Significance of ST-segment elevation during ambulatory monitoring after acute myocardial infarction

Significance ambulatory infarction

of ST-segment elevation during monitoring after acute myocardial

The significance of ST segment elevation during ambulatory monitoring after acute myocardial infarction was examined in 203 patients. Ambulatory monitoring was performed both early (mean 6.4 days [range 3 to 151; N = 201) and late (38 days [range 22 to 931; N = 177), and 174 patients underwent exercise treadmill testing (38 days [range 22 to 931). Cardiac events (death, reinfarctlon, and coronary revascularizatton) were documented during a l-year follow-up period. ST elevation (all silent) occurred in 25 of 201 patients (12%) on early monitoring but in only 4 of 177 (2%) on late monitoring @ < 0.001). Compared with patients (N = 148) without any ST deviation, those with early ST elevation had more pericarditis (8125 [32%] vs 231148 [16%]; p = 0.089) but no more angina or exercise ischemia. The mortality rate tended to be higher in patients with early ST elevation (4/25 [18%] vs 101148 [7%]; p = 0.24), but ST elevation was too infrequent to be a valuable prognostic indicator. ST elevation is not uncommon during ambulatory monitoring early after myocardial infarction but is rare during later monitoring. Such ST elevation is almost always silent, does not usually reflect myocardial ischemia, and is not a useful prognostic indicator. (AM HEART J 1993;125:41.)

Peter Currie, MRCP,

and Stephen Saltissi, MD Liuerpool, United Kingdom

ST segment elevation associated with pain has welldocumented significance in the setting of acute myocardial infarction,l variant angina,2 rest angina,3 and exercise testing41 5; it tends to imply more severe myocardial ischemia than does ST depression.6T 7 The significance of asymptomatic transient ST segment elevation during ambulatory monitoring, however, is less certain. Although in previous studies up to a 19 % prevalence of transient ST segment elevation was found (66% of episodes were silent) in patients with coronary artery disease,sg between 5% and 9% of normal subjects may have similar changes.lOF l1 Moreover, although ST segment elevation on ambulatory monitoring has been accepted in some studies as evidence of transient myocardial ischaemia,12-l4 it has not been previously validated to the same degree as ST depressionr5 and may not have the same diagnostic specificity. Furthermore, the significance of transient ST segment elevation after recent myocardial From the Cardiorespiratory Department, Royal Liverpool University Hospital. Supported in part by the British Heart Foundation and the Mersey Regional Health Authority. Received for publication March 17, 1992; accepted Aug. 10, 1992. Reprint requests: Dr. P. Currie, Cardiology Department, Western General Hospital, Crewe Rd., Edinburgh EH4 ZXU, United Kingdom. 4/l/42166 0002~8703/93/$1.00

+ .lO.

infarction and its relationship to ischemia “remains controversial,“14 especially since many such patients may already have residual baseline ST deviation. While undertaking a study of ambulatory monitoring in patients with recent myocardial infarction, we have attempted to clarify the prevalence, characteristics, and implications of transient ST elevation in 203 largely unselected patients. METHODS

All patients admitted to the Royal Liverpool University Hospital with definite acute myocardial infarction16 were eligible for the study unless they were in Killip class D, had significant valvular disease, left ventricular hypertrophy, ECG conduction defects, or other serious diseases, or were currently taking digitalis. Of 358 patients screened 14 refused consent, 24 died shortly after admission, and eight had been recruited previously. An additional 109 patients were excluded on the basis of the preceding criteria. We therefore performed ambulatory monitoring in 203 patients (152 men and 51 women) with a mean age of 58 years (range 34 to 76). The infarct was anterolatersl in 93 patients (46%), inferoposterior in 110 (54%), and non-Q wave in 47 (23 % ); 36 patients (18 % ) received thrombolytic therapy. Forty-six patients (23%) had had a previous myocardial infarction and 23 (11% ) had diabetes. Ambulatory ST segment monitoring. Ambulatory monitoring was performed by means of the Oxford Medilog 4000-11 (single-channel, real-time) recorder (Oxford In41

42

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Currie and Saltissi

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Table I. Ambulatory monitoring: Procedural details Procedural details

Total patients Leadposition CM5 CM6 cc5 CM3 CM4

Early 201

p Value

171

185(92%) 7 4 3 2 0 0

Late

(3%) (2%) (1%) (1%) (0%) (0%)

CM2 CM1 Drug therapy p-Blockers 71(35%) Nitrates 41(20%) Calciumantagonists 19(9%) At leastonedrug 102(51%) Q wavein recordinglead 31(15%) BaselineST elevation 38 (19%) BaselineST depression 44 (22%)

150 12 5 4 4

(85%) (7%) (3%) (2%) (2%)

l(l%) l(l%) 28 (16%) 33 (19%)


17(10%) 63 (36%)


15(8%)

<0.05
8 (5%)

19(11%)


struments Ltd., Oxfordshire, U.K.), which has previously been validated both at rest and with exercise.17During most ambulatory monitoring performed in this study the modified Vs lead (CM5) was usedroutinely, becausethis leadhasbeenshownto bemore sensitivethan any standard ECG lead for detecting exercise-inducedmyocardial ischemia.18However, the suitability of the recording lead position waschecked before monitoring wasbegun by examining the ECG on an oscilloscope(Cambridge Camtrace, Cambridge Medical Instruments Ltd., Middlesex, U.K.), and if the R wave was not of reasonablevoltage and/or if there was a Q wave then the electrodeswere repositioned. In 31 of 201patients (15%) on early and 15of 177 (8%) on late ambulatory monitoring (Table I), however, a Q wave wasunavoidable in the recording lead despite these measures,although in only eight patients (4 %) on early and one (1% ) on late monitoring wasthe amplitude of the Q wave greater than that of the R wave. Ambulatory recordings (24 hours) were made both early (before discharge)and late (4 to 8 weeksafter admission). Before each recording, patients adopted the supine, right lateral, prone, left lateral, and standing postures and underwent a period of hyperventilation. Any ST segment shift with a changein posturewastaken into account in the analysis (seebelow). Patients were given a diary to record both symptoms and daily activities. ST segment analysis. The magnetic tapes (TDK AD60 cassettes)were replayed (Oxford 4500 system, Oxford Instruments Ltd.) to produce an automatic report of the trends of ST segmentdeviation and heart rate and a summary of arrhythmias. Episodesof ST deviation were identified by scanningthe real-time ST trend and validated on ECG strips printed out at each point of interest with the useof a ~8 magnifying lensand a 0.1 mm graticule. Significant ST elevation wasdefined asat least 30 secondsof 1.0 mm or more ST elevation (above the isoelectric line), measured at 80 msecafter the J point.lg However, if there was

Heart

1993 Journal

any ST elevation during any postural maneuver, an additional 1.0 mm increaseabove this level was necessaryfor significance. Episodes of ST elevation were considered separateif a significant ST shift wasabsent for at least 3 consecutive minutes between them. Transient ST elevation in the presenceof a Q wave in the recording lead was still considered significant, since the meaning of this changeon ambulatory monitoring is uncertain. However, ST elevation, which was clearly related to a postural change-rapid onset with suddenvertical deviation of the ST trend and abrupt return to the isoelectricline-was not consideredsignificant, although such episodeswere noted and analyzed separately. The presenceor absenceof a significant increasein heart rate (arbitrarily chosenasat least 10 beats/min), above the adjacent baselinevalue in associationwith each episodeof ST segmentelevation, wasdetermined from the heart rate trend. The heart rate at the onset of significant ST elevation and the time of onset, associatedsymptoms,and daily activities during each episodewere noted. Daily activities were classified as mental, low-level physical, exertional, resting, and sleep. Exercise testing. Patients (N = 174) underwent treadmill exercisetesting (Marquette CaseII, Marquette Electronics, Inc., Milwaukee, Wis.) at 38 days (mean,range 22 to 93) after admissionwith the Bruce protocol. Twelve-lead ECGs and blood pressure values were recorded every minute during exercise,at the onset of angina, and at peak exercise. Exercise tests were primarily symptom limited but could also be terminated for safety reasons. The test was classified as positive for ischemiain the presenceof planar/downsloping ST depressionof at least 1.0mm measuredat 80 msecafter the J point or an equivalent degreeof ST elevation (in the absenceof a pathologic Q wave in the relevant lead). In the presenceof 0.5 mm or moreresting ST deviation, an additional 1.0 mm of ST shift wasrequired to achieve significance. Prognostic assessment. In-hospital complicationsleft ventricular failure, arrhythmias, pericarditis, and angina pectoris-were recorded and coronary prognostic index were calculated.20-22 At least 12months’ follow-up was achieved in all except one patient (who emigrated) with a meanfollow-up of 414days (median 405). The incidence of major cardiac events (death, nonfatal myocardial infarction, coronary angioplasty, and coronary artery bypass grafting) wasdocumented. Admissionswith angina pectoris, left ventricular failure, or arrhythmias wereaho noted. Statistical analysis. The significance of differences in prevalence of ST elevation during early and late monitoring, configuration of the recording lead ECG, episodesof ST elevation associated with increased heart rate, and prognosiswere compared by meansof chi-square testing incorporating the continuity correction factor where appropriate. Baseline ST segmentlevels were compared by meansof an unpaired t test. RESULTS Ambulatory monitoring. Early ambulatory monitor ing (mean 6.4 days after admission [range 3 to 151) was performed in 201 patients (99% ), and late

Vohme Number

125 1

Holter

0600

1200

1800

ST elevation

after AMI

2400

Time of day Fig. 1. Prevalence and diurnal pattern of transient ST segment elevation during ambulatory monitoring

both early (6 days; N = 201) (--o-)

and late (38 days; N = 177) (- -o- -) after acute myocardial infarction.

recordings (38 [range 22 to 931 days) were obtained in 177 patients (87%). More patients were receiving p-blockers during early compared with late monitoring, but similar numbers were taking nitrates or calcium antagonists (Table I). Q waves and baseline ST segment deviation were more commonly present in the recording lead during early monitoring (Table I). Prevalence of transient ST segment elevation. Transient ST elevation (all episodes silent) was not uncommon on predischarge ambulatory monitoring (25/201 patients; 12 % ) but was considerably less frequent (4/177 patients; 2%) (p < 0.001) on late monitoring (Fig. 1, Table II). The prevalence of early ST elevation during recordings on days 3 to 5 after infarction (12/67 patients; 18%) was also greater (p = 0.065) than during days 6 to 15 (12/134 patients; 9%) in the hospital. The increased prevalence of ST elevation on early monitoring was in direct contrast to the previously described predominance of ST depression on late (32% of patients) compared with early (14 % ) monitoring. 23 No patient had ST elevation on both early and late ambulatory monitoring, only two patients (one early and one late) with ST elevation had any ST depression on the same recording, and only 4 of 18 patients (22% ) with early ST elevation had ST depression during late monitoring. ST elevation and site of infarct. ST elevation was equally common after anterior and inferior infarctions (15/93 patients [lS%] vs 14/110 [13%]). All but one patient with ST elevation had a Q wave infarct; however, in only 7 of 29 patients (24 % ) was there a Q wave present in the recording lead. Only 3 of 29 (10 % ) patients with early or late ST elevation had received coronary thrombolysis (compared with 33/ 174; 19% without any ST elevation).

Table II. Prevalence and characteristics of transient ST

elevation ST elevation episodes Characteristics

No. of episodes Total duration (min) No. with heart rate increase (>lO beats/min) Heart rate at onset (mean + SD)

Early (N= 25)

Late (N= 4)

75 746.0 45(60%)

12 69.5 7(58%)

97.4 c 17.1 109.3 t 30.2

(beats/min) Associatedactivities* Sleep Rest

Mental activity Low-level physical activity Walking Exertion

10 (14%) 28 (39%) 4(6%) 19(27%) 10 (14%) 0 (0%)

O(O%) 8 (67%) 0 (0%) 3 (25%) 1(8%) 0 (0%)

*Unknown in four early episodes.

Among the 25 of 29 patients (86%) with ST elevation who had been monitored with the CM5 lead, 12 of 25 patients (48 % ) had an anterior and 13 (52 % ) an inferior infarct. Of the remaining four patients with ST elevation, two were monitored with the CM6 lead (both with anterior infarcts) and two with the CM1 (one with an anterior and one with an inferior infarct). Characteristics of transient ST elevation (Table II) ST elevation was most common during the day (Fig. l), and 60 % of episodes were associated with periods of increased heart rate; however, many episodes occurred without any change in the heart rate (Fig. 2). Over half the episodes of transient ST elevation occurred at rest or during sleep, whereas the others

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0

-5

American

530

6:00

6:30

7:oo

7130

6:OO

a:30

9:oo

9:30

lo:oo

10:30

11:oo

5:30

6:00

6:30

7:oo

7:30

8:OO

630

930

9:30

1o:oo

lo:30

11:OO

January 1993 Heart Journal

Scale lmV= 10 mm

Fig. 2. Transient episodes of ST segment elevation during ambulatory monitoring after acute myocardial infarction both without (5:45 AM) and with (7:25 AM) an associatedincreasein heart rate.

were associated with low-level physical or mental activity. No episodes of ST elevation were associated with exertion. The median amplitude of ST elevation detected during early monitoring was 1.3 mm (range 1.0 to 4.2 mm) and on late monitoring 1.2 mm (1.0 to 1.8), whereas the median durations on early and late monitoring were 3.25 minutes (range 0.5 to 94.0) and 4.0 minutes (1.0 to 17.0), respectively. In fact, of all the episodes of ST segment elevation detected, 71% were 1.5 mm or less in amplitude and 75 % lasted less than 10 minutes. The baseline ST level was significantly higher (p < 0.0001) in the 25 patients with early transient ST elevation ( f 1.3 + 0.2 mm; mean f SEM) compared with those without (0.0 + 0.1 mm). Transient ST elevation related to postural changes.

An additional four patients on early and six on late ambulatory monitoring had ST elevation (8 and 15 episodes, respectively), which was clearly induced by a change in posture but had not been detected during initial postural screening maneuvers. These episodes had a rapid onset and abrupt termination on the ST trend and usually began over one to two heart

beats with a sudden change of QRS configuration (Fig. 3). In contrast with the other episodes of ST elevation detected, those induced by a change in posture were especially common during sleep (17 of 19 episodes; 89 % ) and 22 of 23 (96 % ) occurred between 9 PM and 6 AM. Furthermore, these episodes usually began at times of relatively low heart rate (68.5 -t 6.4 beats/ min [mean + SD], early and 69.3 f 8.9 beats/min late). Episodes of ST segment elevation induced by postural changes were of low amplitude (only four [17%] were greater than +2.0 mm) and tended to be prolonged (13 of 23; 57 % lasted longer than 15 minutes). Implications of early transient ST elevation. To examine the implications of transient ST elevation, we excluded from analysis the 28 patients with isolated transient ST depression on early monitoring and compared patients with signifkant ST elevation (N = 25) with those without any ST deviation (N = 148) on monitoring. Clinical ouacaa~s (Table III) Pericarditis. This was dependent on the presence of typical posture- or respiration-related chest pain

vohln?a125 Number1

Halter ST elevation after AMI

45

BcaleImV=lOmm

Fig. 3. A, ST trend showing sudden onset (6:25 AM) and abrupt termination (7:40 AM) of episode of ST segment elevation induced by postural change during sleep. B, Sudden change in QRST configuration over two heart beats typical of abrupt termination of ST segment elevation induced by postural change.

and a pericardial rub either alone or in combination. The finding of widespread crescentic ST elevation was confirmatory but not required for the diagnosis. Defined in this way the incidence of clinical pericarditis was increased twofold in patients with transient ST elevation on early ambulatory monitoring. Arrhythmias. Supraventricular arrhythmias during the first 48 hours in the hospital were more common in patients with early ST elevation (Table III), whereas ventricular arrhythmias were no more frequent either in the first 48 hours or during ambulatory monitoring. Coronary prognostic indexes. The coronary prognostic index of Peel et a1.,2o Norris et a1.,21 and Luria et al.22 were not significantly greater in patients with early ST elevation compared with those without ST deviation. Angina pectoris. Early ambulatory ST elevation did not predict the likelihood of angina pectoris during convalescence in the hospital, on follow-up at 4 to 8 weeks, or on exercise testing. Cardiac events at 1 year (Table III). At least 1 year of follow-up was achieved for all but one of the study patients, and two patients died of noncardiac causes. Cardiac mortality and major cardiac events were in-

creased in patients with early ST segment elevation, but patient numbers were too small to achieve statistical significance. Ischemic cardiac events (defined as fatal or nonfatal myocardial infarction, admission with unstable angina pectoris, or coronary revascularization) were no more common in patients with ST elevation. Infarct size. Patients (N = 25) with ST elevation on early monjtoring had significantly @ = 0.002) more Q waves (3.4 -t 0.3, mean t SEM) on their predischarge ,l’2-lead ECG than those (N = 148) without (2.1 + 0.2), and they tended to have higher peak serum creatine kinase levels (1996 + 271 vs 1732 + 104 U/L; p = 0.34). Serum creatine kinase levels were also obtained from two patients with early transient ST elevation on the day after ambulatory monitoring and were normal in both (90 and 71 U/L, respectively). Exercise testing. Patients with early ST elevation (N = 16) achieved significantly (p < 0.05) less total exercise time than patients (N = 135) without any ST change (228.8 + 38.4 vs 308.1 f 12.7 seconds; mean + SEM), although the maximum exercise heart rates achieved by the two groups were similar (137.9 + 4.4 vs 136.3 f: 1.8 beats/min; NS). Whereas

46

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Table III. Clinical correlatesof early transient ST elevation Clinical correlates

ST elevation present (N = 25)

Pericarditia 8 (32%) Supraventriculararrhythmias 7 (28%) Anginapectoris In hospital 6 (24%) 4-8 wk (N = 20,142) 5 (25%) On ExTT (N = 16,135) 3 (19%) CPI (mean+ SEM) Peelet a120 10.2 k 0.8 Norris

et aL21 Luria et a1.22

Cardiacevents Death Major events* Ischemicevents?

No ST deviation (N = 148) p Value 23 (16%) 18 (12%)

<0.05 <0.04

44 (30%) 63 (44%) 55 (41%)

0.73 0.16 0.15

5.4 + 0.6 7.1 f 0.4

8.9 IL 0.4 4.9 + 0.2 6.5 k 0.1

0.15 0.35 0.10

4 (16%) 6 (24%) 4 (16%)

10 (7%) 25 (17%) 30 (20%)

0.24 0.57 0.82

CPI, Coronary prognostic indexes; ExTT, exercise treadmill testing; 5’EM. standard error of the mean. *Death, myocardial infarction, or coronary revascularization. tFata1 or nonfatal myocardial infarction, coronary revascularization, OF unstable angina pectoris.

only 5 of 16 patients (31%) with ST segment elevation on ambulatory monitoring had any exercise ST segment changes (2/16; 13 % exercise ST elevation), 69 of 135 patients (51% ) without any ambulatory ST segment shift had ischemic exercise ST depression or elevation. DISCUSSION

In this study transient ST segment elevation (1.0 mm or more) during ambulatory monitoring was not uncommon (12 % patients) before hospital discharge but was considerably less common (2% ) later. All such episodes were asymptomatic and occurred during low-level mental or physical exertion. In contrast, Gottlieb et all4 found a lower incidence (4 % ) of early transient ST segment elevation after myocardial infarction but required 2 mm ST elevation to achieve significance. l4 Although the lead system used for ambulatory monitoring for each patient was not always identical during early and late monitoring (Table I), it seems unlikely that the sixfold difference in the prevalence of ST elevation during the two recording periods would have been much different even if the lead system had remained constant. The principal findings of this study are (1) although the prognosis after myocardial infarction appears generally worse in those with ST elevation (increased cardiac events, reduced exercise capacity, clinically larger infarcts) ST elevation on ambulatory monitoring is too infrequent to have a useful place in risk stratification, and (2) transient ST elevation af-

January 1993 Heat7 Journal

ter infarction correlates poorly with various independent indicators of myocardial ischemia such as angina pectoris or ST deviation on exercise testing. The mechanism of ST elevation after infarction is currently unknown, but it is clearly important to establish whether or not it reflects transient myocardial ischemia. This study was not designed to investigate pathophysiology but nonetheless does provide some insights into the likelihood of underlying transient myocardial ischemia. In particular, the fact that all episodes of ST elevation were asymptomatic and there was a lack of correlation with myocardial ischemic changes on subsequent exercise testing favors a nonischemic etiology for at least the majority of episodes of ST elevation. It seems most likely that early after myocardial infarction, the ST segment displays a multifactorial and nonspecific transient lability, which is more dependent on factors such as the degree of initial baseline ST elevation, infarct size, pericarditis, and postural changes rather than on ischemia. The lack of correlation between ST elevation and myocardial ischemia after infarction and its differing time course from postinfarction ST depression also suggests that ST elevation and depression in this setting may reflect differences in underlying pathophysiology. It is clear that preliminary ST segment observation during postural maneuvers before ambulatory monitoring does not eliminate false positive transient ST elevation resulting from postural change, since four additional patients on early and six on late ambulatory monitoring clearly displayed the postural ST elevation that had not been observed during baseline postural screening. Others have found similar predominantly nocturnal orthostatic ST segment changes in 42% of subjects without variant angina during ambulatory monitoring,24 whereas frequent episodes of nocturnal ST elevation occurred in 23 % of normal subjects studied by Quyyumi et a1.25 In normal subjects with nocturnal ST elevation the ST segment tends to rise gradually during sleep,25 and presumably such ST elevation, if relatively localized, may be suddenly revealed as the patient rolls over in bed and the position of the heart changes. The causes of silent transient ST segment elevation during ambulatory monitoring early after myocardial infarction are probably multifactorial. Although some of these changes may be ischemic in origin, the majority appear to be nonspecific. In direct contrast to our current understanding of the significance of ambulatory ST depression, and at variance with its significance on exercise tests,5 we found no

evidence that ST elevation

on ambulatory

ing after myocardial infarction

monitor-

had any value as a

Volume Number

125 1

marker for an adverse outcome. In the setting of a recent myocardial infarction, ST segment elevation during ambulatory monitoring, although not uncommon, appears to be a nonischemic phenomenon that appears to possess little diagnostic or prognostic value. We thank the Cardiorespiratory Department at the Royal Liverpool University Hospital for technical assistance. REFERENCES 1.

2. 3. 4.

5. 6.

7.

8.

9.

10.

Askenazi J, Maroko PR, Lesch M, Branwald E. Usefulness of ST segment elevations as predictors of electrocardiographic signs of necrosis in patients with acute myocardial infarction. Br Heart J 1977;39:764-70. Maseri A, Severi S, De Nes M, et al. “Variant” angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol 1978;42:1019-35. Chierchia S, Brunelli C, Simonetti I, Lazzari M, Maseri A. Sequence of events in angina at rest: primary reduction in coronary flow. Circulation 1980;61:759-68. Dunn RF, Bailey IK, Uren R, Kelly DT. Exercise-induced ST-segment elevation: correlation of thallium-201 myocardial perfusion scanning and coronary arteriography. Circulation 1980;61:989-95. Sullivan ID, Davies DW, Sowton E. Submaximal exercise testing early after myocardial infarction. Br Heart J 1984;52:147-53. Guazzi M, Polese A, Fiorentini C, Magrini F, Olivari MT, Bartorelli C. Left and right heart haemodynamics during spontaneous angina pectoris. Comparison between angina with ST segment depression and angina with ST segment elevation. Br Heart J 1975:37:401-13. MacDonald RG, Hill JA,‘Feldman RL. ST segment response to acute coronary occlusion: coronary hemodynamics and angiographic determinants of direction of ST segment shift. Circulation 1986;74:973-9. Weidinger F, Sochor H, Czernin J, Pospischil E, Glogar D. Characteristics of transient ischaemic episodes in patients with silent and symptomatic exercise-induced myocardial ischaemia. Eur Heart J 1988,9:1081-7. Von Arnim T, Hofling B, Schreiber M. Characteristics of episodes of ST elevation or depression during ambulatory monitoring in patients subsequently undergoing coronary angiography. Br Heart J 1985;54:484-8. Deanfield JE, Ribiero P, Oakley K, Krikler S, Selwyn AP. Analysis of ST-segment changes in normal subjects: implications for ambulatory monitoring in angina pectoris. Am J Cardiol 1984;541321-5.

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11. Kohli RS, Cashman PM, Lahiri A, Raferty EB. The ST segment of the ambulatory electrocardiogram in a normal POWlation. Br Heart J 1988;60:4-16. 12. Josephson MA, Lewis HS, Nademanee K, Intarachot V, Lewis H, Singh BN. Abolition of Holter monitor detected silent myocardial ischemia after percutaneous transluminal coronary angioplasty. J Am Co11 Cardiol 1987;10:499-503. 13. Mulcahy D, Keegan J, Crean P, et al. Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients. Br Heart J 1988;60:417-23. 14. Gottlieb SO, Gottlieb SH, Achuff SC, et al. Silent ischemia on Holter monitoring predicts mortality in high-risk postinfarction patients. JAMA 1988,259:1030-5. 15. Levy RD, Shapiro LM, Wright C, Mockus LJ, Fox KM. The haemodynamic significance of asymptomatic ST segment depression assessed by ambulatory pulmonary artery pressure monitoring. Br Heart J 1986,56:526-30. 16. Report of the Joint International Society and Federation of Cardiology/World Health Organization Task Force on Standardization of Clinical Nomenclature. Nomenclature and criteria for diagnosis of ischemic heart disease. Circulation 1979;59:607-9. 17. Sibler S, Vogler AC, Spiegelsberger F, Vogel M, Theisen K. Validation of digital Holter ST segment analysis. J Ambulatory Monitoring 1988;1:145-52. 18. Quyyumi AA, Crake T, Mockus LJ, Wright CA, Rickards AF, Fox KM. Value of the bipolar lead CM5 in electrocardiography. Br Heart J 1986;56:372-6. 19. Quyyumi A, Crake T, Wright C, Mockus L, Fox K. The role of ambulatory ST-segment monitoring in the diagnosis of coronary artery disease: comparison with exercise testing and thallium scintigraphy. Eur Heart J 1987;8:124-9. 20. Peel AA, Semple T, Wang I, Lancaster WM, Dall JLG. A coronary prognostic index for grading the severity of infarction. Br Heart J 1962;24:745-60. 21. Norris RM, Caughey DE, Deeming LW, Mercer CJ, Scott PJ. Coronary prognostic index for predicting survival after recovery from acute myocardial infarction. Lancet 1970;2:485-8. 22. Luria MH, Knoke JD, Margolis RM, Hendricks FH, Kuplic JB. Acute myocardial infarction: prognosis after recovery. Ann Intern Med 1976;85:561-5. 23. Currie P, Saltissi S. Transient myocardial ischaemia after acute myocardial infarction. Br Heart J 1990;64:299-303. 24. Araki H, Koiwaya Y, Nakagaki 0, Nakamura M. Diurnal distribution of ST segment elevation and related arrhythmias in patients with variant angina: a study by ambulatory ECG monitoring. Circulation 1983;67:995-1000. 25. Quyyumi AA, Wright C, Fox KM. Ambulatory electrocardiographic ST segment changes in healthy volunteers. Br Heart J 1983;50:460-4.