Stephen Campbell

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)

Prognostic importance of myocardial ischemia detected by ambulatory monitoring in patients with stable coronary artery disease.

To assess the relations of electrocardiographic measures of ischemia with the development of adverse coronary events, 86 patients with stable coronary artery disease and positive exercise tests for myocardial ischemia underwent ambulatory monitoring of the electrocardiogram. Monitoring was performed after withdrawal of antianginal medications, and prospective follow-up was obtained on routine medical care as prescribed by physicians who were unaware of monitor results. Forty-nine patients (57%) had a total of 426 episodes of ST segment depression; only 60 episodes (14%) were associated with symptoms of angina or an equivalent. During a mean follow-up of 12.5 +/- 7.5 months, there were two cardiac deaths, four myocardial infarctions, four hospitalizations for unstable angina, and 11 revascularization procedures required for new or worsening symptoms in 15 patients. All but one of these events (a hospitalization for unstable angina) occurred in the group of patients with ST segment depression on monitoring (p = 0.003). In multivariate analysis controlling for age, sex, and clinical descriptions of angina, the presence of ischemia on ambulatory monitoring was a significant predictor of outcome, while exercise test characteristics were not. Therefore, ischemia detected by ambulatory monitoring was common in patients with stable symptoms of coronary artery disease, and its presence identified a high-risk group for the development of subsequent unfavorable outcomes while on routine medical therapies.

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)

Features of the exercise test that reflect the activity of ischemic heart disease out of hospital.

To better understand the relationship between the transient myocardial ischemia seen during an exercise test and ischemic activity out of hospital, 39 patients with well-documented coronary artery disease underwent standard treadmill exercise testing (Bruce protocol) and 24 to 48 hr of continuous ambulatory electrocardiographic monitoring during normal daily activities. A total of 245 episodes of transient ischemia were recorded in 21 of 32 patients with positive exercise electrocardiograms (group I), whereas seven patients with negative test results (group II) had no episodes of transient ischemia, during monitoring out of hospital (p less than .01). Certain measures in the exercise test were related to the severity of ischemia out of hospital: there were more episodes and a greater total duration of transient ischemia per 24 hr of ambulatory monitoring in patients who developed ischemic electrocardiographic changes before 6 min of exercise (p less than or equal to .021) or at a heart rate of less than 150 beats/min (p = .005) and in those in whom these ST segment changes persisted for more than 5 min after exercise (p less than or equal to .016). In contrast, there was no relationship between transient ischemia out of hospital and the commonly quoted exercise variables: chest pain, total exercise duration, and the maximum levels of heart rate, systolic blood pressure, and double product. Thus, patients with coronary artery disease and negative exercise electrocardiograms are most unlikely to experience active ischemia during normal daily life.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory monitoring of the digitized electrocardiogram for detection and early warning of transient myocardial ischemia in angina pectoris

Patients with coronary artery disease have frequent asymptomatic episodes of ischemic ST-segment depression. A new solid-state recorder that analyzes the digitized electrocardiogram (ECG) in real time has been tested for accuracy in detection and quantitation of these events by comparison with a direct ECG during exercise testing and a frequency-modulated recorder during ambulatory monitoring. The device can also be programmed to produce a tone at the onset of ischemic ST-segment depression, and this tone is used to initiate self-administration of nitroglycerin in an attempt to control myocardial ischemic events. The solid-state recorder demonstrated adequate sensitivity and specificity during exercise (100% and 92%, respectively) for detection and quantitation of episodes of ischemic ST-segment depression. In addition, Monitor One accurately measured the duration of ischemic events during exercise testing (r = 0.95, p = 0.001) and the number (r = 0.92, p = 0.001) and duration (r = 0.97, p = 0.001) of ischemic events during ambulatory monitoring. When the audible tone was used to initiate use of nitroglycerin, the duration of episodes of ischemic ST-segment depression was reduced from 105 +/- 74 min/24 hours to 58 +/- 49 min/24 hours (p = 0.02). Thus, a solid-state ECG recorder capable of long-term monitoring appears to accurately detect and quantify episodes of ischemic ST-segment depression in patients with coronary artery disease. Also, patients can interact with an audible tone to key self-administration of therapy in an attempt to control asymptomatic episodes of transient myocardial ischemia.

Waking and rising at night as a trigger of myocardial ischemia

A diurnal pattern of changes in transient myocardial ischemia has been well documented in patients with coronary artery disease (CAD) with an increase in the early morning hours. To further investigate potential triggers of ischemia, certain defined and distinct episodes of waking and rising during the nighttime were examined. Of 113 patients who underwent ambulatory monitoring of the electrocardiogram, 466 episodes of ischemia lasting 3,926 minutes were detected in 67 of the patients. In 30 patients who had ischemia at night, 21 reported 36 occasions of waking and rising, and 67% of these events were associated with ST-segment depression. Frequency and duration of ischemia were similar in the nocturnal episodes versus the early morning episodes of ischemia as were the increases in heart rate at 30, 10, 5 and 1 minute before the onset. Even before waking, there was an increase in heart rate beginning approximately 30 minutes before the onset of ischemia. This increase became significant 5 minutes before onset both in the early morning and on rising at night. Patients with nocturnal ischemia had significantly worse clinical signs of CAD. This study shows that rising at night is often associated with episodes of myocardial ischemia and, like the morning events on rising, is likely an important trigger of ischemia in patients with CAD.

Factors determining the activity of ischemic heart disease

Transient regional myocardial ischemia appears to underlie symptoms such as angina pectoris and represents a key pathophysiologic step, since it is an objective marker of disease activity and is capable of causing disabling symptoms and damage to left ventricular myocardium. A study of the characteristics of transient ischemia in and out of the hospital has shown that symptoms are an inconsistent underestimation of these events. Ischemia is generally prolonged, mostly asymptomatic, and usually accompanied by a regional decrease in myocardial perfusion. Studies out of the hospital have also shown that these episodes are frequently triggered by a wide range of ordinary everyday activities. These new features of transient ischemia are worth noting when searching for relevant causes that are present during everyday life and when trying to choose more rational therapy. More detailed studies of patient activity have shown that different levels of mental arousal are the most common triggering mechanism causing ischemia out of the hospital. In addition, the occurrence of transient ischemia during everyday life displays a circadian rhythm, with an increase and peak occurrence between 6:00 A.M. and 12 noon each day. The day-to-day variability of ischemia is marked, indicating functional disturbances of coronary stenoses against a background of a severe reduction in cross-sectional area. The examination of proximal stenoses has shown that the reduction in cross-sectional area is usually underestimated by conventional angiography; pressure gradients across coronary stenoses are common and, with reduced poststenotic blood pressure, can jeopardize perfusion; disturbances of vessel caliber and antegrade flow can accompany many of the ordinary everyday activities known to trigger ischemia detected in Holter tapes studied out of the hospital; and there is clear-cut evidence of endothelial dysfunction in these patients, with reversal of the normal dilator response to acetylcholine and paradoxical constriction of stenoses. This evidence of endothelial dysfunction in humans could be central to the problems of atheromatous narrowing, thrombus, and disturbed vasomotion.

Activity of transient myocardial ischemia out of hospital in coronary artery disease and implications for management

The management of patients with angina pectoris is based largely on the severity of symptoms, coronary anatomy and left ventricular function. The outcome for these patients is highly variable and depends largely on the degree of ischemic damage to the left ventricular myocardium. Recent work suggests that exercise-induced myocardial ischemia with or without angina is associated with a poor prognosis. Ambulatory monitoring of the electrocardiogram has revealed that most patients have frequent and prolonged episodes of transient ischemia out of hospital. These episodes are often asymptomatic and associated with ordinary everyday activities. In addition, ambulatory monitoring has demonstrated that transient ischemia during daily life has a circadian variation with exacerbations and peak density of ischemia in the first 4 to 6 waking hours of the day. Further studies have demonstrated that regional decreases in coronary blood flow occur during these ischemic episodes and have the same features seen out of hospital on continuous monitoring. These newly noted characteristics of transient ischemia raise a number of practical questions for treatment. Is it necessary to relieve all ischemic activity quite apart from that which occurs with chest pain? Does present use of antianginal medication neglect the early morning increases in transient ischemia that occur, and are different dosage regimens required to treat ischemia adequately? Does suppression of all ischemic activity further protect myocardium and improve prognosis for the patient?