Adv. Cardio!., vo!' 22, pp. 154-163 (Karger, Basel 1978)
Asymptomatic Coronary Artery Disease: Detection and Management C.R.CONTI Departments of Medicine and Cardiology, University of Florida College of Medicine, H. Hillis Miller Health Center, Gainesville, Fla.
In this discussion I plan to present some information that may be useful to develop a rational approach to the management of the asymptomatic patient with proven coronary artery disease. In order to do this, it is necessary to review data from sudden death studies, natural history studies of patients with positive stress tests, documented myocardial infarction, and angiographically abnormal coronary arteries. If we analyze the current methods of detecting coronary disease, several problems arise. Firstly, sudden death studies, in most instances do not benefit the individual patient, although some important information has come forth. Secondly, although natural history information is available on patients with documented myocardial infarction, in some instances, the electrocardiographic and clinical evidence of myocardial infarction may have occurred with angiographically normal coronary arteries. Thirdly, although commonly performed in survey studies, exercise testing is not designed to detect coronary artery disease but rather to detect myocardial ischemia. Fourthly, natural history information based on coronary angiographic studies has been reported, but only in symptomatic patients. Coronary angiographic studies have not been performed in a systematic fashion in any group of asymptomatic persons. The reason for this is related to a reluctance of physicians to study asymptomatic individuals. As a result there is very little data available on the natural history of coronary artery disease in patients who are asymptomatic despite the fact that the only precise method of ante mortem detection of the presence or absence of coronary artery disease in the individual patient is coronary angiography.
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Introduction
155
CONTI
Table 1. Predictive implications of stress testing in asymptomatic subjects
Subjects
1969 1971 1974 1975 1975 1976
et al. [6] et al. [7] FROELICHER et al. [8] ARONOW [9] CUMMING et al. [10] CONTI et al. [11]
BRUCE
KATTUS
Developed ischemic heart disease number
%
follow-up, years
22 30 39 13 61 12
3 9 10 6 15 2
13.6 30 25.6 46 24.6 8.3
5 2.5 6.3 5 3 2
177
44
24.6
3.8
A few studies have been published on the predictive implications of a positive stress test in an asymptomatic population [6-11]. These studies are summarized in table I. Of the 177 cases reported, 44 (24.6 %) had some evidence of clinical heart disease developing over a follow-up of 3.8 years. These data, although small in number, are quite similar to the study of ELLESTAD and WAN [4] in symptomatic subjects. Recently, BORER et al. [12], FROELICHER et al. [13] and CONTI et al. [11] have reported asymptomatic subjects with a 'positive' exercise test who underwent coronary angiography. These studies have shown that significant coronary artery stenosis was present in less than 50 % of the total population studied. They emphasized the unreliability of this test to predict the presence, absence or extent of coronary artery disease.
Next, we should examine the natural history of the asymptomatic patient with proven coronary artery disease with or without a positive stress test. Unfortunately, there is no information on the natural history of this subset of patients. Thus, it is necessary to extrapolate from some recent data in symptomatic patients with proven, surgically treatable coronary artery disease. Several reports on the natural history of angiographically documented coronary occlusive disease have been published. One of the most often quoted is that of BRUSCHKE et al. [14]. In two consecutive articles they report the 5-year survival in patients with single, double and triple vessel disease. Patients with normal ventricular function had a 5-year survival of 93 % with one
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Coronary Angiography - Predictive Implications
CONTI
156
vessel, 67 % with two vessels, and 64 % with three vessel disease. Their data also indicates that progressively increasing ventricular dysfunction in patients with one, two, or three vessel disease clearly decreases the 5-year survival.
Sudden Death Studies
KULLER et al. [1] in 1972 reported necropsy findings in patients dying suddenly. In his group of 389 patients there were 194 (50%) who were considered to be asymptomatic prior to their deaths. Necropsy information is available on 121 of the total patients, but unfortunately KULLER does not report what percentage of this 121 were asymptomatic. Despite this deficiency, 103 had triple vessel disease, 18 had double vessel disease, and interestingly, none of the patients had single vessel disease. The obvious interpretation of these data is that severe coronary artery disease portends a high risk of dying suddenly. WEAVER et al. [2] have recently reported an important study on the angiographic findings of patients resuscitated from sudden deaths. They were able to evaluate angiographically 64 patients, of which 18 had been totally asymptomatic prior to sudden death. Unfortunately, the authors did not discriminate between symptomatic and asymptomatic patients, but if one assumes that the distribution of coronary artery disease was the same in both groups, 94 % of the patients had severe stenosis (70 % or greater diameter reduction in one or more major coronary arteries) and 70% had ventricular wall contraction abnormalities. More than half of these patients were considered a suitable candidate for myocardial revascu1arization. The authors followed these patients for an average of 20.5 months and found that 14 (22 %) had a second episode of ventricular fibrillation. Those with a second episode of ventricular fibrillation had a higher incidence of triple vessel disease and more left ventricular dysfunction than those with a single episode of ventricular fibrillation. The authors conclude that angiography can identify individuals with high risk for recurrent ventricular fibrillation.
In 1974 NORRIS et al. [3] reported data relating to prognosis following an acute myocardial infarction. Their study indicates that if patients are asymptomatic, have normal heart size, normal blood pressure, isoelectric ST
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
Myocardial Infarction Studies
Asymptomatic Coronary Artery Disease: Detection and Management
157
segments and no arrhythmias, the yearly mortality is approximately 4 %. Although this study is an important contribution, it is important to emphasize that the presence, absence, or degree of coronary artery disease was not proven in the survivors.
Exercise Testing - Predictive Implications
ELLESTAD and WAN [4] have shown clearly that symptomatic patients with a positive stress test have a higher incidence of a new coronary event occurring each year than individuals with a negative stress test. In addition, those with a positive stress test at low heart rates and mild exercise had a higher incidence than those with a positive stress test at high heart rates, and a greater duration of exercise. GOLDSCHLAGER et al. [5] recently published data on 'The Accuracy of Treadmill Responses in Predicting Coronary Disease in a Group of 410 Patients'. Their study shows that 64 % of 100 patients with a normal treadmill test had evidence of coronary artery disease and 36 did not. However, when ST segment depression occurred, they observed a 99 % incidence of coronary artery disease in patients with downsloping ST segment depression, an 85 % incidence in patients with horizontal ST segment depression, and a 68 % incidence in patients with upsloping ST segment depression. The VA Cooperative Study has reported the survival of 408 medically treated, surgically suitable patients with stable angina pectoris. Their report indicates that the 2-year survival of patients with normal ventricular function and single vessel disease was 97 %, double vessel disease 94 % and triple vessel disease 90%. The addition of abnormal ventricular function in patients with surgically suitable single, double and triple vessel disease decreases the survival rate at 2 years, i. e., triple vessel disease with abnormal ventricular function - 86 % survival at 2 years. It is possible that this angiographic information may not have the same clinical significance in an asymptomatic patient population. However, since there is no data in the asymptomatic group, the figures available must be used to influence our clinical decisions.
The following cases will emphasize the points that have been made.
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Case Presentations
158
CONTI
K K 40 M B P 08170 1
abnormal
Resting ECG Inverted T V4 - V6 Pacing ECG ST Vs LVED P Myocardial lactate extraction
nor ma!
Immediately postexercise Vs -
r-
I
I ,
norma !
Coronary art er iography Norma! Ejection fracti on 70'/,
30 sec postexercise Vs l--+H - -'--l+-l- ~ -+-l-~t-u ' L
Patient K. K., a 40-year-old male surgeon, was referred for evaluation of an abnormal resting electrocardiogram and an abnormal response to exercise stress. He was totally asymptomatic and had a normal blood pressure and normal cardiac examination. Repeat resting electrocardiogram revealed inverted T-waves in V4-V6. Hyperventilation for 2 min failed to change the resting electrocardiogram. Treadmill exercise using the Bruce protocol revealed 2.5 mm square wave ST segment depression in Vs at a heart rate of approximately 155 beats/min, immediately after exercise, which persisted for 30 sec in the postexercise period (fig. I). Hemodynamic investigation revealed a normal resting left ventricular pressure. During pacing-induced tachycardia, the patient developed asymptomatic ST segment depression in lead Vs similar to that seen during exercise. Left ventricular pressure was normal during pacing-induced ST segment depression. Myocardial lactate extraction was normal before, during and after pacing-induced ST segment depression. Coronary angiography revealed no evidence of large vessel coronary artery disease and no obvious missing vessels. Ventriculography revealed normal end-diastolic volume, an ejection fraction of 70 % without contraction abnormalities, mitral regurgitation or mitral valve prolapse (fig. 2). In this patient, the reason for the ST segment depression during stress is totally unclear since the coronary arteries were normal and there was no hemodynamic or metabolic evidence of myocardial ischemia during pacing-induced ST segment depression. Patient A . S., a 53-year-old telephone lineman, was asymptomatic before and after an episode of documented ventricular fibrillation, which occurred during sexual intercourse with his nurse wife. When referred for evaluation his blood pressure was normal and he had a normal cardiac examination. Resting electrocardiogram revealed nonspecific ST-T wave changes. Hyperventilation did not alter the electrocardiogram. Exercise testing revealed ST segment depression of approximately 2 mm in leads II and III and 1 mm in lead V6 at a heart rate of 132 (fig. 3). At no time did the patient notice any chest discomfort during or after exercise. 24-hour ambulatory monitoring revealed several episodes
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Fig. 1. Exercise test, clinical and hemodynamics features of patient K. K.
Asymptomatic Coronary Artery Disease: Detection and Management
159
a, b
d,e Fig. 2. Coronary angiography and ventriculography of patient K. K. (see text).
LVEDP abnormal Myocardial lactate not done extraction
Control HR =74
III
--I,
III
-J~~r ~).
III
Coronary arteriography
100'/, LAD 90'10 C,rc
V4
DimInutive RCA Collaterals RCA and CIrc to LAD
Vs
VentrIculography normal
Exercise HR = 132 No symptoms I..
I~
-A..-.I~
-J~~ ·A
-YWr~
+"+-+r r-r-Hf ~+-l~ L
I
V
6
.....j.
LJl~
Fig. 3. Exercise test, clinical and hemodynamic features of patient A. S.
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A 5 53 M6P 110174 Resting ECG Inverted 1V3-V6 Ambulatory monitoring 51+ and PVCs Pacing ECG 51+ II, III, V6
CONT!
160
of asymptomatic ST segment depression and an occasional PVC close to the T-wave. Hemodynamic investigation revealed a normal resting left ventricular end-diastolic pressure. Pacing-induced tachycardia at a heart rate of 130 beats/min produced ST segment depression in leads II, III and V6, very similar to those that occurred during exercise. During this pacing stress test, the patient did not complain of angina, but noticed that the room seemed 'humid'. In addition, during pacing-induced ST segment depression, the left ventricular end-diastolic pressure was abnormal. Myocardial lactate metabolism was not evaluated. Subsequent coronary angiography (fig. 4) revealed 100 % occlusion of the left anterior descending coronary artery with excellent collateral to the distal LAD from the right and circumflex coronary artery. The left circumflex was 90 % occluded proximally, and the right coronary artery was a diminutive vessel since the posterior descending coronary artery took its origin from the left circumflex. Ventriculography revealed a normal ejection fraction and a normal contraction pattern without evidence of mitral valve prolapse or regurgitation. This patient was not asymptomatic in the true sense of the word since the clinical presentation was that of sudden death. However, he had no angina with stress. It would be interesting to know if exercise, prior to sudden death, would have produced asymptomatic ST segment depression. Subsequent investigation revealed severe multiple vessel coronary occlusive disease in addition to hemodynamic evidence of myocardial ischemia during pacing-induced ST segment depression. The clinical decision for this patient was that he undergo a revascularization procedure. This was accomplished successfully and both the anterior descending and circumflex coronary artery were bypassed. Follow-up angio-
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
Fig. 4. Coronary angiography and ventriculography of patient A. S. (see text).
Asymptomatic Coronary Artery Disease: Detection and Management
161
a
b
c
d Fig. 5. Postoperative angiography in patient A. S. (see text).
Both of these cases, at the opposite ends of the spectrum of coronary disease, illustrate the inadequacies of the resting and stress ECG in the asymptomatic subject. We have had the opportunity to evaluate 13 patients with asymptomatic ST segment depression during exercise; 6 of these 13
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
graphy and hemodynamics performed 6 months after the surgical procedure (fig. 5) revealed that all grafts were patent, there was no new obstructive narrowing of the coronary arteries and ventricular function remained normal. Thus, there was no evidence of operative myocardial infarction. Ambulatory monitoring studies revealed no evidence of asymptomatic ST segment depression or PVCs during a 24-hour period. Repeat exercise test revealed no ST segment depression at a heart rate of 142 beats/min. Pacing-induced tachycardia revealed no ST segment depression at a heart rate of 132, but at a heart rate of 167 there was upsloping ST segment depression in lead II and V6 • The patient had no symptoms during stress testing. A subsequent exercise test was performed 1 year after the surgical procedure and failed to reveal any ST segment depression at a heart rate of 175 beats/min. The patient has remained asymptomatic.
CONTI
162
patients were free of any significant large vessel coronary artery disease. We have recommended that all individuals with asymptomatic exercise-induced ST segment depression undergo further investigation, to include coronary angiography, ventriculography, and studies of lactate metabolism and hemodynamics during stress-induced ST segment depression [15].
Summary Available evidence indicates that coronary angiography is the only precise method available to detect the presence, absence and location of large vessel coronary occlusive disease in asymptomatic subjects. The correlation of a positive exercise test and the presence of coronary artery disease is best in symptomatic patients with typical angina who develop downsloping ST segment depression during or after exercise. Asymptomatic patients with single vessel coronary occlusive disease with or without evidence of myocardial ischemia should be observed and treated medically. Asymptomatic patients with multiple vessel disease with evidence of myocardial ischemia, life-threatening arrhythmias, or sudden death, probably should undergo revascularization procedures. Asymptomatic subjects with multiple vessel disease without evidence of myocardial ischemia, life-threatening ventricular arrhythmias or episodes of sudden death, probably should be observed and treated medically, but could be considered for surgery if operative mortality and morbidity is less than 2 %. Finally, all patients with proven coronary artery disease, symptomatic or not, should use common sense and apply good health practices, i.e., maintain normal body weight, lower cholesterol, if elevated, and control blood pressure.
I
2 3 4 5 6 7
KULLER et at.: Epidemiology of sudden death. Archs intern. Med. 129: 714 (1972). WEAVER, W. D., et at.: Arteriographic findings and prognostic indicators in patients resuscitated from sudden cardiac death. Circulation 54: 895 (1976). NORRIS, R. M., et at.: Prognosis after myocardial infarction. Six year follow-up. Br. Heart J. 36: 786 (1974). ELLESTAD, M. H. and WAN, M. K. c.: Predictive implications of stress testing. Circulation 51: 363 (1975). GOLDSCHLAGER, N., et at.: Treadmill stress tests as indicators of presence and severity of coronary artery disease. Ann. intern. Med. 85: 277 (1976). BRUCE, R., et at.: Stress testing in screening for cardiovascular disease. Bull. N. Y. Acad. Med. 45: 1288 (1969). KATTUS, A., et at.: ST segment depression with near maximal exercise in detection of pre-clinical coronary heart disease. Circulation 44: 585 (1971).
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References
Asymptomatic Coronary Artery Disease: Detection and Management
9
10 11
12 13
14 15
FROELICHER, V. F.; THOMAS, M. M.; PILLOW, c., and LANCASTER, M. c.: Epidemiologic study of asymptomatic men screened by maximal treadmill testing for latent coronary artery disease. Am. J. Cardio!. 34: 770 (1974). ARONOW, W. S.: 5-year follow-up of double Masters test, Maximal treadmill stress test and resting and post-exercise apexcardiograms in asymptomatic persons. Circulation 52: 616 (1975). CUMMING, G. R., et al.: Electrocardiographic changes during exercise in asymptomatic men. Three-year follow-up. Can. med. Ass. J. 112: 578 (1975). CONTI, C. R., et al.: Stress induced ST segment depression in asymptomatic subjects. Clinical, hemodynamic and metabolic observations. Circulation 54: supp!. II, p. 205 (1976). BORER, J. S., et al.: Limitations of the electrocardiographic response to exercise in predicting coronary artery disease. New Eng!. J. Med. 293: 367 (1975). FROELICHER, V. F.; THOMPSON, A. J.; LONGO, M. R., jr.; TRIEBWASSER, J. H., and LANCASTER, M. c.: Value of exercise testing for screening asymptomatic men for latent coronary artery disease. Prog. cardiovasc. Dis. 68: 265 (1976). BRUSCHKE, A. V. G., et al.: Progress study of 590 consecutive non-surgical cases of coronary disease followed 5-9 years. Circulation 47: 1147 (1973). CONTI, C. R.: Management of the asymptomatic patient with a positive stress test. J. Florida med. Ass. 62: 21 (1975).
C. R. CONTI, MD , FA Cc. Professor of Medicine and Chief of Cardiology, University of Florida College of Medicine, H. Hillis Miller Health Center, Gainesville, Fla. (USA)
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8
163
Asymptomatic Coronary Artery Disease: Detection and Management C.R.CONTI Departments of Medicine and Cardiology, University of Florida College of Medicine, H. Hillis Miller Health Center, Gainesville, Fla.
In this discussion I plan to present some information that may be useful to develop a rational approach to the management of the asymptomatic patient with proven coronary artery disease. In order to do this, it is necessary to review data from sudden death studies, natural history studies of patients with positive stress tests, documented myocardial infarction, and angiographically abnormal coronary arteries. If we analyze the current methods of detecting coronary disease, several problems arise. Firstly, sudden death studies, in most instances do not benefit the individual patient, although some important information has come forth. Secondly, although natural history information is available on patients with documented myocardial infarction, in some instances, the electrocardiographic and clinical evidence of myocardial infarction may have occurred with angiographically normal coronary arteries. Thirdly, although commonly performed in survey studies, exercise testing is not designed to detect coronary artery disease but rather to detect myocardial ischemia. Fourthly, natural history information based on coronary angiographic studies has been reported, but only in symptomatic patients. Coronary angiographic studies have not been performed in a systematic fashion in any group of asymptomatic persons. The reason for this is related to a reluctance of physicians to study asymptomatic individuals. As a result there is very little data available on the natural history of coronary artery disease in patients who are asymptomatic despite the fact that the only precise method of ante mortem detection of the presence or absence of coronary artery disease in the individual patient is coronary angiography.
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Introduction
155
CONTI
Table 1. Predictive implications of stress testing in asymptomatic subjects
Subjects
1969 1971 1974 1975 1975 1976
et al. [6] et al. [7] FROELICHER et al. [8] ARONOW [9] CUMMING et al. [10] CONTI et al. [11]
BRUCE
KATTUS
Developed ischemic heart disease number
%
follow-up, years
22 30 39 13 61 12
3 9 10 6 15 2
13.6 30 25.6 46 24.6 8.3
5 2.5 6.3 5 3 2
177
44
24.6
3.8
A few studies have been published on the predictive implications of a positive stress test in an asymptomatic population [6-11]. These studies are summarized in table I. Of the 177 cases reported, 44 (24.6 %) had some evidence of clinical heart disease developing over a follow-up of 3.8 years. These data, although small in number, are quite similar to the study of ELLESTAD and WAN [4] in symptomatic subjects. Recently, BORER et al. [12], FROELICHER et al. [13] and CONTI et al. [11] have reported asymptomatic subjects with a 'positive' exercise test who underwent coronary angiography. These studies have shown that significant coronary artery stenosis was present in less than 50 % of the total population studied. They emphasized the unreliability of this test to predict the presence, absence or extent of coronary artery disease.
Next, we should examine the natural history of the asymptomatic patient with proven coronary artery disease with or without a positive stress test. Unfortunately, there is no information on the natural history of this subset of patients. Thus, it is necessary to extrapolate from some recent data in symptomatic patients with proven, surgically treatable coronary artery disease. Several reports on the natural history of angiographically documented coronary occlusive disease have been published. One of the most often quoted is that of BRUSCHKE et al. [14]. In two consecutive articles they report the 5-year survival in patients with single, double and triple vessel disease. Patients with normal ventricular function had a 5-year survival of 93 % with one
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
Coronary Angiography - Predictive Implications
CONTI
156
vessel, 67 % with two vessels, and 64 % with three vessel disease. Their data also indicates that progressively increasing ventricular dysfunction in patients with one, two, or three vessel disease clearly decreases the 5-year survival.
Sudden Death Studies
KULLER et al. [1] in 1972 reported necropsy findings in patients dying suddenly. In his group of 389 patients there were 194 (50%) who were considered to be asymptomatic prior to their deaths. Necropsy information is available on 121 of the total patients, but unfortunately KULLER does not report what percentage of this 121 were asymptomatic. Despite this deficiency, 103 had triple vessel disease, 18 had double vessel disease, and interestingly, none of the patients had single vessel disease. The obvious interpretation of these data is that severe coronary artery disease portends a high risk of dying suddenly. WEAVER et al. [2] have recently reported an important study on the angiographic findings of patients resuscitated from sudden deaths. They were able to evaluate angiographically 64 patients, of which 18 had been totally asymptomatic prior to sudden death. Unfortunately, the authors did not discriminate between symptomatic and asymptomatic patients, but if one assumes that the distribution of coronary artery disease was the same in both groups, 94 % of the patients had severe stenosis (70 % or greater diameter reduction in one or more major coronary arteries) and 70% had ventricular wall contraction abnormalities. More than half of these patients were considered a suitable candidate for myocardial revascu1arization. The authors followed these patients for an average of 20.5 months and found that 14 (22 %) had a second episode of ventricular fibrillation. Those with a second episode of ventricular fibrillation had a higher incidence of triple vessel disease and more left ventricular dysfunction than those with a single episode of ventricular fibrillation. The authors conclude that angiography can identify individuals with high risk for recurrent ventricular fibrillation.
In 1974 NORRIS et al. [3] reported data relating to prognosis following an acute myocardial infarction. Their study indicates that if patients are asymptomatic, have normal heart size, normal blood pressure, isoelectric ST
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
Myocardial Infarction Studies
Asymptomatic Coronary Artery Disease: Detection and Management
157
segments and no arrhythmias, the yearly mortality is approximately 4 %. Although this study is an important contribution, it is important to emphasize that the presence, absence, or degree of coronary artery disease was not proven in the survivors.
Exercise Testing - Predictive Implications
ELLESTAD and WAN [4] have shown clearly that symptomatic patients with a positive stress test have a higher incidence of a new coronary event occurring each year than individuals with a negative stress test. In addition, those with a positive stress test at low heart rates and mild exercise had a higher incidence than those with a positive stress test at high heart rates, and a greater duration of exercise. GOLDSCHLAGER et al. [5] recently published data on 'The Accuracy of Treadmill Responses in Predicting Coronary Disease in a Group of 410 Patients'. Their study shows that 64 % of 100 patients with a normal treadmill test had evidence of coronary artery disease and 36 did not. However, when ST segment depression occurred, they observed a 99 % incidence of coronary artery disease in patients with downsloping ST segment depression, an 85 % incidence in patients with horizontal ST segment depression, and a 68 % incidence in patients with upsloping ST segment depression. The VA Cooperative Study has reported the survival of 408 medically treated, surgically suitable patients with stable angina pectoris. Their report indicates that the 2-year survival of patients with normal ventricular function and single vessel disease was 97 %, double vessel disease 94 % and triple vessel disease 90%. The addition of abnormal ventricular function in patients with surgically suitable single, double and triple vessel disease decreases the survival rate at 2 years, i. e., triple vessel disease with abnormal ventricular function - 86 % survival at 2 years. It is possible that this angiographic information may not have the same clinical significance in an asymptomatic patient population. However, since there is no data in the asymptomatic group, the figures available must be used to influence our clinical decisions.
The following cases will emphasize the points that have been made.
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
Case Presentations
158
CONTI
K K 40 M B P 08170 1
abnormal
Resting ECG Inverted T V4 - V6 Pacing ECG ST Vs LVED P Myocardial lactate extraction
nor ma!
Immediately postexercise Vs -
r-
I
I ,
norma !
Coronary art er iography Norma! Ejection fracti on 70'/,
30 sec postexercise Vs l--+H - -'--l+-l- ~ -+-l-~t-u ' L
Patient K. K., a 40-year-old male surgeon, was referred for evaluation of an abnormal resting electrocardiogram and an abnormal response to exercise stress. He was totally asymptomatic and had a normal blood pressure and normal cardiac examination. Repeat resting electrocardiogram revealed inverted T-waves in V4-V6. Hyperventilation for 2 min failed to change the resting electrocardiogram. Treadmill exercise using the Bruce protocol revealed 2.5 mm square wave ST segment depression in Vs at a heart rate of approximately 155 beats/min, immediately after exercise, which persisted for 30 sec in the postexercise period (fig. I). Hemodynamic investigation revealed a normal resting left ventricular pressure. During pacing-induced tachycardia, the patient developed asymptomatic ST segment depression in lead Vs similar to that seen during exercise. Left ventricular pressure was normal during pacing-induced ST segment depression. Myocardial lactate extraction was normal before, during and after pacing-induced ST segment depression. Coronary angiography revealed no evidence of large vessel coronary artery disease and no obvious missing vessels. Ventriculography revealed normal end-diastolic volume, an ejection fraction of 70 % without contraction abnormalities, mitral regurgitation or mitral valve prolapse (fig. 2). In this patient, the reason for the ST segment depression during stress is totally unclear since the coronary arteries were normal and there was no hemodynamic or metabolic evidence of myocardial ischemia during pacing-induced ST segment depression. Patient A . S., a 53-year-old telephone lineman, was asymptomatic before and after an episode of documented ventricular fibrillation, which occurred during sexual intercourse with his nurse wife. When referred for evaluation his blood pressure was normal and he had a normal cardiac examination. Resting electrocardiogram revealed nonspecific ST-T wave changes. Hyperventilation did not alter the electrocardiogram. Exercise testing revealed ST segment depression of approximately 2 mm in leads II and III and 1 mm in lead V6 at a heart rate of 132 (fig. 3). At no time did the patient notice any chest discomfort during or after exercise. 24-hour ambulatory monitoring revealed several episodes
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
Fig. 1. Exercise test, clinical and hemodynamics features of patient K. K.
Asymptomatic Coronary Artery Disease: Detection and Management
159
a, b
d,e Fig. 2. Coronary angiography and ventriculography of patient K. K. (see text).
LVEDP abnormal Myocardial lactate not done extraction
Control HR =74
III
--I,
III
-J~~r ~).
III
Coronary arteriography
100'/, LAD 90'10 C,rc
V4
DimInutive RCA Collaterals RCA and CIrc to LAD
Vs
VentrIculography normal
Exercise HR = 132 No symptoms I..
I~
-A..-.I~
-J~~ ·A
-YWr~
+"+-+r r-r-Hf ~+-l~ L
I
V
6
.....j.
LJl~
Fig. 3. Exercise test, clinical and hemodynamic features of patient A. S.
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A 5 53 M6P 110174 Resting ECG Inverted 1V3-V6 Ambulatory monitoring 51+ and PVCs Pacing ECG 51+ II, III, V6
CONT!
160
of asymptomatic ST segment depression and an occasional PVC close to the T-wave. Hemodynamic investigation revealed a normal resting left ventricular end-diastolic pressure. Pacing-induced tachycardia at a heart rate of 130 beats/min produced ST segment depression in leads II, III and V6, very similar to those that occurred during exercise. During this pacing stress test, the patient did not complain of angina, but noticed that the room seemed 'humid'. In addition, during pacing-induced ST segment depression, the left ventricular end-diastolic pressure was abnormal. Myocardial lactate metabolism was not evaluated. Subsequent coronary angiography (fig. 4) revealed 100 % occlusion of the left anterior descending coronary artery with excellent collateral to the distal LAD from the right and circumflex coronary artery. The left circumflex was 90 % occluded proximally, and the right coronary artery was a diminutive vessel since the posterior descending coronary artery took its origin from the left circumflex. Ventriculography revealed a normal ejection fraction and a normal contraction pattern without evidence of mitral valve prolapse or regurgitation. This patient was not asymptomatic in the true sense of the word since the clinical presentation was that of sudden death. However, he had no angina with stress. It would be interesting to know if exercise, prior to sudden death, would have produced asymptomatic ST segment depression. Subsequent investigation revealed severe multiple vessel coronary occlusive disease in addition to hemodynamic evidence of myocardial ischemia during pacing-induced ST segment depression. The clinical decision for this patient was that he undergo a revascularization procedure. This was accomplished successfully and both the anterior descending and circumflex coronary artery were bypassed. Follow-up angio-
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
Fig. 4. Coronary angiography and ventriculography of patient A. S. (see text).
Asymptomatic Coronary Artery Disease: Detection and Management
161
a
b
c
d Fig. 5. Postoperative angiography in patient A. S. (see text).
Both of these cases, at the opposite ends of the spectrum of coronary disease, illustrate the inadequacies of the resting and stress ECG in the asymptomatic subject. We have had the opportunity to evaluate 13 patients with asymptomatic ST segment depression during exercise; 6 of these 13
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 7:29:00 AM
graphy and hemodynamics performed 6 months after the surgical procedure (fig. 5) revealed that all grafts were patent, there was no new obstructive narrowing of the coronary arteries and ventricular function remained normal. Thus, there was no evidence of operative myocardial infarction. Ambulatory monitoring studies revealed no evidence of asymptomatic ST segment depression or PVCs during a 24-hour period. Repeat exercise test revealed no ST segment depression at a heart rate of 142 beats/min. Pacing-induced tachycardia revealed no ST segment depression at a heart rate of 132, but at a heart rate of 167 there was upsloping ST segment depression in lead II and V6 • The patient had no symptoms during stress testing. A subsequent exercise test was performed 1 year after the surgical procedure and failed to reveal any ST segment depression at a heart rate of 175 beats/min. The patient has remained asymptomatic.
CONTI
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patients were free of any significant large vessel coronary artery disease. We have recommended that all individuals with asymptomatic exercise-induced ST segment depression undergo further investigation, to include coronary angiography, ventriculography, and studies of lactate metabolism and hemodynamics during stress-induced ST segment depression [15].
Summary Available evidence indicates that coronary angiography is the only precise method available to detect the presence, absence and location of large vessel coronary occlusive disease in asymptomatic subjects. The correlation of a positive exercise test and the presence of coronary artery disease is best in symptomatic patients with typical angina who develop downsloping ST segment depression during or after exercise. Asymptomatic patients with single vessel coronary occlusive disease with or without evidence of myocardial ischemia should be observed and treated medically. Asymptomatic patients with multiple vessel disease with evidence of myocardial ischemia, life-threatening arrhythmias, or sudden death, probably should undergo revascularization procedures. Asymptomatic subjects with multiple vessel disease without evidence of myocardial ischemia, life-threatening ventricular arrhythmias or episodes of sudden death, probably should be observed and treated medically, but could be considered for surgery if operative mortality and morbidity is less than 2 %. Finally, all patients with proven coronary artery disease, symptomatic or not, should use common sense and apply good health practices, i.e., maintain normal body weight, lower cholesterol, if elevated, and control blood pressure.
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C. R. CONTI, MD , FA Cc. Professor of Medicine and Chief of Cardiology, University of Florida College of Medicine, H. Hillis Miller Health Center, Gainesville, Fla. (USA)
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