Transient Myocardial Ischemia In Patients Research Articles

Efficacy of add-on Danhong injection in patients with unstable angina pectoris: A double-blind, randomized, placebo-controlled, multicenter clinical trial

Ethnopharmacological relevanceDanhong injection (DHI)，which is extracted from Salviae miltiorrhizae and Flos carthami，has been widely prescribed to patients with unstable angina pectoris (UAP) in China. However, a high quality clinical trial is needed. Aim of the studyTo determine whether DHI can relieve symptoms of transient myocardial ischemia in patients with unstable angina pectoris. Materials and methodsA double-blind, placebo-controlled, randomized clinical trial was conducted in nine hospitals in China. Inpatients with UAP with blood stasis syndrome (BSS) were randomized 1:1 to receive DHI or placebo. The primary outcome was improvement rate in the quantification score of angina pectoris. Secondary outcomes included blood stasis syndrome scale, nitrates use, electrocardiogram recordings, PCI procedures, Seattle Angina Questionnaire (SAQ) and biochemical indexes. Results160 participants were enrolled and 159 were analyzed. There was no significant difference in primary outcome as compared with control group at the end of 7-day treatment, but significant difference at 28-day follow up (70.53% [95% CI, 59.97–81.09%] and 54.34% [95% CI, 42.68–65.99%]; P = 0.0423). The BSS score was significantly lower in the DHI group than that in the control group at day 28 (6.49 [6.96] vs 10.53 [9.07], P = 0.0034). In addition, DHI was significantly superior to placebo in the angina stability score of SAQ (91.10 [17.37] versus 78.21 [22.08], P < 0.001). There were no significant differences in other secondary outcome measures. ConclusionsA small decrease in the total effective rate and an increase in the angina stability score were observed 28 days after implementation of DHI in UAP with a total blood stasis syndrome score decrease, but the efficacy was not observed at day 7. The findings support that DHI may potentially relieve clinical symptoms and can benefit angina stability. Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02007187.

Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.

BackgroundThe response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing.Methods and ResultsA total of 356 patients with stable coronary artery disease underwent 99mTc‐sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD34+ and CD34+/chemokine (C‐X‐C motif) receptor 4 PCs were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal‐derived factor‐1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/chemokine (C‐X‐C motif) receptor 4 (−18%, P=0.01) after stress that was inversely correlated with the magnitude of ischemia (r=−0.19, P=0.003). In contrast, patients without ExMI had an increase in CD34+/chemokine (C‐X‐C motif) receptor 4 (14.7%, P=0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P<0.001) in all patients undergoing exercise stress testing regardless of ischemia. However, the change in stromal‐derived factor‐1α level correlated inversely with the change in PC counts in those with ExMI (P=0.03), suggesting a greater decrease in PCs in those with a greater change in stromal‐derived factor‐1α level with exercise.ConclusionsExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C‐X‐C motif) receptor 4 PCs, likely attributable, at least in part, to stromal‐derived factor‐1α–mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.

Nardilysin is a promising biomarker for the early diagnosis of acute coronary syndrome

BackgroundBiomarkers for detection of transient myocardial ischemia in patients with unstable angina (UA) or for very early diagnosis of acute myocardial infarction (AMI) are not currently available. Methods and resultsWe performed two sequential screenings of autoantibodies elevated shortly after the onset of acute coronary syndrome (ACS), and focused on metalloendopeptidase nardilysin (NRDC) among 19 identified candidate antigens. In a retrospective analysis among 93 ACS and 117 non-ACS patients, the serum level of NRDC was significantly increased in patients with ACS compared with that in patients with non-ACS (2073.5±189.8pg/ml versus 775.7±63.4pg/ml, P<0.0001). The area under the curve of NRDC for the diagnosis of ACS was 0.822 by the receiver operating characteristic curves analysis. In the time course analysis in 43 consecutive ACS patients (AMI: N=35 and UA: N=8), serum concentration of NRDC was significantly increased even in UA patients with a peak serum NRDC levels reached at admission both in AMI and UA patients. In a mouse model of AMI, we found an acute increase in serum NRDC and reduced NRDC expression in ischemic regions shortly after coronary artery ligation. NRDC expression was also reduced in infarcted regions in human autopsy samples from AMI patients. Moreover, the short treatment of primary culture of rat cardiomyocytes with H2O2 or A23187 induced NRDC secretion without cell toxicity. ConclusionNRDC is a promising biomarker for the early detection of ACS, even in UA patients without elevation of necrosis markers.

Effects of neuropeptide Y on coronary artery vasomotion in patients with microvascular angina

BackgroundPatients with microvascular angina (exertional angina, positive exercise tests and normal coronary arteriograms) usually have a reduced coronary blood flow reserve. Neuropeptide Y (NPY) is a potent endogenous vasoconstrictor involved in modulation of coronary vasomotor tone and may play a role in microvascular angina. MethodsWe compared the effects of NPY (0.2–1.0pmol/kg, intracoronary) on the vasomotor response of proximal and distal segments of the coronary arteries in 7 patients with microvascular angina, 9 with chronic stable angina, and 9 control individuals. The coronary response to the administration of ergonovine was also assessed in 9 other patients with microvascular angina. Computerized coronary artery diameter measurements were carried out before (baseline) and after the administration of the vasoactive agents. ResultsMean baseline coronary lumen diameters were similar in control, microvascular angina, and coronary artery disease patients. NPY constricted proximal coronary segments by 8±2%, 5±2% and 6±3% and distal segments by 14±2%, 11±2% and 10±2% in control, microvascular angina, and coronary artery disease patients, respectively (p=NS between groups). In patients with microvascular angina, ergonovine constricted proximal coronary segments by 7±1.5% and distal segments by 12.5±3% (p=NS vs. NPY). During NPY administration four microvascular angina patients developed chest pain, ST segment depression, and a marked lengthening of the contrast medium run off, in the absence of epicardial coronary artery spasm. Control individuals and coronary artery disease patients did not experience chest pain, ST segment shifts, or lengthening of the run off during NPY administration. Ergonovine administration caused chest pain and lengthening of the contrast run-off, in the absence of epicardial coronary artery spasm, in one microvascular angina patient. ConclusionsExogenous NPY causes mild epicardial coronary artery constriction which is similar in patients with non-cardiac chest pain, microvascular angina and coronary artery disease. Myocardial ischemia and marked lengthening of the contrast run off in response to NPY occurred in microvascular angina patients but not in control or coronary artery disease patients. An abnormal constrictor response to NPY at the microcirculation level could be the mechanism underlying the ischemic manifestations observed in patients with microvascular angina. Condensed abstract (table of contents)The vasomotor response of proximal and distal coronary artery segments was studied in twenty five patients: 7 microvascular angina, 9 chronic stable angina, and 9 control subjects. Computerized measurements of coronary diameters were carried out before and after the intracoronary administration of neuropeptide Y (NPY) and ergonovine. Constriction of epicardial arteries in response to NPY was mild and not significantly different in control, microvascular angina and coronary artery disease patients. Ergonovine-induced epicardial coronary artery constriction was similar to that of NPY. However, NPY caused transient myocardial ischemia in patients with microvascular angina (probably through constriction of the small intramyocardial vessels), but not in control subjects or coronary artery disease patients.

Abstract P326: Myocardial Ischemia and Mobilization of Circulating Progenitor Cells

Background: Circulating progenitor cells (CPCs) are involved in vascular repair and regeneration. Low levels of CPCs in patients with CAD have been linked to adverse cardiovascular outcomes. The response of CPCs to transient myocardial ischemia in patients with CAD has not been studied before. We aimed to investigate the CPC response to exercise provoked myocardial ischemia (demand ischemia), and compare it to myocardial ischemia detected during pharmacological stress test (flow mismatch). Methods: 570 patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during exercise (69%), or pharmacological stress (31%). myocardial ischemia was defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. CD34+ CPCs were enumerated by flow cytometry at rest and 30 min after stress testing. The change in CPC count was compared between patients with and without myocardial ischemia using mixed linear models. Results: Mean age was 63±9 years, 76% males, 36% with previous myocardial infarction. The incidence of myocardial ischemia was 31% and 41% during exercise and pharmacological stress test, respectively. No difference was observed in resting CPC between patients undergoing exercise vs pharmacological stress test, nor between patients with or without myocardial ischemia. However, patients who developed myocardial ischemia during exercise stress had a significant decrease in CPC with stress in comparison to those without myocardial ischemia (-12% vs 4%, respectively, p=0.006). Furthermore, the change in CPCs was inversely correlated with the magnitude of myocardial ischemia (R=-0.13, p=0.023), suggesting a greater CPC reduction with larger ischemic burden. These findings remained significant even after adjustment for age, gender, race, BMI, previous myocardial infarction, resting levels of CPCs and hematocrit change with stress. No difference was observed in CPC response to pharmacological stress test (change of -1% vs 3%, for patients with and without myocardial ischemia, respectively, p=0.96). Conclusion: Exercise stress-induced myocardial ischemia is associated with a decrease in CPC counts, likely due to increased homing of stem cells to the ischemic myocardium. Whether the extent of CPC uptake has prognostic implication, or whether the CPC response can be altered with intervention needs further investigation.

Association of sustained ventricular arrhythmias with transient myocardial ischemia in patients hospitalized with acute coronary syndrome

Background: Myocardial ischemia is a known substrate for the development of malignant ventricular arrhythmias. Purpose: The purpose of this secondary analysis was to determine the occurrence of ventricular arrhythmias at the time of transient myocardial ischemia in patients hospitalized with acute coronary syndrome (ACS). Methods: Patients who presented to the emergency department at the San Francisco Medical Center, University of California, San Francisco, Calif, with chest pain or anginal equivalent were enrolled in a prospective study involving 12-lead electrocardiogram Holter ST-segment monitoring. Transient myocardial ischemia was defined as a change in ST-segment amplitude of 200 lV or greater in 1 lead or more or 100 lV or greater in 2 leads or more, lasting for at least 60 seconds. An associated arrhythmia was defined as sustained ventricular tachycardia (VT) or ventricular fibrillation during or 10 minutes before or after an ST event. Results: One thousand one hundred thirty-six (emergency department) patients evaluated for chest pain/anginal equivalent were monitored for 24 hours. Of these, 270 patients were hospitalized with a diagnosis of ACS (acute myocardial infarction, n = 95; unstable angina, n = 175). Of the 270 patients, 31 (11%) had a total of 44 STevents (number, 1.4F 1.6; range, 1-10; duration, 27 F 15 minutes). Of the 44 ST events, 24 (55%) had an isolated premature ventricular contraction or ventricular couplet; however, none had associated sustained VT/ventricular fibrillation. The figure below shows the longest sustained arrhythmia (9-beat VT) among the 31 patients, and it occurred in the absence of electrocardiogram signs of ischemia. Conclusions:With current medical management, frequency of ischemia is low in patients hospitalized with ACS, and malignant ventricular arrhythmias were not observed in this cohort.

The R-on-T phenomenon in patients with implantable cardioverter-defibrillators

The R-on-T phenomenon, first characterized by Smirk,1 describes superimposition of a ventricular depolarization (R wave) on the T wave of the preceding beat. Critically coupled ventricular premature complexes (VPCs) are able to induce sustained ventricular tachyarrhythmias (VTs); referring to this property, R-on-T VPCs are generally considered to be particularly hazardous. Conflicting data exist concerning the significance of R-on-T VPCs in acute myocardial infarction.2 Recent studies found an increased incidence of R-on-T VPCs in patients with acute myocardial infarction complicated by spontaneous ventricular fibrillation.3,4 Chiladakis and coworkers,5 however, observed R-on-T VPCs only rarely in 93 patients with thrombolyzed myocardial infarction. In contrast, Turitto et al6 assessed increased R-on-T induction of VTs during transient myocardial ischemia in patients with variant angina. Post-myocardial infarction R-on-T VPCs and other ventricular arrhythmias are of prognostic significance,7 although their classification as the most hazardous arrhythmias in the historical Lown grading system does not appear to be justified.8 In a multivariate analysis, the occurrence of R-on-T VPCs after myocardial infarction was found not to be prognostically significant, whereas QT dispersion >100 ms was strongly related to postinfarction mortality.9 Implantable cardioverter-defibrillators (ICDs) are capable of storing arrhythmia-related intracardiac electrograms and allow unique insight into the mode of onset of VTs, which has been analyzed in a number of studies.10–13 This option, however, until now has not been utilized with respect to R-on-T VPCs.

Association of Transient Myocardial Ischemia With Adverse In-Hospital Outcomes for Angina Patients Treated in a Telemetry Unit or a Coronary Care Unit

Little is known about the frequency or consequences of transient myocardial ischemia in patients admitted to a telemetry unit for treatment of angina. To compare the rate of transient myocardial ischemia in a group of patients with angina treated in a telemetry unit with the rate in a similar group treated in a coronary care unit and to determine if transient myocardial ischemia is associated with adverse in-hospital outcomes. Continuous 12-lead electrocardiography was used to monitor changes in the ST segment in 186 patients in the coronary care unit (1994-1996) and 186 patients in the telemetry unit (1997-2000). Transient myocardial ischemia was defined as a change from baseline of 100 microV or more in the ST segment in 1 or more leads lasting 60 seconds or longer The rate of transient myocardial ischemia was 15% for patients in the telemetry unit and 19% for patients in the coronary care unit. Regardless of hospital unit, patients with transient myocardial ischemia were more likely than those without this complication to experience death or acute myocardial infarction after hospital admission. Most patients did not experience signs or symptoms during transient myocardial ischemia: 71% of patients in the telemetry unit versus 58% of patients in the coronary care unit (P =.28). Transient myocardial ischemia is common among patients with angina treated in a telemetry unit. ST-segment monitoring may be useful for detecting patients with ischemia who may benefit from more aggressive therapies aimed at abolishing ongoing ischemia.

Peak time of occurrence of myocardial ischemia in the coronary care unit

The onset of acute myocardial infarction and sudden cardiac death has a circadian variation, with the peak occurrence between 6 AM and 12 noon. To determine if a circadian variation exists for transient myocardial ischemia in patients admitted to the coronary care unit with unstable coronary syndromes. The sample was selected from patients enrolled in a prospective clinical trial who had had ST-segment monitoring for at least 24 hours and had had at least one episode of transient ischemia. The 24-hour day was divided into 6-hour periods, and comparisons were made between the 4 periods. In 99 patients, 61 with acute myocardial infarction and 38 with unstable angina, a total of 264 (mean +/- SD, 3 +/- 2) ischemic events occurred. Patients were more likely to have ischemic events between 6 AM and noon than at other times. A greater proportion of patients complained of chest pain between 6 AM and noon than during the other 3 periods. However, more than half the patients never complained of chest pain during ischemia between 6 AM and noon. Transient ischemia occurs throughout the 24-hour day; however, ischemia occurs more often between 6 AM and noon. An important nursing intervention for detecting ischemia is continuous electrocardiographic monitoring of the ST segment, even during routine nursing care activities, which are often at a peak during the vulnerable morning hours.

Association of physical fitness and transient myocardial ischemia in patients with coronary artery disease.

To examine the relationship between physical fitness and transient myocardial ischemia (TMI) in the laboratory and during daily life, in a sample of coronary patients with a recent positive exercise test. 47 patients with coronary disease (CAD) participated in laboratory mental and exercise stress testing and 48-hour outpatient Holter monitoring after being withdrawn from ant-ischemic medications. During laboratory testing, left ventricular performance was assessed by radionuclide ventriculography. Physical fitness was assessed by measurement of oxygen consumption during symptom-limited exercise treadmill testing. Higher physical fitness subjects were less likely to exhibit wall-motion abnormalities in response to mental stress (P < .05), and to exercise stress (P < .05) testing. They also had smaller decreases in left ventricular ejection fraction (LVEF) in response to mental stress than less fit subjects (P .056), and exhibited a mean increase in LVEF during exercise, compared to the less fit subjects who exhibited a decrease in LVEF (P < .02). Moreover, higher fit subjects exhibited fewer episodes of TMI (P < .04), for a shorter duration (P < .04), and less total ischemic burden (P < .04) during Holter monitoring. These findings suggest that within a population of CAD patients, higher levels of physical fitness are associated with less TMI assessed in the laboratory and during routine activities of daily living.

Nifedipine in Ischemic Heart Disease

Until the 1980s, Prinzmetal’s variant angina was difficult to treat—nitrates and β-blockers usually did not control symptoms or signs of ischemia. In 1980, Antman et al1 reported the first clinical experience in the United States of the use of nifedipine in patients with Prinzmetal’s angina. They used nifedipine capsules to treat 127 patients with Prinzmetal’s angina, which reduced the weekly occurrences of angina from 16 to 2, reduced nitroglycerin requirements, completely controlled angina in 63% of patients, and reduced the frequency of angina by at least 50% in 87% of cases. Since that time, a number of trials with different calcium channel blockers, including nifedipine, diltiazem, verapamil, amlodipine, and others, have consistently shown that these agents are efficacious in reducing the morbidity of Prinzmetal’s variant angina.2 Additional studies showed that calcium channel blockers, including nifedipine, were effective in patients with chronic stable angina pectoris3 ; they not only reduced symptoms but also reduced objective evidence of ischemia on exercise treadmill tests,4 5 reduced ST-segment changes on ambulatory ECG monitoring,6 increased coronary artery blood flow,7 8 9 and improved ventricular dysfunction associated with ischemia.10 Numerous studies showed that the calcium channel blockers were effective as antihypertensive agents and lacked many of the side effects of diuretics and β-blockers.11 Of course, all drugs have limits, and not all cardiovascular drugs are appropriate for all cardiovascular situations. Calcium channel blockers are no exception. In 1984, Muller et al11 showed for the first time that nifedipine capsules did not reduce the size of myocardial infarction (MI) and did not prevent patients with threatened MIs from infarcting. Patients who received nifedipine capsules in the setting of myocardial infarction had a higher 2-week mortality (7.5%) versus placebo (2.3%) but 6-month mortality was similar between nifedipine-treated (10.8%) and …

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.

Amlodipine reduces transient myocardial ischemia in patients with coronary artery disease: Double-blind circadian anti-ischemia program in Europe (CAPE trial)

Objectives. This study was carried out to determine the effect of the once-daily calcium channel blocking agent amlodipine (halflife 35 to 50 h) on the circadian pattern of myocardial ischemia in patients with chronic stable angina.Background. Myocardial ischemia during normal daily life, both symptomatic and asymptomatic, has been associated with increased risk of cardiovascular morbidity and mortality, and the circadian pattern parallels that for myocardial infarction and sudden death.Methods. The Circadian Anti-Ischemia Program in Europe (CAPE) was a large, 10-week international (63 sites), doubleblind, parallel study. After a 2-week, single-Mind placebo phase, during which stable doses of antianginal treatment were maintained (beta-adrenergic blocking agents in 65% of patients), patients with chronic stable angina with at least three attacks of angina per week, with at least four ischemic episodes or ≥ 20 min of ST segment depression in 48 h of Holter monitoring, were randomized to receive treatment with either 5 mg/day of amlodipine or placebo (2:1 randomization). The dose was increased to 10 mg/day after 4 weeks. During week 7 of treatment, 48-h ambulatory ECG monitoring was repeated.Results. Three hundred fifteen of 1,160 patients screened were eligible, and 250 had complete evaluable data. Compared with placebo, amlodipine significantly reduced both the frequency of ST segment depression episodes (60% for amlodipine vs. 44% for placebo, p = 0.025) and total integrated ST ischemic area (62% mm-min vs. 50% mm-min, p = 0.042). Amlodipine reduced ischemia over the 24 h with the intrinsic circadian pattern maintained. In addition, diary data showed a significant reduction in angina (70% for amlodipine vs. 44% for placebo, p = 0.0001) and in nitroglycerin consumption (67% vs. 22%, respectively, p = 0.0006). Amlodipine and placebo demonstrated similar safety profiles (adverse events 17.3% for amlodipine and 13.3% for placebo; discontinuation rates due to adverse events were 2% vs. 4.4%, respectively).Conclusions. Once-daily amlodipiae, when added to background treatment, significantly reduced both symptomatic and asymptomatic ischemic events over 24 h in patients with chronic stable angina.

Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina

Objectives. This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.Background. Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown.Methods. Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay.Results. One hundred fifty-four patients (30 women, mean [±SEM] age 58.3 ± 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 ± 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01).Conclusions. The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia.

Variability of episodic ST segment depression in chronic stable angina: Implications for individual and group trials of therapeutic efficacy

Objectives. This study was conducted to quantify the variability of episodic ST segment depression in chronic stable angina and enable assessment of the impact of interventions in individual patients and clinical trials.Background. Episodic myoeardial ischemia can be detected by ST segment depression on ambulatory electrocardiographic (ECG) monitoring and may be important for the assessment of outcome. Variability of the number and duration of episodes has important unplications for monitoring and therapeutic strategies.Methods. We studied 36 patients, aged 37 to 77 years (median 60), with stable angina and coronary artery disease by serial ambulatory ECG monitoring for a total of 415 days. A nested analysis of variance was carried out to assess the sources of spontaneous variation, and power function analyses were performed.Results. During 415 days of monitoring, 1,882 episodes of ST segment depression were detected (mean frequency ± SD, 4.5 ±4.1/day, duration 67 ± 87 min/day, 25% in association with pain). Considerable variability was found within and between patients for both the number and the duration of ischemic episodes. For a patient monitored for 24 h before and after treatment, an 81% reduction in the number of episodes would be required to show a significant benefit; if monitoring were performed for 4 days four times before and after therapy, a 46% decrease would be significant. In clinical trials, a true reduction of ≥15% in ischemic episodes is required to have sufficient power to obtain statistical significance.Conclusions. The natural variability of transient myocardial ischemia in patients with chronic stable angina can be quantified and this information used to study the effectiveness of interventions in both individual patients and clinical trials.

Prevalence of pseudoischemic ST-segment changes during ambulatory electrocardiographic monitoring

Ambulatory electrocardiographic monitoring (AEM) is frequently used to record ST-segment changes suggesting transient myocardial ischemia in patients with coronary artery disease. 1 AEM has also been used to assess the efficacy of antiischemic therapy. 2–6 The value of AEM for ischemia monitoring is dependent on the ST-segment changes detected being reliable markers for transient myocardial ischemia. Frequently, before AEM and exercise treadmill tests, technicians perform provocative maneuvers (i.e., position change, hyperventilation and Valsalva maneuver) to elicit ST-segment or T-wave changes that may interfere with electrocardiographic determinations of transient myocardial ischemia. Despite this practice, there are few studies examining the incidence of these electrocardiographic artifacts. One such study found that in subjects without cardiac disease, ST-segment depression or T-wave changes suggesting ischemia seldom occurred. 7 The aim of this study was to determine the prevalence of these pseudoischemic ST-segment or T-wave changes in cardiac patients referred for AEM.

Ambulatory Electrocardiography Evaluation of Asymptomatic, Unstable, and Stable Coronary Artery Disease Patients for Myocardial Ischemia

Transient episodes of myocardial ischemia can be reliably detected by AEM in patients with known CAD. AEM appears to be particularly useful for patients in whom symptom control has been achieved with conventional antianginal drugs because many of these patients (up to 50%) continue to have residual silent ischemia that would otherwise remain undetected. Despite the lack of symptoms, numerous studies in patients with stable and unstable coronary syndromes have shown that the presence of silent ischemia during AEM is associated with an increased risk of subsequent coronary events and cardiac death. Although Holter monitoring is a practical and reliable tool for prolonged evaluation of myocardial ischemia, its routine use can not be advocated until its clinical role has been clearly defined in the ongoing large prospective studies.

Pathophysiology of ischemia in patients with coronary artery disease

C ORONARY atherosclerosis is characterized by subintimal thickening that leads to plaque formation and stenosis.’ During the progression of this pathology in the large epicardial arteries, episodes of transient myocardial ischemia occur and each event is characterized by a reversible decrease in regional myocardial oxygen concentration that characteristically effects a segment of the left ventricle.2 This leads to the failure of systolic and diastolic muscle function, varying degrees of left ventricular failure, and profound metabolic disturbances. This functional expression of coronary artery disease can be induced by provoking disturbances in coronary blood supply and/or increases in myocardial demand for oxygen (ie, during exercise); ischemia also occurs during the activities of everyday life and it can precede damaging clinical events such as acute myocardial infarction, pulmonary edema, and sudden death.?,’ Transient myocardial ischemia in patients with obstructive coronary artery disease occurs in many different clinical syndromes (eg, chronic stable angina, unstable angina, and after myocardial infarction) and its presence always indicates the increased risk of adverse coronary events.2-7 In the majority of patients with ischemia and proven coronary artery disease, there are atherosclerotic stenoses that severely reduce crosssectional area in a segment of at least one epicardial artery. In these circumstances, standardized exercise protocols can provoke and reproduce ischemia and angina at a reproducible level of exercise. These clinical features have nurtured the belief that coronary blood supply is fixed and myocardial demand increases to cause ischemia. Although this concept is useful when considering the benefits of beta-adrenoreceptor blocking drugs, coronary angioplasty and by-pass graft surgery, these therapies probably do not address the disturbed biology of developing atherosclerotic lesions. Clinical studies of transient myocardial ischemia during daily life,8*9 studies of regional myocardial blood flow before and during ischemia”‘-I5 and studies of coronary vasomotion during cardiac catheterization all highlight the active role of the diseased epicardial arteries in causing transient ischemia.16-r9 An enhanced understanding of the biology of atherosclerotic stenoses has clarified pathophysiological mechanisms of myocardial ischemia and has suggested new directions in the development of therapies aimed at physical regression of coronary atherosclerosis and the control of constriction and thrombosis.20.2i This article will focus on transient myocardial ischemia by examining new clinical characteristics and pathogenic mechanisms rather than simply evaluating diagnostic techniques. It will discuss new clinical information about the biology of atherosclerosis and stenoses in relation to the occurrence of ischemia and adverse clinical outcomes. New insights from basic research will only be discussed as they provide fresh directions for clinical research. This paper will focus on transient ischemia rather than myocardial infarction or sudden death and will try to explore the relationship between coronary atherosclerosis, coronary vasoconstriction, and thrombosis as these problems occur in patients.

Plasma levels of atrial natriuretic peptide and tumor necrosis factor-α during transient myocardial ischemia in patients with stable angina

Plasma levels of atrial natriuretic peptide and tumor necrosis factor-α during transient myocardial ischemia in patients with stable angina

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 (>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.