The threshold for myocardial ischemia varies in patients with coronary artery disease depending on the exercise protocol

It is generally accepted that angina pectoris and, presumably, myocardial ischemia occur at a fixed heart rate-systolic blood pressure product in a given patient. This concept of a fixed threshold has recently been challenged. To evaluate the effects of varying exercise intensity on the ischemic threshold, 33 patients with coronary artery disease and provokable myocardial ischemia, documented by thallium-201 myocardial perfusion imaging, underwent two exercise tests 2 to 7 days apart. A symptom-limited incremental treadmill exercise test was followed by a 20 min submaximal treadmill test at an intensity approximating 70% of the peak heart rate attained during the incremental test. During the incremental exercise test, angina pectoris developed in 16 patients and 17 patients were asymptomatic. At least 0.1 mV of ST segment depression developed in all subjects during the incremental exercise test at a mean exercise duration of 5.3 +/- 2.6 min, a rate-pressure product of 19,130 +/- 5,735 and oxygen uptake of 19.6 +/- 7.0 ml/kg per min. During the submaximal exercise test, 28 (85%) of the 33 patients had significant ST segment depression. Of these patients, 24 (86%) were asymptomatic, including 10 patients who had previously reported anginal symptoms during the incremental test. The average time to onset of 0.1 mV ST segment depression during the submaximal test was 8.1 +/- 4.5 min. These changes occurred at a rate-pressure product of 15,250 +/- 3,705 and an oxygen uptake of 14.3 +/- 5.9 ml/kg per min, and were significantly (p less than 0.001) lower than values observed during the graded exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

冠心病患者无症状心肌缺血阈的分析

目的：探讨冠心病患者无症状心肌缺血阈的临床意义。方法：应用24h动态心电监测，检测62例冠心病患者心肌缺血阈值、MIT的变异度、每次缺血发作持续时间和ST段最大位移，以及昼夜缺血次数。结果：共检出506次心肌缺血，93．5％在ST段压低时心率加快，夜间心肌缺血阈值较低，但缺血时间及ST段压低程度明显重于昼间。结论：心肌缺血有不同的机制，应根据情况给予不同的治疗。     

Significance of silent myocardial ischemia during exercise testing in patients with coronary artery disease

To evaluate the significance of ischemic ST-segment depression without associated chest pain during exercise testing, data were analyzed from 2,982 patients from the Coronary Artery Surgery Study (CASS) registry who underwent coronary arteriography and exercise testing and were followed up for 7 years. Patients with proved coronary artery disease (CAD) (at least 70% diameter narrowing) were grouped according to whether they had at least 1 mm of ST-segment depression or anginal chest pain during exercise testing. Four hundred twenty-four had ischemic ST depression without angina (group 1); 232 had angina but no ischemic ST depression (group 2); 456 had both ischemic ST depression and angina (group 3); and 471 had neither ischemic ST depression nor angina (group 4). Sixty-three percent of patients in group 1 and 55% in group 2 had multivessel CAD (difference not significant). The 7-year survival rates were similar for patients in groups 1 (76%), 2 (77%), and 3 (78%), but were significantly better for patients in group 4 (88%, p less than 0.001). Among group 1 patients, survival was related to severity of CAD (p less than 0.001). The 7-year survival rate in group 1 was significantly worse than that in a separate group of 282 patients with ischemic ST depression without angina during exercise testing who had no CAD (95% survival, p less than 0.001). Thus, in patients with silent myocardial ischemia during exercise testing, the extent of CAD and the 7-year survival rate are similar to those of patients with angina during exercise testing. Prognosis is determined primarily by the severity of CAD. In patients without CAD, the survival rate is excellent.     

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)     

Long-term variation in myocardial ischemia during daily life in patients with stable coronary artery disease: its relation to changes in the ischemic threshold.

Long-term variation in the frequency of myocardial ischemia during daily activity in patients with coronary artery disease who do not experience symptomatic changes has not been documented. Because at one point in time, the magnitude of such ischemia is strongly related to the ischemic threshold measured during exercise testing, this study was undertaken to determine whether patients with stable coronary artery disease show long-term variations in the frequency and duration of myocardial ischemia and to establish whether such variability is related to parallel changes in the ischemic threshold during exercise testing. Forty consecutive patients (mean age 61 +/- 8 years) who showed a stable clinical course over greater than or equal to 12 months were studied with a repeat exercise treadmill test and ambulatory electrocardiographic (ECG) monitoring after withdrawal of antianginal medications. The ischemic threshold was determined as the exercise time at 1 mm of ST segment depression. The mean interval to both follow-up evaluations was 15 +/- 3 months. Among the 23 patients with myocardial ischemia on ambulatory ECG monitoring at initial evaluation, the number and duration of ischemic episodes at follow-up were increased in 5 patients (mean increase 3.6 +/- 2 episodes and 123 +/- 98 min), unchanged in 1 patient and decreased in 17 patients (mean decrease 2.6 +/- 2 episodes and 98 +/- 72 min). Of the 17 patients without ischemic episodes at initial evaluation, 3 had evidence of ischemia on follow-up ambulatory ECG monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)     

"Silent" myocardial ischemia during and after exercise testing in patients with coronary artery disease

Although many patients with coronary artery disease (CAD) have a positive exercise test without pain, the frequency and significance of this "silent" ischemia is unclear. Therefore, we studied 122 consecutive clinically stable patients with angiographically defined CAD (greater than 75 per cent luminal stenosis) and a positive exercise test. Seventy-eight patients had pain or anginal equivalent during or after a positive exercise test; 44 did not, including 32 (26 per cent) with no symptoms at all. Patients were evaluated as to age, sex, prior myocardial infarction, congestive failure, hypertension, diabetes mellitus, and digoxin or propranolol therapy--in addition to anginal symptoms before, during, or after the exercise itself. Extent of CAD, presence of collaterals, and left ventricular ejection fraction were also determined. All exercise tests were evaluated for evidence of ST-T abnormalities or prior infarction on the control ECG as well as peak heart rate during exercise and post-exercise degree of ST segment depression. There were no significant differences between patients with and without exercise-induced pain in regard to any of the clinical and angiographic features noted above, demonstrating that "silent" myocardial ischemia during or after exercise testing is not uncommon and is not readily attributable to any obvious clinical or catheterization findings. Further studies are necessary to determine if patients with evidence of "silent" myocardial ischemia are especially prone to sudden death.     

Symptomatic and silent myocardial ischemia during exercise testing in coronary artery disease

During exercise by patients with coronary artery disease (CAD), electrocardiographic evidence of myocardial ischemia may precede the onset of angina or may be unassociated with angina, even at peak levels of stress. However, neither the precise incidence of silent versus symptomatic ischemic episodes nor their interrelation in this setting has been clearly defined. The prevalence of silent and symptomatic myocardial ischemia during treadmill exercise testing was determined in 92 patients with angiographically documented CAD. The study group comprised 77 men (84%) and 15 women (16%) of mean age 57 years (range 32 to 79). Exercise testing resulted in ischemic ST-segment depression (greater than or equal to 1 mm for greater than or equal to 80 ms) only or in association with delayed (greater than or equal to 1 minute) angina in 39 patients (42%); angina only or in association with delayed ST-segment depression occurred in 42 patients (46%); and simultaneous occurrence of angina and ST-segment depression was noted in 11 patients (12%). Analysis of clinical, exercise and angiographic factors (age, sex, history of myocardial infarction, heart rate, maximal ST-segment depression, extent of CAD and left ventricular ejection fraction) revealed no significant correlation with the frequency of symptomatic and silent myocardial ischemia during exercise. Asymptomatic myocardial ischemia occurred commonly during exercise in patients with CAD, but there were no differences in the characteristics of patients with symptomatic and asymptomatic episodes.     

Painless myocardial ischemia in diabetic patients with coronary artery disease: evaluations by treadmill exercise tests

To elucidate the prevalence and features of painless myocardial ischemia among diabetic patients, 44 consecutive patients with angiographically-documented coronary artery disease and positive treadmill tests were examined. They were 26 with diabetes and 18 without it. Painless myocardial ischemia was defined as the absence of chest pain with 1 mm or more ST segment depression during the exercise stress tests. The severity of ischemia was determined by the magnitude of the ST segment depression. Painless myocardial ischemia was observed in 18 of the 26 (69%) diabetics, and in three of the 18 (17%) non-diabetics (p less than 0.005). The frequency of painless ischemia in the diabetics was relatively high regardless of the severity of ischemia, while painless ischemia was less frequent in the non-diabetics with severe ischemia. With a level of 2.5 mm ST depression, 11 of 12 (92%) diabetics were free of pain compared to four of 11 (36%) non-diabetics (p less than 0.01). Absence of chest pain during the exercise tests was not concordant with prior angina in diabetics, as opposed to non-diabetics in whom both clinical and exercise-induced angina developed concordantly. The diabetic patients without chest pain had a higher prevalence of three major diabetic complications such as neuropathy, nephropathy and retinopathy compared to those developing chest pain (p less than 0.025). It was concluded that in diabetics, painless myocardial ischemia is frequently observed during exercise stress tests and its prevalence is relatively high regardless of the severity of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial ischemia during physical exercise in patients with stable coronary artery disease: predictability and prevention

AIMS: We assessed whether exercise-induced myocardial ischemia during intensive group exercise sessions can be predicted in patients with coronary artery disease and stable angina pectoris. METHODS AND RESULTS: Twenty-three patients underwent cardiac catheterization, 201-thallium scintigraphy, and exercise testing prior to participation in group training sessions. Heart rates and myocardial ischemia were documented by Holter monitoring. The individual training heart rate was calculated as a percentage of the maximal heart rate achieved during symptom-limited exercise testing. Myocardial ischemia occurred significantly more often during group exercise sessions (15 of 23 patients) than during treadmill testing (4 of 23 patients, P<0.001). Maximal heart rate (145+/-23 vs. 134+/-21 beats/min, P<0.004) and maximal plasma lactate concentrations (6.0+/-2.9 vs. 4.3+/-2.0 mmol/l, P<0.05) were significantly higher than during symptom-limited exercise testing. Ischemic episodes occurred significantly more often during jogging than during competitive ball games or interval training. Myocardial ischemia occurred in patients who exceeded their individual target training heart rates (43 of 44 episodes; P<0.001). Duration of ischemic episodes did not correlate with any marker obtained at the beginning of the study. CONCLUSION: These data demonstrate that routine diagnostic procedures do not sufficiently identify patients at risk for exercise-induced myocardial ischemia. Ischemic events are only effectively prevented by choosing adequate types of exercise and, above all, by the strict adherence to individual target heart rates.     

冠心病患者运动试验中QRS波时限变化及其意义

目的　探讨冠心病患者运动试验中 QRS波时限变化的意义。方法　分析经冠状动脉造影证实的 6 2例冠心病患者和 16例冠状动脉造影正常者以及 2 0例正常人活动平板试验前后 QRS波时限变化。　结果　对照组和冠状动脉造影正常者运动后 QRS波时限较运动前缩短 (P<0 .0 5 ) ;冠心病组运动后 QRS波时限较运动前明显延长 ,Q RS波延长的程度与冠状动脉病变的数目直接相关。结论　冠心病患者运动后 QRS波时限延长可能是心肌缺血的一个标志     

Large artery stiffness predicts ischemic threshold in patients with coronary artery disease

OBJECTIVES: The goal of this study was to determine whether large artery stiffness contributes to exercise-induced myocardial ischemia in patients with coronary artery disease (CAD). BACKGROUND: Large artery stiffness is an independent predictor of cardiovascular mortality and a major determinant of pulse pressure and, thus, cardiac afterload and coronary perfusion. Clinical relevance of the hemodynamic consequences of large artery stiffening has not previously been demonstrated in relation to myocardial ischemia. METHODS: We hypothesized that stiffer large arteries would reduce myocardial ischemic threshold as assessed by time to ST-segment depression of 0.15 mV during a treadmill exercise test in patients with CAD. Ninety-six patients with CAD (78 men) age 62 +/- 9 years (mean +/- SD) were classified as having single (52 patients), double (31 patients), or triple (13 patients) coronary vessel disease, based on angiographically confirmed stenoses >50%. Systemic arterial compliance, distensibility index, aortic pulse wave velocity, and carotid augmentation index were measured using carotid applanation tonometry and Doppler velocimetry of the ascending aorta, at rest. RESULTS: In univariate analysis, all large artery stiffness/compliance indexes correlated with time to ischemia (p = 0.01 to 0.009). Both carotid (p = 0.007) and brachial (p = 0.001) pulse pressure also correlated inversely with time to ischemia. In multivariate analysis including other major risk factors plus severity of coronary stenosis, indexes of arterial stiffness were significant independent predictors of ischemic threshold. CONCLUSIONS: Within a patient group with moderate CAD, large artery stiffness was a major determinant of myocardial ischemic threshold.     

Prognostic assessment of patients with coronary artery disease by exercise testing

To assess whether exercise testing could help predict cardiac mortality, we analyzed 14 exercise and 10 clinical variables in 292 patients treated medically, who underwent treadmill exercise testing and cardiac catheterization and were followed annually for a mean of 2.5 years. None of the individual variables could accurately predict subsequent cardiac mortality with predictive values ranging from 6% to 44%. Combinations of variables were then analyzed in the subset of 113 patients with multivessel coronary disease. A high-risk subgroup (n = 59) consisting of patients with either severe exercise ischemia (greater than or equal to 2 mm ST depression lasting greater than or equal to 5 minutes involving greater than or equal to 3 leads) or left ventricular dysfunction (treadmill time less than or equal to 3 minutes, S3 gallop, or cardiac enlargement) had a mortality of 20%; this was significantly greater (p less than 0.01) than a low-risk subgroup (n = 54) with neither severe exercise ischemia nor left ventricular dysfunction whose mortality was 2%. We conclude that combining clinical and exercise variables to distinguish high- and low-risk subgroups of patients with similar coronary anatomy is useful in predicting cardiac mortality.     

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.     

Acute effect of sildenafil on myocardial ischemic territories in patients with stable coronary artery disease

ObjectivesTo test the safety of sildenafil in patients with stable coronary artery disease (CAD).MethodsSixty-one patients with stable CAD, documented by coronary angiography were included in this phase I study. Patients were randomized to either single dose sildenafil or matched placebo. Speckle tracking echocardiography was done at baseline and 60 min after sildenafil/placebo intake to calculate peak systolic strain (PSS) of the most severely affected myocardial segments and the global longitudinal PSS.ResultsThe baseline mean segmental PSS in the sildenafil group changed by 52%, −3 ± 1% at baseline versus −7 ± 2% after sildenafil intake, P = 0.01. However, no significant changes were reported in the placebo group, −7 ± 3% at baseline versus −7.25 ± 3%, P = 0.1. The baseline mean global longitudinal PSS in the sildenafil group changed by 9% (−15 ± 4% at baseline versus −18 ± 3% after sildenafil, P = 0.03). In placebo patients, the change was only 3% from baseline (−14.8 ± 2% at baseline compared to −15 ± 2% after placebo intake, P = 0.1). Sildenafil was well tolerated without clinical or hemodynamic deterioration after its intake.ConclusionSildenafil intake is safe in patients with stable CAD, it induced marginal improvements in the peak systolic strain of different myocardial ischemic territories.     

老年冠心病者无症状心肌缺血阈的分析

目的 探讨老年冠心痛者无症状心肌缺血(SMI)时心肌缺血阈(MIT)的发生规律及临床意义.方法 对128例患者进行24h动态心电图(DCG)检测,观察其MIT值、MIT变异度、每次缺血发作持续时间和ST段最大位移,以及昼夜缺血次数.结果 共检测984阵心肌缺血,其中932阵为SMI,93.6%在ST段压低时心率加快,心率增快的高低与缺血的程度呈正相关,夜间MIT较低,缺血时间及ST压低程度明显重于昼间(P<0.05).结论 DCG是临床上检测SMI的重要方法之一,对临床评估SMI的预后及给药有重要临床意义.     

Sauna-induced myocardial ischemia in patients with coronary artery disease.

PURPOSE: Sauna bathing is a popular recreational activity that is generally considered to be safe. However, there have been case reports of adverse cardiac events. We sought to determine whether sauna use caused myocardial ischemia in patients with coronary artery disease. METHODS: Sixteen patients with proven coronary artery disease were submitted to three conditions (rest, exercise, and sauna bathing) with continuous electrocardiographic (ECG) monitoring and regular blood pressure measurements. During each condition, patients were injected with Tc-99 sestamibi followed by nuclear scintigraphic imaging. Perfusion defect scores were calculated in 15 patients. RESULTS: Sauna bathing was well tolerated. There was a mean (+/- SD) increase in heart rate of 32% +/- 20% in the sauna (resting mean heart rate = 60 +/- 9 beats per minute vs sauna mean heart rate = 79 +/- 11 beats per minute, P <0.001) and a 13% +/- 6% drop in systolic blood pressure (resting mean systolic blood pressure = 142 +/- 14 mm Hg vs sauna mean systolic blood pressure = 123 +/- 15 mm Hg, P <0.001). There were no arrhythmias or ECG changes in the sauna. Compared with rest, there was significant ischemia during sauna bathing (average perfusion defect score at rest = -0.44 vs average sauna score = -0.93, P <0.001). The perfusion defect score in the sauna was worse than the resting score in 14 of the 15 patients. Sauna-associated perfusion defect scores were highly correlated with exercise-induced scores (R2 = 0.65, P <0.001). CONCLUSION: In patients with stable coronary artery disease, sauna use is clinically well tolerated but is associated with scintigraphically demonstrated myocardial ischemia.     

Prognostic importance of silent myocardial ischemia detected by intravenous dipyridamole thallium myocardial imaging in asymptomatic patients with coronary artery disease

One hundred seven asymptomatic patients who underwent intravenous dipyridamole thallium imaging were evaluated to determine prognostic indicators of subsequent cardiac events over an average follow-up period of 14 +/- 10 months. Univariate analysis of 18 clinical, scintigraphic and angiographic variables revealed that a reversible thallium defect, a combined fixed and reversible thallium defect, number of segmental thallium defects and extent of coronary artery disease were significant predictors of subsequent cardiac events. Of the 13 patients who died or had a nonfatal infarction, 12 had a reversible thallium defect. Stepwise logistic regression analysis selected a reversible thallium defect as the only significant predictor of cardiac events. When death or myocardial infarction was the outcome variable, a combined fixed and reversible thallium defect was the only predictor of outcome. In patients without previous myocardial infarction, the cardiac event rate was significantly greater in those with an abnormal versus normal thallium scan (55% versus 12%, p less than 0.001). Thus, intravenous dipyridamole thallium scintigraphy is a useful noninvasive test to risk stratify asymptomatic patients with coronary artery disease. A reversible thallium defect most likely indicates silent myocardial ischemia in a sizable fraction of patients in this clinical subset and is associated with an unfavorable prognosis.     

Prediction of severity of coronary artery disease by treadmill exercise testing]

Coronary angiography was performed in 250 patients with a significant ischemic ST segment change detected by symptom-limited maximum treadmill exercise testing, and relationship between anatomical severity of coronary artery disease and parameters in exercise testing was studied. The age of the patients ranged from 34 to 76 years (188 men, 62 women). One-vessel disease (1VD) was presented in 82 patients, two-vessel disease (2VD) in 42, three-vessel disease or left main coronary disease (3VD) in 26, and no significant stenosis was presented in 100 subjects (Normal). Functional aerobic impairement (FAI) was evaluated in each group as a parameter of exercise capacity, myocardial aerobic impairment (MAI) and heart rate impairment (HRI) were also evaluated as a parameter of maximum myocardial oxygen requirements and maximum heart rate, respectively. Using these parameters, discriminant analysis was performed to compare the group with significant coronary artery disease and the Normal group. Also, to compare the group with multi-vessel disease and the group with less than 2VD. Also, the 3VD group and the group with less than 3VD. FAI, MAI and HRI were significantly different (p less than 0.0001) in each group. The discriminant formula to separate the group of significant coronary artery disease from the Normal group was Z = -1.049 + 0.02 [FAI] +0.08 [MAI] +0.03 [HRI]. According to this formula, sensitivity was 92.5% and specificity was 71.5%. The discriminant formula to separate the group with multi-vessel disease from the group with less than 2VD was Z = -4.731 + 0.07 [FAI] +0.106 [MAI] +0.02 [HRI]. According to this formula, sensitivity was 96.3% and specificity was 78.8%.(ABSTRACT TRUNCATED AT 250 WORDS)