Ambulatory Myocardial Ischemia Research Articles

The effect of SGLT2 inhibitors on silent myocardial ischemia

Abstract Background In large cardiovascular (CV) outcome trials, sodium-glucose co-transporter 2 (SGLT2) inhibitors reduced the development of heart failure (HF) in patients with type 2 diabetes (T2DM). Also it reduced CV death and worsening HF events in HFrEF patients. It is unknown whether SGLT2 inhibitors work through glucose-dependent mechanism or it could have other effects not related to glucose on cardiovascular morbidity and mortality in diabetic patients. Its effect on silent ambulatory myocardial ischemia (SAMI) has not been reported yet. In this study we report the effect of SGLT2 inhibitors on (SAMI). Treating silent myocardial ischemia has a prognostic effect and may improve long term mortality of chronic ischemic heart disease (CIHD). Methods We enrolled 44 type 2 diabetic patients with proven stable coronary artery disease (CAD) and at least one episode of on silent ambulatory myocardial ischemia (SAMI) on ambulatory ECG monitoring. All of them were receiving optimal therapy for CIHD and type 2 DM. 22 patients were randomized to receive Dapagliflozin 5mg qd and the other 22 patients received placebo. Ambulatory monitoring was 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, HgbA1c level, and baseline serum cholesterol levels. Holters were read by a blinded cardiologist. Results The Dapagliflozin group experienced a significant reduction in the number of episodes of ST-segment depression compared with the placebo group. ST-segment depression completely resolved in 8 of 22 patients (36%) in the Dapagliflozin group versus 3 of 22 (13%) in the placebo group and the Dapagliflozin group exhibited a highly significant reduction in (SAMI) (P<0.001). By logistic regression, treatment with Dapagliflozin was an independent predictor of (SAMI) resolution. Conclusions Therapy with SGLT2 inhibitors in type2 DM patients results in reduction or resolution of (SAMI) recorded as episodes of ST-segment depression in ambulatory monitoring of the ECG. A larger study is required to confirm this theory and to see the effect of SAMI reduction on long term mortality of CIHD in diabetics. Possible mechanisms for this beneficial effects of SGLT2i includes: Reduction in oxygen supply-demand mismatch, improvement in cardiac microvascular function, modulation of cardiac energy metabolism, reduction in glucotoxicity, reduction in sympathetic nervous system activation and reduction in blood pressure. Funding Acknowledgement Type of funding source: None

Ambulatory monitoring of myocardial ischemia in the 21st century—an opportunity for high frequency QRS analysis

Ambulatory monitoring represents an effective tool for the assessment of silent and transient myocardial ischemia during routine daily activities. Incidence of silent ischemia can provide important prognostic information about patients with coronary artery disease or acute coronary syndrome, as well as about post-myocardial infarction patients. The current technological progress enables development of powerful and miniaturized wearable devices for Holter monitoring. Higher sampling rates, dynamic range, and extended computational and storage capacity allow for considering of more complex methodological solutions such as high-frequency QRS analysis for diagnosing myocardial ischemia. Implementation of suitable methodologies for advanced detection of myocardial ischemia into modern ambulatory monitoring devices creates the potential of making the ambulatory myocardial ischemia monitoring a valuable diagnostic tool in clinical practice.

EFFECT OF CLOPIDOGREL TREATMENT ON STRESS-INDUCED PLATELET ACTIVATION AND MYOCARDIAL ISCHEMIA IN ASPIRIN-TREATED PATIENTS WITH STABLE CORONARY ARTERY DISEASE

Stress may counteract responses to antiplatelet drug treatment. We investigated if adding clopidogrel to aspirin treatment could attenutate stress-induced platelet activation and myocardial ischemia in patients with coronary artery disease (CAD). Thirty-one male patients with documented CAD-treated with aspirin (75-160 mg daily) were randomized to co-treatment with clopidogrel (n = 16) or placebo (n = 15). A symptom-limited exercise test and 48-hour (h) Holter monitoring were performed before and after two weeks of double-blind treatment. Platelet function was assessed by flow cytometry and impedance aggregometry in whole blood. Exercise-induced and ambulatory ischemia was assessed from electrocardiographic (ECG) recordings. Clopidogrel treatment inhibited ADP-induced platelet P-selectin expression by 64% (22-87%), and attenuated the P-selectin response to thrombin (p < 0.001), and platelet aggregation induced by low-dose collagen (p < 0.01). Exercise ( approximately 110W) increased heart rate similarly, and caused approximately 1.8 mm ST-segment depression both before and after treatment. Exercise caused platelet activation, i.e. increased circulating activated single platelets and platelet-platelet aggregates, enhanced the in-vitro responsiveness to ADP or thrombin stimulation, and increased platelet-leukocyte aggregation. Clopidogrel inhibited ADP-induced platelet activation to a similar relative degree at rest and during exercise, but did not attenuate the platelet activating effect of exercise. Addition of clopidogrel to aspirin treatment did not attenuate either ambulatory or exercise-induced ischemia. In conclusion, adding clopidogrel to aspirin treatment inhibited platelet activation by both ADP, thrombin and collagen in vitro, but did not influence the prothrombotic responses to exercise. Intensified antiplatelet treatment did not reduce ECG signs of either exercise-induced or ambulatory myocardial ischemia.

Effect of clopidogrel treatment on stress-induced platelet activation and myocardial ischemia in aspirin-treated patients with stable coronary artery disease

Stress may counteract responses to antiplatelet drug treatment. We investigated if adding clopidogrel to aspirin treatment could attenutate stress-induced platelet activation and myocardial ischemia in patients with coronary artery disease (CAD). Thirty-one male patients with documented CAD-treated with aspirin (75-160 mg daily) were randomized to co-treatment with clopidogrel (n = 16) or placebo (n = 15). A symptom-limited exercise test and 48-hour (h) Holter monitoring were performed before and after two weeks of double-blind treatment. Platelet function was assessed by flow cytometry and impedance aggregometry in whole blood. Exercise-induced and ambulatory ischemia was assessed from electrocardiographic (ECG) recordings. Clopidogrel treatment inhibited ADP-induced platelet P-selectin expression by 64% (22-87%), and attenuated the P-selectin response to thrombin (p < 0.001), and platelet aggregation induced by low-dose collagen (p < 0.01). Exercise ( approximately 110W) increased heart rate similarly, and caused approximately 1.8 mm ST-segment depression both before and after treatment. Exercise caused platelet activation, i.e. increased circulating activated single platelets and platelet-platelet aggregates, enhanced the in-vitro responsiveness to ADP or thrombin stimulation, and increased platelet-leukocyte aggregation. Clopidogrel inhibited ADP-induced platelet activation to a similar relative degree at rest and during exercise, but did not attenuate the platelet activating effect of exercise. Addition of clopidogrel to aspirin treatment did not attenuate either ambulatory or exercise-induced ischemia. In conclusion, adding clopidogrel to aspirin treatment inhibited platelet activation by both ADP, thrombin and collagen in vitro, but did not influence the prothrombotic responses to exercise. Intensified antiplatelet treatment did not reduce ECG signs of either exercise-induced or ambulatory myocardial ischemia.

Medical treatment of myocardial ischemia in coronary artery disease: effect of drug regime and irregular dosing in the CAPE II trial

ObjectivesThe Circadian Anti-ischemia Program in Europe (CAPE II) compared the efficacy of amlodipine and diltiazem (Adizem XL) and the combination of amlodipine/atenolol and diltiazem (Adizem XL)/isosorbide 5-mononitrate on exercise and ambulatory myocardial ischemia during regular therapy and after omission of medication. BackgroundThe optimal medical therapy for ischemia suppression and the impact of irregular dosing using agents with different pharmacologic properties has not been established in patients with coronary disease. MethodsPatients with ≥4 ischemic episodes or ≥20 min of ST segment depression on 72-h electrocardiogram were randomized to amlodipine 10 mg once daily or diltiazem (Adizem XL) 300 mg once daily in a 14-week double-blind randomized multicountry study. In the second phase, atenolol 100 mg was added to amlodipine and isosorbide 5-mononitrate 100 mg to diltiazem (Adizem XL). Ambulatory monitoring (72 h) and exercise testing were repeated after both phases, on treatment and after a 24-h drug-free interval. ResultsBoth monotherapy with amlodipine and diltiazem (Adizem XL) were effective on symptoms and ambulatory and exercise ischemia. Combination therapy reduced ischemia further, with amlodipine/atenolol superior to diltiazem (Adizem XL)/isosorbide 5-mononitrate. Amlodipine/atenolol was significantly superior during the drug-free interval with maintenance of ischemia reduction. ConclusionsAmlodipine, with its intrinsically long half-life alone or together with beta-blocker, is likely to produce superior ischemia reduction in clinical practice when patients frequently forget to take medication or dose irregularly.

Prognostic implications of ambulatory myocardial ischemia and arrhythmias and relations to ischemia on exercise in chronic stable angina pectoris (the Angina Prognosis Study In Stockholm [APSIS

The prognostic significance of ambulatory ischemia, alone and in relation to ischemia during exercise was assessed in 686 patients (475 men) with chronic stable angina pectoris taking part in the Angina Prognosis Study In Stockholm (APSIS), who had 24-hour ambulatory electrocardiographic registrations and exercise tests at baseline (n = 678) and after 1 month (n = 607) of double-blind treatment with metoprolol or verapamil. Ambulatory electrocardiograms were analyzed for ventricular premature complexes and ST-segment depression. During a median follow-up of 40 months, 29 patients died of cardiovascular (CV) causes, 27 had a nonfatal myocardial infarction, and 89 underwent revascularization. Patients with CV death had more episodes (median 5 vs 1; p <0.01) and longer median duration (24 vs 3 minutes; p <0.01) of ST-segment depression than patients without events. For those who had undergone revascularization, the duration was also longer (12 vs 3 minutes; p <0.05). In a multivariate Cox model including sex, history of previous myocardial infarction, hypertension, and diabetes, the duration of ST-segment depression independently predicted CV death. When exercise testing was included, ambulatory ischemia carried additional prognostic information only among patients with ST-segment depression ≥2 mm during exercise. When the treatment given and treatment effects on ambulatory ischemia were added to the Cox model, no significant impact on prognosis was found. Ventricular premature complexes carried no prognostic information. Thus, in patients with stable angina pectoris, ischemia during ambulatory monitoring showed independent prognostic importance regarding CV death. Ambulatory electrocardiographic monitoring and exercise testing provide complementary information, but only among patients with marked ischemia during exercise. Treatment reduced ambulatory ischemia, but the short-term treatment effects did not significantly influence prognosis.

Treatment of stable angina.

Severe atherosclerotic narrowing of one or more coronary arteries is responsible for myocardial ischemia and angina pectoris in most patients with stable angina pectoris. The coronary arteries of patients with stable angina also contain many nonobstructive plaques, which are prone to fissures or rupture resulting in presentation of acute coronary syndromes (unstable angina, myocardial infarction, sudden ischemic death). In addition to symptomatic relief of symptoms and an increase in angina-free walking time with antianginal drugs or revascularization procedures, the recent emphasis of treatment has been to reduce adverse clinical outcomes (coronary death and myocardial infarction). The role of smoking cessation, aspirin, treatment of elevated lipids, and treatment of high blood pressure in all patients and of beta-blockers and angiotensin-converting enzyme inhibitors in patients with diminished systolic left ventricular systolic function in reducing adverse outcomes has been well established. What is unknown, however, is whether any anti-anginal drugs (beta-blockers, long-acting nitrates, calcium channel blockers) effect adverse outcomes in patients with stable angina pectoris. Recent trials evaluated the usefulness of suppression of ambulatory ischemia in patients with stable angina pectoris, but it remains to be established whether suppression of ambulatory myocardial ischemia with antianginal agents or revascularization therapy is superior to pharmacologic therapy targeting symptom relief. Patients who have refractory angina despite optimal medical treatment and are not candidates for revascularization procedures may be candidates for newer techniques of transmyocardial revascularization, enhanced external counterpulsation, spinal cord stimulation, or sympathectomy. The usefulness of these techniques, however, needs to be confirmed in large randomized clinical trials.

Comparison of controlled-onset, extended-release verapamil with amlodipine and amlodipine plus atenolol on exercise performance and ambulatory ischemia in patients with chronic stable angina pectoris

This multicenter, randomized, double-blind, parallel group, placebo lead-in, placebo-controlled study compared the antianginal and anti-ischemic effects of once-daily bedtime dosing of controlled-onset extended-release (COER-24) verapamil to a once-daily morning dosing of amlodipine ± atenolol in patients with chronic stable angina. A total of 551 patients with exercise-induced myocardial ischemia and evidence of coronary artery disease were randomized to a 4-week, forced-dose titration treatment period with (1) COER-24 verapamil 240 mg titrated to 480 mg at bedtime (n = 173), (2) amlodipine 5 mg titrated to 10 mg/day (n = 149), (3) amlodipine 5 mg (titrated to 10 mg) plus atenolol 50 mg/day in the a.m. (n = 154), or (4) placebo (n = 75). Treadmill exercise tolerance testing (standard Bruce protocol), and 48-hour ambulatory electrocardiographic (Holter) monitoring were performed at the end of placebo lead-in and double-blind treatment. Each active treatment significantly improved symptom-limited exercise duration and time to moderate angina (p ≤0.01 vs placebo). For patients with baseline ischemia, amlodipine resulted in a statistically significant increase in total duration of ischemic episodes compared with placebo, whereas COER-24 verapamil and amlodipine plus atenolol resulted in statistically significant decreases compared with placebo and amlodipine. Heart rate at onset of ischemic episodes and ST product were also significantly increased with amlodipine (p <0.05) compared with either COER-24 or amlodipine plus atenolol. COER-24 and amlodipine alone or in combination with atenolol improved exercise capacity in patients with angina pectoris. COER-24 verapamil monotherapy or amlodipine plus atenolol combination therapy were more effective than amlodipine monotherapy in decreasing ambulatory myocardial ischemia, especially during the hours of 6 a.m. to 12 noon.

Amlodipine Versus Diltiazem as Additional Antianginal Treatment to Atenolol

The antianginal efficacy and tolerability of amlodipine and diltiazem were compared in a double-blind randomized trial of 97 patients with angina resistant to atenolol alone. Both amlodipine and diltiazem significantly reduced the frequency of angina attacks (p <0.001) and glyceryl trinitrate consumption (p <0.05 to p <0.01). During Holter monitoring, both treatments reduced the overall frequency of ambulatory myocardial ischemia, although changes did not reach statistical significance. Exercise test parameters (total exercise time, time to angina, time to ST depression, and maximum ST depression) tended to improve with both treatments, but changes did not achieve statistical significance relative to baseline or to each other. Both drugs were generally well tolerated. Adverse events occurred in 15 patients in the amlodipine group (30%) and in 17 patients in the diltiazem group (36%), but patients taking diltiazem reported almost twice as many adverse events (30) patients taking amlodipine (18). Quality of life, as assessed by total Nottingham Health Profile Scores, was not significantly different between treatments. The addition of either once-daily amlodipine or twice-daily sustained release diltiazem improved symptoms in patients with angina resistant to atenolol alone, but diltiazem was associated with more frequent and more serious adverse events.

Effect of Morning Versus Evening Dosing of Diltiazem on Myocardial Ischemia Detected by Ambulatory Electrocardiographic Monitoring in Chronic Stable Angina Pectoris

Myocardial ischemia occurs frequently during daily life and has a circadian pattern similar to that reported for myocardial infarction and sudden death. Because of the increased risk of myocardial ischemia in the morning hours, it has been suggested that the administration of anti-ischemic medication before bedtime may be more effective than the traditional morning dosing. This randomized, double-blind, placebo-controlled, crossover study evaluated the effects of 480-mg/day diltiazem (given either in the a.m. or the p.m.) on myocardial ischemia using ambulatory electrocardiographic monitoring in 68 patients with chronic stable angina and ≥2 minutes of ischemia per 48 hours. During treatment with diltiazem, the duration and number of myocardial ischemic episodes were reduced by 45% (94 to 52 minutes, p <0.004) and by 40% (4.5 to 2.7 episodes, p <0.003), respectively. The duration and number of myocardial ischemic episodes during daytime (6 a.m. to 6 p.m.) hours were also reduced by 52% (74 to 36 minutes, p <0.002) and by 48% (3.1 to 1.6 episodes, p <0.001), respectively. There was no significant difference between a.m. and p.m. dosing. Morning ischemia (6 a.m. to noon), considered separately from daytime ischemia, was also significantly reduced by both a.m. and p.m. dosing regimens, with no difference between the regimens. The results of this study showed that both a.m. and p.m. dosing of long-acting diltiazem were equally effective in suppressing episodes of ambulatory myocardial ischemia at all times.

Circadian variation of ambulatory myocardial ischemia. Triggering by daily activities and evidence for an endogenous circadian component.

The morning peak in myocardial ischemia has been related to diurnal variations in physical and mental activities and to postural changes upon awakening. This study assesses (1) the effects of exogenous activity triggers at different times of the day and (2) the contribution of an endogenous (ie, activity- and posture-independent) circadian vulnerability for ambulatory ischemia. Sixty-three stable coronary artery disease patients underwent ambulatory ECG monitoring and completed a structured diary assessing physical and mental activities. During 2519 hours of observation, a morning increase in ischemia coincided with increases in physical and mental activities, and an evening decrease in ischemia coincided with a decline in activities. During the morning, ischemic versus ischemia-free periods were more likely to occur with high levels of physical activity (P < .001). High physical activity triggered ischemia to a lesser but still significant extent (P < .05) in the afternoon but not in the evening (P = NS). High levels of mental activity triggered ischemia significantly during the morning (P < .04) and evening (P < .04) but not in the afternoon. When a residualized score procedure was used to correct ischemic time for each patient's simultaneously measured activities, for hourly heart rates, or for activity-related heart rate fluctuations, the circadian variation in ischemia was still observed (P < .001), with a peak at 6 AM. A significant increase in ischemia occurred immediately after awakening (P < .05), but activity-adjusted increases in morning ischemia persisted (P < .05) for 2 hours after awakening. Exogenous factors (physical and mental activities) are most potent as triggers of ischemia during the morning hours, and the postural change after awakening contributes to the morning increase in ischemia. There is also evidence for an endogenous, activity-independent circadian influence on ischemic susceptibility that is independent of exogenous factors and that sustains the increase in ischemia upon awakening.

Increased heart rate response to laboratory-induced mental stress predicts frequency and duration of daily life ambulatory myocardial ischemia in patients with coronary artery disease

This study assessed the relation between hemodynamic data during a standardized mental stressor and ambulatory ischemia to determine if laboratory-induced responses could predict the magnitude of daily life ischemia. Forty-two men and 11 women, aged 46 to 79 years (mean 61), with coronary artery disease and exercise-induced ischemia were studied. All patients underwent 24- to 48-hour ambulatory electrocardiographic (ECG) monitoring (mean 43 ± 0.8 hours) and laboratory-induced mental stress using a public speaking task. Hemodynamic data were obtained at rest and every minute during mental stress. Thirty-three of 53 patients (62%) had at least 1 ischemic episode during ECG monitoring. In patients who had ambulatory ischemia, there was a mean number of 7.9 ± 1.8 episodes (mean total duration 79.2 ± 24.1 minutes/48 hours). Significant positive correlations were found for peak heart rate and changes in heart rate during mental stress and ambulatory ischemia (r = 0.353 to 0.462, p < 0.05) in patients who had ambulatory ischemia. There was no correlation between systolic blood pressure during mental stress and ambulatory ischemia. Results of this study demonstrate that heart rate response during laboratory-induced mental stress correlates with magnitude of ischemia on ambulatory ECG monitoring in patients with coronary artery disease.

Transient myocardial ischemia in patients with chronic angina: relation to heart rate changes and variability in exercise threshold

This study was undertaken to assess the relation of ambulatory myocardial ischemia to heart rate changes and variability in exercise threshold in patients with chronic angina. The study involved 118 patients with chronic angina and proven coronary artery disease who had a ‘positive’ exercise test result. All patients underwent a first exercise test followed by a 48-h period of ambulatory electrocardiographic monitoring. A second exercise test was performed 4 days later. A total of 101 ischemic episodes were recorded in 35 patients. The heart rate at the appearance of 1-mm ST segment depression during ambulatory electrocardiographic monitoring was ≥ 20 beats/min lower than that during exercise testing in 58 ischemic episodes (57%, Group A), 10–19 beats/min lower in 26 (26%, Group B), and ≤9 beats/min lower or higher in 17 (17%, Group C). Thirty-five percent of the Group A ischemic episodes, 69% of Group B, and 71% of Group C were preceded by an increase in heart rate of ≥10 beats/min. Thirty patients showed a variable exercise threshold. The prevalence of Group A and B ischemic episodes was not significantly different in patients with fixed or variable exercise threshold, whereas that of Group C episodes was 22% in the former and 0% in the latter ( P = 0.036). These results suggest that increased coronary tone may be one of the mechanisms contributing to modulate the occurrence of transient myocardial ischemia in most patients with chronic angina and transient myocardial ischemia at ambulatory electrocardiographic monitoring. This occurs regardless of whether the patients have a variable or fixed exercise threshold.

Transient Myocardial Ischemia after Myocardial Infarction

Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring in the detection of postinfarction myocardial ischemia. There appears to be a poor association between transient myocardial ischemia and severe left ventricular dysfunction. Transient myocardial ischemia has been shown to provide prognostic information in different subsets of patients with previous myocardial infarction, but there is considerable disagreement about how this is expressed in terms of cardiac events. The precise role of postinfarction ST-segment monitoring in clinical practice has yet to be established.

Effect of autonomic nervous system dysfunction on the circadian pattern of myocardial ischemia in diabetes mellitus

Objectives. The aim of this study was to determine the prevalence and characteristics of ambulatory myocardial ischemia in patients with diabetes mellitus and to delineate the relation between the presence and severity of autonomic nervous system dysfunction and the incidence and time of onset of myocardial ischemia.Background. Conflicting data exist with regard to the circadian pattern of myocardial infarction and other cardiovascular events, such as ambulatory ischemia, in diabetes.Methods. We performed ambulatory electrocardiographic monitoring in 60 patients with diabetes and coronary artery disease. Autonomic nervous system testing was performed in a subgroup of 25 patients with myocardial ischemia after discontinuation of all antianginal medications.Results. Thirty-eight of 60 patients had evidence of ambulatory ischemia; 91% of all ischemic episodes were asymptomatic. The 25 patients with ambulatory ischemia who underwent autonomic nervous system testing had a peak incidence of ischemia between 6 amand noon (46 of 133 ischemic episodes, p < 0.007), compared with the other three 6-h periods. Fifteen of the 25 patients had no or mild autonomic nervous system dysfunction and demonstrated a similar peak incidence of ischemia between 6 amand noon (p = 0.0009). However, the 10 patients with moderate to severe autonomic nervous system dysfunction did not experience a morning peak of ischemia, and the number of ischemic episodes was distributed evenly throughout the day (p = 0.4).Conclusions. Silent ischemia is highly prevalent among patients with diabetes and coronary artery disease. Time of onset of ischemia in diabetic patients follows a circadian distribution, with a peak incidence in the morning hours. However, patients with significant autonomic nervous system dysfunction did not demonstrate such a peak, suggesting that alterations in sympathovagal balance may have an effect on the circadian pattern of cardiovascular events.

Does ambulatory monitoring contribute to exercise testing and myocardial perfusion scintigraphy in the prediction of the extent of coronary artery disease in stable angina?

The role of ambulatory myocardial ischemia detection, in addition to exercise testing and myocardial perfusion scintigraphy, in the prediction of the angiographic severity of coronary artery disease in patients with stable angina was examined. Ninety-seven patients underwent ambulatory electrocardiographic monitoring, exercise testing with scintigraphy, and coronary angiography. In addition to the number of diseased vessels involved, proximal arterial segment and coronary artery jeopardy scores were calculated to evaluate the extent of disease and amount of myocardium at risk. Thirty patients (31%) had 1.8 ± 1.8 episodes/24 hours of ambulatory ischemia (94% of episodes were asymptomatic) and were similar to 67 without ambulatory ischemia in regard to clinical characteristics, left ventricular function and mean number of diseased vessels involved. Proximal arterial segment and coronary artery jeopardy scores were greater in: (1) 30 patients with versus 67 without ambulatory ischemia (3.3 ± 1.8 vs 1.9 ± 1.5 [p = 0.0002] and 6.6 ± 3.6 vs 5.0 ± 3.4 [p = 0.03], respectively); (2) 78 with versus 19 without a positive exercise test (2.6 ± 1.8 vs 1.4 ± 0.8 [p = 0.0001] and 6.1 ± 3.5 vs 3.0 ± 2.5 [p = 0.0003], respectively); and (3) 69 with versus 6 without a positive perfusion scan (2.4 ± 1.8 vs 1.0 ± 0 [p = 0.0008] and 5.5 ± 3.6 vs 2.3 ± 2.0 [p = 0.03], respectively). In multivariate analysis, ambulatory ischemia was the best predictor of the proximal segment score, whereas exercise testing and myocardial perfusion imaging were predictive of the coronary jeopardy score.

Characteristics and clinical significance of ambulatory myocardial ischemia in men and women in the general population presenting with angina pectoris

Objectives. The aim of this study was to determine the frequency and prognostic importance of ambulatory myocardial ischemia and its association with cardiovascular risk factors in men and women in the general population presenting for the first time with typical angina pectoris.Background. Previous studies in selected “low” and “high” risk patients with stable coronary heart disease report a wide range in the frequency of ischemia (24% to 82%) and there is no agreement about whether ambulatory ischemia is of prognostic importance for the generality of patients with stable angina.Methods. Consecutive patients ≤70 years of age from a randomly selected population with no previous coronary heart disease were assessed prospectively, and 96 patients with typical angina and 95 age-, gender- and practice-matched asymptomatic control subjects underwent 24-h ambulatory ST segment monitoring before antianginal therapy. All recordings were analyzed in blinded fashion. Follow-up evaluation of patients with angina to assess for revascularization, myocardial infarction and death was undertaken at a mean of 15.8 months (range 7 to 30) after the initial evaluation.Results. Transient episodes of ischemic ST segment depression were detected in 50 patients (52%) with angina and 9 control subjects (9%). In patients with angina, 159 episodes (71%) were silent, median duration of ischemia was 66 min (range 1 to 782) and mean ± SB ST depression was 2.4 ± 1.1 mm. In logistic regression analysis, serum cholesterol (p < 0.05) and ischemia on exercise (p < 0.01) were independently associated with the presence of ambulatory ischemia in men with angina, but only the latter was significant in women; this may reflect a different pathophysiologic basis for ambulatory ischemia in women. During follow-up, there were 29 events. Kaplan-Meier survival analysis revealed no significant difference in event-free survival between patients with angina who did and did not have ischemic episodes (66% vs. 72%, p = NS).Conclusions. This is the first study representative of new patients with angina pectoris in the general population and shows that ischemia during daily living activities is present in >50% of these patients but appears to be of no prognostic value.

Increased demand versus reduced supply and the circadian variations in ambulatory myocardial ischemia. Therapeutic implications.

HomeCirculationVol. 88, No. 1Increased demand versus reduced supply and the circadian variations in ambulatory myocardial ischemia. Therapeutic implications. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessAbstractPDF/EPUBIncreased demand versus reduced supply and the circadian variations in ambulatory myocardial ischemia. Therapeutic implications. P C Deedwania P C DeedwaniaP C Deedwania Search for more papers by this author Originally published1 Jul 1993https://doi.org/10.1161/01.CIR.88.1.328Circulation. 1993;88:328–331 Previous Back to top Next FiguresReferencesRelatedDetails July 1, 1993Vol 88, Issue 1Article InformationMetrics Download: 106 Copyright © 1993 by American Heart Associationhttps://doi.org/10.1161/01.CIR.88.1.328 Originally publishedJuly 1, 1993 PDF download

Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to anti-ischemic medication. The Angina and Silent Ischemia Study Group (ASIS)

Identification of whether episodes of ambulatory ischemia are caused by increases in myocardial oxygen demand or to episodic coronary vasoconstriction in patients with stable coronary disease may be important to guide selection of optimal anti-ischemic therapy and to gain insight into mechanisms responsible for adverse cardiac events. Mean minute heart rate activity during ambulatory ECG (AECG) monitoring was determined for 50 patients treated with propranolol, diltiazem, nifedipine, or placebo in a randomized, double-blind, crossover trial. Periods of heart rate increases of various magnitudes and durations and starting at various baseline heart rates on each therapy were identified throughout each 48-hour AECG recording, and the proportion of these periods associated with an ischemic episode was determined. The circadian variation of ischemic episodes categorized by the presence or absence of an increase in heart rate was analyzed. Eighty-one percent of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. The likelihood of developing ischemia associated with a heart rate increase was proportional to the magnitude and duration of the heart rate increase and the baseline heart rate before the increases in heart rate: likelihood ranged from 4% when the heart rate increased 5-9 beats per minute and lasted < 10 minutes to 60% when the heart rate increased > or = 20 beats per minute and lasted > or = 40 minutes. The likelihoods of developing ischemia based on changes in the heart rate variables were similar for each of the therapies. Propranolol therapy significantly reduced the magnitude and duration of heart rate increase and the baseline heart rate compared with therapy with placebo, diltiazem, or nifedipine (P < .001). Ischemic episodes associated with a heart rate increase displayed a daytime peak, whereas ischemia occurring without a heart rate increase occurred evenly throughout the day. Propranolol reduced the proportion of heart rate-related ischemic episodes and increased the proportion of non-heart rate-related episodes compared with placebo (P < .02), and nifedipine exerted the opposite effect (P = .005). Multivariate analysis indicated that the probability of developing ischemia was strongly associated with heart rate variables and was unaffected by time of day. Most episodes of ambulatory ischemia are associated with a preceding period of increased heart rate. The likelihood of developing ischemia is predicted by heart rate variables and unaffected by time of day. Anti-ischemic efficacy is generally a result of the medication's efficacy in reducing heart rate variables. A minority of ischemic episodes are not associated with preceding periods of increased heart rate, may be caused by episodic coronary vasoconstriction, and are more effectively reduced by nifedipine than propranolol.

Absence or Presence of Ambulatory Myocardial Ischemia in Patients with Stable Angina Pectoris and Positive Exercise Test: A Multivariate Statistical Analysis

In 166 patients with stable angina pectoris, positive exercise test and angiographically proven coronary artery disease, determinants for the absence or presence of myocardial ischemia during 24-hour ambulatory electrocardiographic (ECG) monitoring were analyzed. Variables were derived from clinical history, electrocardiogram at rest, exercise testing, ambulatory ECG monitoring as well as from cardiac catheterization and were compared in 103 patients with (group A) and 63 patients without (group B) ambulatory myocardial ischemia. In a multiple stepwise discriminant analysis, the most powerful determinants for the presence of ambulatory myocardial ischemia were: (1) R-wave amplitude during ambulatory ECG monitoring (17.2 ± 5.3 vs. 13.8 ±4.6 mm in group A vs. group B; p < 0.001); (2) heart rate at onset of S-T-segment depression during exercise testing (112 ±17 vs. 121 ± 16 beats/ min; p < 0.001), and (3) presence of a stenosis >70% in the left anterior descending coronary artery (76 vs. 59% of the patients; p < 0.05). Furthermore, heart rates during ambulatory ECG monitoring were significantly higher in group A as compared to group B during the morning hours and in the late afternoon; during these periods, ambulatory myocardial ischemia showed a parallel increase. This study shows that the absence or presence of myocardial ischemia during ambulatory ECG monitoring is influenced by the ischemic threshold during exercise testing and involvement of the left anterior descending artery; however, R-wave amplitude and circadian heart rate profile during ambulatory ECG monitoring also play important roles.