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Background: Women have been underrepresented in statin trials, and few data exist on the effectiveness and safety of statins in this gender. We used sequential electron-beam tomography (EBT) scanning to quantify changes in coronary artery calcium (CAC) as a measure of atherosclerosis burden in patients treated with statins., Methods and Results: In a double-blind, multicenter trial, we randomized 615 hyperlipidemic, postmenopausal women to intensive (atorvastatin 80 mg/d) and moderate (pravastatin 40 mg/d) lipid-lowering therapy. Patients also submitted to 2 EBT scans at a 12-month interval (mean interval 344+/-55 days) to measure percent change in total and single-artery calcium volume score (CVS) from baseline. Of the 615 randomized women, 475 completed the study. Mean+/-SD percent LDL reductions were 46.6%+/-19.9% and 24.5%+/-18.5 in the intensive and moderate treatment arms, respectively (P<0.0001), and National Cholesterol Education Program Adult Treatment Panel III LDL goal was reached in 85.3% and 58.8% of women, respectively (P<0.0001). The total CVS% change was similar in the 2 treatment groups (median 15.1% and 14.3%, respectively; P=NS), and single-artery CVS% changes and absolute changes were also similar (P=NS). In both arms, there was a trend toward a greater CVS progression in patients with prior cardiovascular disease, diabetes mellitus, and hypertension, whereas hormone replacement therapy had no effect on progression., Conclusions: In postmenopausal women, intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification. The limitations of this study (too short a follow-up period and the absence of a placebo group) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease.

Objective: Type 1 diabetes increases the risk for coronary artery disease (CAD), but limited information is available regarding the early natural history of this process. Electron beam tomography (EBT) can measure coronary artery calcification (CAC), an early marker for CAD. This study was designed to assess the prevalence and risk factors for CAC in young adults with established type 1 diabetes., Research Design and Methods: A total of 101 subjects aged 17-28 years with type 1 diabetes of over 5 years' duration and no history of heart disease underwent cardiac EBT with calcium scoring. Medical histories were obtained and physical examinations were conducted to document the presence of cardiac risk factors as well as evidence of microvasculopathy and diabetic arthropathy. Laboratory evaluation included measurement of fasting lipoproteins, homocysteine concentration, lipoprotein(a) [Lp(a)], urinary microalbumin, and HbA(1c). Contingency table analysis was used to assess bivariate relationships. Logistic regression was employed to construct a parsimonious model of independent risk factors., Results: Eleven subjects (10.9%) had CAC. Smokers were nearly five times more likely than nonsmokers to have CAC (P = 0.03). In addition, each 0.36-mm/l increment of Lp(a) was associated with a 10% increased risk for CAC (P = 0.05) after controlling for potentially confounding factors. There was no association of other CAD or diabetes risk factors studied with CAC., Conclusions: The prevalence of early CAD as evidenced by CAC in young adults with type 1 diabetes is significant. Smoking and Lp(a) levels independently predict the presence of CAC. Additional study is necessary to delineate the natural history of CAC and the role of risk factor modification to prevent progression of CAD in this high-risk population.

This investigation determined the prevalence of low-density lipoprotein (LDL) subclass distribution abnormalities, elevated lipoprotein(a) (Lp(a)), and elevated total plasma homocysteine in asymptomatic subjects with subclinical coronary artery disease determined by electron beam tomography (EBT). Fifty-five percent of subjects were classified as higher risk patients and 45% as lower risk patients, employing the National Cholesterol Education Program (NCEP) lipid criteria. EBT was performed in 296 consecutive asymptomatic subjects, and blood was analyzed for total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, LDL subclass distribution by S(3) gradient gel electrophoresis, Lp(a), and total homocysteine. Disorders of LDL subclass distribution were the most common disorder with 60.6% of the population expressing a distribution in the small regions IIIa + IIIb of >20%; and this was more common in the NCEP higher risk group (LDL cholesterol > or =130 and/or HDL cholesterol <35 mg/dl) (p <0.0004). A Lp(a) value >25 mg/dl was found significantly more often in the NCEP higher (36.9%) compared with lower (14.3%) risk group (p <0.001). None of the laboratory measurements correlated with the calcium score or calcium score percentile rank, with the exception of a weak correlation of mean LDL peak particle diameter and calcium percentile (r = 0.14, p = 0.02). Determination of metabolic disorders in addition to LDL cholesterol and HDL cholesterol increased the diagnostic yield from 55.1%, based on NCEP lipid criteria, to 84.1% with the addition of LDL subclass distribution, Lp(a), and total homocysteine. We conclude that: (1) disorders of LDL subclass distribution and elevated Lp(a) occur frequently in NCEP higher risk patients with subclinical coronary artery disease and are the only identifiable disorders in lower NCEP risk patients; and (2) electron beam tomographic evaluation and determination of LDL subclass distribution and Lp(a) should be considered for incorporation into primary prevention guidelines.

Electron-beam tomography (EBT) plaque imaging has the potential to fundamentally change the practice of prevention, through application of the following principles: (1) Asymptomatic patients with significant calcified plaque should be considered to have a clinical coronary artery disease risk equivalent. (2) Measurement of nontraditional parameters should be incorporated into the evaluation of patients with calcified plaque. (3) Drug treatment should focus on the asymptomatic patient with subclinical atherosclerosis. (4) Change in plaque rather than change in lipid values should guide treatment.

Objectives: This investigation was designed to determine the relationship between National Cholesterol Education Program (NCEP) ATP-II lipid guidelines and subclinical atherosclerosis, defined by electron beam tomography (EBT) calcified coronary plaque, in asymptomatic women., Background: NCEP guidelines are used to identify women at increased risk for coronary artery disease (CAD) on the basis of low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDLC) values. The relationship of the guidelines to subclinical atherosclerosis is unknown., Methods: A total of 304 asymptomatic women underwent lipid and EBT evaluation and were classified as: 1) NCEP higher risk, with LDLC > or =130 mg/dl and/or HDLC <35 mg/dl, or lower risk with LDLC <130 mg/dl and HDLC > or =35 mg/dl; and 2) EBT+ if any calcified plaque was noted or EBT- if there was no calcified plaque., Results: Forty-two percent of patients were EBT+, with a mean score of 227 and percentile of 73%; 58% were EBT-. Women who were EBT+ had significantly higher total cholesterol, LDLC and triglycerides than EBT- women, but only with ages < or =55 years; women >55 years demonstrated no differences. NCEP higher risk women made up 53.5% of the EBT+ and 37.7% of the EBT- groups; NCEP lower risk women accounted for 46.5% of the EBT+ and 62.3% of the EBT- groups. Assuming a higher risk in subjects with EBT-defined subclinical CAD than in those without, only 58.6% of the total group would be correctly identified by NCEP guidelines as either higher or lower risk, with correct identification of 65.5% of the younger and 52.2% of the older women. There was no correlation between either calcium percentile or score and any lipid measurement., Conclusions: This study demonstrates the shortcomings of employing NCEP guidelines to identify asymptomatic women with subclinical CAD, particularly women >55 years, and suggests increased utilization of EBT for primary prevention in the female population.

Myocardial perfusion imaging plays an important role in the selection of patients for percutaneous transluminal coronary angioplasty (PTCA) by identifying patients with coronary artery disease and by determining the physiologic significance of a particular stenosis, and therefore, the need for PTCA. In the immediate post-PTCA period, it is useful to evaluate patients with recurrent symptoms, but frequent false-positives preclude routine application in asymptomatic patients. The most important role of myocardial perfusion imaging is the evaluation of restenosis with the first 6 months post- angioplasty. It also provides accurate information in symptomatic and asymptomatic patients and in the settings of single and multivessel PTCA and partial and complete revascularization.

Objectives: The purpose of this study was to compare early and late outcomes in patients undergoing PTCA or CABG for triple vessel disease., Background: Although early results of PTCA/CABG randomized trials have recently become available, at present little data exists on long-term medical and socioeconomic effects of these treatment modalities in patients with triple vessel revascularization., Methods: During 1986-87, 76 patients undergoing triple vessel PTCA and 85 patients having triple vessel CABG were selected from a consecutive series of patients having multivessel revascularization. Initial results and 5 year outcome, hospital stay and charges and out-of-work time were assessed from prospectively collected data., Results: Clinical and morphological factors were similar in the PTCA and CABG groups. Hospital success and complications were also similar, except for higher mortality in the CABG cohort (0 vs. 3.5%). Five year follow-up showed no differences in survival, nonfatal infarction and angina-free status; however, there was a difference in need for repeat revascularization (PTCA 55.4% vs. CABG 6.3%, p less than 0.001). Repeat PTCA accounted for 49% of the revascularization in the PTCA cohort. Crossovers were similar (PTCA[CABG 6.8%; CABG[PTCA 6.3%, pNS). Predictors of late death in the entire population were female gender (p less than 0.0001), diabetes (p<0.05) and depressed LVEF (p less than 0.05). The choice of revascularization procedure (PTCA vs. CABG) was not an independent predictor of late death or MI. Analysis of initial hospital charges showed a 2:1 advantage in favor of PTCA but this advantage was lost in late followup due to the need for repeat revascularization in the PTCA group. However, the PTCA cohort lost fewer working days than CABG patients (3017 vs 5874 days) and therefore, lost less wages ($7,022 vs. $14,685)., Conclusions: The study shows that for selected triple vessel disease patients, PTCA and CABG results are comparable after 5 years, though repeat revascularization (mainly due to restenosis) was necessary in the PTCA group to maintain these favorable results. After 5 years, hospital charges are similar in the 2 groups, though out-of-work time and lost wages were 2:1 in favor of PTCA.

Objectives: The objectives of this study were 1) to determine the relationship between the amount of exercise-induced ischemic myocardium and the presence or absence of chest pain and ST segment depression, and 2) to define the incidence and characteristics of "truly silent ischemia," that is, ischemia that is not manifested by symptoms or electrocardiographic (ECG) findings., Background: There are no prior data relating ischemia to chest pain and ST depression. Thallium-201 imaging studies have evaluated perfusion but not ischemia. In contrast, supine bicycle stress echocardiography demonstrates exercise-induced ischemic dysfunction., Methods: Supine bicycle stress echocardiography and arteriography were performed in 130 patients and the severity and geographic extent of ischemic myocardium were compared in three groups. On exercise, Group I patients had both chest pain and ST segment depression (symptomatic ischemia), Group II patients ST depression without chest pain (asymptomatic ischemia) and Group III patients had neither chest pain nor ST depression (truly silent ischemia)., Results: There were no differences among groups in arteriographic characteristics. The incidence of "truly silent ischemia" was 43%. The number of abnormally contracting ischemic segments, average score per segment and sum of scores were virtually identical in Groups I and II and significantly greater than in Group III for the patients (p < 0.01 to < 0.0001), for the vessels as a group (p < 0.01 to < 0.0001) and for the left anterior descending (p < 0.01 to < 0.0001) and right (p < 0.05) coronary arteries. By multivariate analysis, positive findings on the stress ECG was the single most significant variable in relation to the amount of ischemia (p < 0.001); exercise chest pain had no significant relationship., Conclusions: Exercise-induced ST segment depression is the single most significant variable in relation to the amount of ischemic myocardium; exercise-induced chest pain is not related to the amount of ischemia. Patients with "truly silent ischemia" constitute almost 50% of patients with coronary artery disease and have less ischemia than do patients with ECG indications of ischemia, with or without chest pain.

Objectives: The objective of this study was to determine the accuracy of digital supine bicycle stress echocardiography, a new technique for evaluating coronary artery disease during peak exercise., Background: Prior stress echocardiographic techniques have not utilized peak exercise imaging to determine the extent and location of coronary artery disease., Methods: Two-hundred twenty-two patients were studied: 180 underwent both supine bicycle stress echocardiography and coronary arteriography; 42 had a < 5% likelihood of disease. Forty-three patients had normal coronary arteries, 55 had single-vessel, 42 had double-vessel and 40 had triple-vessel coronary artery disease., Results: Supine bicycle stress echocardiography was 93% sensitive, 86% specific and 92% accurate for identifying patients with coronary artery disease irrespective of prior myocardial infarction or achievement of > or = 85% maximal predicted heart rate. The "normalcy" rate in the low probability group was 100%. Supine bicycle stress echocardiography was 87% sensitive, 89% specific and 88% accurate for specific vessel identification. The sensitivity was greatest for the left anterior descending compared with the right coronary artery and the left circumflex coronary artery (95% vs. 81% vs. 78%, p < 0.01) and for vessels in patients with double- and triple-vessel compared with single-vessel disease (90% vs. 89% vs. 78%, p < 0.05). The procedure was significantly more sensitive for detection of vessels with 90% to 100% compared with 50% to 70% diameter stenosis (91% vs. 81%, p < 0.05) and was 88% correct in the prediction of multivessel disease., Conclusions: Supine bicycle stress echocardiography is a highly accurate tool for evaluating coronary artery disease, identifying both the patient with coronary artery disease and the location and extent of disease.

To compare the accuracy of supine bicycle stress echocardiography (SBSE), a new technique for evaluating coronary disease during peak exercise, with tomographic thallium-201 exercise imaging (SPECT), 71 patients were evaluated by SBSE, SPECT, and coronary arteriography. Twenty patients had normal coronary vessels; 22 had single-vessel, 14 had double-vessel, and 15 had triple-vessel disease. There were no differences in sensitivity (90% vs 92%), specificity (80% vs 65%), and accuracy (87% vs 85%) between SBSE and SPECT for the group of 71 patients. The results were similar in patients with and without prior myocardial infarction and with single-, double-, or triple-vessel disease. There were no differences between SBSE and SPECT for disease detection for the group of 213 individual vessels in sensitivity (88% vs 80%), specificity (87% vs 84%), and accuracy (88% vs 82%), but SBSE was more sensitive for the left anterior descending artery (97% vs 82%, p < 0.005) and for arteries involved in triple-vessel disease (93% vs 69%, p < 0.01) and more specific for the right coronary artery (88% vs 66%, p < 0.01). Supine bicycle exercise was associated with significantly lower maximal heart rates than treadmill exercise but with significantly higher systolic and diastolic blood pressures. There were no differences in heart rate x systolic blood pressure. We conclude that SBSE and SPECT are equally reliable for coronary disease detection in patients and for evaluation of disease in specific arteries with the exception of SBSE's higher sensitivity for the left anterior descending artery and arteries involved in triple-vessel disease and higher specificity for the right coronary artery.

The role of supine bicycle stress echocardiography (SBSE) for detecting restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 80 patients: 41 (51%) with single and 39 (49%) with multivessel PTCA (total 129 dilated vessels). Total revascularization was performed in 54 (68%) and partial revascularization in 26 (32%) patients. Restenosis was angiographically demonstrated in 60 patients (75%) and in 72 vessels (56%) 6.1 +/- 2.9 months after PTCA. The results for detecting restenosis were: (1) SBSE versus exercise electrocardiographic sensitivity, 87 versus 55% (p < 0.001); (2) specificity, 95 versus 79%; and (3) accuracy, 89 versus 61% (p < 0.001). SBSE was 83% sensitive, 95% specific and 88% accurate for restenosis detection in specific vessels with comparable results for single versus multivessel PTCA and total versus partial revascularization. Sensitivity, specificity and accuracy were: 91, 93 and 91% for the left anterior descending coronary artery; 77, 94 and 85% for the right coronary artery; and 76, 96 and 88% for the left circumflex coronary artery. Ninety-four percent of the nondilated diseased vessels were correctly identified. It is concluded that SBSE is an excellent tool for identifying restenosis after PTCA.

From July 1, 1990 to February 28, 1991, 533 consecutive patients with 764 target vessels and 1,000 lesions underwent coronary angioplasty. Procedural success was achieved in 92.3%, untoward (major cardiac) events occurred in 3% (0.8% myocardial infarction, 1.3% emergency coronary bypass grafting and 0.9% both; there were no deaths). An unsuccessful uncomplicated outcome occurred in 4.7%. Lesion analysis using a modified American College of Cardiology/American Heart Association classification system showed that 8% were type A, 47.5% were type B and 44.5% were type C (36% of type B and 11% of type C were occlusions). Angioplasty success was achieved in 99% of type A, 92% of type B and 90% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.01). Untoward events occurred in 1.2% of type A, 1.9% of type B and 2% of type C lesions (p = NS). An unsuccessful uncomplicated outcome occurred in 0% of type A, 6% of type B and 7% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.05). Among the unsuccessful uncomplicated outcome group, occlusion occurred in 49%: 38% of type B and 59% of type C lesions. With B1 and B2 subtypes, success was obtained in 95% and 89.5% and untoward events occurred in 1.5% and 2.3% and an unsuccessful uncomplicated outcome in 3.7% and 8%, respectively. C1 and C2 subtyping showed success in 91% and 86%, untoward events in 1.3% and 6% and an unsuccessful uncomplicated outcome in 7.5% and 8.5%, respectively. Among the 764 vessels, success was obtained in 89.5% and untoward events occurred in 2.5% and an unsuccessful uncomplicated outcome in 8%. Assessment of lesion-vessel combinations showed a less favorable outcome with type C lesions and combinations of A-B, B-C and multiple (more than three lesions) type B and C vessels. Statistical analysis of morphologic factors associated with angioplasty success included absence of (old) occlusion (p less than 0.0001) and unprotected bifurcation lesion (p less than 0.001), decreasing lesion length (p less than 0.003) and no thrombus (p less than 0.03). The only significant factor associated with untoward events was the presence of thrombus (p less than 0.003). Predictors of an unsuccessful uncomplicated outcome included old occlusion (p less than 0.0001) and increasing lesion length (greater than 20 mm) (p less than 0.001), unprotected bifurcation lesion (p less than 0.05) and thrombus (p less than 0.03).

One hundred sixteen patients were evaluated to determine the ability of single photon emission computed tomographic (SPECT) thallium-201 exercise and redistribution imaging to detect silent ischemia secondary to restenosis in asymptomatic patients after single and multiple vessel percutaneous transluminal coronary angioplasty and the findings were compared with SPECT imaging detection of restenosis in symptomatic patients. The value of exercise electrocardiography (ECG) and the amount of ischemic myocardium in symptomatic and asymptomatic patients were determined. Forty-one patients were asymptomatic after angioplasty; 77% of these had chest pain before angioplasty. Seventy-five patients had chest pain after angioplasty; 99% of these had chest pain before angioplasty. Restenosis occurred in 61% of asymptomatic and 59% of symptomatic patients and in 46% of the vessels in both asymptomatic and symptomatic patients. Sensitivity, specificity and accuracy for detection of restenosis by SPECT in individual patients were 96%, 75% and 88% versus 91%, 77% and 85%, respectively, in the asymptomatic versus symptomatic groups (p = NS). Sensitivity, specificity and accuracy for restenosis detection in individual vessels were 90%, 89% and 89% versus 84%, 77% and 84%, respectively, in the asymptomatic and symptomatic groups (p = NS), with similar results for the three major arteries. Sensitivity and accuracy of exercise ECG were significantly less than those of SPECT imaging for the patients with silent (40% and 44%) and symptomatic (59% and 64%) ischemia (p less than 0.001). Restenosis of vessels in the patients with silent and symptomatic ischemia was associated with an equal amount and degree of severity of ischemic myocardium in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of tomographic thallium-201 exercise and redistribution imaging in the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 116 patients: 61 (53%) with 1- and 55 (47%) with multivessel PTCA, with a total of 185 dilated vessels. Complete revascularization was performed in 89 (77%) and partial revascularization in 27 (23%) of the patients. Restenosis was angiographically demonstrated in 69 (60%) of the patients and 85 (46%) of the vessels 6.4 +/- 3.1 months after PTCA. Disease progression in previously normal vessels was noted in 11 patients. The results were: (1) for detection of restenosis in the group of patients, single-photon emission computed tomographic (SPECT) versus exercise electrocardiographic sensitivity was 93 vs 52% (p less than 0.001), specificity 77 vs 64%, and accuracy 86 vs 57% (p less than 0.001). The results were similar in the complete and partial revascularization groups. (2) SPECT was 86% sensitive, specific and accurate for restenosis detection in specific vessels with comparable results for 1-versus multivessel PTCA and complete versus partial revascularization. Sensitivity, specificity and accuracy were: 89, 95 and 92% for the left anterior descending coronary artery; 88, 79 and 82% for the right coronary artery; and 76, 83 and 85% for the left circumflex coronary artery. Eighty-one percent of the diseased nondilated vessels were correctly identified. (3) Disease progression to greater than 50% stenosis was detected with 91% sensitivity, 84% specificity and 85% accuracy. SPECT thallium-201 imaging is an excellent tool for the detection of restenosis and disease progression after PTCA in the settings of 1- and multivessel angioplasty and complete and partial revascularization.

Exercise-induced regional wall motion abnormalities on radionuclide angiography have been thought to be a reliable indicator of coronary artery disease. To evaluate their reliability, particularly in patients with valvular heart disease, exercise radionuclide angiography was performed in 12 normal subjects, 35 patients with coronary artery disease and 19 patients with valvular heart disease and normal coronary arteries. Exercise-induced regional wall motion abnormalities were found in none of the normal subjects, 63 percent of the patients with coronary artery disease and 42 percent of those with valvular heart disease and were predominantly inferoapical in location in the group with valvular heart disease. We conclude that exercise-induced regional wall motion abnormalities are not reliable for the detection of coronary artery disease in patients with valvular heart disease.

Left ventricular ejection fraction (LVEF) response to supine bicycle and isometric handgrip exercise was evaluated in 15 patients with documented coronary artery disease (CAD) and stress-induced ischemia using radionuclide angiography. For purposes of analysis, the patients were divided into two groups: group I (n = 7) with single-vessel disease and group II (n = 8) with multiple-vessel disease including 3 with left main artery disease. The studies were repeated 18 days later at similar external workloads to assess reproducibility of both tests. LVEF response to bicycle exercise was different for the two groups. The change in LVEF from rest to peak exercise was +0.04 +/- 0.02 for group I and -0.07 +/- 0.04 for group II (p less than .001). LVEP response to isometric handgrip exercise was not different between the two groups. The change from rest to end of handgrip exercise was -0.02 + 0.02 for group I and -0.05 +/- 0.02 for group II. The reproducibility of LVEF response to bicycle exercise at similar workloads on day 1 and day 19 was good (r = 0.85) while it was poor for isometric handgrip testing (r = 0.67). Our data demonstrate that radionuclide angiographic measurement of LVEF response to supine bicycle exercise testing is superior to LVEF response to isometric handgrip testing in the evaluation of patients with CAD.

Reverse redistribution (RR) i.e., worsening of images from exercise to redistribution, was noted in 21 (7%) of 300 consecutive thallium-201 (201TI) exercise and redistribution myocardial imaging studies. In 13, there were reversible defects consistent with ischemia in addition to redistribution defects. Twenty RR defects were noted in 15 patients who underwent cardiac catheterization; 9 had triple, 4 had double and 2 had single vessel coronary artery disease. Seventeen (85%) of the RR defects were in the distribution of severely diseased vessels; 8 with 100% occlusion and 9 with 90-99% stenosis. The remainder were associated with 50-60% stenoses. Ten RR areas (50%) were supplied by collateral vessels and 3 (15%) by bypass grafts. Fourteen of the 18 (78%) areas studied with left ventriculography were associated with abnormally contracting segments. These results suggest that RR is a marker for significant coronary artery disease.

Unlabelled: To compare the amount of myocardium jeopardized during silent ischemia and painful ischemia, 112 consecutive patients undergoing coronary arteriography with ischemia demonstrated by exercise and redistribution tomographic thallium-201 myocardial imaging (SPECT) were divided into two groups: 84 patients without anginal pain (silent ischemia) and 28 with pain (painful ischemia). The SPECT apical, mid and basal ventricular levels of the short-axis view and the apical portion of the long-axis view were divided into 20 segments. The results were 1) 7.4 +/- 4.7 ischemic segments in silent ischemia and 7.6 +/- 3.7 in painful ischemia (p = NS) with 4.7 +/- 3.6 segments in silent ischemia undergoing total redistribution compared with 5.4 +/- 3.4 in painful ischemia (p = NS); 2) no difference in the incidence of single, double or triple vessel disease between silent and painful ischemic groups; 3) similar anatomic distribution of ischemic segments between the two groups; 4) more positive exercise electrocardiographic (ECG) changes in painful ischemia (70%) than in silent ischemia (32%) (p less than 0.001) with equal amounts of ischemia associated with positive and negative exercise ECG findings., Conclusions: 1) Patients with silent and painful ischemia during exercise have similar amounts of ischemic myocardium demonstrated by tomographic thallium-201 imaging and similar extent of angiographically documented coronary artery disease despite the absence of pain and the lower incidence of positive exercise ECG findings in silent ischemia. 2) Positive and negative exercise ECG findings were associated with similar amounts of ischemic myocardium.

Two noninvasive tests to detect and localize coronary stenoses were compared in a fully blinded protocol. Thallium201 myocardial perfusion imaging (MPI) following maximal treadmill exercise and pharmacologic coronary vasodilation with intravenous dipyridamole (DP) was performed in 33 patients. Thallium201 imaging defects in six myocardial perfusion regions were correlated with stenoses in their respective vascular distributions. Disease severity was determined with coronary arteriograms using a computer-assisted method. 198 myocardial regions were evaluated; 101 were supplied by at least one major artery with a greater than or equal to 50% stenosis (luminal diameter narrowing). The sensitivity and specificity for detecting a greater than or equal to 50% stenosis were 85% and 64% (p less than 0.005), respectively, for DP and 84% and 68% (p less than 0.005) for exercise-thallium201 imaging. A particular combination of anterior and septal imaging defects was useful in detecting left anterior descending artery stenoses proximal to its first septal branch. DP administration was safe in this group of patients; however, 42% experienced transient chest pain. Although the overall sensitivity and specificity of the two methods were not significantly different, DP-MPI appeared more sensitive than exercise-MPI (70% vs 52%, p less than 0.01) in detecting coronary stenoses in the 40% to 60% range. DP-thallium201 MPI provides a useful alternative test for potential coronary disease patients unable to perform maximal exercise.

To evaluate the reproducibility of ejection fraction (EF) and regional wall motion (RWM) analyses by rest and exercise equilibrium radionuclide ventriculography (RNV) in the presence of coronary artery disease (CAD), 18 patients underwent two maximum, multistage supine bicycle exercise studies separated by an interval of 2 weeks. There were no significant differences in EF between the two studies, both at rest (56.0 +/- 13.8% vs 58.2 +/- 11.7%, p = NS) and with exercise (51.1 +/- 17.6% vs 54.3 +/- 17.6%, p = NS) and a highly significant correlation was shown between the two groups of values (rest r = 0.90, exercise r = 0.93, p less than 0.001). There was no significant difference in the change from rest to exercise (-4.9 +/- 12.0% vs -3.8 +/- 11.5%, p = NS) between the two studies and the correlation was highly significant (r = 0.69, p less than 0.01). The interstudy variabilities were 2.2 +/- 6.1% and 1.2 +/- 7.3% for rest and exercise, respectively, and 2.0 +/- 9.2% for the change from rest to exercise. Ninety-four percent of both rest and exercise regions had similar RWM. Eighty-one percent of the abnormally contracting regions were common to both exercise studies. Utilizing conventional criteria for the diagnosis of CAD, 11 patients had abnormal EF response and nine had abnormal RWM response to exercise on both studies. Combining EF and RWM criteria resulted in the diagnosis of CAD in 15 patients in both studies. We conclude that: (1) there were no significant differences in rest and exercise radionuclide EF and RWM between two supine bicycle exercise studies performed 2 weeks apart in patients with stable CAD and there were significant correlations between the two studies; (2) despite these correlations, the interstudy variabilities emphasize the need for the inclusion of reproducibility studies in all evaluations of interventions by exercise radionuclide ventriculography; and (3) the variations in EF and RWM response to exercise result in lack of uniformity between the two studies regarding the diagnosis of CAD based on conventional RNV criteria.

An angiographic assessment of the coronary arteries, the presence and quality of arterial collateralization and segmental left ventricular (LV) wall motion indicated that (a) in the presence of total or subtotal obstruction of a coronary artery, there was a significantly higher incidence of normal motion (p less than 0.001) if the segment of LV wall was supplied by good rather than poor collaterals, and (b) normal wall motion with good arterial collateralization was not associated with abnormal Q waves. It is concluded that a positive correlation exists between the quality of collateral filling and the preservation of LV wall motion in the area supplied.

Acebutolol is a new investigational beta-antagonist which has intrinsic sympathomimetic and cardioselective properties. In this study its effects on the ischemic consequences following supine bicycle exercise were compared to those of propranolol in 16 patients with chronic stable coronary artery disease (CAD) using a double-blind placebo crossover protocol and equilibrium radionuclide ventriculography. In eight patients (group I), the left ventricular ejection fraction (LVEF) at peak exercise fell under control conditions. During chronic acebutolol therapy (400 mg thrice daily), the exercise-induced LVEF (means +/- 1 SD) was significantly higher (37.1 +/- 15.5% versus 42.2 +/- 14.3%; p less than 0.05). The corresponding values during placebo and during propranolol (80 mg thrice daily) were 39.2 +/- 12.3% versus 43.4 +/- 14.8% (p = 0.07). In eight patients (group II) in whom supine bicycle exercise produced increases in LVEF, both acebutolol (58.8 +/- 5.4% versus 53.8 +/- 4.4%) and propranolol (57.8 +/- 5.7% versus 54.1 +/- 4.9%) attenuated the increases. In neither group was the resting LVEF reduced by acebutolol or propranolol. The data show that acebutolol and propranolol are approximately equipotent in minimizing the radionuclide left ventriculographic manifestations of myocardial ischemia induced by supine bicycle exercise.

The diagnostic and prognostic significance of plasma inactive creatine kinase B protein (CK-Bi) levels measured by radioimmunoassay was determined in various ischemic myocardial syndromes. In 120 stable angina patients free of pain at time of blood sampling, mean CK-Bi level was 114 +/- 42 (SD) micrograms-equiv/ml; 195 micrograms-equiv/ml (95% confidence interval) represented upper limit of normal. In seven coronary artery disease (CAD) patients atrial pacing induced ischemia was not associated with increased coronary sinus CK-Bi. Of 201 consecutive patients with suspected acute infarction (AMI), 45 developed ECG criteria of transmural AMI with concomitant increased plasma CK-Bi levels (498 +/- 133, range 372-718 micrograms-equiv/ml). Elevated CK-Bi levels in evolving transmural AMI were detected before raised CK enzyme activity. Elevated plasma CK-Bi levels also occurred in acute pericarditis and in unstable angina. In the 84 patients not developing ECG changes or elevated plasma CK activity, their plasma CK-Bi levels were also normal and no coronary events occurred in the next 6 months. The remaining 55 patients had nontransmural AMI, with 15 also having elevated plasma CK and CK-Bi levels, of whom six developed re-AMI in the next 3 months. In the other 40 nontransmural AMI patients, plasma CK-Bi levels (350 +/- 65 micrograms/equiv/ml, range 228 to 445) increased significantly without associated CK activity rise, and 24 developed re-AMI (three fatal) in the next 6 months. These data suggest that: (1) plasma CK-Bi protein radioimmunoassay measurement provides a sensitive means for detecting myocardial necrosis or inflammation and (2) elevated plasma CK-Bi levels in coronary disease patients during myocardial ischemic pain may afford identification of a CAD clinical subset at high risk of subsequent AMI.

Twenty-four patients with coronary artery disease were studied during cardiac catheterization to determine the effects of sustained isometric handgrip exercise and intravenous dipyridamole and their combination on coronary and systemic hemodynamics and measured coronary luminal caliber. During 4 to 5 minutes of 25 percent maximal handgrip, blood pressure and heart rate increased 24 and 19 percent, respectively, coronary sinus flow increased to 1.7 x baseline value, and epicardial coronary arteries constricted to increase predicted flow resistance by 40 percent in 36 diseased arterial segments. After a 4 minute intravenous infusion of dipyridamole (0.56 mg/kg body weight), systemic pressure decreased 8 percent, heart rate increased 23 percent, coronary sinus flow increased to 2.4 x baseline value and coronary luminal caliber was unchanged. During isometric handgrip initiated 6 minutes after the infusion of dipyridamole, systemic pressure and heart rate increased to 14 and 31 percent, respectively, above control values, coronary sinus flow increased to 3.3 x baseline value (3.8 x baseline value in patients with normal anterior perfusion) and stenotic flow resistance increased by 36 percent. The response of coronary flow to the combined stresses was 68 percent greater than the response to dipyridamole alone (p less than 0.02); these flow levels exceed values previously reported for the human coronary circulation. Aminophylline plus nitroglycerin appears to assure patient safety.