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.     

Characteristics of silent and symptomatic myocardial ischemia during daily activities

In 191 patients with proven coronary artery disease, 24-hour Holter monitoring detected 587 transient episodes of ST depression during daily activities. Of that total, 424 episodes were silent (72.3%) and 163 were symptomatic (27.7%). There were no statistically significant differences between silent and symptomatic episodes as to their mean duration (15.1 vs 14.3 minutes, respectively), heart rate at onset of ST depression (93 vs 96 beats/min, respectively), heart rate at the time of maximal ST depression (114 beats/min, both) and mean maximal ST depression (1.9 vs 2.0 mm, respectively). Of the 191 patients, 104 (55%) had only silent episodes, 33 (17%) only symptomatic episodes and 54 (28%) had both types ("mixed"). All patients, regardless of episode type, were of similar age, received comparable medical therapy, had a similar extent of angiographically documented coronary artery disease and similar episode characteristics. However, mixed-episode patients had significantly more ischemic episodes per day (4.8) than silent-episode (2.6) and symptomatic-episode (1.9) patients (p less than 0.001 for both) and a longer total period of daily ischemia (60 minutes), than the other 2 groups (36 and 28 minutes, respectively, p less than 0.001 for both). Of the 191 patients, 97 (51%) had had a previous myocardial infarction. The characteristics of their silent and symptomatic episodes were similar to the 94 (49%) patients without infarction, except for a longer duration of the silent episodes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic and therapeutic considerations in silent myocardial ischemia

Attempts at diagnosis and treatment of silent myocardial ischemia appear to be justified in patients with known or suspected coronary artery disease. A positive exercise test result or ambulatory electrocardiographic monitoring showing ST-segment deviation is an appropriate indication for adjustment of anti-ischemic therapy. With the documentation of more severe ischemia, angiography should be considered to determine the extent of coronary artery disease. Medical therapy, antianginal agents and risk reduction may improve survival. When ischemic involvement is severe, as in 3-vessel disease, interventional surgery may be required, whether or not ischemia is accompanied by angina. Selected clinical practice cases are presented to illustrate these diagnostic and therapeutic considerations, and are followed by group discussion.     

Prognostic implications of silent myocardial ischemia: prediction of events?

In patients with stable and unstable angina pectoris, the occurrence of transient ST-T-wave alterations during ambulatory electrocardiographic monitoring is helpful in identifying a subgroup of patients who are especially likely to have severe atherosclerotic coronary artery disease and a guarded prognosis over the subsequent 1 to 12 months. Because the majority of these episodes are not accompanied by chest pain, it seems logical to conclude that recurrent episodes of silent myocardial ischemia signal a high likelihood of severe coronary artery disease and carry a poor short-term prognosis.     

Calcium antagonists for Prinzmetal's variant angina, unstable angina and silent myocardial ischemia: therapeutic tool and probe for identification of pathophysiologic mechanisms

The calcium antagonists provide a unique tool to reduce myocardial oxygen demand and prevent increases in coronary vasomotor tone. For patients with Prinzmetal's variant angina, diltiazem, nifedipine and verapamil are extremely effective in preventing episodes of coronary vasospasm and symptoms of ischemia. Unstable angina pectoris is a more complex pathophysiologic syndrome with episodes of ischemia due to increases in coronary vasomotor tone, intermittent platelet aggregation or alterations in the underlying atherosclerotic plaque. Each of the calcium antagonists is effective as monotherapy in decreasing the frequency of angina at rest. Nifedipine is the only calcium antagonist that has been studied in a combination regimen with beta blockers and nitrates for patients with unstable angina, and control of angina is better with the combination regimen than with either form of therapy alone. Although symptoms of myocardial ischemia in unstable angina are reduced by calcium antagonists, these agents do not seem to decrease the incidence of adverse outcomes. Antiplatelet therapy appears to improve morbidity and mortality in patients with unstable angina, suggesting that thrombus formation may play a central role in that disorder. Episodes of silent or asymptomatic myocardial ischemia, identified by ST-segment monitoring, occur in a variety of disorders of coronary disease. Among patients with Prinzmetal's variant angina and unstable angina, episodes of silent ischemia appear to be as frequent as episodes of angina and the calcium antagonists are effective in decreasing episodes of ischemia regardless of the presence or absence of symptoms. Persisting episodes of silent ischemia among patients with unstable angina despite maximal medical therapy identify patients at high risk for an early unfavorable outcome. Among patients with stable exertional angina, episodes of silent ischemia may be up to 5 times as frequent as episodes of angina, and may be due to increases in coronary vasomotor tone, transient platelet aggregation or increases in myocardial oxygen demand. Preliminary experience suggests that calcium antagonists and beta blockers are effective in decreasing episodes of silent ischemia in patients with stable exertional angina and that a combination regimen may be more effective than either form of therapy alone.     

Silent myocardial ischemia: prognostic significance and therapeutic implications

Evidence is now accumulating which strongly suggests that prognosis of patients with painless myocardial ischemia determined either by ambulatory ECG monitoring or exercise testing may be no different than the prognosis of patients who have overt clinical manifestations of myocardial ischemia associated with transient ischemic ECG changes. In my view the goal of therapy for patients with clinical manifestations of coronary artery disease should be the elimination of myocardial ischemia. Medical therapy, coronary angioplasty, or coronary artery surgery should be rendered and then followed by objective documentation of therapeutic efficacy.     

Detection of silent myocardial ischemia in patients with angina using continuous electrocardiographic monitoring

In patients with effort angina, ST-segment depression is a reliable indicator of transient myocardial ischemia. Ambulatory electrocardiographic monitoring can detect episodes of ST-segment depression with and without chest pain in patients with coronary heart disease. This test provides valuable information about the presence, frequency, magnitude, and duration of transient myocardial ischemia and associated trigger factors.     

Asymptomatic or silent myocardial ischemia in angina pectoris: pathophysiology and clinical implications

Patients with angina pectoris often have asymptomatic myocardial ischemia, which can be detected by exercise testing, ambulatory (Holter) monitoring, and other diagnostic methods. Studies suggest that the presence of frequent and prolonged episodes of ischemia are associated with an adverse prognosis. Standard antiangina strategies have been found to be effective in reducing exercise and spontaneous episodes of ischemia. However, whether the targeted suppression of all ischemic activity should be a therapeutic goal remains unresolved and is the focus of current research efforts.     

Hemodynamic,electrocardiographic, and metabolic effects of fructose diphosphate on acute myocardial ischemia

The hemodynamic, electrocardiographic, and metabolic responses of dogs with acute myocardial ischemia to intravenous administration of fructose-1,6-diphosphate (FDP) were assessed.Analysis of the results (compared to dextrose control) revealed evidence of major improvement of LVEDP and cardiac output, significant decrease of the ST segment, and large increases of ATP and CP in the ischemic district and to a lesser degree in the normally perfused myocardium. These results indicate that FDP intervenes in the Embden-Meyerhof pathway not only as a high energy substrate but also as a metabolic regulator influencing the activity of phosphofructokinase and that of pyruvate kinase. FDP also stimulates glycolysis in dog erythrocytes and increases their ATP and 2–3 DPG content by a factor of 2.The most significant finding in these studies is that this biochemical intervention appears to restore the depressed activity of glycolysis in ischemic myocardium.     

Characterization of silent ischemia in patients with unstable angina: prognostic and therapeutic implications

The occurrence of silent ischemia in various ischemic myocardial syndromes has attracted increasing attention. In unstable angina hemodynamic monitoring has suggested that the symptomatic and silent episodes of ischemia do not differ significantly. In two discrete studies we determined the characteristics and prognostic significance of silent ischemic episodes in unstable angina. In one study with 41 patients, there were 781 episodes of ischemia in Holter recordings: 392 (50%) with ST-segment depression, 242 (31%) with ST-elevation, 45 (6%) with ST-elevation and depression in different leads, 70 (9%) with pseudonormalization of T waves and 32 (4%) with T wave augmentation. Ventricular arrhythmias were associated with 18% of the episodes. The mean duration of ischemia was 14 minutes (range 30 seconds to almost twelve hours), the majority being less than five minutes. Only 154 (20%) of the 781 episodes of ischemia were associated with pain. Conversely, 77 episodes of chest pain were not associated with electrocardiographic changes. Analysis of the temporal sequence of heart rate during the development of ischemia (analysed in 415 episodes) showed that in only 43 (10%) the heart rate at the beginning of ischemia was significantly (exceeding 6 beats/minute) greater than that at five minutes (baseline) preceding the onset of ischemia. At the peak of ischemia, the mean heart rate increase was 10% and returned to baseline at the end of the ischemic episode. The data indicate that 80% of ischemic episodes in unstable angina are silent and over 90% are not triggered by increases in heart rate indicating that increased oxygen demand is an uncommon cause of ischemia in unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)     

An update to silent myocardial ischemia: pathophysiological, diagnostic, and therapeutic approaches

Silent myocardial ischemia (SMI) is a common ischemia process which can be defined as objective evidence of myocardial ischemia without chest pain or other equivalent indications. SMI can occur in totally asymptomatic patients, as well as in patients who have documented coronary artery disease (CAD) and who, on exercise and/or during Holter monitoring, may show ischemic changes. The precise mechanism for pathogenesis and pathophysiology of SMI remains to be clarified. A great deal has been learned about the role of beta-adrenergic receptors, adenylyl cyclase, and guanine nucleotide binding proteins (G proteins) in the myocardial ischemic process of SMI. Moreover, standard exercise test and long-term ECG recordings have proved to be of great value, especially when performed jointly, however, in this field there is still room for expanded knowledge. Pharmacological interventions to date have demonstrated the beneficial effects of beta-adrenergic receptor antagonists and/or calcium antagonists as contributing substantially to reducing both frequency and duration of SMI episodes. However, therapeutic options to improve the prognosis of SMI appear to be limited.     

Intravenous diltiazem versus nitroglycerin for silent and symptomatic myocardial ischemia in unstable angina pectoris

For 18 patients consecutively admitted to the coronary care unit for unstable angina, 48-hour electrocardiographic Holter monitoring was performed after they were randomly assigned in a single-blind fashion to 1 of 2 treatment groups. The first group was treated with acetylsalicylic acid (ASA) and intravenous nitroglycerin, the second with ASA and intravenous diltiazem. All of the patients treated with nitroglycerin still had ischemic episodes after 48 hours (33% were symptomatic), in contrast with 11% of the diltiazem group (11% asymptomatic). Maximal ST-segment depressions of symptomatic and asymptomatic episodes were significantly different; and no significant increases in heart rate were observed either during the 15 seconds before ischemia began or during the ischemic episode. During the 48 hours, the diltiazem group had significantly fewer ischemic episodes (17) than did the nitroglycerin group (145). We concluded that "on-line" ST-segment observation is of prime importance for monitoring unstable angina; that the majority of the ischemic episodes associated with unstable angina are silent; and that intravenous diltiazem could be an effective pretreatment for patients who must undergo mechanical or surgical therapy.     

Comparison of the oxygen deficit and ischemia pain threshold in patients with silent and symptomatic myocardial exercise-induced ischemia

In 39 patients with angiographically documented coronary artery disease and silent or symptomatic myocardial ischemia under exertion it was investigated if there is a difference in forearm skeletal muscle ischemia and ischemic pain threshold. The degree of myocardial ischemia was determined by plethysmographically measured reactive hyperemia. In 12 asymptomatic and eight symptomatic patients maximal reactive hyperemia was induced by ischemic work in the forearm skeletal muscle. After termination of ischemia there was a significantly higher reactive hyperemia at 20, 90, and 180 s in the asymptomatic patients. Furthermore, nine asymptomatic and 10 symptomatic patients underwent symptom-limited ischemic work until weakness or pain developed. Under these conditions reactive hyperemia as a parameter of oxygen deficiency was higher in the asymptomatic patients. The difference was not statistically significant. There was, however, a significantly higher incidence of ischemic pain in the symptomatic patients. It can be concluded that patients with asymptomatic myocardial ischemia tolerate a higher oxygen deficit in the working forearm and have a higher pain threshold than patients with symptomatic ischemia.     

Treatment of silent myocardial ischemia

Long-term studies regarding the effect of treatment on prognosis are lacking, but the adverse implications suggested for silent ischemia support aggressive management. Treatment of silent ischemic episodes is possible utilizing a large variety of agents. Optimal detection and quantitation methods are still being developed, but guidelines for treatment should be similar to those for treatment of symptomatic ischemia.