Ischemia in the ambulatory setting--the total ischemic burden: relation to exercise testing and investigative and therapeutic implications

To establish the relation between treadmill exercise testing and ambulatory St segment monitoring in the detection of ischemia in patients with coronary artery disease, and to assess whether standard medical therapy affects any such relation, 277 patients with stable angina and angiographically documented coronary artery disease were studied with treadmill exercise testing and 48 h ambulatory ST segment monitoring. One hundred forty-six patients (52%) were studied while receiving no routine antianginal therapy, and 131 (48%) while receiving standard medical therapy. In 187 patients (67%) the exercise test was positive for ischemia. During 11,964 h of ambulatory monitoring, 881 episodes of ischemia (645 [73%] silent) were recorded, of which 809 (92%) occurred in patients with a positive exercise test. The mean heart rate at the onset of ischemic episodes during ambulatory monitoring was significantly less than that at the onset of 1 mm ST segment depression during exercise testing (94.5 versus 105.9 beats/min, p less than 0.0001). However, the frequency of ambulatory ischemic episodes was strongly related to a positive exercise test (p less than 0.001), and this relation was similar for both silent and painful ischemia (p less than 0.0001 for both) and in patients who were and were not receiving therapy (p less than 0.0001 for both). The total duration of ischemia was similarly related to a positive exercise test (p less than 0.0001). Only one patient with a negative exercise test had frequent (greater than 5/day) episodes of ischemia on ambulatory monitoring and had documented coronary artery spasm. Thus, exercise testing identifies the majority of patients likely to have significant ischemia during their daily activities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relation between left ventricular function at rest and with exercise and silent myocardial ischemia.

The prognostic value of radionuclide measures of left ventricular function at rest and exercise is well established. Some studies have suggested that the frequency and duration of silent ischemia during ambulatory monitoring provide similar prognostic information; however, studies comparing these two techniques have not been performed. This study examines the relation between left ventricular function at rest and exercise-induced ischemia assessed by radionuclide ventriculography with myocardial ischemia during ambulatory electrocardiographic (ECG) monitoring. Of the 155 patients with coronary artery disease studied, 88% had left ventricular dysfunction with exercise, defined as failure of the ejection fraction to increase by greater than 4% with exercise, and 33% of patients had left ventricular dysfunction at rest (ejection fraction less than 45%); 52% had transient episodes of ST segment depression during 48-h ambulatory ECG monitoring. Exercise-induced left ventricular dysfunction during radionuclide ventriculography was extremely sensitive (94%) in detecting patients with ischemic episodes during ambulatory ECG monitoring; however, only 55% of patients with exercise-induced left ventricular dysfunction had ST segment depression during ambulatory monitoring. Moreover, patients with left ventricular dysfunction at rest had a lower prevalence of transient episodes of ST segment depression (31%) than did patients with normal left ventricular function at rest (62%) (p = 0.008). The relation between prognostically important variables during exercise radionuclide ventriculography and the number and duration of transient episodes of ST depression was examined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Silent ischemia: a clinical update

Silent ischemia is a common finding in coronary artery disease and occurs more frequently than painful episodes in the total ischemic burden. Since painless ischemia places limits on the history, it can encourage physicians to spend more time studying and treating the electrocardiogram and less time with patients, potentially leading to a deterioration in doctor-patient relationship and care. Silent ischemia should be considered only in patients 35 years of age or older who: (a) have a strong family history of early coronary artery disease, or (b) have two major coronary risk factors. Verification is made by performing an electrocardiographic exercise stress test and followed by a thallium-201 electrocardiographic stress test when the electrocardiograms are equivocal. In females it is best to proceed directly to a thallium-201 electrocardiographic stress test because of the frequency of false positives on the exercise electrocardiograms. The results will help determine the indications for further studies and subsequently the need for drug or interventional management. Frequently a history in which symptoms of lower esophageal disorders, hiatal hernia, gastric disease and arthritic pains mimic angina or in fact coexist with ischemic heart disease makes the clinical diagnosis of angina more elusive and difficult. However, a careful unhurried history and an exercise stress test can often differentiate the etiology of the chest pains. A 24-hour ambulatory electrocardiographic recording aids in measuring the total ischemic burden. When the diagnosis and severity of the ischemic syndrome is established, a course of medical therapy tailored to the symptoms and with defined end points is initiated. Since silent ischemia and angina frequently coexist, suppression of the frequency and severity of the anginal episodes will also reduce the episodes of silent ischemia. Symptomatic improvement is thus a guide in the treatment of the total ischemic syndrome. Drug management will usually consist of two or more of the following drugs: a nitrate, beta blocker, calcium channel blocker, and aspirin. A 24-hour ambulatory electrocardiographic recording is helpful in assessing the efficacy of medical management of silent ischemia. Failures in drug management should proceed with coronary angiography, and when indicated, followed by percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery.     

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)     

Exercise test predictors of ambulatory silent ischemia during daily life in stable angina pectoris

The predictive value of several exercise test parameters in identifying stable angina patients at risk of silent myocardial ischemia during daily life were examined. A total of 97 patients with coronary artery disease, stable angina and ambulatory electrocardiographic data were evaluated. Of the 86 patients with a positive exercise test, 39 (group 1) had greater than or equal to 1 episodes of ST-segment depression and 47 (group 2) did not develop ST changes during ambulatory electrocardiographic monitoring. Comparison of the exercise test parameters between the 2 groups revealed early onset of ischemia during exercise tests as the single most significant (p less than 0.0005) predictor of ambulatory silent ischemia. The other exercise test parameters showing significant differences between the 2 groups were the peak exercise heart rate (117 +/- 23 vs 126 +/- 20 beats/min, p less than 0.05) and peak systolic blood pressure (160 +/- 27 vs 176 +/- 27 mm Hg, p less than 0.01), both of which were significantly lower in the group 1 patients. These data were used to derive simple mathematical formulas for calculating the risk of ambulatory silent ischemia. These results demonstrate that stable angina patients at risk of silent ischemia during daily life can be accurately identified by evaluation of selected exercise test parameters.     

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.     

Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris

A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes. After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning. Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography. During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less than 0.05). Time to greater than or equal to 1 mm ST depression was significantly greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72 seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than 0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p less than 0.02 for both). The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment. Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes.     

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

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

Transient myocardial ischemia during daily life in patients with syndrome X

Nineteen patients with syndrome X (typical exertional angina, positive exercise test response [at least 0.1 mV of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries) underwent continuous 48-hour electrocardiographic (ECG) monitoring during unrestricted daily life. Fifty-eight ischemic episodes of at least 0.1 mV of ST-segment depression were observed in the same ECG leads that showed ST depression during stress testing: 28 (48%) were accompanied by anginal pain and 30 (52%) were asymptomatic. No significant differences were found between painful and silent ST-segment depression with regard to the number of episodes, their temporal distribution, magnitude, duration or heart rate (HR) at onset of ST-segment depression. In the minute preceding ischemic ST shifts, HR did not change in 33% of episodes or increased by less than 10 beats/min in 28%. HR at onset of ST depression was significantly lower during ambulatory ECG monitoring than during exercise testing (98 ± 18 vs 117 ± 18 beats/min, p < 0.01). During ambulatory monitoring, 85 episodes of sinus tachycardia (exceeding by 10 to 80 beats/min the HR that triggered ischemia during exercise testing) occurred in the absence of angina or ST-segment shifts. The results of this study suggest that in patients with syndrome X, (1) myocardial ischemia frequently develops during daily life; (2) silent ischemia is an important component of this syndrome; and (3) increased oxygen demand in the presence of impaired coronary vasodilatory capacity is not the only cause of myocardial ischemia. Active mechanisms that transiently reduce coronary flow may act and explain occurrence of angina at rest and with minimal exertion.     

Effects of titrated beta blockade (metoprolol) on silent myocardial ischemia in ambulatory patients with coronary artery disease

This study investigates effects of beta-adrenergic blockade on total silent ischemic time assessed by ambulatory electrocardiographic monitoring and its relation to heart rate and time of day in ambulatory men with coronary artery disease. Metoprolol, when titrated to optimal dose in a controlled trial in 9 patients, reduced both total silent ischemic time (from 156 +/- 65 to 20 +/- 15 minutes, p = 0.04) and frequency of silent ischemic episodes (from 8 +/- 2 to 2 +/- 2 episodes, p = 0.03) compared with placebo. Mean daily heart rate was reduced, from 82 +/- 2 beats/min during placebo to 58 +/- 1 beats/min, as was heart rate at onset of 1 mm of ST-segment depression (106 +/- 2 to 74 +/- 4 beats/min, both p less than 0.001). Heart rate increased 10 +/- 1 beats/min during silent ischemia with placebo therapy, but increased only 4 +/- 1 beats/min during metoprolol treatment (p less than 0.03). During placebo administration the largest proportion of silent ischemic time occurred between 0600 and 1200 hours. Metoprolol attenuated this circadian variation in silent ischemia while reducing (p less than 0.05) total silent ischemic time in all periods. Thus, beta-adrenergic blockade reduces the frequency of silent myocardial ischemic episodes and total silent ischemic time, while mean daily heart rate and heart rate at onset of ischemia and maximal ischemia decrease. Metoprolol treatment also attenuates circadian variation of silent ischemia. These data may be interpreted to suggest that beta-adrenergic activation operates in the pathogenesis of silent myocardial ischemia and its circadian variation.     

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.     

Prevalence and patterns of silent myocardial ischemia during daily life in stable angina patients receiving conventional antianginal drug therapy

The prevalence and patterns of silent myocardial ischemia were evaluated in 105 stable angina patients receiving conventional antianginal drug therapy. During 2,520 hours of electrocardiographic monitoring, silent ischemia was detected in 45 (43%) patients. A total of 188 ischemic episodes was observed; 163 (87%) were silent and accounted for a total ischemic duration of 5,771 minutes. There was no difference in the baseline clinical characteristics between the patients with and without ambulatory silent ischemia. However, patients with silent ischemia on ambulatory electrocardiographic monitoring had earlier onset of ischemia during exercise testing. The highest density of silent ischemic events occurred between 6 A.M. and 6 P.M. Comparison of the class or combination of antianginal agents used by the 2 groups revealed no difference. However, in patients with silent ischemia the mean duration per event was shorter for those receiving 2 (p less than 0.05) or more (p = 0.001) antianginal agents compared to those receiving monotherapy. The average duration of silent ischemia per event was significantly less (p less than 0.001) in patients receiving beta blockers. These results demonstrate that silent ischemia during ordinary daily activities occurs frequently despite conventional antianginal drugs prescribed for control of symptoms.     

Dissociation of exercise tolerance and total myocardial ischemic burden in chronic stable angina pectoris

Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.     

Myocardial ischemia during daily activities: the importance of increased myocardial oxygen demand

The role of increased myocardial oxygen demand in the pathophysiology of myocardial ischemia occurring during daily activities was evaluated in 50 patients with coronary artery disease and exercise-induced ST segment depression. Each patient underwent ambulatory electrocardiographic (ECG) monitoring for ST segment shifts during normal daily activities and symptom-limited bicycle exercise testing with continuous ECG monitoring. All 50 patients had ST depression greater than or equal to 0.1 mV during exercise. A total of 241 episodes of ST depression were noted in the ambulatory setting in 31 patients; only 6% of these were accompanied by angina pectoris. Significant (0.1 mV) ST depression during ambulatory monitoring was preceded by a mean increase in heart rate of 27 +/- 12 beats/min. Patients with ischemia during daily activities developed ST depression earlier during exercise (7.9 +/- 4.4 vs. 14.2 +/- 6.4 min, p less than 0.001) and tended to have significant ECG changes at a lower exercise heart rate and rate-pressure product than did those without ST depression during ambulatory monitoring. In the 31 patients with ischemia during daily activities, the mean heart rate associated with ST depression in the ambulatory setting was closely correlated with the heart rate precipitating ECG changes during exercise testing (r = 0.74, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of coronary artery bypass surgery and angioplasty on the total ischemic burden: a study of exercise testing and ambulatory ST segment monitoring.

To assess the effects of standard therapeutic interventions on the total ischemic burden, 86 patients with stable angina underwent 48 hours of ambulatory ST segment monitoring and treadmill exercise testing before and at a mean of 10 weeks after coronary artery bypass surgery (CABG) (group 1, N = 46) or percutaneous transluminal coronary angioplasty (PTCA) (group 2, N = 40). There were 72 male and 14 female patients with a mean age of 56.4 years. All patients had documented coronary artery disease (24, single-vessel; 28, two-vessel; 34, three-vessel disease). Both groups were characteristically similar apart from more severe coronary artery disease (p less than 0.001) and more previous myocardial infarctions (p less than 0.05) in group 1. Groups with CABG and PTCA had significant prolongation of exercise time after intervention (group 1: 7.6 to 9.8 minutes, p less than 0.0001; group 2: 8.1 to 10.0 minutes, p less than 0.001), and both interventions led to a significant reduction in ischemic responses (group 1: 33 to 4, p less than 0.001; group 2: 20 to 13, p less than 0.05) to exercise. During a total of 7643 hours of ST segment monitoring, 253 episodes of ischemia were recorded in 3768 hours before and 44 ischemic episodes in 3875 hours after intervention (group 1, 113 episodes in 24 patients and 21 episodes in 10 patients; group 2, 140 episodes in 13 patients and 23 episodes in six patients). Both interventions reduced the mean frequency of ischemia per 24 hours (group 1: 1.24 to 0.22 episodes per 24 hours; p less than 0.01; group 2: 1.9 to 0.3 episodes per 24 hours; p less than 0.05). Almost 28% (N = 24) of resting electrocardiographic findings were altered as a result of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-dose single administration of isosorbide dinitrate: effect on diurnal distribution of transitory myocardial ischemia in patients with stable angina pectoris

We studied the effect of a monotherapy of isosorbiddinitrate on symptomatic and asymptomatic ischemic episodes in 15 ambulatory patients with chronic stable angina pectoris, positive exercise test, and coronary stenosis greater than 70%. Transient ST-segment depression (greater than 0.1 mV for at least 1 min) was documented by 48-h Holter monitoring during a control period without anti-ischemic therapy and at the end of 14 days of treatment with 120 mg o.d. isosorbiddinitrate slow-release. In the control period, 68 asymptomatic and 28 symptomatic ischemic episodes were detected; most of the episodes occurred in the morning between 6.00h and 12.00h (41 episodes) and in the afternoon between 12.00h and 18.00h (36 episodes). Under anti-ischemic therapy the number of episodes and the total duration of ischemia was reduced by 46% and 53%, respectively (p less than 0.01). The anti-ischemic effect was most evident during the morning and the afternoon; the ischemic episodes during the evening and the night were not significantly diminished. It is concluded that in patients with stable angina pectoris a single high-dose of isosorbiddinitrate significantly reduces the number and duration of transient ischemic episodes during daily life.     

Effects of nisoldipine on myocardial ischemia during exercise and during daily activity

The antiischemic properties of nisoldipine, a dihydropyridine calcium antagonist, were assessed in a multicenter, double-blind, placebo-controlled trial by repeated exercise testing and 72-hour ambulatory electrocardiographic monitoring in 82 patients with coronary artery disease. Patients with positive treadmill stress test results and greater than or equal to 2 ischemic episodes per 24 hours were included in this study. Administration of all chronic antiischemic medications except beta blockers were discontinued. During the first week all patients received placebo twice daily. During the second and third weeks, 41 patients received nisoldipine 10 mg and 41 patients received placebo twice daily. In the placebo group there were no changes in exercise parameters or in ambulatory electrocardiographic parameters. In the nisoldipine group, exercise duration increased from 403 to 448 seconds (p = 0.0035), time to 1 mm of ST depression increased from 224 to 298 seconds (p = 0.002), time to pain increased from 241 to 321 seconds (p = 0.01), and maximal ST depression was reduced from 2.6 to 2.3 mm (p = 0.002). Among the ambulatory electrocardiographic parameters in the nisoldipine group, only the number of episodes was reduced, from 14.4 to 11.6 (p = 0.0013) per patient. There was no significant reduction in total ischemic time (132 vs 120 minutes per patient). No significant side effects were observed. This is the largest clinical trial to date on the effects of nisoldipine on myocardial ischemia. The results indicate that nisoldipine was effective in improving all exercise parameters and only partially effective in suppressing ischemia during daily activity.     

Significance of silent myocardial ischemia after coronary artery bypass surgery.

The prevalence and prognostic significance of transient myocardial ischemia after coronary artery bypass grafting (CABG) were evaluated. In 3 studies, ischemia was found in an average of 24% of patients by ambulatory electrocardiographic monitoring at 3-12 months after CABG. An average of 36% of patients in 3 other studies experienced ischemic ST-segment depression during exercise testing at 4-50 months after CABG. Of the ischemic episodes, 77% were silent during exercise testing. In the Coronary Artery Surgery Study (CASS) randomized patient subsets, survival at 12 years was significantly lower for patients who had either silent or symptomatic ischemia during exercise testing at 6 months after CABG compared with those who had no ischemia.     

Prediction of the frequency and duration of ambulatory myocardial ischemia in patients with stable coronary artery disease by determination of the ischemic threshold from exercise testing: importance of the exercise protocol

The relation between ambulatory myocardial ischemia and the results of exercise testing in patients with ischemic heart disease remains undefined, because of the dissimilar results of previous reports. To further investigate this issue and, in particular, to ascertain the importance of the exercise protocol in determining that relation, 70 patients with stable coronary artery disease underwent 48 h ambulatory electrocardiographic (ECG) monitoring and treadmill exercise tests after withdrawal of medications. Patients exercised using two different protocols with slow (National Institutes of Health [NIH] combined protocol) and brisk (Bruce protocol) work load increments. Exercise duration was longer with the NIH combined protocol (14.1 +/- 5 versus 6.8 +/- 2 min; p less than 0.0001), but the maximal work load and peak heart rate achieved were greater with the Bruce protocol (9.8 +/- 2 versus 6.5 +/- 2 METs, and 142 +/- 19 versus 133 +/- 22 beats/min, respectively; p less than 0.0001). A close inverse correlation between exercise testing and the results of ambulatory ECG monitoring was observed using the NIH combined protocol; the strongest correlation was observed between time of exercise at 1 mm of ST segment depression and number of ischemic episodes (r = -0.86; p less than 0.0001). With the Bruce protocol a significantly weaker inverse correlation was found (r = -0.35). The mean heart rate at the onset of ST segment depression was similar during monitoring and during exercise testing with the NIH combined protocol (97.2 +/- 13 versus 101.0 +/- 17 beats/min, respectively) but it was significantly higher (110.4 +/- 13) when using the Bruce protocol (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)