Detection, frequency and clinical significance of silent myocardial ischaemia in patients with chronic stable angina

Forty-two patients (mean age 50 years) with chronic stable angina pectoris were subjected to exercise treadmill testing, coronary arteriography and left ventricular cineangiography. Twenty-one of these patients also underwent Holter monitoring for 24 hours. On exercise treadmill testing, angina was the endpoint in 24 (57%), while 18 (43%) developed significant ST segment depression without symptoms. Holter monitoring in 27 patients revealed a total of 248 episodes of myocardial ischaemia of which 210 (84%) were asymptomatic. ST segment depression at 80 mS from J point varied from 1 to 4 mm, and the average duration of ischaemic episodes during Holter monitoring was 9 minutes (range 30 seconds to 1 hour). Heart rate during the ischaemic episodes varied between 65-85 beats/minute. Coronary angiography revealed triple vessel disease in 22 (52%) and double vessel and single vessel involvement in 10 (24%) each. Left ventricular ejection fraction was less than 50% in only 3 (7%) patients. Thus silent myocardial ischaemia is detected frequently in patients with angina pectoris. It occurs during routine daily activity, and on exercise. Heart rate at which silent myocardial ischaemia occurs is much less during daily activity as compared to exercise induced ischaemia. All patients who were detected to have silent myocardial ischaemia had significant coronary artery disease. These findings are of prognostic and therapeutic value.     

Abrupt cessation of short-term continuous treatment with isosorbide dinitrate may cause a rebound increase in silent myocardial ischaemia in patients with stable angina pectoris.

OBJECTIVE: To examine by Holter electrocardiographic monitoring the effect of abruptly stopping nitrate treatment in patients with stable angina pectoris. PATIENTS: 12 men with confirmed ischaemic heart disease and stable exertional class 3 angina (Canadian). All had episodes of horizontal or down sloping ST segment depression during 24 hour electrocardiographic monitoring. All were nitrate responders. DESIGN: Each patient was given isosorbide dinitrate (10-30 mg four times a day) and placebo (four times a day) for three days in a randomised crossover trial. There was a washout period of 3-5 days between the two treatment periods. Holter monitoring was performed on the third day of isosorbide dinitrate and placebo administration and on the first day of their withdrawal. RESULTS: When treatment with isosorbide dinitrate was stopped there was a significant increase in the total number and duration of painless episodes of myocardial ischaemia. During placebo and isosorbide dinitrate administration 8 patients had episodes of painless myocardial ischaemia whereas after isosorbide dinitrate cessation they were recorded in all 12 patients. Episodes of silent myocardial ischaemia at rest appeared in 4 patients after isosorbide dinitrate withdrawal. CONCLUSION: Abrupt cessation of short-term continuous nitrate treatment in patients with severe angina may cause a rebound increase in myocardial ischaemia which is predominantly silent.     

Influence of the autonomic nervous system on circadian patterns of myocardial ischaemia: comparison of stable angina with the early postinfarction period.

OBJECTIVE--To compare the circadian rhythm of myocardial ischaemia in patients with stable angina with that in patients in the early postinfarction period with particular emphasis on the role of the autonomic nervous system. PATIENTS--44 patients with stable angina and ischaemia on treadmill testing (group A) were compared with 131 patients in the early postinfarction period (group B). All had 48 hour ambulatory Holter monitoring. SETTING--Coronary care unit and cardiology department of a district general hospital. DESIGN--Prospective, between group, comparative study. RESULTS--337 ischaemic episodes occurred in 35 patients in group A and 370 ischaemic episodes occurred in 65 patients in group B. 34% of patients in group A had only silent episodes of ischaemia compared with 97% in group B (p < 0.0001). In group A ischaemic episodes showed a circadian rhythm that peaked during the daytime hours (p < 0.0001), but this was not seen in group B. Both the high (0.15-0.40 Hz) and low (0.04-0.15 Hz) frequency spectral components of heart rate variability showed a clear circadian rhythm (p < 0.0001); peak values occurred during the sleeping hours, although this pattern was less pronounced in group B. The ratio of low to high frequency variability (a measure of sympathovagal balance) showed a peak in daytime hours in group A (p < 0.002), but this was not seen in group B. CONCLUSION--In stable angina, myocardial ischaemia peaks during the day and is associated with a similar circadian rhythm of sympathovagal balance. In the early postinfarction period both the ischaemic and sympathovagal rhythms are severely diminished or lost altogether. Circadian changes in sympathovagal tone may explain, at least in part, the circadian rhythm of ambulatory myocardial ischaemia in patients with stable angina.     

Prognostic significance of transient myocardial ischaemia after first acute myocardial infarction: five year follow up study.

OBJECTIVE--To assess the five year prognostic significance of transient myocardial ischaemia on ambulatory monitoring after a first acute myocardial infarction, and to compare the diagnostic and long term prognostic value of ambulatory ST segment monitoring, maximal exercise testing, and echocardiography in patients with documented ischaemic heart disease. DESIGN--Prospective study. SETTING--Cardiology department of a teaching hospital. PATIENTS--123 consecutive men aged under 70 who were able to perform predischarge maximal exercise testing. INTERVENTIONS--Echocardiography two days before discharge (left ventricular ejection fraction), maximal bicycle ergometric testing one day before discharge (ST segment depression, angina, blood pressure, heart rate), and ambulatory ST segment monitoring (transient myocardial ischaemia) started at hospital discharge a mean of 11 (SD 5) days after infarction. MAIN OUTCOME MEASURES--Relation of ambulatory ST segment depression, exercise test variables, and left ventricular ejection fraction to subsequent objective (cardiac death or myocardial infarction) or subjective (need for coronary revascularisation) events. RESULTS--23 of the 123 patients had episodes of transient ST segment depression, of which 98% were silent. Over a mean of 5 (range 4 to 6) years of follow up, patients with ambulatory ischaemia were no more likely to have objective end points than patients without ischaemic episodes. If, however, subjective events were included an association between transient ST segment depression and an adverse long term outcome was found (Kaplan-Meier analysis; P = 0.004). The presence of exercise induced angina identified a similar proportion of patients with a poor prognosis (Kaplan-Meier analysis; P < 0.004). Both exertional angina and ambulatory ST segment depression had high specificity but poor sensitivity. The presence of exercise induced ST segment depression was of no value in predicting combined cardiac events. Indeed, patients without exertional ST segment depression were at increased risk of future objective end points (Kaplan-Meier analysis; P < 0.0045). These findings may be explained in part by a higher prevalence of left ventricular dysfunction in patients without ischaemic changes in the exercise electrocardiogram (P < 0.05). CONCLUSION--There seem to be limited reasons to perform ambulatory ST segment monitoring in survivors of a first myocardial infarction who can perform exercise tests before discharge. Patients at high risk of future myocardial infarction or death from cardiac causes are not identified. Ambulatory monitoring and exertional angina distinguish a small subset of patients who will develop severe angina pectoris demanding coronary revascularisation during follow up. Patients without exercise induced ST segment depression comprise a high risk subgroup in terms of subsequent objective end points. The role of ambulatory ST segment monitoring performed in unselected patients immediately after infarction when risk is maximal remains to be clarified.     

Effect of exercise training on the total ischaemic burden: an assessment by 24 hour ambulatory electrocardiographic monitoring.

OBJECTIVE--To examine the effect of prolonged high intensity exercise training on total ischaemic burden in men with chronic stable angina pectoris. DESIGN--A randomised controlled trial based on 24 hour ambulatory electrocardiographic monitoring of patients on two occasions a year apart. SETTING--Cardiology department of a large general hospital. SUBJECTS--40 men under 60 years of age with chronic stable angina pectoris and no previous myocardial infarction. RESULTS--After training the exercise group showed a 30% reduction in frequency of ST segment depression. There were significant reductions in painful episodes of ischaemia and those triggered by changes in heart rate. There was also a trend towards a reduction in silent ischaemia and episodes not triggered by changes in heart rate. The duration of ischaemic episodes was also reduced. No significant change in frequency or severity of dysrhythmia was shown. CONCLUSIONS--Exercise training reduces total ischaemic burden in patients with angina pectoris by reducing the frequency and duration of all types of ischaemic episode.     

Assessment of Holter ST monitoring for risk stratification in patients with acute myocardial infarction treated by thrombolysis.

OBJECTIVES--To evaluate the role of Holter ST monitoring for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis. BACKGROUND--The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment. There is now a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). Preliminary evidence indicates that Holter ST monitoring may be of prognostic value in patients with acute myocardial infarction, but there are limited data available in patients treated by thrombolysis. METHODS--Prospective observational study of 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis. All underwent 48 hour Holter ST monitoring early after thrombolysis (mean 83, range 48-180 hours) and were followed up for eight (range three to 12) months. RESULTS--Recurrent ischaemic events occurred in 45 patients (fatal reinfarction 17, non-fatal reinfarction 12, unstable angina 16). Also four patients died as a result of progressive heart failure, and a further 15 patients required revascularisation. Analysis of the Holter data showed that 32% of patients had at least one episode of isolated ST depression (> or = 0.1 mV) and 41% either ST depression or elevation (> or = 0.2 mV). Ischaemic episodes were silent in 95% of cases. Event free survival analysis showed a significant association between Holter findings and recurrent ischaemic events (ST depression: p = 0.009; ST depression or elevation: p = 0.002). The association remained significant when the end point was restricted to fatal or non-fatal reinfarction (ST depression: p = 0.005; ST depression or elevation p = 0.001), the period of greatest risk for patients with an abnormal recording occurred early after investigation. An abnormal Holter recording identified patients at risk of early (within 30 days) reinfarction with 79% sensitivity and 60% specificity. Although positive predictive accuracy was low (11%), a normal Holter recording was associated with 98% negative predictive accuracy. CONCLUSIONS--In patients treated by thrombolysis, ST change on Holter monitoring may be useful for identifying patients at increased risk of recurrent ischaemic events, and in particular early reinfarction.     

Different mechanisms for the relief of angina after coronary bypass surgery. Physiological versus anatomical assessment.

To determine the physiological effect of coronary artery bypass surgery and the mechanisms for pain relief, 15 patients with exertional angina were studied before and after operation. Before the operation conventional tests included exercise tests (all positive) and coronary angiography (all patients had greater than or equal to 70% stenosis of major vessels). In addition, ambulatory electrocardiographic monitoring during 48 hours detected 92 episodes (greater than or equal to 1 mm) of ST depression. Regional myocardial perfusion was assessed with positron tomography using rubidium-82 (t1/2 78 s) and this showed reversible inhomogeneity with absolute regional reduction of cation uptake after exercise in all 15 patients. After coronary surgery 10 of the 15 patients had (a) no angina, (b) patent grafts (three or more), (c) no evidence of ischaemia during ambulatory monitoring out of hospital, and (d) homogeneous perfusion with reversal of the disturbances in regional myocardial perfusion after exercise. After operation one of the 15 patients had no angina and showed silent infarction in the segment that was previously ischaemic but supplied by a patent graft. All but one of the remaining patients had no angina, patent grafts, but disturbances of regional myocardial perfusion with silent ischaemia on exercise. Two of these patients continued to have asymptomatic and ischaemic episodes of ST depression during ambulatory monitoring out of hospital. This physiological study of regional myocardial perfusion in patients in hospital and in those with ischaemia out of hospital showed that three different mechanisms may account for the relief of pain--improved perfusion, infarction, and silent ischaemia. Silent ischaemia in particular raises puzzling pathophysiological and therapeutic questions that may affect prognosis and the interpretation of clinical trials.     

Painful and silent myocardial ischaemia during exercise testing

The study was designed to clarify the clinical and angiographic attributes of patients with exercise induced silent myocardial ischaemia. The sample consisted of 102 patients who had ischaemic exercise electrograms (greater than or equal to 1 mm ST segment depression) and had a significant angiographic stenosis (greater than 50% diameter stenosis), in at least one of the major coronary arteries. In 61 patients (60%) painful ischaemia was observed during exercise (group A) while in 41 patients (40%) only ST depression (silent ischaemia) occurred (group B). The groups were similar with respect to age, sex, history of diabetes and all angiographic parameters including the Gensini coronary score. A history of prior myocardial infarctions was observed more frequently (p less than 0.01) in patients with silent ischaemia (group B). Prior myocardial infarction may be a factor causing silent myocardial ischaemia.     

Transient myocardial ischaemia after acute myocardial infarction

The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications.     

Transient myocardial ischaemia after acute myocardial infarction.

The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications.     

Effect of exercise training on the total ischaemic burden: an assessment by 24 hour ambulatory electrocardiographic monitoring

Objective—To examine the effect of prolonged high intensity exercise training on total ischaemic burden in men with chronic stable angina pectoris.Design—A randomised controlled trial based on 24 hour ambulatory electrocardiographic monitoring of patients on two occasions a year apart.Setting—Cardiology department of a large general hospital.Subjects—40 men under 60 years of age with chronic stable angina pectoris and no previous myocardial infarction.Results—After training the exercise group showed a 30% reduction in frequency of ST segment depression. There were significant reductions in painful episodes of ischaemia and those triggered by changes in heart rate. There was also a trend towards a reduction in silent ischaemia and episodes not triggered by changes in heart rate. The duration of ischaemic episodes was also reduced. No significant change in frequency or severity of dysrhythmia was shown.Conclusions—Exercise training reduces total ischaemic burden in patients with angina pectoris by reducing the frequency and duration of all types of ischaemic episode.     

Prognostic significance of silent exertional myocardial ischaemia in symptomatic men without previous myocardial infarction.

A total of 360 consecutive male patients with complaints of chest pain and documented coronary artery disease underwent a maximal exercise test combined with thallium myocardial scintigraphy. Patients with a history of previous myocardial infarction were excluded. During follow-up (46 months; from 12 to 96) 27 patients died and 26 had a first non-fatal myocardial infarction. The 6-year survival rate and the 6-year event-free rate were 81 and 71%. Four variables contributed independently to the prognosis (Cox Model): the number of diseased vessels, the angiographic ejection fraction, the age and a multivariate score of the exercise test. From these patients, 227 had an abnormal response to exercise (ST-segment depression greater than or equal to 0.1 mV); in 138 patients, angina pectoris was induced during exercise while 89 patients had no pain during exercise (silent ischaemia). These 89 patients with silent exertional ischaemia were matched to 89 patients with exertional angina pectoris, according to the above-mentioned four prognostic predictors. The two groups of patients had similar signs of ischaemia during exercise (ST-segment depression and thallium perfusion score). The 6-year survival rates (81 and 81.5%) and the 6-year event-free rates (71 and 70.5%) were similar in the two groups. Thus, in men without previous myocardial infarction, silent exertional ischaemia bears the same prognosis as exertional ischaemia attended by angina pectoris.     

Characteristics of silent and painful ischaemia during ambulatory monitoring in patients with coronary arterial disease

We compared the characteristics of silent and painful ischaemia during ambulatory ST segment monitoring in 288 patients with documented coronary arterial disease and stable angina. During 12,436 hours of monitoring, 890 ischaemic episodes were recorded, of which 652 (73%) were silent. Silent and painful ischaemic episodes were similar in terms of heart rate at onset of ischaemia, increase in heart rate prior to ischaemia, duration of ischaemia, and percentage of episodes not preceded by an increase in heart rate. Change in the mean maximal ST segment was greater during painful ischaemic episodes (P less than 0.01). Silent ischaemia is characteristically painful ischaemia without the pain.     

Silent ischemia after myocardial infarct

The Framingham study demonstrated that 25% of all episodes of acute myocardial infarction (AMI) do not present clinical symptoms, and are later recognized in a routine ECG. Silent ischaemia is frequently found after acute myocardial infarction, and has been identified in 25-60% of the patients according to the results of different studies and the different criteria employed for diagnosis. Silent ischaemia after AMI, as well as angina, is related with the presence and extent of severe coronary lesions located in the infarct related coronary artery or in other vessel not responsible for the acute episode of necrosis. The prognostic significance of silent ischaemia after AMI has not been well established. In some studies the painless ST segment depression during an exercise test soon after AMI presented the same prognostic value that the ST segment depression accompanied by angina, but in others the symptomatic episodes were a better predictor of major events and long term survival after the infarct. Several studies employing ambulatory ECG monitoring (Holter) also seem to indicate that the painless and transient episodes of ST segment depression identify a group of patients with worse prognosis, but in these studies the patients were selected, introducing a clear bias in the results of these investigations. Finally, asymptomatic transient perfusion defects in thallium studies clearly identify a group of high risk patients with a higher incidence of complications and higher mortality rate than the patients with negative thallium studies. The efficacy of anti-ischaemic drugs or myocardium revascularization procedures, including surgery, has not been studied in patients with silent ischaemia after acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential autonomic mechanisms underlying early morning and daytime transient myocardial ischaemia in patients with stable coronary artery disease.

OBJECTIVES--To see whether autonomic regulatory mechanisms play a part in transient myocardial ischaemia in patients treated with beta blockers. DESIGN--Prospective study. SETTING--Outpatients' clinic. PATIENTS--51 consecutive patients with angiographically documented coronary artery disease, stable angina, and transient myocardial ischaemia despite beta blockade. INTERVENTIONS--24 hour ambulatory electrocardiographic monitoring for analysis of variability in ST depression and heart rate. MAIN OUTCOME MEASURES--Numbers of episodes of ischaemia, with an ST depression of > or = 0.1 mV 80 ms after the J point that lasted > or = 60 s at an interval of > or = 60 s from a previous ischaemic episode. Heart rate at onset of ischaemia. Normalised spectral analysis of heart rate variability; ratio of low to high frequency power to assess the sympathovagal balance. RESULTS--Despite treatment, 258 episodes of transient ischaemia were recorded. At heart rates at onset of ischaemia of < 70 beats per minute a high ratio of low to high frequency power accompanied the ischaemic events and was paralleled by a remarkably reduced high frequency power. The high ratio--that is, enhanced sympathetic tone during ischaemia--was mainly found in the early morning. By contrast, ischaemic episodes with heart rates at onset of > or = 70 beats per minute were not associated with significant changes in the parameters of autonomic function. CONCLUSIONS--During beta blockade the residual transient ischaemia is associated with decreased variability in heart rate. In particular, in ischaemic episodes with a low heart rate at onset the neural regulation of the heart plays a part. Apparently, variability in heart rate is not sufficiently modified by beta blockers to prevent all ischaemia. The ischaemia related change in the autonomic nervous system during the early morning is in agreement with previous studies, showing increased cardiovascular risk at this time of the day.     

Silent myocardial ischaemia in patients referred for coronary bypass surgery because of angina: a comparison with patients whose symptoms were well controlled on medical treatment.

The frequency and characteristics of silent ischaemia were prospectively studied in 114 patients with confirmed coronary artery disease and angina. Fifty seven patients who had angina that was not adequately controlled by standard medications were referred for elective coronary artery bypass surgery (group 1). Fifty seven other patients had symptoms that were well controlled on medical treatment (group 2). Patients underwent treadmill exercise testing (n = 109) and 48 hours of ambulatory ST segment monitoring (total 5125 hours). Patients in group 1 had more severe coronary artery disease and a shorter time to 1 mm ST segment depression and maximal exercise. Twenty two patients in group 1 (38%) and 16 in group 2 (28%) had greater than or equal to 1 episode of silent ischaemia during 48 hours of ST monitoring. There was no significant difference in the mean frequency of silent ischaemic episodes in 24 hours between the two groups (group 1 0.72 v group 2 0.64); however, the mean frequency of painful ischaemic episodes in 24 hours was greater in group 1 patients (0.51) than in group 2 (0.11). In both groups the frequency of silent ischaemia was significantly related to a positive exercise test, as was the total duration of silent ischaemia. The circadian variation of silent ischaemia showed a peak of episodes in the evening in both groups. The frequency of silent ischaemia in patients with coronary artery disease and angina receiving standard antianginal medications was not related to the severity of symptoms, but was significantly related to a positive exercise test. Thirty three percent of the patients studied had evidence of silent ischaemia during 48 hours of ambulatory ST segment monitoring; however, only four patients (3.5%) had frequent (>/=5) daily episodes of silent ischaemia.     

Gradation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB.

A newly developed, highly sensitive immunoassay for creatine kinase MB isoenzyme was evaluated in 68 patients with or without different types of ischaemic heart disease. Patients were classified on the basis of clinical criteria in four groups: no ischaemic heart disease, stable angina, unstable angina, and acute myocardial infarction. Enzyme concentration in patients with stable angina was the same (even during exercise) as seen in the patients without ischaemic heart disease. Patients with unstable angina, however, could be divided into two groups. One group showed clear evidence of severe myocardial ischaemia by serial changes and higher mean values of creatine kinase MB up to 40 hours after the onset of symptoms, whereas in the remainder values were stable and resembled those seen in the patients without ischaemic heart disease. The changes in concentration correlated with signs of repetitive ischaemic episodes deduced from continuous ST segment monitoring during the first 24 hours after admission. These findings indicate that patients with unstable angina are a heterogenous group. In some, severe and prolonged ischaemia can be detected by a serological assay with high sensitivity.     

Silent myocardial ischaemia in patients referred for coronary bypass surgery because of angina: a comparison with patients whose symptoms were well controlled on medical treatment

The frequency and characteristics of silent ischaemia were prospectively studied in 114 patients with confirmed coronary artery disease and angina. Fifty seven patients who had angina that was not adequately controlled by standard medications were referred for elective coronary artery bypass surgery (group 1). Fifty seven other patients had symptoms that were well controlled on medical treatment (group 2). Patients underwent treadmill exercise testing (n = 109) and 48 hours of ambulatory ST segment monitoring (total 5125 hours). Patients in group 1 had more severe coronary artery disease and a shorter time to 1 mm ST segment depression and maximal exercise. Twenty two patients in group 1 (38%) and 16 in group 2 (28%) had greater than or equal to 1 episode of silent ischaemia during 48 hours of ST monitoring. There was no significant difference in the mean frequency of silent ischaemic episodes in 24 hours between the two groups (group 1 0.72 v group 2 0.64); however, the mean frequency of painful ischaemic episodes in 24 hours was greater in group 1 patients (0.51) than in group 2 (0.11). In both groups the frequency of silent ischaemia was significantly related to a positive exercise test, as was the total duration of silent ischaemia. The circadian variation of silent ischaemia showed a peak of episodes in the evening in both groups. The frequency of silent ischaemia in patients with coronary artery disease and angina receiving standard antianginal medications was not related to the severity of symptoms, but was significantly related to a positive exercise test. Thirty three percent of the patients studied had evidence of silent ischaemia during 48 hours of ambulatory ST segment monitoring; however, only four patients (3.5%) had frequent (>/=5) daily episodes of silent ischaemia.     

Gradation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB.

A newly developed, highly sensitive immunoassay for creatine kinase MB isoenzyme was evaluated in 68 patients with or without different types of ischaemic heart disease. Patients were classified on the basis of clinical criteria in four groups: no ischaemic heart disease, stable angina, unstable angina, and acute myocardial infarction. Enzyme concentration in patients with stable angina was the same (even during exercise) as seen in the patients without ischaemic heart disease. Patients with unstable angina, however, could be divided into two groups. One group showed clear evidence of severe myocardial ischaemia by serial changes and higher mean values of creatine kinase MB up to 40 hours after the onset of symptoms, whereas in the remainder values were stable and resembled those seen in the patients without ischaemic heart disease. The changes in concentration correlated with signs of repetitive ischaemic episodes deduced from continuous ST segment monitoring during the first 24 hours after admission. These findings indicate that patients with unstable angina are a heterogenous group. In some, severe and prolonged ischaemia can be detected by a serological assay with high sensitivity.     

Holter monitoring and silent myocardial ischemia

Angina is not a very sensitive indicator of myocardial ischaemia. In patients with coronary disease 75 percent of ischaemic episodes are asymptomatic. Holter monitoring enables such silent episodes to be detected in daily life, this method becoming more sensitive when pursued for several days. The procedure is facilitated by a new generation of Holter recorders fitted with microprocessors that digitalize electrocardiograms. Silent episodes occur in the same circumstances as painful episodes, with a peak of incidence between 6 a.m. and noon, but they are often somewhat shorter. In patients with stable angina, as in those with unstable angina and after infarction, silent ischaemia is of poor prognosis. Holter monitoring therefore is useful in patients with known coronary disease to identify subjects at risk and to evaluate the effectiveness of anti-ischaemic treatments.