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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.

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.

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 and hypothesis: Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for chronic angina. However, its usefulness has been felt to be limited in patients with angiographically demonstrated triplevessel coronary artery disease (CAD), in accord with the hypothesis that a patent vessel is necessary for transmission of the EECP-augmented coronary artery pressure and volume to the distal coronary vasculature. Methods: The effect of revascularization [coronary artery bypass grafting (CABG)] prior to EECP was examined in 60 patients with CAD and chronic angina (35 without and 25 with prior CABG). Patients were grouped by the extent of CAD (single-, double-, triple-vessel disease in the unrevascularized group) and by the extent of residual disease (number of stenotic native vessels unbypassed or supplied by a stenotic graft in the CABG group). Significant CAD or graft stenoses were defined as stenoses demonstrating ≥ 70% luminal diameter narrowing. Benefit was assessed by improvement in postEECP treatment over pretreatment radionuclide stress testing. Results: Radionuclide stress testing demonstrated a comparable favorable response (80 vs. 71 %; p = NS) in patients with prior CABG versus unrevascularized patients. Enhanced external counterpulsation was highly and comparably effective in patients with unrevascularized native single- and double-vessel CAD and in patients with CABG with residual single-and double-vessel CAD (88 vs. 80%; p = NS). Most notably, CABG significantly increased the beneficial response to EECP in those patients with triple-vessel CAD and stenotic grafts compared with unrevascularized patients with triplevessel CAD (80 vs. 22%; p < 0.05 by chi-square test). Conclusion: The results suggest a new role for EECP as an effective treatment for post CABG ischemia, despite extensive CAD and even in the presence of stenotic grafts.

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.

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.

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

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.

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.

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.

Quantitative analysis of the single and repeated cine left ventriculogram was performed in 20 patients with coronary artery disease to determine both the intrinsic variance of individual beats separated by different time intervals and variance between analyses of different observers. In addition, ventriculograms obtained from left ventricular injections of contrast medium prior to coronary arteriography were compared to ventriculograms obtained from either left ventricular or pulmonary artery injections after arteriography. The time period between studies varied from 30 minutes to 90 minutes to four days. Analysis of the same ventriculogram by different observers resulted in an average difference in ejection fraction of 0.05 (pNS). The average difference in ejection fraction was 0.02 between two early beats of the same ventriculogram (pNS). The average difference between sequential ventriculograms was 0.07 (pNS), but individual variations greater than 0.10 were not uncommon, particularly between studies done before and after arteriography, or several days apart. Patients exhibiting wide variance in ejection fractions between two studies either had wide variance in other hemodynamic measurements or degree of asynergy, or both. This study provides a frame of reference for analysis of sequential ventriculograms in patients with coronary artery disease, especially in evaluating changes in the state of the disease or the effects of therapy. It is especially important that: (1) standard hemodynamic measurements be made before ventriculography, (2) the same radiographic techniques repeated whenever possible, and (3) the same person analyze the two ventriculograms.

Regional myocardial blood flow was measured using the inert gas washout technique and the Anger scintillation camera following injection of 133Xe into the coronary artery. By applying compartmental analysis to 30-minute washout curves, three compartments were delineated, representing blood flow to fat (IIIF) and myocardium (IM and IIM). Regional heterogeneity of flow was a highly sensitive index of coronary artery disease. Functional images delineated areas of altered perfusion better than quadrantic flow values. Gamma camera images of initial xenon distribution identified patients with severely altered flow.

Radionuclide measurements of regional left ventricular ejection fraction were evaluated as a quantitative index of regional left ventricular function. Left ventricular regional ejection fractions were derived from background-corrected, time-activity curves in 43 patients assessed by both gated equilibrium radionuclide angiocardiography and left ventricular contrast angiography. From a single, modified left anterior oblique projection, the regional change in background corrected counts was determined in each of three anatomic regions. The normal range for regional radionuclide ejection fraction was determined in 10 patients with normal contrast ventriculograms and without obstructive coronary artery disease at coronary arteriography. Regional ejection fraction was compared with percent segmental axis shortening and extent of akinetic segments in corresponding regions of the contrast ventriculogram. Radionuclide and roentgenographic methods were in agreement as to the presence or absence of abnormal wall motion in 83 of 99 left ventricular regions (84%) in 33 patients evaluated prospectively. Comparison of regional ejection fraction demonstrated significant differences between regions with roentgenographically determined normokinesis (75 +/- 3%, mean +/- SEM), hypokinesis (44 +/- 3%, p less than 0.0005) and akinesis (24 +/- 5%, p less than 0.005). We conclude that the left ventricular regional ejection provides a reliable quantitative assessment of regional left ventricular performance.

Thirty-three patients with angina (31 men and 2 women, age 33 to 68 years, 52 ¯ ), as well as signs and symptoms of severe left ventricular dysfunction, were evaluated for coronary revascularization surgery. All had multiple vessel coronary artery disease and at least one prior myocardial infarction. Cardiac catheterization demonstrated abnormally elevated left ventricular end-diastolic pressure (LVEDP), low cardiac output, and depressed resting biplane systolic ejection fraction (SEF) ranging from 18 to 45 per cent ( 31 ¯ per cent). To evaluate potential myocardial function, a premature ventricular contraction was introduced during the ventriculogram and the SEF of the postextrasystolic potentiated (PESP) beat calculated and compared to a sinus beat SEF. Patients were separated into two groups based on the increase in SEF: those with >0.10 augmentation (24 patients) and those with

In order to assess potential improvement in abnormal left ventricular (LV) wall motion, eighteen subjects — sixteen with obstructive coronary artery disease and LV asynergy and two with no evidence of organic heart disease — were studied by cardiac catheterization and cineangiography. Ventriculograms were performed at rest and during a constant infusion of l-epinephrine (EPI) at 1-4 µg/min after an average of nine minutes steady state. EPI infusion induced augmentation of LV contraction pattern in both normal subjects and in all normal zones in the sixteen subjects with asynergy, and in no instance was contraction in a normal zone rendered abnormal. Eleven of sixteen patients showed improved contraction in previously asynergic areas, two of whom also demonstrated paradoxical motion in an abnormal zone. Of a total of forty-four resting asynergic zones, twenty-three exhibited an improved contraction pattern with EPI, one showed depressed contraction, two demonstrated both an increase and deterioration in the same zone (paradoxical motion), and eighteen showed no change. Quantitative motion analysis generally corroborated these qualitative ventriculographic observations. Heart rate, LV systolic pressure and LV end-diastolic pressure increased slightly with EPI, but were not significantly changed from control values. While there was wide variation in end-diastolic volume in the subjects with asynergy, EPI resulted in an increase in both stroke volume and ejection fraction, the latter significantly ( P < 0.05). In the four subjects who subsequently underwent aneurysmectomy, preoperative lack of improvement with EPI correlated with a pathologic diagnosis of fibrosis. Other than angina pectoris of brief duration in two subjects, EPI provoked no untoward reactions, arrhythmias or complications. It is concluded that LV motion abnormalities can be improved or changed in certain cases by the inotropic stimulus of EPI, suggesting residual contractile ability; the agent may differentiate between zones of potentially functional cardiac muscle and frank fibrosis.

Nineteen patients with coronary artery disease were studied to determine the significance of reduced regional myocardial blood flow (50 ml/min per 100 g or less) in areas of abnormal wall motion. Regional myocardial blood flow was measured in four regions of the left ventricle with an Anger camera after the injection of xenon-133 into the left main coronary artery. Abnormal wall motion was evaluated with biplane left ventriculography at rest and during postextrasystolic potentiation, a potent inotropic stimulus. Abnormal wall motion was defined as hemiaxis shortening of less than 20 percent. Four hemiaxes were designated as corresponding to the four regions of myocardial blood flow. Of 76 hemiaxes evaluated in the 19 patients, 54 manifested normal wall motion and 22 abnormal wall motion; 8 of the 22 hemiaxes had reduced regional myocardial blood flow. In these 8, hemiaxis shortening increased 6 ± 2 percent (mean ± standard error of the mean) above values at rest during postextrasystolic potentiation (with normalization of hemiaxis shortening in only 1 of the 8), compared with an increase of 19 ± 4 percent ( P P

Despite the large number of studies dealing with the natural history of angiographically defined coronary artery disease, there is still a paucity of data on the prognosis of totally asymptomatic persons. From the small number of reported studies, it appears that prognosis in selected asymptomatic patients may be better than that of symptomatic patients. However, the annual mortality rate in the subgroup of asymptomatic patients with triple vessel disease was as high as 4 to 5% in some studies that included patients with prior myocardial infarction or mild symptoms, or both. This has reinforced the views of those who advocate a more aggressive medical/surgical approach to asymptomatic patients with left main and triple vessel disease, especially if they have had a prior infarction. Although several small series of surgically treated patients have been reported to have excellent short-term survival rates, the absence of adequate control groups in nearly all of these studies has left the issue of prophylactic revascularization unresolved. Until there is more knowledge of prognosis in patients not operated on, it is likely to remain unresolved.

Silent myocardial ischemia is one of the most important clinical manifestations of asymptomatic coronary artery disease, along with silent myocardial infarction. It may well be a forerunner of sudden cardiac death. Although our understanding of the pathophysioiogic mechanisms of the syndrome is still unresolved, we do know that prognosis in certain subsets of patients is far from benign. For that reason, aggressive therapy is recommended in asymptomatic patients with advanced disease, especially if they have already experienced a myocardial infarction, silent or otherwise.

In order to compare levophase ("forward") ventriculograms to standard (selective) LV cineangiography, 10 patients with coronary artery disease were studied by (1) selective injection of contrast medium into the LV cavity followed by (2) injection into the right ventricle and filming the levophase. Biplane cineangiograms were used to calculate the end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), and ejection fraction (EF). Values for the two respective techniques were then compared. Not only were correlation coefficients for the two methods low, but there was also a statistically significant difference between the two SVI (66 +/- 26 ml. for selective and 53 +/- 25 ml. for levophase injection; p less than 0.02) and the two EF (67 +/- 7 per cent for selective and 52 +/- 12 per cent for levophase injection; p less than 0.01). Levophase cineangiograms therefore significantly underestimate the LV ejection fraction when compared to standard (selective) LV cineangiography. These differences must be considered when evaluating greatly divergent interinstitutional survival rates for patients with low EF who undergo coronary artery bypass surgery, and when selecting candidates for bypass surgery on the basis of the angiographic data.

There is some evidence that alterations in pain perception are present in patients with coronary artery disease and painless myocardial ischemia, but whether endorphins are implicated is still unclear. Further studies are also needed to document the validity of various theories of the cardiac pain mechanism itself, especially the existence of specific nociceptive sympathetic fibers.

To evaluate noninvasively-induced postextrasystolic potentiation (PESP) of ischemic or apparently infarcted regions of myocardium, an external mechanical cardiac stimulator (develoepd by Zoll) was used to induce ventricular extrasystoles during M-mode echocardiography in 29 patients with coronary artery disease and in four control subjects. Twenty-five patients had > 75 per cent stenosis of the left anterior descending artery including 13 with ECG evidence of anteroseptal myocardial infarction; 21 patients had > 75 per cent stenosis of the right coronary and/or left circumflex arteries, including 11 with ECG evidence of inferior and/or posterior myocardial infarction. Twenty-four regions with reduced wall excursion showed varying effects of PESP: eight regions improved to the normal range, while 16 did not. Twelve of the latter had ECG evidence of prior infarction. Similarly, regions of asynergy that did not respond at all to PESP were usually, but not always, seen in patients with infarctions. Based on prior ventriculographic-histopathologic correlates, non-responding regions are probably totally scarred with irreversible contraction abnormalities, whereas regions with evidence of contractile reserve are potentially viable. Because the ECG and resting echocardiogram are not totally accurate predictors of contractile reserve, noninvasively induced PESP may be a useful adjunct technique in delineating local contractile reserve in patients with echocardiographic evidence of hypocontractile myocardium of uncertain viability.

The increase in left ventricular ejection fraction produced by postextrasystolic potentiation or epinephrine infusion has been used to demonstrate inotropic contractile reserve in patients with coronary artery disease and a depressed ejection fraction (less than 0.50). Prior studies have shown that a change in ejection fraction of 0.10 or more after postextrasystolic potentiation or epinephrine infusion is helpful in discriminating those patients with a better short-term (1 year) prognosis whether treated medically or surgically. This study related inotropic contractile reserve to 5 year prognosis in 54 patients receiving postextrasystolic potentiation or epinephrine infusion between 1971 and 1974. Current left ventricular function in surviving patients was assessed with radionuclide ventriculograms whenever possible. Five year survival was significantly better in patients with an initial change in ejection fraction greater than 0.10 in both the surgically treated group (16 of 20 versus 5 of 15, p less than 0.01) and the medically treated group (6 of 8 versus 1 of 11, p less than 0.01). Furthermore, among the surviving patients in the surgical group, current ejection fraction in the radionuclide ventriculogram was significantly greater in patients who demonstrated inotropic contractile reserve in their 1971 to 1974 contrast left ventriculogram. These findings support the concept that coronary revascularization enhances function of ischemic but viable myocardium.

An additional angiographic sign for determining coronary artery dominance is proposed. This sign is based on the anatomic pattern of the infraventricular branches in the left anterior oblique view. It is especially helpful in patients in whom the right coronary and/or left circumflex coronary arteries are completely occluded and distal vessels are filled via collaterals.

Regional myocardial specific blood flow (regional specific flow) was measured at rest and during contrast hyperemia after the intracoronary injection of xenon-133. The changes in regional specific flow were transient, resulting in some compromise in one of the underlying restraints of the inert gas washout method, namely, the presence of a steady state. Therefore, to determine the clinical utility of this technique, regional specific flow values obtained with this method were correlated with the presence and severity of coronary artery disease as assessed from the coronary arteriogram and left ventriculogram. Regional specific flow during contrast hyperemia was 186+/- 11 (mean +/- 1 standard error of the mean) ml/min per 100 g in control patients and 115+/-5 in patients with coronary artery disease. There was an inverse relation between regional specific flow during contrast hyperemia and the percent coronary stenosis when the stenosis was 40 percent or greater (r = 0.70, P less than 0.001). Regional specific flow was significantly less in patients with asynergy (77 +/- 10 ml/min per 100 g) than in patients with normal ventricular function (105 +/- 5) distal to coronary stenoses of greater than 75 percent. Thus regional specific flow measured during contrast hyperemia using the xenon washout technique and the Anger camera differentiated patients with normal coronary arteriograms from those with coronary artery disease. With this technique, good correlation was shown between regional specific flow and the percent coronary stenosis and presence of ventricular wall abnormalities. The information obtained with this method may provide prognostic information concerning suitability for surgical intervention.

Boston, Massachusetts Neither the fraction of the general population with severe multivessel but asymptomatic coronary artery disease (CAD) nor the natural history of this syndrome is known. Epidemiologic studies of unexpected sudden death [l] as well as clinical and/or postmortem studies of “silent” myocardial infarction [2] suggest that such persons may be more common than many physicians realize. Assuming that it would be beneficial to diagnose this syndrome before the occurrence of a morbid event, how can this best be done?

To evaluate the diagnostic potential and hemodynamic significance of exercise-induced multiple-lead QRS changes, we studied exercise test responses in 230 patients with chest pain syndromes undergoing Bruce protocol exercise tests. When increases in the R waves of multiple ECG leads (epsilon R) plus ST segment change greater than 1 mm were present, 74 of 75 patients (99%) had coronary disease; this was a higher percentage than that achieved with either measurement alone or when ST change was combined with increase in R in a single lead. Sixty-four of the 75 patients (85%) had multivessel disease, the most severe form of coronary artery disease. Left ventricular end-diastolic pressure (both at rest and after left ventriculography), presence and degree of resting ventricular asynergy, and ejection fraction were all significantly more abnormal in patients whose epsilon R increased, regardless of ST-segment change. Further, in patients who stopped exercise because of cardiac symptoms, exercise duration and the product of heart rate times blood pressure were significantly lower when epsilon R increased. Thus, the mechanism for the increase in epsilon R with exercise in patients with coronary artery disease appears to be related to abnormalities in left ventricular function.

Improved global or segmental wall motion following revascularization suggests potential reversibility of ischemic left ventricular dysfunction in coronary artery disease (CAD). This study evaluates the effectiveness of post-extra systolic potentiation (PESP) to detect latent residual contractile function. Quantitative left ventriculography was performed in 15 patients with CAD (including seven with significant asynergy) and in three normal controls. During the ventriculogram, a single extra-systole was introduced by an R-wave coupled stimulator (R-stimulus interval averaged 398 msec, with an average mA of 2.4). PESP improved segmental axis shortening in 51 of 55 normal axes and 15 of 17 hypokinetic or akinetic axes. It also increased both ejection fraction and mean rate of circumferential fiber shortening in 17 of 18 patients. No significant arrhythmia occurred with this technique. A single interposed beat with PESP in one ventriculogram is a safe, effective method to detect residual potential contractile function in myocardium that may be hypokinetic or akinetic under conditions of the study.

The cold pressor test is a potent alpha-adrenergic vasoconstrictor stimulus, but its effect on regional myocardial blood flow in patients with coronary artery disease is unknown. In this study, 17 patients with chest pain syndromes who were receiving beta-adrenergic-blocking drugs underwent regional myocardial blood flow determination by the xenon-133 technique before and after the cold pressor test. Nineteen of 28 regions analyzed were distal to significant coronary artery lesions (greater than 70% reduction of luminal diameter), while the remainder were in patients with normal coronary arteries. Patients with normal and stenotic coronary arteries had a similar increase in heart rate-pressure product, but in patients with normal coronary arteries, regional myocardial blood flow increased in nine of nine regions (average increase 11.6 +/- 1.3%, p less than 0.01) while either decreasing or remaining unchanged in 14 of 19 regions distal to coronary artery lesions (average decrease 13.6 +/- 1.6%, p less than 0.05). This difference between groups was significant (p less than 0.01), demonstrating an inappropriate reduction of regional myocardial blood flow and suggesting that alpha-adrenergic vasoconstriction may contribute to myocardial ischemia.

Ambulatory electrocardiographic monitoring is useful in documenting characteristics of both painful and silent myocardial ischemia occurring during out-of-hospital activities in patients with angina and coronary artery disease (CAD), but few data are available concerning silent myocardial ischemia during ambulatory electrocardiographic monitoring in asymptomatic patients with CAD. Accordingly, 480 hours of ambulatory electrocardiographic monitoring were recorded in 10 asymptomatic patients with CAD not receiving cardiac drugs (48 hours/patient). All 10 patients had silent myocardial ischemia on treadmill exercise testing, with initial ST-segment depression at 2 to 6 minutes in 7 patients and more than 6 minutes In 3 patients. During ambulatory electrocardiographic monitoring, 64 episodes of silent myocardial ischemia (1 mm of ST-segment depression for at least 1 minute) were recorded, ranging from 1 to 17 episodes/patient/48 hours. Of the 64 silent myocardial ischemic episodes, 30 (47%) occurred between 6 AM and noon. Duration of silent myocardial ischemia was 798 minutes (range 1 to 80). ST-segment depression ranged from 1 to 4.5 mm. Heart rate at onset of the episodes on ambulatory electrocardiographic monitoring ranged from 65 to 150 beats/min (mean 98), which was significantly less than that during treadmill exercise testing in the same patients (mean 120). At cardiac catheterization, 7 patients had 2- or 3-vessel CAD and 3 had 1-vessel CAD. Thus, silent myocardial ischemia is common during daily life in asymptomatic CAD patients with positive treadmill exercise tests.

Fifty patients with coronary artery disease were studied with biplane left cineventriculography (right and left anterior oblique views). Volumetric analyses were compared with those of 10 normal patients also studied with simultaneous biplane ventriculography. In normal subjects there was good agreement between minor diameters in the right and left anterior oblique views, and between ventricular volumes and ejection fractions determined by single plane and biplane techniques. In patients with coronary artery disease there was more scatter in these values, especially when asynergy was present. Loss of ventricular symmetry probably explains this disparity. By providing visualization of all five zones of the left ventricular wall, the biplane technique allowed a comprehensive evaluation of ventricular asynergy and overall function. The clinical profile of the 50 patients with coronary artery disease demonstrated that optimal candidates for biplane ventriculography are patients with prior myocardial infarction, left ventricular enlargement and clinical evidence of abnormal hemodynamic status.

The omnicardiogram is a new technique in which various leads of the standard electrocardiogram are digitized and subjected to a nonlinear mathematical transformation so as to detect subtle degrees of abnormality not apparent in the original electrocardiogram. Its usefulness in the detection of heart disease was studied in 121 male patients with a normal resting 12 lead electrocardiogram who underwent selective coronary cineangiography for a chest pain syndrome. In normotensive patients with a normal resting electrocardiogram, an abnormal omnicardiogram was recorded in 81 percent of those with three vessel disease, 67 percent of those with two vessel disease and 41 percent of those with one vessel disease. Nineteen percent of patients with normal coronary arteries or nonobstructive coronary artery disease had false positive tracings. The omnicardiogram was abnormal in 81 percent of patients with hypertension whether or not coronary artery disease was present. A double Master exercise test was performed by 109 of the 121 patients. In normotensive patients results of the test were positive in 67 percent of those with three vessel disease, 31 percent of those with two vessel disease and 14 percent of those with one vessel disease. There was a 4 percent rate of false positive tracings. Thus in our study, the omnicardiogram appeared to be superior to the Master test and to provide a useful new approach to detection of coronary artery disease in male patients with a normal resting electrocardiogram.

Prognosis in the various forms of asymptomatic coronary artery disease is not precisely defined but available data suggest that it may not be as benign as previously thought. This is especially true in patients with silent myocardial ischemia, 3-vessel disease and poor exercise tolerance, because many of these patients may go on to sudden death or myocardial infarction. It is also true in patients with silent myocardial infarctions, because prognosis in this type of myocardial infarction is similar to that of patients with symptomatic infarctions.

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.

To evaluate the prognostic importance of anginal symptoms, 44 patients with angiographically defined coronary artery disease and no anginal symptoms at time of cardiac catheterization were selected from the Duke Harvard Collaborative Data Bank. They were "matched" with 127 symptomatic patients in the Data Bank who had similar coronary anatomy and ventricular function. Follow-up data indicated that the patients without anginal symptoms had a significantly better prognosis over a 7 year period than did those with symptoms: Annual mortality in the asymptomatic group was 2.7 percent compared with 5.4 percent in the group with angina (P 0.05). Although the patient population was a highly selective one and the matching categories were relatively broad, these results suggest that the presence of anginal symptoms may be an important independent correlate of prognosis in patients with coronary artery disease. The absence of angina did not preclude the presence of multivessel disease and did not necessarily imply a benign prognosis, because the yearly mortality rate was nearly 5 percent in the subgroup of asymptomatic patients with three vessel disease.

Stress-strain relations (σ-ε) were obtained in the form dσ/dε = kσ + c, where k is a stiffness constant. Utilizing the pressure-volume relation dP/dV = αP, the elastic stiffness (dσ/dε) and k were evaluated at end diastole in ten patients with normal ventricles (N), in 34 patients with coronary artery disease (CAD), and in 22 patients with primary myocardial disease. This latter group was classified into Type I (normal contraction patterns and elevated end-diastolic pressure), Type II (hypertrophy without obstruction), and Type III (hypokinetic and/or asynergic). The mean values and standard error of the means ( sem ) of k and elastic stiffness were 14.8 ± 0.7, 329 ± 54 gm/cm 2 (N); 17.8 ± 0.3, 684 ± 80 gm/cm 2 (CAD); 18.2 ± 0.5, 1133 ± 127 gm/cm 2 (Type I); 22.4 ± 1.2, 833 ± 150 gm/cm 2 (Type II); 18.7 ± 0.6, 1623 ± 348 gm/cm 2 (Type III). These studies indicate that 1) dP/dV, wall stress, and volume-mass ratio are the important determinants of stiffness, 2) normal stiffness levels can be recorded from hypertrophied ventricles, 3) CAD patients with end-diastolic pressure ≦ 12 mm Hg have normal stiffness levels, 4) normal contraction patterns and normal stiffness levels are not necessarily related.

Because left ventricular (LV) diastolic function is abnormal in patients with coronary artery disease (CAD), pulsed Doppler echocardiography was used to evaluate LV filling before and after coronary artery bypass grafting (CABG). Filling was evaluated by Doppler in 2 studies: (1) in a group of 41 unpaired patients (11 with angiographically normal coronary arteries, 14 with CAD but without CABG and 16 at 1 week after CABG) and (2) in a group of 12 patients with CAD before and 1 week after CABG. Doppler sampling at the level of the mitral anulus was analyzed for the deceleration half-time and for the ratio of peak late (A) to peak early (E) filling velocity, measures reflecting early ventricular filling and the relative contribution of atrial contraction to ventricular filling. In the first study the deceleration half-time was significantly prolonged in both CAD and CABG groups. The late to early peak transmitral velocity ratio, however, was significantly prolonged only in the nonrevascularized CAD patients. In the second group of CAD patients studied before and 1 week after surgical revascularization, both the late to early peak transmttral velocity ratio and the deceleration half-time showed significant postoperative improvement. Thus, patients with CAD showed impairment in early LV filling and a compensatory increase in the proportion of filling with active atrial contraction. Successful CABG appears to result in normalization of early filling and decreased reliance on active atrial transport.

To determine the value of a multivariate approach for the analysis of the treadmill exercise tolerance test (ETT), 237 patients referred for evaluation of chest pain who underwent a standard Bruce protocol ETT and coronary arteriography were studied. Predictive value of a positive ETT was 0.78 (43/55) using 1.0--1.9 mm ST segment depression criterion, 0.97 (59/61) using greater than or equal to 2.0 mm ST segment depression. When the 1.0--1.9 mm ST criterion was combined with peak systolic blood pressure-heart rate product (double product) less than or smaller than 23,000, exercise duration less than 6 minutes, and ST depression for greater than 3 minutes into recovery, predictive value improved to 0.89 in 18 patients with any two of the above. Predictive value for multivessel disease was also improved using non-ST criteria. Predictive value of a negative ETT for absence of coronary artery disease was 0.60 (29/48), and was 0.86 (12/14) if double product was greater than or equal to 30,000. Presence of chest pain during ETT did not improve predictive value of any type of test. Digitalis ingestion in 33 patients was not associated with decreased predictive value of a positive test. These data suggest that the predictive value of both positive and negative ETT in a symptomatic population can be improved with a multivariate approach.

The transverse plane QRS loop vectorcardiogram (VCG) was analyzed in 102 consecutive patients, angiographically proven to have coronary artery disease (CAD), whose right anterior oblique left ventriculogram showed severe asynergy (akinesis or marked hypokinesis) of the anterior and apical segments. Eighty-four of the 102 loops were considered to be diagnostic of severe asynergy because similar loops were not found in patients with CAD with less severe asynergy of either or both segments or in normal control subjects. Eighty-two of the 84 showed a uniformly abnormal pattern. Posterior vectors exhibited partial or complete clockwise "rotation" and were much more prominent than early anterior forces. In fact, the latter were often absent. In the other two VCG's at least the early half of the loop displayed prominent anterior vectors. The ECGs showed marked variability of the QRS in leads V-2-V-6. Abnormal Q waves were present in only 63 of the 102. The numbers of these leads showing abnormal Q waves varied from one to all of these positions.

One hundred and ten patients with chest pain syndromes and resting electrocardiograms demonstrating ST-T abnormalities and/or prior transmural myocardial infarctions were studied by means of the Master's two-step exercise test and selective coronary cine arteriography. Criteria for negativity were modified so that subjects with postexercise heart rates less than 110 beats/min, who did not develop significant ST-segment changes, were excluded from evaluation. Eighty-six per cent of the coronary artery disease group and 27% of the normal coronary artery group had positive postexercise electrocardiograms. Conversely, of the patients with positive results, 88% had anatomic coronary artery disease. With this degree of stress, positive responses ≧2 mm were invariably associated with multi-vessel disease. The type of pre-existing ECG abnormality did not influence either the frequency or severity of positive responses. False-negative subjects had no distinctive features relating to type of abnormal electrocardiogram, or location of vessel involvement, although most of these patients had significant disease of only one major coronary artery.

To evaluate the diagnostic potential of various readily available clinical procedures, 100 selected patients suspected of having coronary-artery disease were studied by both coronary cinearteriography and a selected pattern of standard tests and observations. Sixty-two patients had angiographic evidence of obstructive coronary atherosclerosis; 38 did not. Although individual clinical abnormalities were often unreliable indicators of coronary-artery disease, their diagnostic accuracy increased markedly when they were used in combination with one another to form a clinical index. This index, determined through multiple discriminant analysis, accurately diagnosed 94 of the 100 cases. The index was then applied to a prospective series of 100 similarly selected patients. Ninety-two were correctly diagnosed. In both the original study group and the prospective series, index values less than 100 were rarely associated with coronary atherosclerosis. Conversely, patients with indexes above 100 almost alwa...

To evaluate several types of cardiovascular stress tests adaptable to the cardiac catheterization laboratory, modified ventricular function curves were constructed in 60 selected patients with a chest pain syndrome by plotting left ventricular stroke work index (SWI) against left ventricular end-diastolic pressure (EDP). After infusion of angiographic contrast medium, all normal control subjects exhibited an ascending ventricular function curve (λ[ΔSWI/ΔEDP]>0.1). Nine of the 10 patients with coronary artery disease and abnormal resting dynamics had a flat or depressed ventricular function curve. Twenty-six of the 37 patients with coronary artery disease and normal resting dynamics also had a depressed ventricular function curve. Nine normal subjects, when challenged by both static and dynamic exercise, exhibited an ascending ventricular function curve similar to the response to angiographic contrast medium. When 21 patients with coronary artery disease and normal dynamics underwent stress, flat or depressed ventricular function curves were seen in 71 percent of patients after infusion of angiographic contrast medium, 48 percent of the patients after static exercise, and 38 percent of patients after dynamic exercise. No patient with a normal response to the contrast medium had an abnormal response to either form of submaximal exercise. Thus, the combined hypervolemic and myocardial depressant effects of angiographic contrast medium serve as a convenient and reliable intervention to elicit left ventricular dysfunction in patients with coronary artery disease and normal ventricular function at rest.