Asymptomatic myocardial ischemia as a predictor of cardiac events after coronary artery bypass grafting for stable angina pectoris

Thirty-six patients with chronic stable angina were studied before and after coronary artery bypass grafting (CABG) to assess the prevalence and prognostic implications of asymptomatic myocardial ischemia obtained by ambulatory monitoring. Ambulatory monitoring performed during medical therapy before CABG detected 66 episodes of transient ischemia, 54 (82%) being asymptomatic. All patients were asymptomatic or with minimal symptoms 3 months after CABG. Additional ambulatory monitoring was performed for 36 hours. There were 39 episodes of silent ischemia detected in the 12 patients of group 1, whereas no episodes of ST-segment shift occurred in the 24 patients of group 2. Coronary artery bypass grafting reduced the frequency of transient ischemia by 41% (p less than 0.05) compared with medical therapy, whereas the number of ischemic episodes in group 1 increased from 23 during medical therapy to 39 episodes after CABG (41%, p less than 0.05). During a follow-up of 9 months, 8 cardiac events occurred: 6 in group 1 comprising sudden death (1), revascularization (2), and angina (3) and 2 in group 2, including revascularization (1) and angina (1) (p = 0.005). Kaplan-Meier analysis demonstrated that asymptomatic myocardial ischemia was correlated with a significant cumulative probability of cardiac events (p less than 0.025) and multivariate analysis of 11 variables showed that silent ischemia was the most powerful predictor of cardiac events (p less than 0.005). Silent ischemia was a forerunner for angina pectoris in some patients, whereas angina did not occur during the follow-up period in others. This study does not reveal whether or not these patients are at higher risk for cardiac events during long-term follow-up.     

Association between silent myocardial ischemia and prognosis: Insensitivity of angina pectoris as a marker of coronary artery disease activity

The clinical syndrome of angina pectoris was accurately described over 200 years ago by Sir William Heberden. However, in recent years, we have learned that many episodes of myocardial ischemia occur that are not accompanied by symptoms of angina pectoris. These silent ischemic episodes may be detected either during exercise testing, using electrocardiographic criteria that can be combined with scintigraphic studies evaluating myocardial blood flow (thallium perfusion studies) or left ventricular function (gated blood pool scans). In addition, continuous electrocardiographic (Holter) monitoring can be used for the detection of transient ST-segment changes; these changes on Holter monitoring have been correlated with abnormalities of myocardial perfusion and function, indicating that they represent true ischemic events.

Studies have shown that patients with coronary artery disease who have evidence of ongoing ischemia, whether symptomatic or silent, have an increased risk for experiencing subsequent cardiac events than patients without evidence of ischemia. Many studies have demonstrated that ischemia during an exercise study after myocardial infarction identifies patients at high risk for recurrent cardiac events, whether or not the ischemia is associated with angina pectoris. Holter monitoring has allowed for the detection of ischemic events out of hospital in ambulatory patients. Studies in stable angina patients have shown that there are many asymptomatic episodes in this setting, which are often occurring at low heart rates during activities of everyday life, without an apparent significant increase in myocardial oxygen demands, and these episodes may even be precipitated by mental stress. Several studies have suggested that the presence of ongoing silent ischemia in unstable angina patients and postinfarction patients can identify those at higher risk for cardiac events. The results of these studies will be discussed.

The treatment of coronary artery disease has been for the most part symptomatic, with the primary goal of relieving symptoms of angina pectoris. Several exceptions include patients with left main disease or severe proximal 3-vessel disease, who have extensive amounts of myocardium at risk and who are generally referred for bypass surgery.

These new data indicating that the presence and severity of asymptomatic ischemia have adverse prognostic implications suggest that therapy should be directed at reducing the total ischemic profile, i.e., symptomatic and asymptomatic episodes. Guidelines for appropriate screening and therapeutic strategies will be discussed.     

Perception threshold of angina and transient myocardial ischemia in ambulatory electrocardiography]

AIM OF THE STUDY. We studied the predictive value of prolonged angina perception threshold in identifying patients with stable coronary artery disease at risk of silent myocardial ischemia during daily life. METHODS AND RESULTS. 71 patients with documented coronary artery disease (previous myocardial infarction or stenotic lesion > 60% at angiography) underwent a symptom-limited exercise test and out-of-hospital Holter monitoring after drug withdrawal. A second exercise test was performed before disconnecting the dynamic EKG in order to validate the ST-depression recorded during ambulatory monitoring. 23 patients (32.4%) (Group A) had angina perception threshold > 60 sec after onset of ischemia (ST > 1 mm), while in 48 (67.7%) the delay in the perception of angina was shorter than 60 sec (Group B). The demographic, clinical and angiographic variables did not influence the angina perception threshold; however, this parameter was the most powerful predictor of ambulatory ischemia among the two groups (4.8 vs 2.8 p < 0.02), and in particular of the painless episodes (3.8 vs 1.8 p < 0.002). Moreover, the silent ischemic time was longer in patients of group A (4362 vs 1774 sec p < 0.017). Finally, the event-free survival was similar in the two groups of patients during the 2 years of follow-up (cardiac death 1 vs 3, nonfatal myocardial infarction 1 vs 1, aorto-coronary bypass 2 vs 7, PTCA 2 vs 2, unstable angina 0 vs 2), total events 6 vs 15 p = ns. CONCLUSIONS. These results demonstrate that the patients at risk for silent ischemia during ambulatory monitoring may be identified simply by evaluating their angina perception threshold during exercise test; however, silent ischemia does not have an adverse prognostic value.     

Myocardial dysfunction in silent myocardial ischemia as demonstrated by ambulatory radionuclide left ventricular function studies.

Until recently, it has not been possible to combine both ambulatory electrocardiographic monitoring, monitoring and ambulatory left ventricular function monitoring, but new developments have helped solve this problem. A technique based on the nuclear probe was introduced in the early 1980s to allow continuous recording of left ventricular volumes and ejection fraction over a 4 to 6 hour period during ambulatory activities following a single injection of radioisotope; the device was termed the VEST. In addition to validation studies, left ventricular function during ambulatory activities of various types has been measured with the VEST, and there are now several reports that document reduction in left ventricular ejection fraction in patients with coronary artery disease. These episodes meet the criteria for silent ischemia: objective evidence of myocardial ischemia in the absence of angina or anginal equivalents. Thus, patients with coronary artery disease can be followed for hemodynamic evidence of myocardial ischemia (even when they are not aware of the episodes) and results of therapy better monitored than by the ambulatory ECG alone.     

Preoperative silent myocardial ischemia. Has it prognostic significance?

We studied the prognostic significance of preoperative silent myocardial ischemia in patients undergoing coronary artery bypass grafting (CABG). Nonfatal and fatal perioperative myocardial infarction were regarded as prognostically important endpoints. Ninety-five patients (9 women) with stable-effort angina pectoris were studied during their hospital stay in the surgery ward before CABG. Silent ischemia was detected using Holter monitoring; all patients had Holter monitoring 76 +/- 9 h before surgery using Marguette Laser Holter and Cardiodata Prodigy systems. Two-channel electrocardiographic recordings were used which included CM5 and a modified inferior lead. Effort was taken to avoid leads with pathological Q waves and resting ST segment abnormalities. The mean duration of the monitoring was 27.9 +/- 11.3 h. Three patients (3.2%) had angina pectoris during these observations, 1 of them with significant ST depression. Silent ST depression was found in 12 patients (12.6%). Twelve patients (12.6%) had perioperative myocardial infarction. Perioperative myocardial infarction was more common in patients with silent ischemia: 4/12 vs. 8/83; chi 2 = 4.48955, p = 0.0341. Our results suggest that Holter monitoring identifies a group of patients with a higher probability of perioperative myocardial infarction. In the future, it may be possible to study different methods to prevent this surgical complication.     

Contemporary management of silent ischemia: the role of ambulatory monitoring

Silent ischemia is highly prevalent among patients with ischemic heart disease and is associated with a poor prognosis in moderate/high risk outpatients who either exhibit exercise- or pharmacological-induced myocardial ischemia, or in those patients who demonstrate silent ischemia following an acute coronary syndrome. Pharmacotherapy, including beta-blockers, angiotensin-converting enzyme inhibitors, statins, calcium channel antagonists and antiplatelet agents, have all demonstrated a reduction in silent ischemia and an improvement in cardiac prognosis. The management of patients with ischemic heart disease is currently based on patients' report of anginal symptoms: documentation of silent ischemia, usually using ambulatory electrocardiography, is not incorporated into the routine management of coronary artery disease. Yet studies comparing ambulatory electrocardiography with exercise testing have shown these tests to be complementary. We review the evidence concerning the prognostic value of ambulatory electrocardiography for monitoring silent ischemia and the prognostic value of attenuating silent ischemia. Mitigation of silent ischemia improves cardiac prognosis and ambulatory electrocardiographic monitoring before and after treatment of silent ischemia can play a valuable role in the management of coronary artery disease.     

Clinical significance and management of silent myocardial ischemia in patients with angina pectoris and myocardial infarction

The present study was canued out to clarify the relationship between silent myocardial ischemia in patients with angina pectoris and onset of myocardial infarction, and the former's prognostic significance. The peak incidences of onset of myocardial infarction in patients were at 2 a.m., 9 a.m., 2 p.m., 8 p.m., and 9 p.m., and the peak onsets of transient silent myocardial ischemia in angina pectoris patients were at 9 a.m., 2 p.m., 8 p.m., and 9 p.m. Thus the most likely onset times were almost the same with both events. Of 169 patients with coronary artery disease admitted for treatment, 128 patients had no anginal attacks during follow-up and the remaining 41 had persistent angina despite adequate medical treatment. Holter monitoring electrocardiography was performed twice with the non-angina patients, during admission. Of these 128 patients, 54 showed no silent myocardial ischemia on either of the electrocardiographic recordings, 34 showed silent ischemia with the first Holter monitoring but not with the second one, and the remaining 41 showed silent myocardial ischemia on both tests. The subsequent incidences of "cardiac events" were 9.4%, 14.7%, and 36.6%, respectively for these three groups. Therefore, it is concluded that the presence of silent myocardial ischemia is closely related to onset of myocardial infarction and is an important prognostic factor in patients with coronary artery disease.     

Clinical importance of silent ischemia]

Objective signs of myocardial ischemia without angina pectoris or its equivalents define the syndrome of silent myocardial ischemia. Its significance lies in the prevalence and prognostic implications. As a prevalence, asymptomatic coronary heart disease can be found in 2.5% of men 40 to 60 years old. Silent myocardial ischemia is frequently found in patients with unstable coronary syndromes. The Framingham Study showed 25% of all myocardial infarctions as unrecognized by patients and physicians. The prognostic implications of silent myocardial ischemia are shown in large studies on prognosis of pathologic exercise-ECG's. Asymptomatic patients with pathologic exercise-ECG have always been recognized as having a significantly increased risk of myocardial infarction and death. Recently, many studies showed a worse prognosis for patients with asymptomatic transient ischemia on Holter-ECG. This can be found in patients with stable angina pectoris, unstable angina pectoris, patients with peripheral arterial disease, and patients after myocardial infarction. It becomes clear that prognosis is not defined by the pain, but by the severity of ischemia. Silent ischemia has to be viewed together with the severity of the underlying coronary heart disease. This synopsis will define the necessary steps for further diagnosis and treatment.     

Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina

Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in greater than 50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring. Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p less than 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p less than 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.     

Silent myocardial ischemia. A clinical perspective.

Silent myocardial ischemia has been shown to occur far more frequently than anginal episodes in patients with coronary artery disease. Both an increase in myocardial oxygen demand and abnormalities of coronary vasomotor tone appear to play a significant role in the genesis of silent ischemia. Recent data show that in excess of 40% of patients with stable angina have frequent episodes of silent ischemia. The presence of silent ischemia predicts an increased risk of coronary events and cardiac death. Based on these data, it has been proposed that anti-ischemic therapy should be directed toward control of total ischemic burden. Although several recent studies have demonstrated efficacy of various antianginal drugs in reducing the number and duration of silent ischemic episodes, none has demonstrated beneficial effect on the associated adverse prognosis.     

Effects of asymptomatic ischemia on long-term prognosis in chronic stable coronary disease

BACKGROUND. Ischemia on ambulatory electrocardiographic monitoring has been shown to adversely affect short-term prognoses in patients with unstable angina, after myocardial infarction, and with chronic stable angina. METHODS AND RESULTS. In this long-term study, we followed 138 patients (mean age, 59 +/- 9 years) with chronic stable angina and positive exercise tests for cardiac events (e.g. death, myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery). In 105 patients, ambulatory electrocardiographic monitoring was performed after all antianginal medication was withheld for 48 hours. In 26 patients, the diagnostic tests were repeated while on their usual medication. In addition to the 105 patients, 33 patients had their monitoring performed only while on their usual medication. During 37 +/- 17 months of follow-up, there were nine deaths, nine myocardial infarctions, and 35 revascularization procedures. In patients monitored off medication, Cox survival analysis showed that the occurrence of ischemia on electrocardiographic monitoring was the most significant predictor of death and myocardial infarction in the subsequent 2 years (p = 0.02) and all adverse events for 5 years (p = 0.009). Patients who were monitored on medication and did not have ischemia (n = 18) appeared to have more adverse events than patients who had no ischemia while being monitored off medication (n = 43). CONCLUSIONS. Asymptomatic ischemia on ambulatory electrocardiographic monitoring in patients with stable angina predicts death and myocardial infarction for 2 years and all adverse events for 5 years. Monitoring performed while on medication may show no ischemia; however, this may not indicate low risk of future coronary events.     

Left ventricular function abnormalities as a manifestation of silent myocardial ischemia

A large body of evidence exists indicating that left ventricular dysfunction is a common occurrence in patients with severe coronary artery disease and represents silent or asymptomatic myocardial ischemia. Such dysfunction probably occurs early in the time course of every ischemic episode in patients with coronary artery disease whether symptoms are eventually manifested or not. The pathophysiology of silent versus symptomatic left ventricular dysfunction due to ischemia appears to be identical. Silent ischemia-related left ventricular dysfunction can be documented during spontaneous or stress-induced perturbations in the myocardial oxygen supply/demand ratio. It also may be detected by nitroglycerin-induced improvement in ventricular function or by salutary changes in wall motion following revascularization. Silent left ventricular dysfunction is a very early occurrence during ischemia and precedes electrocardiographic abnormalities. In this light, its existence should always be kept in mind when dealing with patients with ischemic heart disease. It can be hypothesized that because silent ischemia appears to be identical to ischemia with symptoms in a pathophysiologic sense, prognosis and treatment in both cases should be the same.     

Silent myocardial ischemia: diagnosis, clinical significance and management

With the inception of continuous ECG monitoring with high-fidelity reproduction of the ST-segment, silent myocardial ischemia has been regarded with increasing importance in the detection and management of coronary artery disease. With the aid of a variety of invasive and noninvasive methods, the validity of ST-segment depression as indicative of myocardial ischemia, even in the absence of symptoms, has been adequately documented. In completely asymptomatic subjects with positive evidence of silent ischemia in the exercise ECG or Holter monitoring, the risk of developing a future manifestation of coronary artery disease may be up to ten-fold higher than in individuals with negative tests In patients with established coronary artery disease, concomitant use of continuous ECG monitoring and exercise testing, methods which complement each other rather than being mutually exclusive, a substantial number of patients with otherwise typical angina pectoris may be found to have silent ischemic episodes. An adequate differentiation between those with symptomatic and those who are asymptomatic based on characterization with respect to age, sex, hypertension, coronary anatomy, etc., has not been successful. Patients with silent ischemia during exercise may also exhibit more episodes of silent ischemia during daily activities and up to 75% of ischemic episodes may be asymptomatic. In general, however, silent ischemia during exercise appears more common than silent ischemia only during daily activities. In the latter case, since there is usually no increase in heart rate, the pathophysiology is regarded as dissimilar from that associated with exercise-induced ischemia. While the presence of silent ischemia appears quite common in patients after acute myocardial infarction, its occurrence, to date, has not been confirmed to carry additional risk, whereas in unstable angina, the association of silent ischemia is indicative of a higher probability of subsequent cardiac events.     

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.     

Diagnostic and prognostic value of ambulatory ECG (Holter) monitoring in patients with coronary heart disease: a review

Silent ischemia, the most common expression of atherosclerotic heart disease, affects approximately 30–50% of patients during their activities of daily living. The present review provides a comprehensive and practical summary of current knowledge on perioperative myocardial ischemia through MEDLINE searches up to June 2005, using keywords including “silent ischemia,” “transient ischemia,” and “Holter monitoring.” Holter monitoring (i.e., continuous ambulatory ST-segment monitoring) is an effective tool for assessing the frequency and duration of silent transient myocardial ischemia, particularly in patients who are post-acute myocardial infarction (MI), those with acute coronary syndromes (ACS), and in patients in the acute post-operative period. Holter monitoring allows for further risk stratification of patients who have a positive exercise ECG by collecting long-term ECG data on ischemic and arrhythmic events while patients perform routine activities. Both the presence and increased duration of transient ischemia as detected by continuous ST-segment Holter monitoring are associated with increased rates of coronary events and mortality. Holter monitoring may aid in the identification of patients and subgroups of patients with ACS who may derive the greatest benefit from antiplatelet and antithrombotic therapy. Indeed, many ongoing and upcoming trials of pharmacotherapy include ischemia on Holter monitoring as an endpoint.     

Comparison of silent and symptomatic ischemia during exercise testing in men

OBJECTIVE: To compare angina and ST-segment depression during exercise testing, as markers for coronary artery disease. DESIGN: Retrospective analysis of exercise test responses and cardiac catheterization results. SETTING: A U.S. Veterans Affairs medical center. PATIENTS: Four hundred and sixteen men who were referred for the evaluation of symptoms, postmyocardial infarction testing, or both. Two hundred patients had no clinical or electrocardiographic evidence of previous myocardial infarction, whereas 216 were survivors of a previous myocardial infarction. INTERVENTIONS: All patients did a standard exercise test and had diagnostic coronary angiography with ventriculography within an average of 32 days (range, 0 to 90 days) of their exercise test. RESULTS: Two hundred patients without a previous myocardial infarction were divided into four groups: the no ischemia group had 80 patients; the angina pectoris only group had 23 patients; the silent ischemia group had 40 patients; and the ST-segment depression and angina pectoris group had 57 patients. In patients without a previous myocardial infarction, exercise-induced ST-segment depression was a better marker than exercise-induced angina for the presence of any coronary artery disease (P less than 0.005). Patients with symptomatic exercise-induced ischemia had a higher prevalence of severe coronary artery disease than did those with only silent ischemia (30% compared with 20%; 95% CI, - 7.3% to 27.0%; P = 0.005). For the 216 survivors of a myocardial infarction, divided into the same four groups, ST-segment depression again was a better marker for the presence of severe coronary artery disease compared with angina alone (P = 0.08). The prevalence rates of severe coronary artery disease in the no ischemia plus myocardial infarction group, the angina pectoris only plus myocardial infarction group, the silent ischemia plus myocardial infarction group, and the ST-segment depression and angina pectoris plus myocardial infarction group were 10%, 9%, 23%, and 32%, respectively (P less than 0.01). CONCLUSIONS: Exercise-induced ST-segment depression is a better marker for coronary artery disease than is exercise-induced angina. Symptomatic ischemia during the exercise test is a better marker for severe coronary artery disease than is silent ischemia.     

Localization of a Coronary Stenosis, Left Ventricular Function, and Pain Perception During Myocardial Ischemia in Patients with One-Vessel Disease

Silent Myocardial Ischemia and Endogenous Pain Modulation. A total of 97 patients with asymptomatic and 69 patients with symptomatic myocardial ischemia and one-vessel disease were compared with respect to the location of coronary stenosis and left ventricular wall motion abnormalities. All symptomatic and asymptomatic patients exhibited reproducible objective signs of myocardial ischemia in exercise tests, ischemia being always silent in the asymptomatic group. Right coronary artery stenosis (and left circumflex artery stenosis) was more frequently observed in asymptomatic patients, left artery descending stenosis more often in symptomatic patients. Left ventricular wall movement abnormalities with posterobasal or diaphragmatic localization were significantly more often associated with the absence of angina pectoris pain. The present results could contribute to the understanding of the mechanisms underlying the absence of pain in silent myocardial ischemia. A possible explanation for these results would be that stimulation of inhibitory vagal afferents, which are preferentially distributed in the inferior ventricle wall, may play a role of the suppression of pain perception in myocardial ischemia.     

Frequency and importance of silent myocardial ischemia identified with ambulatory electrocardiographic monitoring in the early in-hospital period after acute myocardial infarction

The incidence and clinical significance of silent myocardial ischemia occurring in the early period after acute myocardial infarction (AMI) was studied in 59 patients who had an uncomplicated early course after admission for AMI. Calibrated 2-lead ambulatory electrocardiographic monitoring performed for 39 +/- 2 hours starting 4 +/- 1 days after AMI identified silent myocardial ischemia, defined as greater than or equal to 1 mm ST-segment change lasting greater than or equal to 2 minutes, in 27 patients. These patients had 5 +/- 1 episodes lasting a median of 11 minutes/episode (range 2 to 36 minutes/episode). Patients with and without silent ischemia had comparable baseline demographics, were receiving similar anti-ischemic medications and had similar severity of coronary disease by angiography. No reinfarctions occurred during the in-hospital period. Fourteen of 27 patients (52%) with silent ischemia had greater than or equal to 1 in-hospital clinical ischemic event (pulmonary edema, n = 5, cardiac death, n = 1, and postinfarction angina, n = 11). In contrast, only 7 of 32 patients without silent ischemia (22%) had greater than or equal to 1 in-hospital event (pulmonary edema, n = 1, cardiac death, n = 1, and postinfarction angina, n = 6). The frequency of ischemic events was significantly greater in patients with silent ischemia compared to those without silent ischemia, p less than 0.02. Silent ischemia occurs frequently very early after AMI and identifies a group of patients who are at increased risk for adverse in-hospital clinical outcomes.     

Incidence of acute myocardial infarction in patients with exercise-induced silent myocardial ischemia

Fifty-five patients with angiographically proved coronary artery disease (CAD) underwent Bruce protocol exercise stress testing with thallium-201 imaging. Twenty-seven patients (group I) showed myocardial hypoperfusion without angina pectoris during stress, which normalized at rest, and 28 patients (group II) had a similar pattern of reversible myocardial hypoperfusion but also had angina during stress. Patients were followed for at least 30 months. Six patients in group I had an acute myocardial infarction (AMI), 3 of whom died, and only 1 patient in group II had an AMI (p = 0.05), and did not die. Silent myocardial ischemia uncovered during exercise stress thallium testing may predispose to subsequent AMI. The presence of silent myocardial ischemia identified in this manner is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.     

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.