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.     

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.     

Active transient myocardial ischemia during daily life in asymptomatic patients with positive exercise tests and coronary artery disease

The management of asymptomatic patients with coronary artery disease (CAD) is controversial, and the level of "activity" of their CAD during normal daily life remains largely unknown. To examine this question, ambulatory Holter monitoring of ST segments was performed out of the hospital in 7 asymptomatic subjects with CAD during normal daily activities. Their condition was detected because they all had a silent positive exercise test and angiographically proved CAD. During a total of 384 hours of monitoring, 37 asymptomatic episodes of ST depression (1 mm or greater and lasting at least 30 seconds) were recorded in 5 of the patients. Most episodes (68%) were 10 minutes or less in duration but ranged from 1 to 253 minutes, and most (70%) had a maximal ST depression of 1 to 2 mm. A small increase in heart rate, ranging from 1 to 34 beats/min, preceded 65% of the episodes, but 35% were associated with no change or even a decline before the onset of ischemia. Fifty-four percent of the episodes occurred during rest or usual light physical activity, 8% during sleep and only 38% during exercise, including 1 prolonged bout while jogging. During 78% of the episodes, the subjects rated their mental activity as usual and only 14% occurred during mental stress. In addition, a distinct diurnal variation was noted with 57% of the ischemia occurring between 0600 and 1200 hours (p = 0.008). Therefore, most asymptomatic subjects had active transient ischemia during daily life, with many of the characteristics already described in symptomatic subjects with CAD.     

Silent myocardial ischemia as a manifestation of asymptomatic coronary artery disease: what is appropriate therapy?

Silent myocardial ischemia is one of the most important clinical manifestations of asymptomatic coronary artery disease, along with silent myocardial infarction. It may well be a forerunner of sudden cardiac death. Although our understanding of the pathophysiologic mechanisms of the syndrome is still unresolved, we do know that prognosis in certain subsets of patients is far from benign. For that reason, aggressive therapy is recommended in asymptomatic patients with advanced disease, especially if they have already experienced a myocardial infarction, silent or otherwise.     

Sleep-disordered breathing and myocardial ischemia in patients with coronary artery disease

STUDY OBJECTIVES: To examine the occurrence of nocturnal myocardial ischemia and its relationship to sleep-disordered breathing (apneas and oxygen desaturations) in randomly selected men and women undergoing coronary angiography because of angina pectoris. DESIGN: An observational study using an overnight sleep study and Holter recording to examine disordered breathing (oxyhemoglobin desaturations > or = 4% and apnea-hypopneas), heart rates, and ST-segment depressions (> or = 1 mm, > or = 1 min). SETTING: University Hospital, Ume?, a teaching hospital in northern Sweden. PATIENTS: One hundred thirty-two men and 94 women referred for consideration of coronary intervention were randomly included, by lot. RESULTS: ST-segment depressions occurred in 59% (134 of 226) of the patients, and nocturnal ST-segment depressions occurred in 31% (69 of 226). A ST-segment depression occurred within 2 min after an apnea-hypopnea or desaturation in 12% (27 of 226) of patients. This temporal association was seen in 19% of nocturnal ST-segment depressions (71 of 366), more frequently in men (p < 0.01) and in more severely disordered breathing (p < 0.001). Most of these ST-segment depressions were preceded by a series of breathing events: three or more apnea-hypopneas or desaturations or both in 70% (50 of 71). CONCLUSION: Episodes of nocturnal myocardial ischemia are common in patients with angina pectoris. However, a temporal relationship between sleep-disordered breathing and myocardial ischemia is present only in a minority of the patients, but occurs more frequently in men and in more severely disordered breathing.     

Circadian variation of transient myocardial ischemia in patients with coronary artery disease

To examine whether a significant circadian variation of transient myocardial ischemia exists and to better understand the character of such variation, 32 patients with chronic stable symptoms of coronary artery disease underwent one or more days of ambulatory monitoring of ischemic ST segment changes during daily life. A total of 251 episodes of ischemic ST segment depression occurred in 24 (75%) of the 32 patients with a median duration of 5 min (range 1 to 253). A significant circadian increase in ischemic activity was found with 39% of episodes and 46% of total ischemic time occurring between 6 A.M. and 12 P.M. (p less than .05 and p = .02, respectively). In 21 patients with ST segment depression during the 6 hr after waking and the 6 hr before sleep, 68% of episodes occurred in the morning compared with 32% in the evening. There were no significant differences in heart rate at onset, heart rate at 1 min before onset, and activity score associated with ST segment depression. The proportion of minutes showing ST segment depression when the heart rate was above the lowest rate associated with ST segment depression was significantly greater in the morning compared with the evening (26% vs 15%; p = .03). Thus the early morning increase in ST segment depression does not appear to be explained by differences in extrinsic activity and/or stress measured by physical activity score and heart rate response. More importantly, this phenomenon is often ignored by the usual patterns of drug administration for angina.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Exercise-induced myocardial ischemia in patients with coronary artery ectasia without obstructive coronary artery disease

BACKGROUND: Aetiology, clinical significance and treatment options for coronary artery ectasia/aneurysm is not clear. OBJECTIVE: We sought to determine whether exercise can induce coronary ischemia in patients with coronary artery ectasia/aneurysm without significant coronary stenosis. METHODS: Coronary artery ectasia was defined as 1.5-2-fold, aneurysm as >2-fold luminal dilatation of the adjacent normal segment. The study patients could have irregularities with ectatic coronaries but they did not have stenotic lesions >50% with visual assessment of two blinded observers. Patients having coronary artery ectasia or aneurysm with prior myocardial infarction, dilated cardiomyopathy, valvular heart disease, bundle branch block, significant ST-T changes were excluded. The control group was formed from a well matched population of 32 patients with normal coronary arteries who have not performed a treadmill test before coronary angiography. The study group underwent a symptom limited treadmill test if they did not have one before coronary angiogram, all control patients underwent treadmill test. RESULTS: Thirty-three patients with coronary artery ectasia/aneurysm (ranging from one to three vessels) but without significant stenosis were derived from 4470 cardiac catheterization procedures between January 1998 and July 2000. In the study group, 17 of the patients had positive treadmill tests with respect to five patients in the control group (P = 0.004). In subgroup analysis, diffuse ectasia/aneurysm (involving 2-3 vessels) was found to be strongly related with ischemia (P = 0.005) with respect to local disease. CONCLUSION: Coronary artery ectasia/aneurysm may lead to exercise induced ischemia, especially in the diffuse form.     

Silent myocardial ischemia in diabetic and nondiabetic patients with coronary artery disease

Background: Patients with diabetes mellitus are at increased risk for CAD; silent ischemia is reported to be frequent in diabetic populations. The aim of the present study was to evaluate the prevalence of silent ischemia in diabetic and nondiabetic patients with assessed CAD. Methods and results: We recruited a total of 618 patients with CAD: 309 were consecutive diabetic patients and 309 were age- and gender-matched nondiabetic patients. Myocardial ischemia was evaluated both during daily life and during exercise testing. Angina pectoris during daily life was more frequent in diabetic than in nondiabetic patients (80% vs. 74%, P<0.05). The anginal pain intensity either during daily life or acute myocardial infarction (MI), the prevalence of a previous MI, the extent of CAD and ergometric parameters were similar in diabetics and nondiabetics. Silent ischemia during exercise was documented in 179 (58%) diabetics and in 197 (64%) nondiabetics (nonsignificant, ns). Both diabetics and nondiabetics with silent exertional myocardial ischemia differed from symptomatic subjects in higher heart rate values (P<0.01), systolic blood pressure (P<0.01), rate–pressure product (P<0.001), work load (P<0.01) and maximum ST-segment depression at peak exercise (P<0.05). Conclusions: The incidence of silent myocardial ischemia during exercise was similar in diabetic and nondiabetic CAD patients. Surprisingly, diabetics showed a higher prevalence of angina pectoris during daily activity than nondiabetics. A significant association between the presence of symptoms during daily life and exercise was observed in both groups. Our results may contribute to the planning of the clinical management of diabetic CAD patients and confirm the individual attitude to pain of CAD patients independent of the presence of diabetes.     

Coronary artery spasm in the genesis of myocardial ischemia

Angina pectoris that is mainly caused by coronary artery spasm (coronary spastic angina) has 1 or more of the following characteristics: (1) the attack occurs at rest, (2) the attack is associated with ST-segment elevation on the electrocardiogram (not necessarily so in case of old myocardial infarction), (3) the attack has a variable exercise threshold, and (4) the attack is suppressed by calcium antagonists but not by beta-adrenergic blocking agents. By this criteria, coronary artery spasm is involved in the development of most angina pectoris in patients with 1-vessel disease. The role of coronary artery spasm in the development of acute myocardial infarction is still controversial. However, in this study, injection of nitroglycerin, 0.2 mg, into the totally or subtotally occluded coronary artery either released the occlusion or improved the patency in 13 of the 69 patients (18.8%) with acute transmural myocardial infarction in whom coronary arteriography was performed within 4.0 +/- 1.9 hours of the onset of symptoms. Thus, coronary artery spasm appears to play a role in the production of acute myocardial infarction in these patients.     

Characteristics of silent myocardial ischemia during out-of-hospital activities in asymptomatic angiographically documented coronary artery disease

Ambulatory electrocardiographic monitoring is useful in documenting characteristics of both painful and silent myocardial ischemia occurring during out-of-hospital activities in patients with angina and coronary artery disease (CAD), but few data are available concerning silent myocardial ischemia during ambulatory electrocardiographic monitoring in asymptomatic patients with CAD. Accordingly, 480 hours of ambulatory electrocardiographic monitoring were recorded in 10 asymptomatic patients with CAD not receiving cardiac drugs (48 hours/patient). All 10 patients had silent myocardial ischemia on treadmill exercise testing, with initial ST-segment depression at 2 to 6 minutes in 7 patients and more than 6 minutes in 3 patients. During ambulatory electrocardiographic monitoring, 64 episodes of silent myocardial ischemia (1 mm of ST-segment depression for at least 1 minute) were recorded, ranging from 1 to 17 episodes/patient/48 hours. Of the 64 silent myocardial ischemic episodes, 30 (47%) occurred between 6 am and noon. Duration of silent myocardial ischemia was 798 minutes (range 1 to 80). ST-segment depression ranged from 1 to 4.5 mm. Heart rate at onset of the episodes on ambulatory electrocardiographic monitoring ranged from 65 to 150 beats/min (mean 98), which was significantly less than that during treadmill exercise testing in the same patients (mean 120). At cardiac catheterization, 7 patients had 2- or 3-vessel CAD and 3 had 1-vessel CAD. Thus, silent myocardial ischemia is common during daily life in asymptomatic CAD patients with positive treadmill exercise tests.     

Ambulatory electrocardiography evaluation of asymptomatic, unstable, and stable coronary artery disease patients for myocardial ischemia.

Transient episodes of myocardial ischemia can be reliably detected by AEM in patients with known CAD. AEM appears to be particularly useful for patients in whom symptom control has been achieved with conventional antianginal drugs because many of these patients (up to 50%) continue to have residual silent ischemia that would otherwise remain undetected. Despite the lack of symptoms, numerous studies in patients with stable and unstable coronary syndromes have shown that the presence of silent ischemia during AEM is associated with an increased risk of subsequent coronary events and cardiac death. Although Holter monitoring is a practical and reliable tool for prolonged evaluation of myocardial ischemia, its routine use can not be advocated until its clinical role has been clearly defined in the ongoing large prospective studies.     

Clinical significance of exercise-induced silent myocardial ischemia in patients with coronary artery disease

Exercise-induced silent myocardial ischemia is a frequent feature in patients with coronary artery disease. The purpose of this study was to compare the clinical and angiographic characteristics of 269 patients who complained of chest pain during an exercise test (group I) with those of 204 who developed exercise-induced silent myocardial ischemia (group II). Group I patients more frequently had anginal symptoms of class III and IV of the Canadian Cardiovascular Society than did group II patients, who had milder symptoms (p less than 0.001). The only angiographic difference observed between the two groups was a slightly but significantly higher left ventricular end-diastolic pressure in group II patients (p less than 0.05), who also showed a longer exercise duration (p less than 0.01) with a higher heart rate-systolic pressure product (p less than 0.01) and more pronounced ST segment depression at peak exercise (p less than 0.001). Moreover, ventricular ectopic beats during exercise were more frequently observed in group II patients (p less than 0.05). Coronary bypass surgery was performed in 45% of patients of group I and in 24% of patients of group II (p less than 0.05). Survival curves of medically treated patients did not show any statistically significant difference between the two groups. Thus, although patients with a defective anginal warning system may have more pronounced signs of myocardial ischemia and a greater incidence of ventricular arrhythmias during exercise, their long-term prognosis is not different from that of patients who are stopped by angina from the activity that is inducing myocardial ischemia.     

醋柳黄酮治疗老年冠心病的疗效观察

目的：观察醋柳黄酮治疗老年冠心病心肌缺血的临床疗效。方法：78例冠心病，随机分为治疗组（40例）与对照组（38例）。对照组常规治疗应用硝酸异山梨酯与阿司匹林。治疗组在常规治疗基础上，加用醋柳黄酮15mg，3次／d，连续3个月。每例于治疗开始前1日与结束次日，进行血脂、血液流变学与动态心电图（Holter）检测。结果：服醋柳黄酮3个月，血清总胆固醇（TC），甘油三酯（TG），低密度脂蛋白-胆固醇（LDL—C）水平明显下降（P〈0．01），高密度指蛋白-胆固醇（HDL—C）水平明显上升（P〈0．05），较对照组显著（P〈0．01）；血液流变学指标如全血粘度、血浆比粘度等均显著下降（P〈0．01或〈0．05），且优于对照组（P〈0．05）。Holter监测示心肌缺血的发作次数及其持续时间，两组均明显减少（P〈0．01、〈0．05），但治疗组减少更著（P〈0．05）。醋柳黄酮治疗未见不良反应。结论：醋柳黄酮有调脂与改善血液流变性作用，治疗老年冠心病安全、有效。     

Prognostic implications of symptomatic versus asymptomatic (silent) myocardial ischemia induced by exercise in mildly symptomatic and in asymptomatic patients with angiographically documented coronary artery disease

Patients with coronary artery disease (CAD) may undergo periods of reversible myocardial ischemia without experiencing angina. To study the prognostic implications of "silent" myocardial ischemia induced by exercise, exercise electrocardiography and radionuclide angiography were performed in 131 consecutive patients with CAD, preserved left ventricular (LV) function at rest and mild or no symptoms during medical therapy. All patients who died during medical therapy were in the subgroup of patients with 3-vessel CAD in whom exercise-induced ischemia developed, which was characterized by both a decrease in LV ejection fraction and ST-segment depression. Patients in whom angina pectoris developed during exercise (54% of all patients) had a greater prevalence of this combined ischemic response to exercise than patients without angina (61% vs 27%, p less than 0.001) and also a greater prevalence of left main or 3-vessel CAD (59% vs 25%, p less than 0.001). However, when inducible ischemia was demonstrated, risk stratification and prognosis were the same whether the ischemic episode was symptomatic or silent. Among patients having both a reduction in ejection fraction and a positive ST-segment response, the likelihood of significant left main narrowing (13% vs 26%), 3-vessel CAD (56% vs 51%) and death during subsequent medical therapy (16% vs 9%) was similar in patients with silent compared to those with symptomatic ischemia. These data indicate that patients in whom angina develops during exercise have a greater prevalence of high-risk coronary anatomy and of inducible ischemia than patients without angina. However, once inducible ischemia is documented, the symptomatic response to exercise appears irrelevant for prognostic or risk stratification considerations.     

Lack of ouabain effect on pacing-induced myocardial ischemia in patients with coronary artery disease

Sixteen patients with significant two and three vessel coronary artery disease but without clinical congestive heart failure were studied during rapid atrial pacing before and after infusion of 0.015 mg/kg of ouabain. Seven patients with a decreased (less than 50 percent) election fraction and nine patients with a normal election fraction had a significant (P < 0.05) increase in resting arterial systolic pressure after the administration of ouabain. However, resting values for coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and myocardial lactate extraction did not change significantly in either group. During pacing, patients with a decreased ejection fraction demonstrated more ischemia than patients with a normal ejection fraction; however, the administration of ouabain did not significantly alter pacing-related changes in coronary sinus flow, myocardial oxygen consumption, myocardial lactate extraction, ischemic electrocardiographic changes or onset of chest pain in either group. The administration of ouabain has a negligible effect on coronary hemodynamics, myocardial metabolism or clinical signs of ischemia in patients with coronary artery disease with normal or abnormal left ventricular function.     

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.