Joan Barry

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.

Effect of Cholesterol Reduction on Myocardial Ischemia in Patients With Coronary Disease

BACKGROUND Cholesterol lowering is associated with a reduction in cardiovascular morbidity and mortality. This study sought to determine whether cholesterol lowering also results in a reduction of myocardial ischemia during daily life. METHODS AND RESULTS We enrolled 40 patients with proven coronary artery disease, total serum cholesterol between 191 and 327 mg/dL, and at least one episode of ST-segment depression on ambulatory ECG monitoring. Twenty patients were randomized to an American Heart Association Step 1 diet plus placebo (placebo group) and 20 to the same diet plus lovastatin (treatment group). Serum cholesterol and LDL cholesterol levels and ambulatory monitoring were repeated after 4 to 6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, and baseline serum cholesterol levels. The treatment group had lower mean total and LDL cholesterol levels at study end and experienced a significant reduction in the number of episodes of ST-segment depression compared with the placebo group. ST-segment depression was completely resolved in 13 of 20 patients (65%) in the treatment group versus 2 of 20 (10%) in the placebo group. The treatment group exhibited a highly significant reduction in ischemia (P < .001). By logistic regression, treatment with diet and lovastatin was an independent predictor of ischemia resolution. CONCLUSIONS Cholesterol lowering with lovastatin appears to be effective in eliminating myocardial ischemia during daily life in a significant proportion of patients.

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)

Frequency of ST-segment depression produced by mental stress in stable angina pectoris from coronary artery disease

Physical exertion is a well-documented trigger of transient myocardial ischemia in patients with coronary disease. More recently, studies have shown that mental stress may also be a cause of myocardial ischemia. The purpose of this study was to examine the relationship of physical activities and perceived mental states to myocardial ischemia while patients were going about their normal daily activities. Twenty-eight patients with documented coronary artery disease underwent ambulatory monitoring of the electrocardiogram. Physical activity and perceived mental status were recorded by patients in a diary which was then graded according to intensity of the activity. Analyses of the continuous electrocardiographic recordings were done separately from the analysis of the diaries. The time of each episode of ischemia, the duration of each episode in minutes and the number of episodes in each 24-hour period were calculated. A total of 372 episodes of ST-segment depression occurred in 912 hours of monitoring. Ischemic events occurring during usual physical and usual mental activities were most frequent (36%). Twenty-six percent of ischemic episodes occurred during increased physical activity, but usual mental activities. Interestingly, 22% of the ischemic events occurred at high levels of mental stress, but low physical activity. Ten percent of episodes occurred during sleep. Although the majority of events occurred during usual daily activities, when duration of ischemia was normalized for time spent in each category, increasing physical or mental activity was associated with an increasing duration of ischemia per unit (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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

BackgroundIschemia 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 ResultsIn 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 of 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). ConclusionsAsymptomatic 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.

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)

Long-term prognosis of myocardial ischemia detected by holter monitoring in peripheral vascular disease☆

To assess the long-term prognostic significance of myocardial ischemia, as measured by ambulatory electrocardiographic monitoring, in patients with occlusive peripheral arterial disease, 176 eligible patients scheduled for elective peripheral arterial surgery at Brigham and Womens Hospital were prospectively studied. All patients were monitored preoperatively without alterations to baseline medications. Prospective follow-up was obtained during routine medical care as provided by blinded, independent physicians and by subsequent telephone contact with the patients. Thirty-two patients (18%) had a total of 75 episodes of myocardial ischemia, 73 (97%) of which were asymptomatic. During a mean follow-up period of 615 days, there were 9 cardiac deaths, 1 occurring in-hospital after peripheral vascular surgery, and 13 nonfatal myocardial infarctions, 4 occurring in-hospital after peripheral vascular surgery. Cardiac events occurred in 12 of 32 patients with ischemia (38%), including 6 cardiac deaths, and in 10 of 144 patients without ischemia (7%), including 3 cardiac deaths (risk ratio 5.4, 95% confidence interval 2.6 to 11.4). The sensitivity of ischemia was 55%, the specificity was 87%, the positive predictive value was 38%, and the negative predictive value was 93%. In a multivariate Cox proportional-hazards model controlling for age, gender, coronary risk factors, history of angina, myocardial infarction, coronary artery disease and antianginal medications, the presence of ischemia was the only independent predictor of outcome. In patients with peripheral arterial disease, who often are unable to perform adequate exercise testing, ambulatory monitoring for myocardial ischemia is a significant independent predictor of 1- to 2-year prognosis.

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.