Circadian variation of transient myocardial ischemia in the early out-of-hospital period after first acute myocardial infarction

Circadian rhythms have been demonstrated in acute myocardial infarction (AMI) and in other clinical cardiac dysfunctions. The purpose of this study was to elucidate whether a circadian pattern of transient myocardial ischemia exists after first AMI. Prospectively, 24-hour ambulatory ST-segment monitoring was initiated at discharge on day 11 +/- 5 in 123 consecutive survivors of first AMI. A total of 93 ischemic episodes (91 asymptomatic) occurred in 21 of the 123 patients (17%) (mean duration of 30 minutes, range 4 to 292). A significant circadian rhythm of transient myocardial ischemia was found with a peak activity occurring in the evening hours (p less than 0.01). Thus, 43% of ischemic episodes and 42% of ischemic time occurred between 6 P.M. and 12 midnight. The characteristics of morning and evening episodes were similar, except for the heart rate at maximal ST-segment depression, which was significantly higher during morning episodes (p less than 0.02). Patients with transient myocardial ischemia had a diurnal distribution similar to the circadian variation displayed during ischemic activity. Thus, 16 of the 21 patients had ischemic episodes from 6 P.M. to 12 midnight versus 10 patients from 6 A.M. to 12 noon (p less than 0.01). The 24-hour mean minimal heart rate was significantly higher in patients with than without ischemic episodes (p less than 0.02). In conclusion, this study has established a significant circadian peak of transient myocardial ischemia in the evening hours in survivors of first AMI. Whether the pattern displayed is due to endogenous biologic functions or cyclic variations, or both, in the external environment needs to be clarified.     

Circadian distribution of the characteristics of ischemic episodes in patients with stable coronary artery disease

To determine the circadian distribution of episodes of myocardial ischemia, studies were performed in 111 patients with chronic stable angina pectoris, positive exercise test results and angiographically proven coronary artery disease. During 24 hours of ambulatory electrocardiographic monitoring, 101 symptomatic and 298 asymptomatic ischemic episodes (ST-segment depression greater than 1 mm, duration greater than 1 minute) were observed. The number of ischemic episodes and the cumulative duration of ischemia showed a circadian variation with the highest values between 8 and 10 A.M. and between 4 and 5 P.M. associated with a similar circadian variation of heart rate. Mean duration of ischemic episodes, maximal amplitude of ST-segment depression during ischemic episodes and increase in heart rate before the onset of ischemic episodes showed no significant circadian variation. Heart rate at the onset of ischemic episodes and maximal heart rate during ischemic episodes were lower between midnight and A.M. than during other times of the day. The morning and afternoon increase in ischemic activity is not paralleled by changes reflecting a decrease in myocardial oxygen supply during these periods (heart rate at onset of ischemia, heart rate increase before onset of ischemia), but is paralleled by a similar circadian variation of heart rate. The circadian variation in ischemic activity is predominantly based on a comparable variation in myocardial oxygen requirements.     

Patterns and behavior of transient myocardial ischemia in stable coronary disease are the same in both men and women: A comparative study

Objectives. This study sought to compare the circadian variations in transient ischemic activity, mean heart rate and ischemic threshold between women and men with coronary artery disease.

Background. There is a circadian variation in ischemic activity, onset of myocardial infarction and sudden cardiac death in patients with coronary artery disease, but studies assessing ischemia have incorporated predominantly male subjects.

Methods. Thirty-one women and 45 men underwent at least 48 h of ambulatory ST segment monitoring.

Results. There was a similar and significant circadian variation in ischemic activity in both women and men (p < 0.001 and p < 0.0001, respectively), with a trough at night, a surge in the morning and a peak between 1 and 2 , corresponding to a similar circadian variation in mean hourly heart rate (p < 0.0001) that was not different between men and women (p = 0.28, power to detect a shift 99.9%). Mean heart rate at onset of ischemia (ischemia threshold) had similar variability in women and men (p = 0.96), and harmonic regression analysis confirmed a significant circadian variation (p < 0.0001), with a trough at night and a peak during activity hours. Heart rate increased significantly in the 5 min before ischemia throughout the 24 h (p < 0.0001), with no gender differences in the pattern of preonset to onset heart rate changes over time (p = 0.52); the smallest differences were recorded in the middle of the night. The majority of ischemic episodes (80%) had a heart rate increase >5 beats/min in the 5 min before ischemia, but there were no gender differences.

Conclusions. Women with coronary artery disease have a pattern of ischemic activity and underlying pathophysiologic mechanisms very similar to men. The importance of increase in myocardial oxygen demand in the genesis of ischemia in both men and women is reflected by similar magnitude of heart rate increases before ischemia. The lower ischemic threshold during the nocturnal hours, when blood pressure is also lower, is consistent with a circadian variation is underlying coronary vascular tone.     

The clinical characterization and prognostic significance of episodes of transient myocardial ischemia in patients with a recent myocardial infarct

The incidence and prognostic significance of silent myocardial ischemia were assessed in 175 patients who survived a first acute myocardial infarction (AMI). This was done by means of a 24-hour continuous ECG monitoring which was performed before discharge. Twenty-six out of 175 patients (14.8%) showed one episode or more of S-T segment depression; 19 of these reported no pain at all while the other 7 reported both painful and painless episodes. A total of 65 ischemic episodes were registered; of these 53 (81.5%) were painless and 12 (18.5%) were painful. No difference in the duration of ischemic episodes or in heart rate at the onset of S-T segment depression was detected for painless or painful episodes. The S-T segment depression episodes showed a peak in the morning but were higher in the afternoon and this circadian pattern was statistically significant both with regard to duration (p less than 0.05) and to the number of episodes (p less than 0.05). Cardiac death occurred in 5 of the 26 patients (19.2%) with S-T segment depression during continuous ECG monitoring, and in 5 of the 149 (3.4%) without S-T segment depression (p less than 0.01). In patients with ischemia duration greater than 60 min/24 hours, the mortality rate was higher (p less than 0.05). No cardiac events (unstable angina, non-fatal re-infarction, balloon angioplasty and/or coronary by-pass) occurred in 117 out of 149 patients (78.5%) without ST-segment depression, while these events were observed in 13 out of the 26 patients (50%) with ischemic episodes during Holter monitoring (p less than 0.01). Sensitivity and specificity of S-T segment depression was respectively 29.3 and 89.5% for cardiac death and cardiac events considered together.(ABSTRACT TRUNCATED AT 250 WORDS)     

心绞痛患者528次缺血性ST段下移分析

83例心绞痛患者经24小时动态心电图监测到528次缺血性ST段下移,分析结果表明:1.在心绞痛患者缺血性ST段下移中,无症状性心肌缺血占75％,发生次数是有症状的3倍;2.缺血性ST段下移,85％与活动有关;3.缺血性ST段下移有明显的昼夜分布规律,上午6—10时为发作高峰,占全天总次数32％。提示在冠心病治疗中应重视包括无症状性心肌缺血在内的总缺血负荷,并结合缺血的昼夜分布规律调整给药时间。     

Circadian variation in ischemic threshold. A mechanism underlying the circadian variation in ischemic events.

BACKGROUND. There is a circadian pattern in the occurrence of cardiac events in patients with coronary artery disease. Whether changes in coronary vascular tone contribute to these phenomena is unknown. We measured the ischemic threshold, defined as either the heart rate or rate-pressure product at 1-mm ST segment depression during treadmill exercise and used it as an index of the lowest coronary vascular resistance; the premise was that when ischemic threshold became lower, coronary vascular resistance was higher, and vice versa. METHODS AND RESULTS. Fifteen patients (group A) with stable coronary artery disease underwent four identical treadmill exercise tests in 24 hours, and ischemic threshold was measured as the heart rate at the onset of 1-mm ST depression. Before each treadmill test, postischemic forearm vascular resistance was measured after 5 minutes of forearm occlusion, using strain-gauge plethysmography. Sixteen additional patients (group B) underwent two treadmill tests at 8 AM and 1 PM, and ischemic threshold was measured as the heart rate-blood pressure product at 1-mm ST depression. A circadian variation was noted: In group A, the heart rate-derived ischemic threshold was lower at 8 AM and 9 PM compared with noon and 5 PM (p less than 0.03). Also, in group B, the rate-pressure product-derived ischemic threshold was 8 +/- 2% lower at 8 AM compared with 1 PM (p = 0.008). A circadian variation parallel to the observed variation in ischemic threshold was also noted in the postischemic forearm blood flow, which was lower in the morning and at night (p less than 0.004). There was a strong correlation between postischemic forearm blood flow and ischemic threshold (p less than 0.0001), such that ischemic threshold was lower at the time of day when postischemic forearm blood flow was lower, and vice versa. CONCLUSIONS. A lower ischemic threshold in the morning suggests that the ischemia-induced coronary vascular resistance is increased at this time, a finding supported by a similar variation in postischemic forearm vascular resistance. Parallel changes in forearm and coronary resistance suggest that generalized (neural or humoral factors) rather than local factors are responsible for the observed circadian changes. Increased coronary tone in the mornings may not only contribute to the higher incidence of transient ischemia but may help trigger acute cardiac events at this time.     

Role of increases in heart rate in determining the occurrence and frequency of myocardial ischemia during daily life in patients with stable coronary artery disease.

OBJECTIVES. The goal of this study was to investigate the role of increases in heart rate in the development of ischemic episodes recorded during ambulatory electrocardiographic (ECG) monitoring in patients with stable coronary artery disease and to establish the importance of such increases in determining the frequency of ambulatory myocardial ischemia. BACKGROUND. The factors that determine the occurrence and frequency of episodes of myocardial ischemia that patients with stable coronary artery disease experience during daily life have not been clearly defined. In particular, the role of increases in heart rate in the development of myocardial ischemia is controversial. METHODS. To address these issues, 54 patients (42 men and 12 women, mean age 60.5 +/- 8 years) with proved coronary artery disease who had > or = 1 mm ST segment depression during exercise testing underwent an exercise treadmill test with use of the National Institutes of Health combined protocol and a 48-h period of ambulatory ECG monitoring. The exercise ischemic threshold was determined as the heart rate at the onset of ST segment depression during exercise testing. RESULTS. During monitoring, 48 (89%) of the 54 patients had at least one episode of ST segment depression (mean +/- SD 6.6 +/- 5 episodes, range 0 to 22). The majority (320 of 359 or 89%) of ischemic episodes were preceded by an increase in heart rate > or = 10 beats/min; the most significant increase (22.3 +/- 10 beats/min) occurred during the 5-min period before the onset of the episode. An ischemic episode occurred 80% of the times the heart rate reached the exercise ischemic threshold. A strong correlation was observed between the number of times the exercise ischemic threshold was reached during monitoring and both the number and the duration of ischemic episodes (r = 0.90 and 0.71, respectively, p < 0.0001). CONCLUSIONS. Increases in heart rate that exceed the exercise ischemic threshold are commonly observed before the onset of episodes of ambulatory myocardial ischemia in patients with stable coronary artery disease. Moreover, such increases constitute an important determinant of the frequency of myocardial ischemia during daily life. These findings may explain the variability observed in the number of ischemic episodes and may have important implications for the mechanisms that contribute to myocardial ischemia in daily life and for the clinical evaluation of patients with coronary artery disease.     

ST segment analysis in 24-hour long-term ECG in patients with stable angina pectoris and angiographically detected coronary sclerosis

ST-segment analysis on 24-hour Holter ECG was performed in 64 patients with angiographically proven coronary artery disease, a positive exercise test and chronic stable angina. During 125 days of recording, 494 episodes of transient ST-segment depression were observed, at an average of 4.0 +/- 3.7 episodes (1-13 episodes, median: 3 episodes) per day. The duration of ST depression per episode was 13.2 +/- 14.4 min (1-90 min; median: 8 min). No episodes of ST-elevation were observed. Only 27 (5.5%) ischemic episodes occurred during the night, between midnight and 6:00 a.m., but they were frequently observed during the morning hours between 7:00 and 12:00 a.m. Nearly all episodes of ischemia were preceded by an increase in heart rate. However, heart rate at the onset of significant ST-segment depression was significantly lower during Holter monitoring than during exercise test (p less than 0.001); this indicates that factors additional to the increase in myocardial demand might be relevant for transient myocardial ischemia during daily life. 382 of the 494 episodes (77.3%) of ischemia were asymptomatic; heart rate at the onset of ST-segment depression was similar in symptomatic and asymptomatic episodes; however, in asymptomatic episodes, maximal heart rate was significantly lower (p less than 0.001) and the duration of the episodes significantly longer (p less than 0.001). The percentage of asymptomatic episodes was very high in patients with one-vessel disease, whereas the duration and amount of ST-segment depression, as well as heart rate, at the onset of ischemia, were not dependent on the extent of coronary artery disease.     

Myocardial ischemia in patients awaiting coronary artery bypass grafting

The results of ambulatory ECG monitoring are described in a group of patients that have not previously been characterized. Fifty men who were initially seen for elective CABG surgery underwent 48 hours of continuous ambulatory ECG monitoring. ST segment deviation from baseline, trended every 15 seconds, was quantified for duration, maximum ST segment change, area under the ST segment-time curve (AUC), and average ST segment change for the episode (AUC/duration). Ischemic episodes, 87% of which were silent, occurred in 42% of the patients. Symptomatic episodes had greater maximum ST segment change than silent episodes (-2.4 vs -1.9 mm; p less than 0.05) but were shorter in duration (11 vs 18 minutes; p less than 0.05). Episodes that were unrelated to heart rate, that is, episodes with less than 20% increase in heart rate over the baseline rate at the onset of ischemia, made up 75% of all ischemic events and occurred in 90% of patients (19 of 21). Heart rate-related and unrelated ischemic episodes did not differ in duration, maximum ST segment change, AUC, or average ST segment change. It was concluded that: (1) as with patients with unstable angina, patients with severe coronary artery disease continue to have frequent episodes of silent myocardial ischemia despite intensive medical therapy; (2) painful episodes have greater maximum ST segment change but are shorter than silent ones; (3) most ischemic episodes (75%) occur without an initial increase in heart rate; and (4) heart rate-related and unrelated episodes are quantitatively similar.     

Myocardial ischemia during everyday life in patients with arterial hypertension: prevalence, risk factors, triggering mechanism and circadian variability

INTRODUCTION: The objective of the present study was to investigate the prevalence, the risk factors, the hemodynamic triggering mechanisms, the circadian variability of ST segment depression (ST depression) and the effect of day and night fall in blood pressure on the prevalence of ST depression in hypertensive patients. MATERIALS AND METHODS: In a multicentric study in Germany, 1,244 CardioTens registrations (combined 24-h ambulatory blood pressure measurement/electrocardiography with ST segment triggering; Meditech, Budapest, Hungary) from patients with arterial hypertension were consecutively monitored and evaluated centrally at the University of Bonn. Inclusion criterion was treated or untreated arterial hypertension. The ST segment was measured in accordance with the "1 : 1 : 1 rule" (horizontal or descending ST depression by 1 mm, 1 min duration, 1 min interval from the previous episode). RESULTS: ST segment depression was observed in 250 (20.1%) patients; 90.3% of the transient ST-segment depression was silent (without angina pectoris). Ambulatory 24-h blood pressure measurement, but not office-based blood pressure measurement, was predictive for the occurrence of ST-segment depression. Risk factors for ST-segment depression were the Sokolow index > or =3.5 mV, smoking status, severity of coronary heart disease, use of diuretics, reduced left ventricular function, pulse pressure > or =60 mmHg and increase of double product (1,000 mmHg/min). A significant rise of the systolic/diastolic blood pressure (+8+ or -18/+7+ or -10 mmHg), of the heart rate (+12+ or -13/min) and of the double product (+2,471+ or -2,517 mmHg/min) was found during the transient ST depression as compared with the corresponding 24-h ambulatory blood pressure measurement mean values (P<0.0001 for all parameters specified). In most intermittent ST depressions, a rise of the double product was seen (n=789 episodes), and in the remaining 239 ST depressions, a fall of the double product was observed. ST depressions with fall of the double product showed a circadian distribution with a peak in the late evening. ST depression accompanied by a rise in double product showed two peaks (one in the early morning and one in the late evening). The prevalence of ST depression was significantly higher (28.6%) in extreme dippers than in dippers (18.2%), risers (21.8%) and non-dippers (19.6%). CONCLUSIONS: ST depressions have a high prevalence of 20.1% in hypertensive patients. Clinical predictors for the occurrence of ST-segment depression were classical risk factors and cardiac target organ damage. Office-based blood pressure measurement was not a useful measuring tool for forecasting the likelihood of ST-segment depression. ST depressions were triggered inter alia by variations of blood pressure and the heart rate. The circadian variability of the ST depressions is crucially affected by the pressure double product characteristics on which the ST depression is based.     

Diltiazem in spontaneous angina: double-blind cross-over study with Holter monitoring

Using Holter monitoring the Authors compared the effectiveness of diltiazem 120 mg every 8 hours for three consecutive days with the results of a placebo administered with the same regimen, following a double-blind completely balanced cross-over trial in 20 patients with angina at rest. During treatment with diltiazem the total number of recorded ischemic episodes was 100, during treatment with placebo the total number was 357 (Tab. I); P less than 0.01 at analysis of variance (Tab. II). Ischemic episodes during treatment with diltiazem had a shorter duration (3.9 versus 5.1 min.), less marked ST segment shifts (1.3 versus 2 mm), and were less symptomatic (20% versus 29%) than ischemic episodes during placebo (Tab. III). No significant differences at a paired t test were noted. Diltiazem was more effective in the morning (12 p.m. - 12 a.m.: from 187 to 34 ischemic episodes) than in the evening (12 a.m. - 12 p.m.: from 170 to 66 ischemic episodes) (Fig. 1); P less than 0.01 at the chi-square test (Tab. IV). Diltiazem reduced the number of ischemic episodes with ST segment elevation, peaking of T waves and negative T wave inversion (from 188 to 39) more than the number of episodes with ST segment depression (from 169 to 61) (Tab. V); P less than 0.05 at the chi-square test. In conclusion, in patients with angina at rest, diltiazem reduces the incidence and seems to reduce the severity of ischemic episodes, too.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence of ventricular arrhythmias during transient myocardial ischemia in patients with stable coronary artery disease

To determine the incidence of ventricular arrhythmias related to episodes of transient myocardial ischemia during ambulatory electrocardiographic (ECG) monitoring, 97 patients with stable angina pectoris, angiographically proved coronary artery disease and an abnormal exercise test were studied. A total of 573 episodes with ST segment depression were documented: in 118 episodes (21%) the patients were symptomatic and in 455 (79%) they remained asymptomatic. Ventricular arrhythmias (greater than 5 premature ventricular beats/min, bigeminy, couplets or salvos of premature ventricular beats) occurred during 27 (5%) ischemic episodes in a subset of 10 patients (10%) (group A). The other 87 patients (90%) (group B) showed exclusively ischemic episodes without ventricular arrhythmias. Comparison of patients in group A and group B showed no differences in hemodynamic, angiographic, exercise testing and ambulatory ECG monitoring data. Ischemic episodes with and without ventricular arrhythmias showed a similar duration and amplitude of ST segment depression and a comparable heart rate at the onset of ischemia. Both types of ischemic episodes, with and without arrhythmias, occurred predominantly during the morning hours between 6:00 AM and noon, and both types remained asymptomatic to within similar percentages. The data demonstrate that ventricular arrhythmias are related to transient myocardial ischemia in only a few patients with stable angina pectoris; these arrhythmias are related neither to the degree of ischemia during ambulatory ECG monitoring nor to the occurrence of anginal symptoms.     

State of the art in stress testing and ischaemia monitoring

Electrocardiography remains the most widely used method for detecting myocardial ischemia. ST segmentabnormalities in the resting 12-lead electrocardiogram in subjects with angina and coronary risk factors seem todefinitely indicate ischemic heart disease and an adverse prognosis. ST depression during exercise testing is thefirst line provocative test for ischemic heart disease although it has a mean sensitivity of only 68% anda slightly higher specificity (77%). The presence or absence of chest pain in patients with anischemic ST response to exercise testing does not change the risk of future ischemic events. However, STdepression during the recovery period is associated with increased risk both for acute coronary events andcoronary death, whereas silent ischemia during recovery is an even stronger predictor than during exercise. Theamplitude of ST depression has not been documented to reflect the magnitude of ischemia. Therefore, new methodsare under investigation such as adding R and Q wave amplitude criteria, maximal ST/heart rate slope, linearregression analysis of the heart rate related change in ST depression and a score integrating ST segment amplitudeand slope changes. The demonstration of episodic ST segment depressions in the ambulatory setting, even withoutaccompanying chest pain, are an expression of transient ischemia and such episodes seem to represent a poorprognosis. In the hospital setting, ST depression detected by continuous monitoring is related to the clinicaloutcome. ST segment monitoring during the first 6–9 hours after coronary care unit admission providesimportant prognostic information on-line and considerably improves early risk stratification. Such continuous STmonitoring overcomes some of the limitations of static monitoring, as it improves the likelihood of capturing themaximal point of ST deviation, as well as early episodes of reocclusion that are manifest as recurrent STelevation.     

Pathophysiology of silent myocardial ischemia during daily life. Hemodynamic evaluation by simultaneous electrocardiographic and blood pressure monitoring

The role of myocardial oxygen demand in the genesis of silent myocardial ischemia was evaluated by measuring the heart rate and blood pressure changes preceding the silent ischemic events during daily life in 25 men with proven coronary artery disease. Simultaneous 24-48-hour ambulatory electrocardiographic and blood pressure monitoring were performed during unrestricted daily activities. Of the 92 transient ischemic events recorded during monitoring, 85 (92%) were silent. Sixty-one percent of the silent events were preceded by an increase in the heart rate of 5 beats/min or more. Seventy-three percent of the silent ischemic events showed an average increase of 10 mm Hg in systolic blood pressure within 6 minutes preceding the onset of ST segment depression. The silent ischemic events showed a circadian pattern with a high density (34% of total events) between 6:00 AM and noon. The increase in heart rate and blood pressure paralleled the increase in silent ischemic events during these hours. These results showing significant (p less than 0.001 for both) increases in heart rate and blood pressure preceding a majority of silent ischemic events suggest that increase in myocardial oxygen demand plays a significant role in the genesis of silent ischemia. This pathophysiological mechanism has important therapeutic implications.     

Circadian variation in ischemic threshold in patients with stable angina: relation to plasma endothelin-1

To investigate circadian variation in ischemic threshold in chronic coronary heart disease (CHD) and its relation to plasma endothelin-1 (ET-1), 21 patients with stable angina underwent treadmill exercise tests twice within a day, performed at 8-9 AM for the first test and at 3-4 PM for the second one. Ischemic threshold was defined as the heart rate at the onset of 1 mm ST segment depression during exercise tests. Blood samples were taken at 5 minutes before each exercise test, and plasma ET-1 was measured for determining the possible relation to ischemic threshold in patients with CHD. The results showed that the heart rate-ischemic threshold in individual patients varied by 10 +/- 1% (range, 2-15%) in the morning and 9 +/- 1% (range, 2-14%) in the afternoon, while there was a mean (11.2%) reduction in the ischemic threshold between 2 time points, with the ischemic threshold being significantly lower in the morning compared with that in the afternoon (115 +/- 22 bpm vs 128 +/- 31 bpm p<0.04). ET-1 values were 6.20 +/- 2.44 ng/L in the morning hours and 4.02 +/- 1.61 ng/L in the afternoon hours, with a statistical significant difference (p<0.01). In conclusion, the present study indicated that circadian variation of plasma levels of ET-1 was likely to be one of the most likely mechanisms involved in reduction in the ischemic threshold in the morning hours.     

Variability of transient myocardial ischemia in ambulatory patients with coronary artery disease

Ambulatory electrocardiographic (ECG) monitoring of patients with chronic stable angina has demonstrated frequent and prolonged episodes of ischemic ST segment depression, but its clinical use requires an understanding of the components and extent of variability. Therefore, variations in the frequency and duration of episodes of ST segment depression were evaluated with ambulatory ECG recording at daily, weekly, and monthly intervals in 42 patients with chronic stable angina and known coronary artery disease. Data were analyzed with a nested analysis of variance design that yields estimates of variance components. From the estimates of variance components, power calculations and minimum significant percent reductions in frequency and duration of ischemia were derived. During 4,656 hours of ambulatory ECG monitoring, 1,262 episodes of ischemic ST segment depression were detected. The frequency of episodes was 6.3 +/- 0.45/24 hr (mean +/- SEM), and the duration of episodes was 18.3 +/- 2.8/24 hr. Because of variability over time, the ability to detect significant changes was dependent upon the number of subjects, length of monitoring period, and intervals between monitoring periods. In a clinical trial, for example, a sample size of 25 patients monitored for 48 hours with 1 week between control and test conditions would require a 65% reduction in frequency, whereas a sample size of 50 patients monitored under similar conditions would require a 46% reduction in frequency, to attribute the change with 90% power to a therapeutic intervention rather than to a spontaneous variation. When monitoring a single patient for 48 hours with 1 week or 1 month between control and repeat monitoring sessions, episodes of ischemic ST depression must be eliminated to detect significant therapeutic changes in ischemic activity at the 95% confidence level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise

BACKGROUND. Silent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear. METHODS AND RESULTS. Sixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p = 0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 +/- 148 from 296 +/- 154 seconds (p = 0.005). Although less frequent with diltiazem administration (45 versus 54 patients, p less than 0.03), exercise-induced ST depression was more often asymptomatic (98% versus 72% of patients, p less than 0.0001). CONCLUSIONS. Diltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease.     

Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients

One hundred and fifty unselected patients with documented coronary artery disease were studied to establish the frequency and characteristics of silent myocardial ischaemia. Patients underwent ambulatory ST segment monitoring off all routine antianginal treatment (total 6264 hours) and exercise testing (n = 146). Ninety one patients (61%) had a total of 598 episodes of significant ST segment change, of which 446 (75%) were asymptomatic. Twenty seven patients (18%) had only painless episodes; 14 (9%) patients only painful episodes; 50 patients (33%) had both painless and painful episodes. The mean number of ST segment changes per day was 2.58 (1.95 silent); however, 11 patients (7%) had 50% of all silent episodes, and 48 patients (32%) had 91% of all silent episodes. Fifty nine patients (39%) had no ST segment changes on ambulatory monitoring, and 73 patients (49%) had no evidence of silent ischaemia. Episodes of silent ischaemia occurred with a similar circadian distribution to that of painful ischaemia, predominantly between 0730 and 1930. There was a similar mean rise in heart rate at the onset of both silent and painful episodes of ischaemia. Silent ischaemia was significantly more frequent in patients with three vessel disease than in those with single vessel disease, and was also significantly related to both time to 1 mm ST depression and maximal exercise duration on exercise testing. There was a highly significant relation between the mean number and duration of episodes of silent ischaemia in patients with positive exercise tests when compared with those with negative tests. No episode of ventricular tachycardia was recorded in association with silent ischaemic change.     

Silent myocardial ischaemia in chronic stable angina: a study of its frequency and characteristics in 150 patients.

One hundred and fifty unselected patients with documented coronary artery disease were studied to establish the frequency and characteristics of silent myocardial ischaemia. Patients underwent ambulatory ST segment monitoring off all routine antianginal treatment (total 6264 hours) and exercise testing (n = 146). Ninety one patients (61%) had a total of 598 episodes of significant ST segment change, of which 446 (75%) were asymptomatic. Twenty seven patients (18%) had only painless episodes; 14 (9%) patients only painful episodes; 50 patients (33%) had both painless and painful episodes. The mean number of ST segment changes per day was 2.58 (1.95 silent); however, 11 patients (7%) had 50% of all silent episodes, and 48 patients (32%) had 91% of all silent episodes. Fifty nine patients (39%) had no ST segment changes on ambulatory monitoring, and 73 patients (49%) had no evidence of silent ischaemia. Episodes of silent ischaemia occurred with a similar circadian distribution to that of painful ischaemia, predominantly between 0730 and 1930. There was a similar mean rise in heart rate at the onset of both silent and painful episodes of ischaemia. Silent ischaemia was significantly more frequent in patients with three vessel disease than in those with single vessel disease, and was also significantly related to both time to 1 mm ST depression and maximal exercise duration on exercise testing. There was a highly significant relation between the mean number and duration of episodes of silent ischaemia in patients with positive exercise tests when compared with those with negative tests. No episode of ventricular tachycardia was recorded in association with silent ischaemic change.     

Coronary heart disease and silent myocardial ischemia]

Silent myocardial ischemia was studied in 100 patients with coronary heart disease (CHD), proved by the coronary arteriogram (at least one major coronary artery narrowed by > or = 50%). The study demonstrated that 51 of 100 patients with CHD had episodes of myocardial ischemia by Holter monitoring. In the 51 patients, during daily activities, through 24-hour Holter monitoring, 239 transient episodes of ST depression were detected, 161 of the total were asymptomatic (67.4%). There were no statistically significant differences in the heart rate and the product of heart rate and systolic blood pressure before ST depression between asymptomatic and symptomatic episodes. The heart rate at the time of maximal ST depression during both asymptomatic and symptomatic ischemia increased by 13 and 22 beats/min, respectively, over those before ST depression (P < 0.01); whereas the increase in heart rate during symptomatic ischemia was more significant than during asymptomatic ischemia (P < 0.01). The increase of product of heart rate and systolic blood pressure at the time of maximal ST depression during asymptomatic and symptomatic ischemia were 22.2 and 35.4, respectively, over those before ST depression (P < 0.01). The incidence of silent ischemic episodes in patients with single vessel disease was 81.7% and those with multivessel disease was 61.3% (P < 0.01). The frequency of silent ischemic episodes was maximal (36% of total number of ischemic episodes) between 6 a.m. and 12 a.m. during 24-hour, whereas the incidence of silent ischemic episodes in patients with single vessel disease was similar to that in patients with multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)