who were studied before and six monthsafter the operation. For positive tests the end point was defined as a net ST segment depressionof 0-1 mv 80 ms after the J point of the ECG. For negative tests the end point was 85% of theage-predicted maximal heart rate response. One patient who was not able to attain either ofthese points after the operation was excluded. In the remaining 18 patients three indices were
used in the analysis. First, the heart rate (HR) and the product of heart rate and systolic bloodpressure (RPP) were measured at the defined level of ST segment depression during positiveexercise tests to yield HR/ST and RPP/ST threshold respectively. Second, the HR and RPPwere measured at the end point of the negative tests. Third, the duration of exercise till the endpoint of the tests was measured. In each patient the duration of the postoperative test was longerthan that of the preoperative test. While all the patients had a positive exercise test before theoperation, the test was negative in 11 after it. In 10 of these 11 patients the HR and RPP at-tained at the end point of the postoperative test had increased; the HR and RPP remainedunchanged in one patient. Positive tests were still present in seven of the 18 patients. In five ofthese the HR/ST threshold and RPP/ST threshold were greater after than before operation,and they remained unchanged in two. An improvement in myocardial blood supply after aorto-coronary bypass was suggested indirectly by the ability to attain, during exercise, a higher HRand RPP at the end point of the test. The test proved especially valuable in patients who re-
tained a positive exercise test after the operation.
Aortocoronary bypass is widely used in the treat-ment of coronary artery disease. While it has beenshown that the operation is associated with anacceptable rate of graft patency, evidence that itleads consistently to reversal of regional myo-cardial ischaemia especially in patients with morethan one bypass graft has been scarce.' 2 Recentlya non-invasive exercise test with an objective endpoint was used to study the effects of physicaltraining in patients with angina pectoris caused bycoronary artery disease.3 It was shown that theability to attain during exercise a greater heartrate and systolic blood pressure at a predeterminedlevel of ischaemic ST segment depression, could
Address for reprint requests: Professor RJ Linden, Department ofCardiovascular Studies, The University ofLeeds, Leeds LS2 9JT.
be attributed to an improvement in myocardialblood supply.3The present study was planned prospectively to
investigate whether, using this method in patientsin whom a bypass operation had been performed,there was an improvement in myocardial bloodsupply.
Subjects and methods
Nineteen consecutive patients, in whom the diag-nosis of angina pectoris caused by coronary arterydisease was established by the ischaemic responseduring exercise electrocardiography and by sel-ective coronary arteriography, were investigatedbefore and after aortocoronary bypass. Patients
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Aortocoronary bypass surgery and myocardial ischaemia
with hypertension, valve disease, or cardiac ar-rhythmia, patients with resectable aneurysm of theleft ventricle, and patients who had to be main-tained on digoxin, beta-blockers, or nifedipinewere excluded from the study. In the 19 patientsbeta-blocker therapy was stopped under medicalsupervision during admission to hospital before theoperation, for at least five days to allow exercisetesting. Critical coronary arterial stenosis, definedas a decrease in the diameter of 75% or more inone or more of the major vessels was a pre-requisite for the operation. The operative tech-nique was identical in all the patients and includedextracorporeal circulation before incision of thecoronary arteries. Saphenous vein grafts wereused to bypass the coronary lesions.
Exercise electrocardiography was performed inall patients the week before and six months afterthe operation, and the results were analysed with-out previous knowledge of the extent of the cor-onary lesions or the details of the operation.
EXERCISE TESTThe patients attended the laboratory at least twohours after the most recent meal. They weretested on an electrically braked bicycle ergometer(Elema Schonander, type 380). The exercise testconsisted of two stages, the first involving con-tinuous exercise and the second discontinuousexercise as previously described.3
Continuous testIn this stage the patients pedalled at 60 rpm againstthe presented workload, initially 150 kpm.min'I(24-5 W), and then stepwise increases at three-minute intervals, each of 150 kpm.min-' (24.5 W).Three possible end points of the test were defined:a positive test when the end point was ST seg-
ment depression on the ECG recorded from CM,position; a negative test indicated by the absenceof ST segment depression when the patient attained85% of age-predicted maximal heart rate response;and an indeterminate test when the exercise hadto be terminated because of chest pain, multipleventricular ectopic beats, or fatigue, and not be-cause of the occurrence of ST segment depression,or because the patient attained the described tar-get in terms of heart rate response.4
Discontinuous testAfter 40 minutes rest, patients with positive testsperformed a second test in which incrementalwork loads were separated by rest periods. Theinitial load was the same as that which initiallyresulted in the highest heart rate response before
the onset of positive ST depression. Subsequentloads were increased stepwise by 25 kpm.min'I(4-1 W) until the described positive end point ofthe test. The heart rate (beats.mint1) was obtainedfrom the ECG. The systemic blood pressure wasmeasured, using en electronic sphygmomanometer(Elag-Koln), at every workload when the heartrate attained a steady value.
In positive tests, ST segment depression-that is,the end point of the test-was defined as a net STsegment depression of 0*1 mv 80 ms after the Jpoint of the ECG, in the presence or absence ofanginal pain. This end point served as the refer-ence level at which the duration of the continuoustest was measured. The heart rate (HR) andsystolic blood pressure (SBP) at this level of STsegment depression during the discontinuous testwere measured to yield the HR/ST threshold andthe threshold of the product of HR and SBP(RPP/ST threshold).
In negative tests, the values of HR and RPPattained at the end point of the continuous testwere included in the analysis.
Accuracy of measurementsAdequate reproducibility of the measurement ofHR/ST threshold has been previously demon-strated in anginal patients. The 95% tolerancelimit with 95% confidence of repeated measure-ment is 2*5 beats.min'1.3The performance of the electronic sphygmo-
manometer (Elag-Koln) was validated by compar-ing it with a random zero sphygmomanometer(Sreeharan and Linden, 1979; unpublished obser-vations). Sixty-six pairs of observations in 11patients showed that the regression slope did notdiffer significantly from unity; SBP (Elag-Koln)average data being greater than SBP of the ran-dom zero sphygmomanometer by an average of1 mmHg (0 133 kPa) (SEM 0 65 mmHg; 0-086kPa). The random error (two SD) of the differencebetween duplicate observations was 6&2 mmHg(0*82 kPa) for Elag-Koln and 6 0 mmHg (0-80 kPa)for the random zero sphygmomanometer.
Results
Nineteen male patients with an average age of51-8 years (range 38-64 yr) were investigated. Sixhad a history of myocardial infarction. Details ofcoronary arteries bypassed are shown in table 1.All patients survived the operation and nonedeveloped a perioperative or postoperative myo-cardial infarction as assessed by serial elec-trocardiographic recordings (resting 12 lead
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Table 1 Details of coronary vessels bypassed in19 patients
Coronary artery Number ofpatients
One vessel Two vessels Three vessels
AD 2 -AD, RCA - 7 -CIRCUM, RCA - 4 -AD, CIRCUM - 1 -AD, CIRCUM, RCA - - 5
AD, anterior descending; circum, circumflex; RCA, right coronaryartery.
electrocardiogram) and by enzyme studies. At thetime of assessment none of the patients was incardiac failure and no medical therapy had beenstarted. All the patients were managed identicallyby the same surgical team and without knowledgeof the results of exercise tests. At the time of thepostoperative exercise tests none of the patientswas incapacitated symptomatically. The bodyweight of each patient was within 8% of thatmeasured before the operation.
All the patients were tested before and sixmonths after the operation. All patients beforeoperation had a positive result. After operation,seven patients retained a positive result, and 11patients had a negative result; the test in the re-maining patient (19) was indeterminate and wasnot included in the analysis (table 2).
Table 2 Results of exercise tests in the postoperativeperiod
Details of the 11 patients in whom the resultof the exercise test changed from positive beforeto negative after operation, are shown in table 3.In 10 of these, the HR and RPP attained at theend point of the exercise test were greater afteroperation. Each patient was able to exercise at a
higher level of HR and RPP in the later test andin every instance the increase in level of HR at-tained during exercise exceeded the tolerance limitof measurement. In the remaining patient (16) thechanges in HR were within the tolerance limit ofmeasurement and there was a decrease in RPP.
Table 3 Changes in the response to exercise testingin 11 patients in whom the test was negative afterthe operation
Patient End point Endpoint En.-I point rate Durationangina heart rate pressure product* (min)before after (beats.min-') before after before after
*Units of rate pressure product. mmHg. min-1 102 (kPa. min-' 102;conversion factor 7-52.+Anginal pain at the end point.-No anginal pain at the end point of the exercise.
Considering all the patients in this group, HRincreased from an average 1 13'9 beats.min-1(range 82-143) to an average 141P5 beats.min-1(range 135-150), a mean increase of 27-6 beats.min-' (2p<0-001; paired t test). The mean RPPincreased from 178&5 mmHg.min-1 102 (range 98-257) [23-74 kPa.min-1 102 (range 13'0-34'2)] toan average 230-6 mmHg.min-1 102 (range 203-270 [30-67 kPa.min-1 102 (range 270-35 9)],that is, a mean increase of 52'2 mmHg.min-1 102(6-94 kPa.min-1 102; 2p<0-001; paired t test).
While before operation the end point of the testwas always associated with anginal pain, none ofthese 11 patients experienced anginal pain in thesecond test. The duration of exercise performedby each patient was greater in the postoperativethan in the preoperative test (2p<0-001; pairedt test).
In seven patients, the result of the exercise testremained positive after the operation-that is,ST segment depression during exercise was re-
tained (table 4). The HR/ST threshold showedchanges which exceeded the tolerance limit ofmeasurement during sequential exercise testing infive patients only. Each patient was able toexercise after operation at a greater HR and RPPat the same level of ischaemic ST segment de-pression compared with the preoperative test. Inthe remaining two patients (17, 18) the changes inHR/ST threshold were within the tolerance limitof measurement, and the changes in RPP/STthreshold were small. In these seven patients theHR/ST threshold increased from an average 1113beats.min-I (range 94-130) to an average 127-0beats.min-1 (range 110-145), a mean increase of
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15-7 beats.min'1 (2p<0O002; paired t test). TheRPP/ST threshold increased from an average 183-1mmHg min-' 102 (range 122-265) [24 35 kPa.min-' 102 (range 16*2-35-2)] to an average 215-6mmHg.min'1 102 (range 138-269) [28 67 kPa.min-' 102 (range 184-35-8)] that is a mean in-crease of 32-4 mmHg min-' 102 (4-31 kPa.min'1102; 2p<0-05; paired t test). While ischaemic STsegment depression was always associated withanginal pain in preoperative tests, only two outof the seven patients experienced anginal pain inpostoperative tests. After operation the durationof exercise performed by each patient was longerthan before (2p<0 005; paired t test).
Discussion
There is widespread concern regarding the lack ofunequivocal evidence that aortocoronary bypasseffects a relatively long-lasting improvement orprolongs life in patients with symptomatic coronaryartery disease in spite of reports of an acceptableincidence of graft patency.1 2 The reported studieson the effectiveness of myocardial revascularisationhave shown variable results, partly because of theuse of subjective methods and partly because ofthe difficulty in demonstrating reversal of ischaemiain more than one ischaemic region, especially inpatients who retain evidence of myocardialischaemia after the operation. Qualitatively forinstance, the subjective relief of angina pectorismay be brought about by other factors in additionto improvement in the supply of blood to the myo-cardium-for example, perioperative myocardialinfarction, denervation of the ischaemic zone, anda placebo effect.2 5-7
Objective studies on the ability of bypass sur-gery to improve the supply of blood to the myo-cardium, have used both invasive and non-invasivetechniques.
INVASIVE METHODSThe results of studies of left ventricular functionin terms of segmental contractility, pressure, vol-ume and flow parameters, myocardial blood flow,and regional myocardial perfusion have yieldedvariable results in respect of sequential improve-ment or deterioration in a given patient, despitegraft patency.8-20Using these methods, especially in patients with
more than one bypass graft, it is difficult to deter-mine which coronary lesions are the critical onesin any given patient. Similar difficulties have beenexperienced in the use of myocardial imagingduring exercise; in patients with multi-vesseldisease it has been difficult to detect all the diseasesites.2' For example, a normal scan, at rest andduring exercise, does not totally exclude an oc-cluded graft, and a perfusion defect during exer-cise has been obtained when the grafts werepatent.22 Thus, from these studies it is possible toconclude that a successful bypass in terms ofanatomical patency of the grafts does not neces-arily indicate functional improvement in oxygenavailability to ischaemic regions of the myocar-dium, so that the functional effects cannot bepredicted.
NON-INVASIVE METHODSExercise electrocardiography provides an objectiveand non-invasive method of provoking ischaemicST segment depression,4 and has potential for thequantitative evaluation of the balance betweenmyocardial oxygen requirement and avail-ability23 24 It is yet to be demonstrated conclusivelythat myocardial imaging would provide a moresensitive technique in detecting myocardial is-chaemia as compared with exercise electrocardiog-raphy.25 26 A recent account of the assessment ofaortocoronary bypass using exercise thallium-201myocardial imaging and exercise electrocardiog-raphy suggested that the latter "may be misleadingafter aortocoronary bypass operation".27 However,a symptom-limited exercise test was used, "a tar-get heart rate was not used" and the heart rateresponse attained by each patient was not given.It is not possible from the data in that report toconclude whether the absence of abnormal elecru-cardiographic changes during exercise would labelthe test results negative or indeterminate. Alsobecause the end point of both exercise electro-cardiography and exercise imaging was not ob-jectively determined, it is not clear whether bothtests were terminated at an intensity sufficient toprovoke myocardial ischaemia. For example, aftercoronary bypass, a positive exercise test was said
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to develop "at heavy work loads" in four patientsin whom exercise thallium imaging showed noevidence of ischaemia. Therefore in that report,27it is not possible to compare the results of exerciseelectrocardiography with those of exercise imaging.
Exercise testing has been used to study theeffect of coronary bypass first in terms of improve-ment in exercise performance-that is, an increasein the duration of exercise and maximal oxygenconsumption. It is also used to determine theability to increase myocardial blood supply-thatis, the ability to exercise to a higher heart rateand systolic blood pressure and therefore to ahigher myocardial oxygen consumption beforeangina occurs.28 However, it has been recognisedthat changes in exercise performance can be influ-enced not only by the effect of revascularisationbut by the response of the patient to surgical pro-cedures,2 29 and by the patients' physical activityand conditioning before and after operation.30 Theuse of a subjective sensation such as anginal painas the end point for a positive response has ob-vious limitations. It has been shown that shamprocedures may influence pain patterns,29 and thatpain relief can be affected by factors other thanmyocardial revascularisation. Most of the exer-cise testing which has been used indirectly to studychanges in myocardial blood supply in patientsundergoing coronary bypass, has been symptom-limited.7 9 13 16 27 30-39
In one report heart rate and systolic blood press-ure at the end point of the test were measured dur-ing treadmill exercise tests in three groups ofpatients before and after coronary bypass.40 Thegroups included 10 patients with patent grafts, fourpatients with "partial revascularisation," and sixpatients with occluded grafts. The response at STsegment depression of 0.1 mv could be analysed inonly 10 patients, seven, one, and two in each grouprespectively, because of abnormal baseline ECGrecordings. All the seven patients with patentgrafts had a negative test after the operation; inthe remaining three patients who retained a posi-tive test after the operation the heart rate and theheart rate-pressure product responses at ischaemicST segment depression showed no improvement.However, data on the tolerance limits of measure-ments of the heart rate and systolic blood pressurewere not given. Only a small group of patientscoud be investigated. In particular, there was nomention in the report of the problem of whetherpatients in whom a positive test is retained couldhave benefited from the operation.40 In the faceof multiple grafting procedures it is important todemonstrate whether or not improvement in the
I Y Luksic et al
supply of blood to the myocardium has occurredin spite of only "partial revascularisation".
PRESENT STUDYIn the present study the techniques of Raffo et al3were used. They measured heart rate and systolicblood pressure attained at a defined level ofischaemic ST depression (HR/ST threshold andRPP/ST threshold) during exercise in patientswith angina pectoris caused by coronary arterydisease. In the present investigation the levels ofHR and RPP attained at the end point of exercisetests were assessed in each of 18 patients beforeand after coronary bypass. In 11 patients a nega-tive exercise test was obtained after the operation,and 10 of these patients attained higher HR andRPP at the end point of the test after operation.Such results have been interpreted as indicating anability to attain a higher level of myocardialoxygen consumption during exercise, perioper-ative myocardial infarction having been ex-cluded.28 30 32 34 40 In the present investigation noneof the patients developed a perioperative or post-operative myocardial infarction before final exer-cise testing, and they were therefore considered tohave shown changes indicating improvement inthe supply of blood to the myocardium.
In seven patients, a positive exercise result per-sisted after the operation. Five of these patientsshowed an increase in HR/ST threshold and RPP/ST threshold, indicating an improvement in theability to exercise to a higher heart rate and sys-tolic blood pressure before the occurrence of thesame level of ischaemic ST segment depression.In contrast, the remaining two patients showed nosignificant change in these thresholds. An increasein these thresholds after a period of physical train-ing in patients with ischaemic heart disease hasbeen shown to reflect an increase in myocardialoxygen consumption at the same level of ischaemicST segment depression.3 Such an increase afteraortocoronary bypass indicates improvement inmyocardial blood supply. Therefore, these fivepatients were considered to have benefited func-tionally, despite retaining evidence of myocardialischaemia after the operation.We conclude that a simple and non-invasive exer-
cise test can be used to demonstrate indirectly animprovement in the supply of blood to the myo-cardium in patients who have undergone aorto-coronary bypass. The technique has been shownto be of special value in patients who retain apositive exercise test after the operation and yetwere improved.
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Aortocoronary bypass surgery and myocardial ischaemia
We are grateful to the British Heart Foundationand the Wellcome Trust for financial support.
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