Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study.

BACKGROUND: Chest pain in the absence of obstructive coronary artery disease (CAD) is common in women; it is frequently associated with debilitating symptoms and repeated evaluations and may be caused by coronary microvascular dysfunction. However, the prevalence and determinants of microvascular dysfunction in these women are uncertain. METHODS: We measured coronary flow velocity reserve (coronary velocity response to intracoronary adenosine) to evaluate the coronary microvasculature and risk factors for atherosclerosis in 159 women (mean age, 52.9 years) with chest pain and no obstructive CAD. All women were referred for coronary angiography to evaluate their chest pain as part of the Women's Ischemia Syndrome Evaluation (WISE) study. RESULTS: Seventy-four (47%) women had subnormal (<2.5) coronary flow velocity reserve suggestive of microvascular dysfunction (mean, 2.02 +/- 0.38); 85 (53%) had normal reserve (mean, 3.13 +/- 0.64). Demographic characteristics, blood pressure, ventricular function, lipid levels, and reproductive hormone levels were not significantly different between women with normal and those with abnormal microvascular function. Postmenopausal hormone use within 3 months was significantly less prevalent among those with microvascular dysfunction (40% vs 60%, P =.032). Age and number of years past menopause correlated with flow velocity reserve (r = -0.18, P =.02, and r = -0.30, P <.001, respectively). No significant associations were identified between flow velocity reserve and lipid and hormone levels, blood pressure, and left ventricular ejection fraction. CONCLUSIONS: Coronary microvascular dysfunction is present in approximately one half of women with chest pain in the absence of obstructive CAD and cannot be predicted by risk factors for atherosclerosis and hormone levels. Therefore, the diagnosis of coronary microvascular dysfunction should be considered in women with chest pain not attributable to obstructive CAD.

Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory).

The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant ( > 50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in < 10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p < 0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk.

Results of the study to determine rotablator and transluminal angioplasty strategy (STRATAS).

Rotational atherectomy is used to debulk calcified or complex coronary stenoses. Whether aggressive burr sizing with minimal balloon dilation (<1 atm) to limit deep wall arterial injury improves results is unknown. Patients being considered for elective rotational atherectomy were randomized to either an "aggressive" strategy (n = 249) (maximum burr/artery >0.70 alone, or with adjunctive balloon inflation < or = 1 atm), or a "routine" strategy (n = 248) (maximum burr/artery < or =0.70 and routine balloon inflation > or =4 atm). Patient age was 62 +/- 11 years. Fifty-nine percent routine and 60% aggressive strategy patients had class III to IV angina. Fifteen percent routine and 16% aggressive strategy patients had a restenotic lesion treated; lesion length was 13.6 versus 13.7 mm. Reference vessel diameter was 2.64 mm. Maximum burr size (1.8 vs 2.1 mm), burr/artery ratio (0.71 vs 0.82), and number of burrs used (1.9 vs 2.7) were greater for the aggressive strategy, p <0.0001. Final minimum lumen diameter and residual stenosis were 1.97 mm and 26% for the routine strategy versus 1.95 mm and 27% for the aggressive strategy. Clinical success was 93.5% for the routine strategy and 93.9% for the aggressive strategy. Creatine kinase-myocardial band (CK-MB) was >5 times normal in 7% of the routine versus 11% of the aggressive group. CK-MB elevation was associated with a decrease in rpm of >5,000 from baseline for a cumulative time >5 seconds, p = 0.002. At 6 months, 22% of the routine patients versus 31% of the aggressive strategy patients had target lesion revascularization. Angiographic follow-up (77%) showed minimum lumen diameter to be 1.26 mm in the routine group versus 1.16 mm in the aggressive group, and the loss index 0.54 versus 0.62. Dichotomous restenosis was 52% for the routine strategy versus 58% for the aggressive strategy. Multivariable analysis indicated that left anterior descending location (odds ratio 1.67, p = 0.02) and operator-reported excessive speed decrease >5,000 rpm (odds ratio 1.74, p = 0.01) were significantly associated with restenosis. Thus, the aggressive rotational atherectomy strategy offers no advantage over more routine burr sizing plus routine angioplasty. Operator technique reflected by an rpm decrease of >5,000 from baseline is associated with CK-MB elevation and restenosis.

Physical activity and functional capacity measurement in women: a report from the NHLBI-sponsored WISE study.

Physical activity and functional capacity have not been assessed by questionnaire for criterion validity in women. We wished to evaluate the ability of a physical activity and a functional capacity assessment questionnaire to predict functional capacity measured by treadmill exercise stress testing, as well as correlate with cardiac risk factors and angiographic coronary artery disease (CAD) in women. In a National Heart, Lung and Blood Institute (NHLBI)-sponsored cross-sectional population study involving four academic medical centers, 476 women with cardiac risk factors undergoing coronary angiography for evaluation for suspected myocardial ischemia were enrolled in the Women's Ischemia Syndrome Evaluation (WISE). The main outcome measures were functional capacity measured during symptom-limited exercise treadmill testing, cardiac risk factors, and CAD, using core laboratory-determined measures. Physical activity measured by the Postmenopausal Estrogen and Progesterone Intervention physical activity questionnaire (PEPI-Q) and functional capacity measured by the Duke Activity Status Index (DASI) questionnaire, correlated with functional capacity measured in metabolic equivalents (METS), as estimated during symptom-limited exercise treadmill testing (r = 0.27, p = 0.001 and r = 0.31, p = 0. 0002, respectively). The DASI was a significant independent predictor of functional capacity even after adjustment for cardiac risk factors, and the PEPI-Q was not. The DASI and PEPI-Q scores were inversely associated with higher numbers and levels of cardiac risk factors, as well as angiographic CAD. The DASI questionnaire is a reasonable correlate of functional capacity achieved during symptom-limited treadmill exercise testing in women with suspected myocardial ischemia. Lower functional capacity or physical activity measured by the DASI and PEPI-Q, respectively, is associated with more prevalent cardiac risk factors and angiographic CAD. These findings suggest that the DASI and, to a lesser extent, the PEPI-Q have criterion validity for use in health-related research in women.

In vivo uptake of radiolabeled antibody to proliferating smooth muscle cells in a swine model of coronary stent restenosis.

UNLABELLED: Z2D3 is a monoclonal chimeric antibody fragment that is directed against a protein expressed on the surface of proliferating smooth muscle cells. The purpose of this study was to investigate the uptake of 111In-labeled Z2D3 F(ab')2 in a swine model of coronary neointimal proliferation after overexpansion coronary stenting. METHODS: Twenty-two domestic swine underwent overexpansion coronary stenting of 2 vessels. Fifteen swine survived 2-4 wk, at which time they received an injection of 111In Z2D3 F(ab')2 and underwent planar imaging. After the swine were killed, the hearts were excised and imaged on the detector. The cross-sectional area of each stented vessel was measured with digital morphometry. RESULTS: Pathology could be correlated with imaging for 24 vessels. The cross-sectional area of stenosis comprising neointimal proliferation ranged from 8% to 95%, with a mean +/- SD of 41% +/- 21%. The maximal stenosis ranged from 13% to 95%, with a mean of 51% +/- 20%. Seventeen of 24 vessels (71%) showed focal uptake on in vivo imaging, and 7 of 24 (29%) did not. Twenty of 24 (83%) showed uptake on ex vivo imaging. Of 11 stented vessels with maximal vessel stenosis less than 50%, 7 (64%) showed uptake both in vivo and ex vivo, and of 13 stented vessels with maximal vessel stenosis greater than 50%, 10 (77%) showed uptake both in vivo and ex vivo. CONCLUSION: Uptake of a radiolabeled antibody directed against a component of proliferating neointimal tissue can be visualized in the coronary arteries on in vivo imaging using a scintillation gamma camera.

Accuracy of dipyridamole SPECT imaging in identifying individual coronary stenoses and multivessel disease in women versus men.

BACKGROUND: Older women frequently undergo dipyridamole perfusion imaging and can have advanced coronary artery disease, but little data exist on the accuracy of perfusion imaging in detecting disease in individual vascular territories and multivessel disease in women, compared with men. METHODS AND RESULTS: From a database of patients undergoing myocardial single photon emission computed tomography (SPECT) perfusion imaging, 107 unselected sequential patients (58 women, 49 men) who underwent sestamibi dipyridamole stress and cardiac catheterization within 6 months of each other were identified. Data were analyzed to compare sensitivities for detection of individual coronary stenoses and multivessel disease. The concordance between perfusion image results and cardiac catheterization for individual coronary territories for women was 75%, and for men, it was 65% (P = .09). In women, the presence of disease of the left anterior descending coronary artery was detected more frequently than it was in men, 84% versus 44% (P = .004). The detection of disease in the territories of the left circumflex and right coronary arteries was similar for both groups. For women, the accuracy of perfusion imaging in identifying the presence/absence of multivessel coronary disease was 64%, compared with 71 % for men (P = not significant). CONCLUSIONS: The accuracy of dipyridamole sestamibi SPECT imaging in detecting multivessel disease was similar for men and women. The sensitivity of dipyridamole sestamibi SPECT imaging in detecting disease of the left anterior descending artery was better in women.

Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms.

BACKGROUND: After hospitalization for chest pain, women are more likely than men to have normal coronary-artery angiograms. In such women, myocardial ischemia in the absence of clinically significant coronary-artery obstruction has long been suspected. Most methods for the detection of the metabolic effects of myocardial ischemia are highly invasive. Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy is a noninvasive technique that can directly measure high-energy phosphates in the myocardium and identify metabolic evidence of ischemia. METHODS: We enrolled 35 women who were hospitalized for chest pain but who had no angiographically significant coronary-artery obstructions and 12 age- and weight-matched control women with no evidence of heart disease. Myocardial high-energy phosphates were measured with 31P-NMR spectroscopy at 1.5 tesla before, during, and after isometric handgrip exercise at a level that was 30 percent of the maximal voluntary grip strength. We measured the change in the ratio of phosphocreatine to ATP during exercise. RESULTS: Seven (20 percent) of the 35 women with chest pain and no angiographically significant stenosis had decreases in the phosphocreatine:ATP ratio during exercise that were more than 2 SD below the mean value in the control subjects without chest pain. There were no significant differences between the two groups with respect to hemodynamic variables at rest and during exercise, risk factors for ischemic heart disease, findings on magnetic resonance imaging and radionuclide perfusion studies of the heart, or changes in brachial flow during the infusion of acetylcholine. CONCLUSIONS: Our results provide direct evidence of an abnormal metabolic response to handgrip exercise in at least some women with chest pain consistent with the occurrence of myocardial ischemia but no angiographically significant coronary stenoses. The most likely cause is microvascular coronary artery disease.

Preconditioning myocardium with demand ischemia in the presence of a critical coronary artery stenosis.

The relative importance of adrenergic stimulation and demand ischemia as important preconditioning stimuli remains unclarified. The purpose of this investigation was to use a partial coronary stenosis to define the preconditioning role of demand ischemia. Dobutamine was infused intravenously before coronary occlusion in closed-chest swine with and without an artificial coronary stenosis in the mid-left anterior descending coronary artery. Control animals had no stenosis and did not receive dobutamine before occlusion. All three groups underwent 45 minutes of occlusion followed by 120 minutes of reperfusion. At baseline, regional myocardial blood flow in the area at risk was reduced in animals with a stenosis, but global left ventricular systolic function, measured by gated blood pool scan, was equivalent in all three groups. Animals with and without a stenosis received equivalent catecholamine stress with dobutamine, but only animals with a stenosis manifested ischemia during the infusion. At 2 hours after reperfusion, infarct size as a percentage of the area at risk was smaller in animals with a stenosis given dobutamine. Demand ischemia preconditions myocardium in closed-chest swine. Increased demand alone without ischemia had marginal preconditioning effects. This may have clinical relevance to patients with severe stenoses exposed to stressful stimuli before the development of myocardial infarction.

Influence of pre-PTCA strategy and initial PTCA result in patients with multivessel disease: the Bypass Angioplasty Revascularization Investigation (BARI).

BACKGROUND: In PTCA patients with multivessel coronary artery disease, incomplete revascularization (IR) is the result of both pre-PTCA strategy and initial lesion outcome. The unique contribution of these components on long-term patient outcome is uncertain. METHODS AND RESULTS: From the Bypass Angioplasty Revascularization Investigation (BARI), 2047 patients who underwent first-time PTCA were evaluated. Before enrollment, all significant lesions were assessed by the PTCA operator for clinical importance and intention to dilate. Complete revascularization (CR) was defined as successful dilatation of all clinically relevant lesions. Planned CR was indicated in 65% of all patients. More lesions were intended for PTCA in these patients compared with those with planned IR (2.8 versus 2.1). Successful dilatation of all intended lesions occurred in 45% of patients with planned CR versus 56% with planned IR (P<0. 001). In multivariable analysis, planned IR (versus planned CR), initial lesions attempted (not all versus all intended lesions attempted), and initial lesion outcome (not all versus all attempted lesions successful) were unrelated to 5-year risk of cardiac death or death/myocardial infarction but were all independently related to risk of CABG. CONCLUSIONS: Overall, a pre-PTCA strategy of IR in BARI-like patients appears comparable to a strategy of CR except for a higher need for CABG. Whether the use of new devices may attenuate the elevated risk of CABG in patients with multivessel disease and planned IR remains to be determined.

The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report.

OBJECTIVES: The Women's Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute-sponsored, four-center study designed to: 1) optimize symptom evaluation and diagnostic testing for ischemic heart disease; 2) explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenoses, and 3) evaluate the influence of reproductive hormones on symptoms and diagnostic test response. BACKGROUND: Accurate diagnosis of ischemic heart disease in women is a major challenge to physicians, and the role reproductive hormones play in this diagnostic uncertainty is unexplored. Moreover, the significance and pathophysiology of ischemia in the absence of significant epicardial coronary stenoses is unknown. METHODS: The WISE common core data include demographic and clinical data, symptom and psychosocial variables, coronary angiographic and ventriculographic data, brachial artery reactivity testing, resting/ambulatory electrocardiographic monitoring and a variety of blood determinations. Site-specific complementary methods include physiologic and functional cardiovascular assessments of myocardial perfusion and metabolism, ventriculography, endothelial vascular function and coronary angiography. Women are followed for at least 1 year to assess clinical events and symptom status. RESULTS: In Phase I (1996-1997), a pilot phase, 256 women were studied. These data indicate that the WISE protocol is safe and feasible for identifying symptomatic women with and without significant epicardial coronary artery stenoses. CONCLUSIONS: The WISE study will define contemporary diagnostic testing to evaluate women with suspected ischemic heart disease. Phase II (1997-1999) is ongoing and will study an additional 680 women, for a total WISE enrollment of 936 women. Phase III (2000) will include patient follow-up, data analysis and a National Institutes of Health WISE workshop.

Dobutamine stress echocardiography in women with chest pain. Pilot phase data from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE).

OBJECTIVES: The aim of this project was to assess the utility of dobutamine stress echocardiography (DSE) for evaluation of women with suspected ischemic heart disease. BACKGROUND: Most investigations addressing efficacy of diagnosis and treatment of coronary artery disease (CAD) have been performed in predominantly male populations. As part of the Women's Ischemia Syndrome Evaluation (WISE) study, DSE was assessed in women participating at the University of Florida clinical site. METHODS: Women with chest pain or other symptoms suggestive of myocardial ischemia and clinically indicated coronary angiography were eligible for the WISE study. Enrolled subjects underwent DSE using a modified protocol. Coronary stenosis was assessed by core laboratory quantitative coronary angiography (QCA). RESULTS: The 92 women studied ranged in age from 34 to 82 years (mean 57.5). All women had > or = 1 major risk for CAD, and most (89, 97%) had > or = 2 risk factors. In 78 women (85%), left ventricular wall motion was normal at baseline and during peak infusion. The remaining 14 women had wall motion abnormalities during DSE. By QCA, 25 women (27%) had > or = 50% coronary stenosis, including 10 with single-vessel obstruction. Dobutamine stress echocardiography was abnormal in 10 of these 25 women, yielding overall sensitivity of 40%, and 60% for multivessel stenosis. Exclusion of women with inadequate heart rate response yielded overall sensitivity of 50%, and 81.8% for multivessel stenosis. Dobutamine stress echocardiography was normal in 54 of the 67 women with < 50% coronary narrowing, specificity 80.6%. CONCLUSIONS: Dobutamine stress echocardiography reliably detects multivessel stenosis in women with suspected CAD. However, DSE is usually negative in women with single-vessel stenosis, and in the larger subset without coronary stenosis. Ongoing protocols of the WISE study are expected to improve diagnostic accuracy in women with single-vessel disease, as well as provide important data in the substantial number of women with chest pain but without epicardial coronary artery stenosis.

Is a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization acceptable in nondiabetic patients who are candidates for coronary artery bypass graft surgery? The Bypass Angioplasty Revascularization Investigation (BARI).

OBJECTIVES: Our objective was to determine whether a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization (IR) compromises long-term patient outcome. BACKGROUND: Complete angioplasty revascularization (CR) is often not planned nor attempted in patients with multivessel coronary disease, and the extent to which this influences outcome is unclear. METHODS: Before randomization, in the Bypass Angioplasty Revascularization Investigation, all angiograms were assessed for intended CR or IR via angioplasty. Outcomes were compared among patients with IR intended if assigned to angioplasty, randomized to coronary artery bypass graft surgery (CABG) versus angioplasty; and within angioplasty patients only, among patients with IR versus CR intended. RESULTS: At 5 years, there was a trend for higher overall (88.6% vs. 84.0%) and cardiac survival (94.5% vs. 92.1%) in CABG versus angioplasty patients with IR intended. The excess mortality in angioplasty patients occurred solely in diabetic subjects; overall and cardiac survival were similar among nondiabetic CABG and angioplasty patients. Freedom from myocardial infarction (MI) at 5 years was higher in nondiabetic CABG versus angioplasty patients (92.4% vs. 85.2%, p = 0.02), vet was similar to the rate observed (85%) in nondiabetic CABG and angioplasty patients with CR intended. Five-year rates of death, cardiac death, repeat revascularization and angina were similar in all angioplasty patients with IR versus CR intended. However, a trend for greater freedom from subsequent CABG was seen in CR patients (70.3% vs. 64.0%, p = 0.08). CONCLUSIONS: Intended incomplete angioplasty revascularization in nondiabetic patients with multivessel disease who are candidates for both angioplasty and CABG does not compromise long-term survival; however, subsequent need for CABG may be increased with this strategy. Whether the risk of long-term MI is also increased remains uncertain.

Novel perfusion sleeve for use during balloon angioplasty: initial clinical experience.

The perfusion sleeve (PS) is an "over-the-balloon" catheter designed to add perfusion capability to standard PTCA catheters. To evaluate the clinical effectiveness of this device, eight patients underwent standard PTCA with the PS retracted in the guide (Inflation 1-Control) and after deployment of the PS (Inflation 3-Control). Between standard inflations the PS was advanced and aligned with the already positioned PTCA balloon which was inflated for up to 15 minutes (Inflation 2-Perfusion). TIMI III flow was present in 5/7 and TIMI II flow in 2/7 patients during Inflation 2-Perfusion. Absolute ST segment shift (mm) on the ECG was significantly less at 3 minutes and prior to balloon deflation with the PS in place (1.0 +/- 1.4 and 1.1 +/- 1.1 mm) compared to Inflation 1-Control and Inflation 3-Control (2.6 +/- 1.3 and 2.3 +/- 0.3 mm) respectively (P < or = 0.05). Use of the PS in conjunction with standard PTCA is feasible, provides perfusion during prolonged balloon inflations and reduces the magnitude of ischemia.

Clinical and detailed angiographic findings in patients with ambulatory electrocardiographic ischemia without critical coronary narrowing: results from the Asymptomatic Cardiac Ischemia Pilot (ACIP) Study.

BACKGROUND: Patients with ambulatory electrocardiographic (AECG) ST-segment depression and critical coronary narrowing are known to be at increased risk for adverse outcome, but little is known about patients with AECG ST-segment depression without critical coronary narrowing. HYPOTHESIS: The objectives of this study were to characterize the coronary angiographic pathology in patients with AECG ST-segment depression but without critical (< 50% diameter stenosis) coronary narrowing and to compare demographic and clinical findings in these patients with those enrolled in the Asymptomatic Cardiac Ischemia Pilot Study with AECG ST-segment depression and critical (> or = 50% diameter stenosis) coronary narrowing. METHODS: Coronary angiograms from patients with AECG ST-segment depression were reviewed in a central laboratory and quantitative measurement of percent stenosis was performed. Clinical and angiographic comparisons were made between patients with and without critical coronary narrowing. RESULTS: Patients without critical coronary narrowing (n = 64) were younger (p = 0.02), less likely to be male (p < 0.001) or to have risk factors for coronary atherosclerosis or a history of myocardial infarction (p < 0.001), and had fewer ischemic episodes per 24 h on the screening AECG (p = 0.02) than patients with critical coronary narrowing (n = 441). Of patients without critical narrowing, one half had angiographic evidence for coronary artery disease (> or = 20% stenosis) and 60% had an ejection fraction > 70%. CONCLUSIONS: Patients with AECG ST-segment depression without critical coronary narrowing are heterogeneous, with half having measurable coronary artery disease. Demographically and clinically, they appear to be different than patients with AECG ST-segment depression with critical coronary narrowing.

Relation between ambulatory electrocardiographic monitoring and myocardial perfusion imaging to detect coronary artery disease and myocardial ischemia: an ACIP ancillary study. The Asymptomatic Cardiac Ischemia Pilot (ACIP) Investigators.

OBJECTIVES: This study sought to explore the relation between markers of ischemia detected by ambulatory electrocardiographic (AECG) monitoring and stress myocardial perfusion single-photon emission computed tomography (SPECT). BACKGROUND: Stress myocardial SPECT and AECG monitoring are both utilized in evaluating patients with coronary artery disease. However, information is limited regarding the relation between the presence and extent of ischemia as detected by these two modalities. METHODS: This was an ancillary study of the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial. One hundred six patients with previous coronary angiography underwent AECG monitoring and stress SPECT within a close temporal time period. The frequency and duration of ischemia as assessed by AECG monitoring and the total and ischemic stress-induced myocardial perfusion defect sizes as assessed by SPECT were quantified in separate core laboratories. Multivariate logistic regression and linear regression analysis were used to determine associations between AECG and SPECT abnormalities with regard to angiographic, demographic and treadmill exercise variables. RESULTS: Seventy-four percent of patients with significant (> or = 50%) coronary artery stenosis had SPECT abnormalities, whereas 61% had ischemia by AECG monitoring. The most important predictors of SPECT abnormalities were severity (p < 0.001) of coronary artery stenosis, followed by total exercise duration (p = 0.016) and patient age (p = 0.04). The only predictor of AECG abnormalities was the presence of ST segment depression on the initial exercise treadmill test (p = 0.021). Only a 50% concordance for normalcy or abnormalcy was observed between the SPECT and AECG results, and no relation was observed between the frequency or duration of AECG ischemia and the quantified total or ischemic myocardial perfusion defect size as assessed by SPECT. CONCLUSIONS: Ischemia as detected by AECG monitoring does not correlate with the presence and extent of ischemia as quantified by stress SPECT. Because these techniques appear to detect different pathophysiologic manifestations of ischemia, they may be complementary in more fully defining the functional significance of coronary artery disease and, in particular, which patients are at highest risk for adverse cardiac events.

A detailed angiographic analysis of patients with ambulatory electrocardiographic ischemia: results from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study angiographic core laboratory.

OBJECTIVES: The purpose of this Asymptomatic Cardiac Ischemia Pilot (ACIP) data bank study was to characterize angiographic features of coronary pathology of patients enrolled in the ACIP study. BACKGROUND: Ischemia during ambulatory electrocardiographic (AECG) monitoring is associated with increased morbidity and mortality. Reports relating AECG ischemia to severity or complexity of coronary artery disease are few in number and small in size and have produced conflicting results. METHODS: Coronary angiograms from patients with asymptomatic AECG ischemia enrolled in the ACIP study were reviewed at a central core laboratory. Quantitative measurement of percent stenosis and Thrombolysis in Myocardial Infarction flow grades were used to assess the severity of coronary artery disease. Lesions were also evaluated for the presence of intracoronary thrombus, ulceration and lumen contour as indicators of stenosis complexity. In addition, comparisons were made with 27 patients screened for the ACIP study, but who were found ineligible because they did not have AECG ischemia on 48-h Holter monitoring. RESULTS: A total of 329 (75%) of 439 patients with AECG ischemia had multivessel coronary artery disease. Proximal stenoses > or = 50% diameter reduction were common in patients with AECG ischemia (62.2%), as were proximal stenoses > or = 70% (38.7%). Features suggesting complex plaque were found in 50.1% of patients with AECG ischemia. CONCLUSIONS: Multivessel coronary artery disease, severe proximal stenoses and features of complex plaque were observed frequently in patients who exhibited AECG ischemia. The presence of severe and complex coronary artery disease may explain, in part, the increased risk for adverse outcome associated with ischemia during activities of daily life.

Results of percutaneous transluminal coronary angioplasty in unstable angina and non-Q-wave myocardial infarction. Observations from the TIMI IIIB Trial.

BACKGROUND: This report describes the results of percutaneous transluminal coronary angioplasty (PTCA) in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB Investigation. METHODS AND RESULTS: PTCA was performed before hospital discharge in 444 of 1473 patients with either unstable angina pectoris or non-Q-wave myocardial infarction (NQWMI) enrolled in TIMI IIIB. Angiographic success was observed in 96.1% of patients. For the entire cohort, the cumulative incidences of death and infarction at 1 year were 2.0% and 8.2%, respectively. The periprocedural incidence of myocardial infarction was 2.7%; emergency coronary bypass surgery, 1.4%; and death, 0.5%. By 1 year of follow-up, 122 patients (28.0%, Kaplan-Meier) had an additional revascularization procedure, 75 (61.5%) had PTCA only, 30 (24.6%) had coronary bypass surgery only, and 17 (13.9%) had both procedures. The results of PTCA were not improved by routine pretreatment with intravenous tissue plasminogen activator (TPA). Periprocedural myocardial infarction was more common among patients receiving TPA than placebo (odds ratio [OR], 2.19; P = .03) and among those with unstable angina than those with NQWMI (OR, 15.5; P = .007). No difference in outcome was observed when patients were analyzed according to age (OR, 1.06; P = .092) or sex (OR, 1.54; P = .51). Variables predictive of poor outcome were PTCA within the first 24 hours of enrollment, PTCA site being the left anterior descending coronary artery, and unsuccessful angiography. CONCLUSIONS: In TIMI IIIB, PTCA was performed for patients with unstable angina and NQWMI with a very high rate of angiographic success and a low incidence of complications. By 1 year, repeat revascularization was performed in 28.0% of patients. Routine pretreatment with thrombolysis did not enhance outcome.

Clinical and arteriographic characterization of patients with unstable angina without critical coronary arterial narrowing (from the TIMI-IIIA Trial).

Previous studies have reported that some patients presenting with unstable angina are found at coronary angiography to have no critical coronary stenosis. This study evaluated the clinical presentation and arteriographic findings in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI-IIIA) trial, which assessed the effect of tissue-type plasminogen activator added to conventional therapy on the coronary arteriographic findings in patients presenting with ischemic pain at rest. Three hundred ninety-one patients were enrolled in the TIMI-IIIA trial and underwent coronary arteriography within 12 hours of enrollment. Fifty-three patients (14%) had no luminal diameter stenosis of a major coronary artery of > or = 60% on the baseline arteriogram. Compared with patients with unstable angina with an identifiable culprit lesion, patients without critical coronary obstruction were more likely to be women and non-white and less likely to have ST-segment deviation on the presenting electrocardiogram. Arteriography in such patients revealed no visually detectable coronary stenosis in half of the group; the remaining patients had noncritical coronary narrowing (i.e., < 60% luminal diameter stenosis) without morphologic features (ulceration or thrombus) suggestive of unstable or active coronary plaque. Nearly one third of the patients without critical coronary stenosis had impaired angiographic filling, suggesting a possible pathophysiologic role for coronary microvascular dysfunction. These patients with unstable angina and no critical coronary obstruction had an excellent short-term prognosis; 2% died or had myocardial infarction compared with 18% of patients with critical obstruction.

Safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator potentially suitable for either prehospital or in-hospital administration.

The safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator (rt-PA) potentially suitable for either pre- or in-hospital administration were assessed in 60 patients with acute myocardial infarction in an open label coronary angiographic study. The regimen consisted of a 20-mg bolus dose followed 30 min later by a delayed infusion of 80 mg over 2 h. This regimen was designed to facilitate prehospital administration of rt-PA. Infarct-related artery patency (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) was observed in 40 of 53 patients at 60 min (75.5%, 95% confidence intervals [CI] 61% to 84%) and in 55 of 60 patients at 90 min (91.7%, 95% CI 80% to 95%) after the rt-PA bolus. By 90 min the majority of patients (55%) exhibited TIMI grade 3 flow; infarct artery patency at 120 min was 84.9%. During hospitalization definite recurrent ischemia occurred in nine patients (15%); nonfatal recurrent infarction was noted in one (1.7%). Four patients (6.7%) experienced major bleeding, including one with intracranial bleeding. There were seven deaths (11.7%). Mortality was significantly influenced by the occurrence of cardiogenic shock, which was present in five patients at the time of enrollment. Blood fibrinogen levels were obtained before and during rt-PA infusion. At baseline and 30 and 150 min after the bolus dose, the mean fibrinogen level (+/- SD) was 284.83 +/- 77.39, 237.96 +/- 76.92 and 192.04 +/- 57.82 mg/dl, respectively. Compared with the baseline value, there was a significant (p less than 0.05) decrease in fibrinogen at both 30 and 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)