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Emergency room visit and re-Hospitalization within 30 days leads to significant health care burden in patients with symptomatic atrial fibrillation (AFIB). We postulated that an Atrial Fibrillation Wellness Program (AFWP) by initiating risk factor modification along with a specific resource for

Silent myocardial ischemia is defined as objective documentation of myocardial ischemia in the absence of angina or anginal equivalents. Since its original description in the 1970s, it has undergone intensive investigation, and its clinical significance is now well established. This review will serve as an update on the pathophysiology, detection, prevalence, prognosis, and treatment of silent ischemia in both asymptomatic patients and those with angina, whether stable or unstable. ### Pain Studies No discussion of silent ischemia is complete without consideration of the cardiac pain mechanism. Although much has been learned about this subject, much is still uncertain. The afferent fibers that run in the cardiac sympathetic nerves are usually thought of as the essential pathway for the transmission of cardiac pain (Figure 1). The atria and ventricles are abundantly supplied with sympathetic sensory innervation; from the heart, the sensory nerve endings connect to afferent fibers in cardiac nerve bundles, which in turn connect to the upper 5 thoracic sympathetic ganglia and the upper 5 thoracic dorsal roots of the spinal cord. Within the spinal cord, impulses mediated by this sympathetic afferent route probably converge with impulses from somatic thoracic structures onto the same ascending spinal neurons. This would be the basis for cardiac pain referred to the chest, wall, arm, back etc. In addition to this “convergence-projection theory,” the contribution of vagal afferent fibers must be acknowledged for an explanation of cardiac pain referred to the jaw and neck. How these vagal fibers are activated remains unclear. Furthermore, somatic localization of ischemic pain cannot predict the site of myocardial ischemia (anterior, inferior, or lateral) from one patient to the next. Figure 1. Mechanisms of cardiac pain. From Droste and Roskamm (used with permission).4 The actual “trigger” that stimulates the sensory nerve endings remains elusive. If a chemical pain stimulus is involved, …

Improvements in coronary stents have made planned direct coronary stenting technically feasible, though safety, acute success, cost-effectiveness, and long-term results remain to be determined. Sequential patients eligible for direct stenting were prospectively characterized and treated with either direct or secondary stenting. Major adverse cardiovascular events (MACE) such as cardiac death, myocardial infarction (MI), target vessel ischemia, or revascularization (TVR) were followed for 6 months post-PCI. Enrollment included 128 direct (1.38 lesions/patient) and 69 secondary (1.39 lesions/patient) stented patients. Direct stenting was successful in 99% (with 5% crossover to secondary stenting) without major procedural complications and with a similar rate of vessel wall dissection or no-reflow phenomenon (2.3% vs. 2.1%; P > 0.05) as the secondary stenting group. There was a trend toward less postprocedural CPK-MB elevation in the nonacute MI patients with direct vs. secondary stenting (3% vs. 11%, respectively). At 6 months, there were no statistically significant differences in overall MACE. Direct stenting has a high success rate, low complication rate, and durable long-term results. Procedural cost and time savings, less contrast use and radiation exposure make direct stenting attractive in properly selected patients. Cathet Cardiovasc Intervent 2001;54:158–163. © 2001 Wiley-Liss, Inc.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for coronary artery disease. The mechanism of action is felt to be hemodynamic. The complex hemody namic effects have been simply quantified by calculating a previously described effectiveness ratio (ER). The EECP Clinical Consortium, a clinical registry of 37 centers, prospectively enrolled 395 chronic stable angina patients (79 women, 316 men, mean age 66 years) to examine the relation of the ER to posttreatment improvement in Canadian Cardiovascular Society angina class (CCS). Women and the elderly underwent planned subgroup analysis. The ER was calcu lated during the first and last hours of a 35-hour course of EECP treatment. After EECP, CCS improved by at least 1 class in 88% of patients, 87% of men and 92% of women (p = NS), and in 89% of patients ≤ 66 years and 88% of patients > 66 years old (p = NS). The initial and final ER were similar in patients with and without improvement in CCS. Significant first-hour ER differences were seen between men and women (0.96 ±0.03 vs 0.76 ±0.04, p < 0.005), and between ages ≤ 66 and > 66 years old (1.04 ±0.04 vs 0.81 ±0.03, p < 0.0001). However, all subgroups responded equally well to EECP treatment. EECP is effective in improving CCS in chronic stable angina patients; it has comparable effects in men and women and across a broad range of ages. The hemodynamic effect of EECP (ER) does not predict improvement in CCS and may indicate that other factors, such as neuro- hormonal changes, may have a significant role in mediating the observed EECP benefits.

Enhanced external counterpulsation (EECP) is a noninvasive technique that has shown promise in the treatment of ischemic coronary artery disease. Patients undergoing EECP were tested for alterations in psychosocial state associated with treatment. Overall perception of health and quality of life improved with EECP. There was also significant improvement in levels of depression, anxiety, and somatization but no change in levels of anger or hostility. On most measures, change was more significant for subjects who showed objective evidence of resolution of ischemia. Given the known predictive relationship between depression and mortality from cardiac disease, the improvement in depression scores through EECP indicates a finding of potential importance that may warrant further study in future research.

A rational approach to the treatment of chronic myocardial ischemia requires an appreciation of the pathophysiology of coronary artery disease and the treatment options available. Any factor that causes an imbalance between myocardial oxygen supply and demand can provoke ischemia. Myocardial oxygen requirements rise with increases in heart rate, contractility, or left ventricular wall stress. Myocardial oxygen supply is determined by coronary artery flow and myocardial oxygen extraction. Anti-anginal medications are the mainstay of anti-ischemic management and act to correct the balance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. These medications include nitrates (which act principally by venous vasodilation, but also probably by coronary dilation), beta-blockers (which act mainly by reducing heart rate and cardiac contractility), and calcium channel blockers (which act principally by arterial and coronary vasodilation). The choice of therapy and its effectiveness depend on the underlying cause of ischemia. The complimentary mechanisms of action of these drug classes suggest that their use in combination may result in a greater reduction in myocardial oxygen demand than that achieved with monotherapy. In addition, the pharmacological actions of some of these drugs may serve to offset the undesirable side effects associated with others, for example, the reflex tachycardia produced by some calcium channel blockers may be offset by beta-blocker therapy. Finally, aspirin and lipid-lowering drugs and the potential role for anti-oxidants must also be considered in combination therapy. Invasive techniques for myocardial ischemic management, such as coronary artery bypass and coronary angioplasty, improve myocardial oxygen supply by relieving or circumventing the atherosclerotic obstruction responsible for ischemia. Surgery is the preferred technique in patients with certain medical conditions, for example, those with triple-vessel disease, but is not recommended in patients with mild angina unless left main artery disease is present.

Silent myocardial ischemia, whether it occurs at rest or during exercise, is associated with an unfavorable prognosis and may lead to sudden cardiac death. Agents used to treat silent myocardial ischemia have included nitrates, beta-blockers, and calcium antagonists (CAs). Despite treatment with traditional anti-ischemic agents, studies have shown that up to 40% of patients who receive what is considered to be clinically optimal antianginal therapy continue to have daily episodes of silent myocardial ischemia. The use of nitrates and beta-blockers is sometimes confounded by issues of tolerance and tolerability. Although the CAs have been found to be effective in decreasing the duration and frequency of episodes of silent ischemia, in general beta-blockers produce a greater reduction in these variables. Thus a need for effective and tolerable anti-ischemic agents persists. A new class of CAs, the tetralol derivatives, may show promise in this regard. The first of this new class, mibefradil, is characterized by selective blockade of T-type calcium-ion channels and has been shown in a few studies to reduce the frequency and duration of asymptomatic ischemic episodes in patients with stable exertional angina pectoris. Large-scale clinical trials are necessary before the efficacy and tolerability of this new CA can be compared fully with those of the beta-blockers and currently available CAs.

BACKGROUND Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia. METHODS AND RESULTS A multicenter, randomized, double-blind, placebo-controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/- SD, 3.6 +/- 4.2 versus 1.7 +/- 4.6 episodes, P < .001) and average duration (30 +/- 3.3 versus 16.4 +/- 6.7 minutes, P < .001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4 +/- 4.6 to 3.1 +/- 6.0 episodes and 36.6 +/- 4.1 to 30 +/- 5.5 minutes). Event-free survival improved in atenolol-treated patients (P < .0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P = .001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P = .175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol. CONCLUSIONS Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.

The risk of infarction and sudden death is considerable in patients with silent ischemia, whether it occurs alone or is interspersed with episodes of angina. The ischemic activity can be modified or even abolished, most effectively with beta-blocker and nitrate therapy. But it is not yet clear whether treatment improves outcome, although the limited available data suggest that it does.

The effects of metoprolol on early infarct expansion after acute myocardial infarction were studied in rats (n = 54) that underwent either left coronary artery ligation (MI) or sham operation. Immediately after surgery, the rats received either metoprolol (M) by mouth, which had been dissolved in drinking water, for 72 hours supplemented with three intraperitoneal doses over the first 24 hours or no treatment (H2O). Three days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure and analyzed morphometrically. Infarct size was nonsignificantly lower in the metoprolol-treated group compared with the untreated group (38% +/- 5% MI-M vs 48% +/- 3% MI-H2O, p = 0.10) Compared with infarcted untreated rats, infarcted metoprolol-treated rats had a lower heart rate (322 +/- 13 beats/min MI-M vs 452 +/- 19 beats/min MI-H2O, p0.001), lower left ventricular systolic pressure (63 +/- 4 mm Hg MI-M vs 90 +/- 6 mm Hg MI-H2O, p = 0.004), and lower +dp/dt (1340 +/- 169 mm Hg/sec MI-M vs 2872 +/- 273 mm Hg/sec MI-H2O, p0.001), but left ventricular end-diastolic pressure and cardiac index did not differ between the two groups. Left ventricular weight corrected for body weight was higher in infarcted rats treated with metoprolol compared with infarcted untreated rats (2.76 +/- 0.07 gm/kg MI-M vs 2.41 +/- 0.09 gm/kg MI-H2O, p0.05). The initial slope of the pressure-volume relationship Ki, an index of operative volume stiffness, was lower in infarcted rats treated with metoprolol compared with infarcted untreated rats (p = 0.03). There were, however, no significant differences in the expansion index, thinning ratio, or left ventricular volume between the two infarcted groups. Thus metoprolol therapy begun in the immediate postinfarction period promotes an increase in left ventricular weight and reduces operative volume stiffness but has no significant effect on indexes of early infarct expansion.

Eighteen patients with chronic angina despite surgical and medical therapy were treated with an improved system of enhanced external counterpulsation (EECP) (1 hour daily for a total of 36 hours). Patients underwent a baseline treadmill thallium-201 stress test. After EECP treatment, a thallium stress test was repeated for the same exercise duration. One week after treatment, patients also underwent a maximal stress test. All patients improved in anginal symptoms and generally decreased antianginal medications, with 16 obtaining complete relief from angina. Pre- and post-thallium stress testing performed for the same duration showed complete resolution of ischemic defects in 12 patients (67%), reduction in the area of ischemia in 2 (11%), and no change in 4 (22%). Thus, a decrease in myocardial ischemia was observed in 14 patients (78%; p less than 0.01). The exercise duration of maximal stress testing after EECP significantly improved from 8.14 +/- 0.71 to 9.72 +/- 0.77 minutes (p less than 0.005), although the double product did not change significantly. Analysis of these 2 tests in the subgroup of 14 patients with improvement in thallium studies showed significant increases in both exercise duration (8.58 +/- 0.66 to 10.44 +/- 0.59 minutes; p less than 0.001) and double product (21,827 +/- 2,044 to 24,842 +/- 1,707 mm Hg.beats/min; p less than 0.01). The improvement in reperfusion defects and increase in exercise duration are reflections of improved perfusion to ischemic regions of the myocardium. EECP uses additional thigh balloons and sequenced balloon inflation, effecting a significant increase in diastolic augmentation over previously available methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Until recently, it has not been possible to combine both ambulatory electrocardiographic monitoring and ambulatory left ventricular function monitoring, but new developments have helped solve this problem. A technique based on the nuclear probe was introduced in the early 1980s to allow continuous recording of left ventricular volumes and ejection fraction over a 4 to 6 hour period during ambulatory activities following a single injection of a radioisotope; the device was termed the VEST. In addition to validation studies, left ventricular function during ambulatory activities of various types has been measured with the VEST, and there are now several reports that document reduction in left ventricular ejection fraction in patients with coronary artery disease. These episodes meet the criteria for silent ischemia: objective evidence of myocardial ischemia in the absence of angina or anginal equivalents. Thus, patients with coronary artery disease can be followed for hemodynamic evidence of myocardial ischemia (even when they are not aware of the episodes) and results of therapy better monitored than by the ambulatory ECG alone.

BACKGROUND Experimental animal and clinical studies indicate that blood platelets have an important role in atherosclerosis and formation of thrombi. Prospective studies presenting evidence of an association between blood platelet count and cardiovascular mortality have not been performed. METHODS AND RESULTS From 1973 to 1975, blood platelets were counted, and their responsiveness to aggregating agents was studied in healthy middle-aged men. The aim was to assess the possible association between these variables and coronary heart disease. At 13.5 years of follow up, a significantly higher coronary heart disease mortality was observed among the 25% of subjects with the highest platelet counts. Platelet aggregation performed in a random subsample (150 of the 487 men), moreover, revealed that the 50% with the most rapid aggregation response after ADP stimulation had significantly increased coronary heart disease mortality compared with the others. These associations could not be explained by differences in age, lipids, blood pressure, or smoking habits. CONCLUSIONS The present study is the first to present conclusive, prospective evidence of an association between platelet concentration and aggregability and long-term incidence of fatal coronary heart disease in a population of apparently healthy middle-aged men.

Calcium channel blockers are among the most effective antiischemic therapies currently available. These agents afford a reduction in vascular smooth muscle tone by interrupting the excitation-contraction coupling process dependent on calcium transport. The efficacy of calcium channel blockers in patients with myocardial ischemia is probably due in large part to their effects on coronary circulation. In experimental models of coronary occlusion, these agents have been demonstrated to increase coronary vasodilation and coronary blood flow. Recruitment of coronary vasodilator reserve by nifedipine has been demonstrated indirectly via enhancement of left ventricular function in a canine model. Additionally, calcium channel blockers have been shown to modify the reactive hyperemic response usually seen after coronary artery occlusion. These changes in coronary resistance vessels, which normally regulate myocardial blood flow in response to metabolic requirements, have important clinical implications. Larger collateral vessels are also affected by calcium channel blockers, although the results observed in experimental models are not as clear cut. Although techniques for measuring coronary blood flow in humans are more limited, considerable data have accumulated on the effects of calcium channel blockers in humans. Assessments of coronary vasodilation using quantitative angiography have produced variable results. However, improved myocardial perfusion, as measured by thallium-201 scintigraphy after administration of nifedipine, and beneficial effects on coronary blood flow and coronary vascular resistance as assessed using the precordial xenon-133 washout technique before and after sublingual administration of nifedipine have been observed. Overall, such studies have not only shown the clinical usefulness of calcium channel blockers, but have broadened our understanding about the complex interplay of their mechanisms of action.

The treatment of refractory chronic angina pectoris presents an increasing problem for all physicians caring for patients with coronary artery disease because of the large number of individuals who have either failed multiple revascularization procedures or are not appropriate candidates for such procedures. The aim of this study was to review the safety, efficacy, and clinical applicability of a noninvasive technique (external counterpulsation) for the treatment of angina pectoris. A MEDLINE search for all English language abstracts, meeting presentations, journal articles, and reviews from 1960 through December 2005 was conducted. Of the 194 citations in the literature, 60 appeared before 1983 when the enhanced version of the technique (the one that is presently used) was first reported. Criteria for further evaluation of the 134 post-1983 citations were either (1) randomized trial, (2) observational study of at least 10 patients, or (3) investigations into possible mechanisms. Of the 134 citations, 45 were used for data extraction. Observational studies from the United States, Asia, and Europe have demonstrated improvement in symptoms, reduction in anginal episodes, better quality of life, and improved exercise performance in over 5000 patients. The only randomized study (Multicenter Study of Enhanced External Counterpulsation) confirmed these findings as well as the continuation of clinical benefits at least 1 year posttreatment. Although the mechanisms by which diastolic augmentation achieves these beneficial results are still under investigation, this is a promising noninvasive therapy in a group of patients with limited treatment options.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for chronic stable angina. Despite intensive risk factor modification, a patient required two surgical coronary revascularizations and seven multivessel angioplasties over a 26‐monfh period, demonstrating recurrent unstable angina and persistent thallium perfusion defects despite revascularization. Post EECP, angina was relieved, thallium defects were resolved, and the patient has remained asymptomatic for 36 months.

Silent myocardial ischemia is now in its fourth decade of recognition as a clinical syndrome within the spectrum of coronary artery disease. Prior decades have seen important research into the pathophysiology, detection, prevalence, prognosis, and therapy of this syndrome. More recent developments have continued to add data to each of these areas, with particular emphasis on the comparative value of various diagnostic procedures and the effect of therapy on prognosis. While controversy still exists concerning proper screening guidelines for the asymptomatic population, there is a growing consensus that some form of stress testing in high-risk individuals (ie, those with multiple coronary risk factors) is appropriate.

False aneurysms of the mitral-aortic intervalvular fibrosa are rare and usually complicate aortic valve endocarditis. We report a case of a false aneurysm of the mitral-aortic intervalvular fibrosa after recent bioprosthetic aortic valve replacement in the absence of endocarditis.

The pathophysiology of myocardial ischemia is related to a mismatch between coronary blood flow and myocardial oxygen requirements. In most patients with coronary artery disease, the angina threshold is not fixed but varies throughout the day. The exercise test is probably still the most important noninvasive diagnostic test. Patients with chronic ischemia may or may not demonstrate painful symptoms during ischemic episodes. Prognosis in patients with chronic ischemia relates to the severity of coronary artery disease and the degree of left ventricular dysfunction plus objective documentation of ischemia. Major therapeutic agents for patients with chronic ischemia are antianginal drugs (nitrates, β-blockers, calcium blockers), antiplatelet drugs (aspirin), and revascularization procedures (coronary angioplasty, coronary artery surgery).

Background: Enhanced external counterpulsation (EECP) is a noninvasive treatment for coronary artery disease (CAD) that has been used successfully in patients not responding to medical and/or surgical therapy. Hypothesis: The study was undertaken to evaluate the effect of EECP on long-term prognosis in such patients. Methods: Major adverse cardiovascular events (MACE) were tracked in 33 patients with CAD treated with EECP. Patients were subgrouped based on whether or not they demonstrated an early improvement in radionuclide stress perfusion imaging (Responders vs. Nonresponders) and followed for MACE over a mean follow-up of 5 years. Patient population characteristics included 73% with multivessel disease; 45% with prior myocardial infarction(s); and 61% who had undergone either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), or both. Results: There were 26 of 33 (79%) Responders, and 7 of 33 (21%) Nonresponders. Subsequent MACE over the 5-year follow-up included four deaths and eight patients with cardiovascular events [acute myocardial infarct (4), new CABG or PTCA (6), valve replacement (1), unstable angina (1)]. Nonresponders had significantly (p

Since their introduction into clinical use several decades ago, the beta blockers have proven enormously successful anti- ischemic, anti-hypertensive and antiarrhythmic agents. They have been especially useful in improving morbidity and mortality after acute myocardial infarctions (MI).

Enhanced external counterpulsation (EECP) is a noninvasive ECG-timed procedure that employs sequential balloon inflation and deflation in the lower extremities to provide diastolic augmentation and systolic unloading.1 Open clinical trials conducted at the University Hospital and Medical Center, State University of New York at Stony Brook, demonstrated that treatment with EECP resulted in a significant decrease in anginal frequency, improved cardiac flow in radionuclide scans and increased exercise tolerance.1 These results, however, were achieved without the benefit of a control population against which to conpare results of treatment. MUST-EECP, the first national, randomized, placebo- controlled trial of EECP, was conducted to provide such a control group and to evaluate EECP results at study centers other than Stony Brook.

Over 25 years ago we prepared a classification system for silent myocardial ischaemia that we hoped would make it easier for future researchers to study the pathophysiogical basis for the syndrome, establish prognosis, and determine appropriate management protocols.1 In our categorization, Cohn Type I refers to asymptomatic individuals without known coronary artery disease (CAD) and Cohn Types II and III to patients with known CAD. Those with prior myocardial infarctions (MIs) who are asymptomatic are Type II, and those with CAD and both silent and symptomatic ischaemic episodes are Type III.1 In the last decade a dedicated group of Swiss cardiologists led by Dr Mathias Pfister of the Basel University Hospital have conducted a long-term series of clinical studies involving patients with Types I and II silent ischaemia. By providing a ‘new look’ at the syndrome of silent ischaemia they have contributed important clinical data to aid in its management. They have now described the results of anti-ischaemia drug therapy in Type I patients (studied in their SWISS I trial);2 their SWISS II data dealing with Type 2 patients and also recently published3 will be commented on later in this editorial. Investigations into silent ischaemia have been centred on either its pathophysiology, prevalence, prognosis, or treatment, or the effect of treatment on prognosis.4 Although recent pain studies have not yet been able to pinpoint the … Corresponding author. Tel: +1 631 444 1061; fax: +1 631 444 1054. E-mail address: pcohn{at}notes.cc.sunysb.edu

Background: Enhanced external counterpulsation (EECP) has been demonstrated to be an effective treatment for angina and exertional ischemia in patients with coronary disease. Hypothesis: It is hypothesized that the ability of EECP to enhance the recruitment or development of coronary collaterals in coronary artery disease may be determined by the relative magnitude of diastolic augmentation (DA) and systolic unloading (SU). This study examines the relation between the proposed EECP effectiveness ratio (DA/SU), as assessed by finger plethysmography, and changes in descending aortic flow as assessed by Doppler echocardiography in 15 patients during EECP. Methods: Varying external cuff pressures (0-275 mmHg) were used to generate a range of DA/SU ratios. The effect on aortic antegrade systolic and retrograde diastolic flow was assessed by Doppler echocardiography to determine whether there was an optimal EECP effectiveness ratio that maximizes the hemodynamic effects of EECP. With increasing DA/SU there was an initial positive linear increase in both systolic and diastolic flow volume. Systolic flow maximized at an effectiveness ratio of 1.5 and diastolic flow at a ratio of 2.0. Result: Therefore, effectiveness ratios (DA/SU) in the range of 1.5-2.0 are optimal for maximizing the hemodynamic effects of EECP.

The effect of treatment with enhanced external counterpulsation (EECP) on exercise hemodynamics and myocardial stress perfusion in 27 patients with chronic stable angina was studied. A majority (22/27 or 81%) of patients improved their exercise tolerance after EECP treatment, and a similar percentage (21/27 or 78%) of patients improved their radionuclide stress perfusion images. Post-EECP maximal exercise heart rate and blood pressure, while demonstrating a linear relation with exercise duration, did not increase significantly despite the increased exercise duration. This suggests that the increase in exercise duration after treatment with EECP is due to both improved myocardial perfusion and altered exercise hemodynamics. EECP therapy thus appears to exert a "training' effect, decreasing peripheral vascular resistance and the heart rate response to exercise. Coronary disease patients may improve their exercise tolerance after EECP because of both improved myocardial perfusion and a decrease in cardiac work load.

Despite the introduction of new mechanical techniques for revascularization, pharmacologic therapy continues to be the mainstay of antianginal therapy. The conventional antianginal medications, which include nitrates, beta blockers, and calcium channel blockers, act to correct the imbalance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. All three are appropriate for the management of angina caused by a fixed coronary obstruction, but nitrates and calcium channel blockers, which not only reduce demand but also increase supply, are preferred in cases of angina believed to involve a significant increase in vasomotor tone. Because of the different yet complementary mechanisms of action of the three classes of anti-ischemic drugs, use of these agents in combination is a rational approach to the treatment of angina unresponsive to monotherapy. Such combinations have been shown to enhance the therapeutic response achieved with single-agent therapy. In addition, the pharmacologic action of one of the components of the combination regimen may serve to offset side effects typically associated with the other.

Reperfusion that is too late to salvage ischemic myocardium reduces early infarct expansion, and captopril therapy favorably alters long-term left ventricular remodeling. To study whether the beneficial effects of these two therapies are additive, we examined the effects of captopril therapy after late reperfusion on left ventricular remodeling after acute myocardial infarction. Female Sprague-Dawley rats ( n = 67) were randomly assigned to one of four groups: group 1, sham surgery and no treatment; group 2, left coronary artery ligation and no treatment (myocardial infarction [r MI]; group 3, left coronary artery ligation, reperfusion 2 hours later, and no treatment (late reperfusion [LR]); and group 4, left coronary artery ligation, reperfusion 2 hours later, and captopril treatment (LR-Cap). Captopril therapy (2 gm/L of drinking water) was begun in the LR-Cap group in the immediate post-operative period and continued for 20 days. Twenty-one days postoperatively, hemodynamic measurements were made before and after volume loading. The rats were killed, their hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure for morphometric analysis. Compared with the MI group, the LR group had a lower expansion index and a higher thinning ratio. There were no differences in hemodynamics, left ventricular volumes, or other morphometric indexes between the two groups. Compared with the MI and LR groups, the LR-Cap group had lower peak left ventricular end-diastolic pressure, lower left ventricular volume, lower left and right ventricular weights, and a leftward shift of pressure-volume curves. There were no differences in the expansion index or the thinning ratio between the LR and LR-Cap groups. Thus captopril therapy after late reperfusion additionally improves hemodynamics, attenuates left ventricular cavity dilation, attenuates an increase in left and right ventricular weights, and alters the pressure-volume relationship of the left ventricle.

Infrared thermography was used to measure and map precordial skin temperature in 60 patients undergoing elective coronary angiography; 9 patients were normal and 51 had coronary artery disease (CAD). Thermograms were graded by quartile area (zero to 4 plus) and magnitude of thermal asymmetry (recorded as degrees celsius). The presence, mean area and degree of thermal asymmetry were significantly greater in patients with CAD. Twenty-two patients subsequently underwent successful revascularization with angioplasty with a highly significant decrease in the presence, magnitude and degree of thermal asymmetry. The results demonstrate that CAD is associated with precordial thermal asymmetry. The area and magnitude of thermal asymmetry is greater in patients with CAD than in control subjects without angiographically significant CAD. Successful revascularization changed the asymmetric precordial pattern to a more symmetric one. Infrared thermography is a promising technique for the detection of CAD before and after revascularization.

Left ventricular remodeling following acute transmural myocardial infarction may result in early left ventricular enlargement. To characterize the effects of milrinone on components of early left ventricular dilation, rats (n = 120) underwent left coronary artery ligation or sham surgery. In the immediate postoperative period, rats received either no treatment or milrinone (3.17 ± 0.08 mg/kg/day) dissolved in drinking water for 20 days. Twenty-one days after the initial surgery, hemodynamic measurements were made. The rats were then put to death and the hearts arrested in diastole were excised and fixed at a constant pressure for morphometric analysis. To examine the effects of milrinone on the relative contribution of infarcted and noninfarcted segments to early left ventricular dilation after acute myocardial infarction, a subgroup of infarcted rats chosen randomly was put to death 3 days after the initial surgery for morphometric analysis. Compared with infarcted untreated rats, infarcted milrinone-treated rats had a lower left ventricular volume (1.41 ± 0.07 ml/kg vs 2.16 ± 0.19 ml/kg, p < 0.001), lower left ventricular wall stress (0.64 ± 0.03 vs 0.91 ± 0.06, p < 0.001), and a lower expansion index (1.61 ± 0.12 vs 2.61 ± 0.22, p < 0.001). Morphometric analysis revealed that the noninfarcted segment length did not differ between the two infarcted groups either 3 days or 21 days after left coronary artery ligation. Infarct segment length also did not differ between the two infarcted groups at 3 days, but at 21 days infarct segment was shorter in the milrinone-treated group compared with the untreated group (p < 0.03). An increase in infarct segment length/total endocardial circumference ratio between day 3 and day 21 was observed only in the untreated group of rats. Thus milrinone begun in the immediate postinfarction period in a rat myocardial infarction model attenuates left ventricular dilation when hearts are examined 3 weeks later. This attenuation of early postinfarction left ventricular dilation with milrinone appears to be related to its effects on infarct zone remodeling.

Traditionally, myocardial ischemia has been viewed as an imbalance in the supply and demand of myocardial oxygen. Stable angina is usually considered to involve a fixed lesion, whereas unstable angina involves a fixed lesion as well as such components as platelet aggregation, thrombotic processes, and vasospasm. Variant angina involves primarily vasospasm. A newer concept holds that most angina results from mixed mechanisms in which both fixed lesions and vasomotor alterations play a role. These mechanisms are responsible for mixed ischemic events, characterized by episodes at varying levels of exertion, with or without anginal pain. This concept would seem to be supported by the occurrence of silent ischemia in the setting of stable, unstable, or variant angina, despite differing pathophysiologic conditions. Ischemic events have important prognostic significance; unfortunately, many are unrecognized by patients. The question whether the treatment of ischemic events will improve prognosis remains a matter of debate.

T HE EXERCISE TEST is the established procedure for assessing ischemic responses, arrhythmic potential, and cardiac performance in persons with known or suspected heart disease. It is also used for determining prognosis. In this regard, it is important to note that the exercise test is important not only in clinical studies focused on subjects with known heart disease but also in epidemiological surveys of apparently healthy populations. In the latter populations, this procedure is often used to evaluate the reliability of electrocardiographic and hemodynamic responses to stress in predicting the occurrence of overt cardiac events without necessarily subjecting positive responders to coronary angiography. Whether the prognostic data gleaned from the epidemiological studies (and the less numerous angiographic studies) of apparently healthy individuals justifies any type of screening policy for the population at large remains a controversial issue.

Although silent ischemia may be linked to increases in cardiovascular morbidity and mortality, the long-term effects of a strategy aimed at the detection and treatment of this asymptomatic condition have not been fully explored. We therefore have developed the Atenolol Silent Ischemia Trial (ASIST), the first multicenter, randomized, prospective study of the prognostic implications of silent ischemia in asymptomatic and minimally symptomatic patients with coronary artery disease. Inclusion criteria for study patients were documented coronary artery disease, evidenced angiographically or by previous myocardial infarction, and transient ischemia, evidenced by abnormalities of regional wall motion, stress thallium-201, or exercise electrocardiogram. The main objective of ASIST is to assess the influence of frequency and duration of symptomatic and asymptomatic ischemic episodes on the occurrence of fatal and nonfatal cardiac events. Atenolol, a beta 1-selective adrenergic blocker, was chosen as the therapeutic intervention because of its potential benefits in treating both symptomatic and asymptomatic ischemia. Ambulatory electrocardiographic monitoring will be used to measure the frequency and duration of ischemic episodes during daily life. The predictive ability of short-term (4-week) effects on long-term (52-week) response to atenolol treatment is also being assessed, along with the economic impact of this diagnostic and therapeutic strategy. Given the current emphasis on reducing morbidity and mortality associated with coronary artery disease, ASIST results should shed light onto the long-term management and prognostic implications of this otherwise asymptomatic condition.

That myocardial infarctions can occur without pain or other recognizable symptoms is not a new concept; in fact, one of the pioneers in clinical cardiology, Herrick, noted it in his landmark paper published in 1912 [1]. Anecdotal reports throughout the 1930s and 1940s from Kennedy, [2] Boyde and Weblow, [3] Gorham and Martin, [4] and Stroud and Wagner, [5] maintained interest in this seeming paradox [2–5]. Roseman [6] reviewed the literature in 1954 and found that 220 cases of this syndrome had been reported, some in more detail than others.

Both the short-term and now long-term (over a 3-year period) clinical benefits of EECP appear to be maintained in almost all patients treated for chronic disabling angina. That most patients maintained their 3-year benefits suggests that long-term improvement in myocardial perfusion can occur. Future angiographic studies are planned to evaluate collateral function in these patients.