Prognostic value of stress echocardiogram in patients with angiographically significant coronary artery disease

The purpose of this study was to evaluate the prognostic value of stress echocardiography in patients with angiographically significant coronary artery disease (CAD). Two hundred sixty patients (mean age 63 ± 10 years, 58% men) who underwent stress echocardiography (41% treadmill, 59% dobutamine) and coronary angiography within 3 months and without intervening coronary revascularization were evaluated. All patients had significant CAD as defined by coronary stenosis ≥70% in major epicardial vessels or branches (45% had single-vessel disease, and 55% had multivessel disease). The left ventricle was divided into 16 segments and scored on a 5-point scale of wall motion. Patients with abnormal results on stress echocardiography were defined as those with stress-induced ischemia (increase in wall motion score of ≥1 grade). Follow-up (3.1 ± 1.2 years) for nonfatal myocardial infarction (n = 23) and cardiac death (n = 6) was obtained. In patients with angiographically significant CAD, stress echocardiography effectively risk stratified normal (no ischemia, n = 91) in contrast to abnormal (ischemia, n = 169) groups for cardiac events (event rate 1.0%/year vs 4.9%/year, p = 0.01). Multivariate logistic regression analysis identified multivessel CAD (hazard ratio 2.53, 95% confidence interval 1.16 to 5.51, p = 0.02) and number of segments in which ischemia was present (hazard ratio 4.31, 95% confidence interval 1.29 to 14.38, p = 0.01) as predictors of cardiac events. A Cox proportional-hazards model for cardiac events showed small, significant incremental value of stress echocardiography over coronary angiography (p = 0.02) and the highest global chi-square value for both (p = 0.004). In conclusion, in patients with angiographically significant CAD, (1) normal results on stress echocardiography conferred a benign prognosis (event rate 1.0%/year), and (2) stress echocardiographic results (no ischemia vs ischemia) added incremental prognostic value to coronary angiographic results, and (3) stress echocardiography and coronary angiography together provided additive prognostic value, with the highest global chi-square value.     

Intravascular ultrasound for angiographically indeterminant left main coronary artery disease

The precise diagnosis of the presence of significant left main coronary artery disease has profound prognostic and therapeutic implications. Coronary cineangiography has shown to be imprecise and inaccurate to determine the percent stenosis of the left main coronary artery. We report a case with significant left main coronary artery disease in whom coronary cineangiography was in discordance with the clinical data and intravascular ultrasonography. Based on the intravascular ultrasound findings, the patient underwent coronary artery bypass graft surgery. Therefore, the intravascular ultrasonography may be the procedure of choice for assessing indeterminant left main coronary artery lesions by coronary angiography.     

Reproducibility of serial intravascular ultrasound measurements in patients with angiographically silent coronary artery disease after heart transplantation

BACKGROUND: Intracoronary ultrasound (ICUS) imaging is the most sensitive method for the early detection and serial evaluation of vasculopathy of transplants. Both lack of agreement between observers and lack of agreement between serial, independent pullback procedures (repeatability), which can result in a variable intraluminal catheter position may limit the reproducibility of ICUS measurements. OBJECTIVE: To evaluate the reproducibility of serial measurements of standard linear and area cross-sectional coronary dimensions in patients with non-obstructive transplant vasculopathy. METHODS: We performed ICUS imaging of patients without angiographic evidence of obstructive epicardial coronary artery disease after heart transplantation. A 30 MHz phased-array transducer was used. Two independent pullbacks of the left anterior descending coronary artery were performed and recorded on CD-ROM for off-line quantitative analysis of the most severely diseased site. Agreement of observers and repeatability of serial measurements were calculated by the use of linear regression analysis and Bland-Altman plots. RESULTS: Regarding agreement of observers, correlation coefficients for intra-observer agreement ranged from r = 0.98 to r = 0.99; those for interobserver agreement ranged from r = 0.87 to r = 0.98. Serial measurements of the identical coronary artery cross-section within independent catheter pullback procedures were possible for 104 of 112 target lesions (92.90/%). Correlation coefficients ranged from r = 0.91 to r = 0.97 (for lumen diameter r = 0.91, for lumen area r = 0.93, for vessel diameter r = 0.91, for vessel area r = 0.97, for thickness of plaque r = 0.96 and for area of plaque 0.94). The mean difference of measurements was around zero for all parameters with SD from 0.13 to 0.4 mm for linear parameters and from 1.53 to 1.82 mm2 for area parameters. CONCLUSION: Serial intravascular ultrasound measurements are highly reproducible without any evidence of systematic error and a SD of differences of measurements beyond the maximal spatial resolution of currently available intravascular ultrasound catheters.     

Intima-media thickness of the common carotid artery is the significant predictor of angiographically proven coronary artery disease

BACKGROUND: Previous studies have shown a relationship between intima-media thickness (IMT) of the common carotid artery and coronary artery disease (CAD). The role of IMT in the prediction of significant CAD has not been established. OBJECTIVES: To investigate the diagnostic accuracy of IMT measurement and the detection of carotid plaques in relation to cardiovascular risk factors in the prediction of significant CAD. PATIENTS AND METHODS: One hundred and seventy patients (121 men and 49 women; average age 58 +/- 11 years) undergoing selective coronary angiography were examined by carotid ultrasound. IMT was measured. Plasma lipid concentrations and other risk factors were determined. RESULTS: Angiographically proven significant CAD was found in 138 (81%) of all patients. Carotid plaques were detected in 98 (58%) of all patients. Presence of carotid plaques in common carotid artery (P<0.001) and male sex (P<0.005) were found to be categorical risk factors for significant CAD but in multiple regression analysis only age (P=0.15), IMT (P<0.01), high density lipoprotein (HDL) cholesterol (P=0.02) and, less significantly, total cholesterol (P=0.09) were found to be independent parameters for the prediction of significant CAD. IMT of 0.75 mm was determined as a cut-off point for the detection of significant CAD (sensitivity 78%, specificity 79%, positive predictive value 95%, negative predictive value 41%, odds ratio 12.9, 95% CI 3.5 to 47.6). CONCLUSION: The increase in IMT is the significant positive predictor of angiographically proven CAD; other predictors are high age, low HDL cholesterol and, less significantly, high total cholesterol. Presence of carotid plaques and male sex do not add any new information for the prediction of CAD once the predictors are considered.     

Intravascular ultrasound assessment of longitudinal plaque distribution patterns in patients with angiographically silent coronary artery disease after heart transplantation

AIMS: The purpose of this three-dimensional intracoronary ultrasound (ICUS) study was to assess longitudinal plaque distribution patterns in patients with angiographically silent coronary artery disease (CAD) after heart transplantation (HTX). METHODS AND RESULTS: Out of 334 patients without diameter stenosis >/=25% determined by coronary angiography, 321 underwent successful three-dimensional ICUS (30 MHz) of the left main coronary artery (LMCA) and all segments of the left anterior descending coronary artery (LAD). Early plaque formation was found in 296 patients (92.2%). Single (focal CAD, n = 65) or multiple (polyfocal CAD, n = 77), discrete coronary lesions were found in 142 patients and continuous plaque formation of at least one entire coronary segment (diffuse CAD) in 154 patients. Using multivariate regression analysis, male sex (P = 0.01), increasing post-transplantation time (P = 0.003) and increasing donor age (P = 0.001) were independent clinical predictors for diffuse CAD. Both focal and diffuse CAD most frequently affected the proximal LAD (88% compared with 89.6%, NS). The mean intimal index of each LAD segment was significantly higher in patients with diffuse CAD (P < 0.001) and showed a proximal-to-distal decline in patients with focal/polyfocal (LMCA, 10.1 +/- 14.3, LAD-6, 30.1 +/- 17.4%, LAD-7, 16.3 +/- 14.1%, LAD-8, 4.6 +/- 11.1%; P < 0.001) and diffuse (LMCA, 27.0 +/- 16.0, LAD-6, 47.8 +/- 16.1%, LAD-7, 41.9 +/- 14.5%, LAD-8, 24.9 +/- 23.3%; P < 0.01) CAD. CONCLUSION: Evaluation of longitudinal plaque distribution after HTX by three-dimensional ICUS revealed a time-dependent increase in the incidence of diffuse CAD and a proximal-to-distal decline in frequency and magnitude of early plaque formation.     

Cocaine use in an urban medical population and the development of angiographically significant coronary artery disease

Cocaine is a common drug of abuse in the United States. Although long-term cocaine use has been associated with premature coronary artery disease (CAD), the relationship between cocaine use and the presence of angiographically significant CAD (> or =70%) is not clear. A retrospective analysis of all patients who had undergone cardiac catheterization at an urban medical center over a 1-year period was performed. Five hundred twelve patients were enrolled in the study; 84 (16.4%) had evidence of cocaine use, and 111 (21.7%) were admitted with a myocardial infarction. At the time of cardiac catheterization, 31 (36.9%) cocaine-positive patients had > or =70% stenosis in at least one epicardial vessel, compared with 200 (46.7%) cocaine-negative patients (p = 0.09). Although a trend toward an association was noted on unadjusted analysis, after adjusting for CAD risk factors, cocaine use was not associated with angiographically significant CAD (odds ratio, 0.9; 95% confidence interval, 0.55-1.5; p = 0.7).     

Presentation and late outcome of myocardial infarction in the absence of angiographically significant coronary artery disease

To determine the natural history of myocardial infarction (MI) in the absence of angiographically significant (no lesion greater than or equal to 50% diameter stenosis) fixed coronary artery disease (CAD), clinical and angiographic data and late outcome were studied in 43 such patients. The mean age was 45 +/- 11 years; 32 patients (74%) were cigarette smokers. Mild fixed CAD, present in 38 patients (88%), was more frequent in the artery supplying the MI zone (p less than 0.01). Filling defects or serial angiographic resolution of obstruction in the artery supplying the MI zone were present in 14 patients (33%). At late follow-up, 14 major cardiac events occurred in 9 patients, including revascularization in 3, recurrent MI in 6 and cardiac death in 5. Of 35 patients undergoing catheterization within 1 year of the index MI, cumulative risk of a major cardiac event was 9 +/- 4, 12 +/- 5 and 20 +/- 7% at 3, 19 and 37 months, respectively. Myocardial infarction in the absence of significant fixed CAD tends to occur in young smokers with mild CAD in the artery serving the MI zone. Superimposed intracoronary thrombus can be frequently implicated. In these patients, subsequent major cardiac events may occur more frequently than previously reported.     

Detection of coronary artery disease with a continuous infusion of definity ultrasound contrast during adenosine stress real time perfusion echocardiography

BACKGROUND: Myocardial perfusion imaging during adenosine stress is an accurate method of detecting physiologically relevant coronary artery disease. METHODS: Real time perfusion echocardiography (RTPE) was compared to nuclear scintigraphy (rest Thallium, stress Sestamibi) in 40 patients with intermediate to high pretest probability. RTPE was performed with a continuous infusion of intravenous microbubbles (Definity; Bristol Myers Squibb) and intermittent high mechanical index impulses, with visual examination of both the replenishment rate and plateau intensity of contrast. RESULTS: Of the 119 coronary artery territories compared, SPECT and RTPE were in agreement in 105 (88% agreement; kappa 0.67). In patients who went on to quantitative coronary arteriography (QCA), there were three who had normal appearing radionuclide SPECT during adenosine, but subendocardial perfusion defects with RTPE. In all three cases, QCA confirmed the presence of a >50% diameter stenosis in the abnormal territory. CONCLUSIONS: We conclude from this study that adenosine stress imaging with RTPE is an accurate method of detecting coronary artery disease. The higher resolution of RTPE may identify subendocardial defects that would otherwise have gone undetected with radionuclide imaging.     

Silent myocardial ischaemia in patients with angiographically proven coronary artery disease

Twenty patients with angiographically proven coronary artery disease (CAD) were evaluated by Holter monitoring for assessment of total ischaemic burden during daily activities. Thirteen patients revealed ischaemia on Holter monitoring (symptomatic-2, silent-4 and both types-7). As compared to symptomatic ischaemia, the silent myocardial ischaemic episodes were more frequent (25 vs 10 episodes), longer in duration (15-53 minutes vs 8-45 minutes), occurred at lower heart rates (65-75/minute (mean 68) vs 70-90 per minute (mean 76) and silent ischaemic episodes exceeded symptomatic ones in both morning (10 vs 4) and evening (15 vs 6) peaks. Occurrence of symptomatic as well as silent ischaemia had no relation to rest, activity, left ventricular functions, and there was no difference in the extent (1-3mm) and type (horizontal or downsloping) of ST-segment depression. We conclude that in patients with significant coronary artery disease, silent myocardial ischaemia is more frequent than the symptomatic ischaemia during daily activities. It occurs at lower heart rates, lasts longer, and bears no relation to rest, activity or left ventricular function. Evening peaks may be as frequent or more than the morning peaks. Holter monitoring thus is helpful for assessment of total ischaemic burden in CAD patients.     

Body fat distribution in men with angiographically confirmed coronary artery disease

Body fat distribution and its relationship to coronary artery disease and established cardiovascular risk factors have been studied in a cohort of 286 men aged between 30 and 74 years undergoing coronary angiography. 207 (72.4%) patients showed stenosis (greater than 30%) or occlusion of one or more coronary arteries. whereas the remaining 79 (27.6%) men were free of coronary lesions and served as a control group. 112 men with angiographically defined coronary artery disease had an additional history of myocardial infarction. Body fat distribution was assessed by determining the waist-to-hip circumference ratio. A stepwise logistic regression analysis revealed that in addition to LDL-cholesterol (P = 0.0001) and age (P = 0.0005) an abdominal type of body fat distribution (P = 0.0129) is also a significant risk indicator for the occurrence of coronary artery disease (CAD) independent of body weight and other factors such as total cholesterol, HDL-cholesterol, triglycerides, insulin, systolic and diastolic blood pressure. The results of this study suggest that an abdominal type of fat distribution is associated with an increased risk of coronary artery disease.     

Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease

Acetylcholine causes endothelium-dependent dilation of normal arteries in most animal species. The effect of acetylcholine on normal human coronary arteries is controversial. Pathologic studies and epicardial echocardiography have shown that diffuse atherosclerosis is often present despite angiographic evidence of discrete coronary artery disease (CAD). Therefore, we postulated that acetylcholine would cause vasoconstriction of coronary arteries that are angiographically normal in patients with CAD. Coronary artery diameter, measured by automated quantification of digitized cineangiograms, was determined before and after the intracoronary infusion of 0.2 mM acetylcholine at 0.8-1.6 ml/min. The diameter of stenotic or irregular segments of six atherosclerotic coronary arteries decreased from 1.80 +/- 0.42 mm before acetylcholine to 1.26 +/- 0.46 mm after acetylcholine (p = 0.0025). Acetylcholine had a significantly different effect on the diameter of two groups of coronary arteries that are angiographically normal. Acetylcholine caused a 0.16 +/- 0.09-mm increase in the diameter of 14 normal coronary arteries in patients without CAD, whereas it caused a 0.26 +/- 0.12-mm decrease in the diameter of 14 normal coronary arteries in patients with CAD (p less than 0.01). Thus, the normal response to intracoronary acetylcholine is vasodilation, suggesting that endothelium-derived relaxing factor is released from normal human coronary endothelium. The vasoconstrictive effect of acetylcholine in the angiographically normal coronary arteries of patients with CAD suggests the presence of a diffuse abnormality of endothelial function.     

Alterations in contrast medium-induced coronary reactive hyperemia after bepridil in patients with coronary artery disease

The acute effects of an intravenous infusion of bepridil (BEP) (4 mg . kg-1) on left ventricular (LV) hemodynamics, coronary sinus blood flow (CSBF), and myocardial metabolism were studied in eight patients with coronary artery disease. In contrast with data previously reported with calcium channel blockers, BEP induced an elevation in LV end-diastolic pressure from 12.0 +/- 7.1 to 20.1 +/- 7.2 mm Hg (mean +/- SD, p less than 0.001) and a fall in LV dp/dt max from 1339 +/- 302 to 1177 +/- 251 mm Hg . sec-1 (p less than 0.01). This significant alteration in LV function is likely to be explained by the lack of effect on heart rate and aortic pressure observed after an acute intravenous infusion of BEP. Myocardial oxygen consumption (MVO2) increased from 448 +/- 272 to 498 +/- 273 mumol . min-1/100 g LV (p less than 0.05) as did CSBF from 79.5 +/- 42.7 to 92.1 +/- 45.1 ml X min-1/100 g LV (p less than 0.01). Lactate extraction fell from 0.33 +/- 0.17 to 0.15 +/- 0.17 (p less than 0.05). A contrast medium-induced coronary reactive hyperemia (HPR) evidenced an increased hyperemic volume from 9.5 +/- 3.6 to 12.1 +/- 4.5 ml/100 g LV (p less than 0.01) and HPR duration from 23.3 +/- 6.9 to 32.3 +/- 15.4 sec (p less than 0.05) after BEP. However, the peak/resting CSBF ratio was blunted after BEP from 1.74 +/- 0.18 to 1.61 +/- 0.12 (p less than 0.05), evidencing a net effect of BEP on HPR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of microvascular disease in patients with significant coronary artery disease

Coronary flow velocity reserve (CFVR) measurement using intracoronary Doppler techniques has been increasing accepted for the assessment of physiological significance of epicardial stenosis and the functional changes after coronary interventions. However, large discrepancy exists concerning the acute changes of CFVR immediately after intervention. The purpose of this study was to investigate the prevalence of microvascular dysfunction in patients with significant coronary artery disease. Intracoronary Doppler flow measurements were performed in a total of 212 patients who underwent coronary interventions because of significant epicardial stenosis using 0.014" Doppler flow wire (Cardiometrics, Inc, Mountain View, CA). Intracoronary bolus injection of adenosine (12 micrograms for the right coronary and 18 micrograms for the left coronary arteries) was used to induce hyperemic reaction. CFVR was registered as the ratio of average peak velocity during hyperemia (hAPV) to at baseline (bAPV). Successful coronary interventions either by percutaneous transluminal coronary balloon angioplasty (PTCA) or by stenting could significantly improve the CFVR. In 80 patients with PTCA, the bAPV elevated from 16.6 +/- 2.1 cm/s to 20.6 +/- 13.4 cm/s and hAPV from 30.1 +/- 15.9 cm/s to 45.2 +/- 17.7 cm/s (both p < 0.001) with PTCA and the CFVR increased from 1.94 +/- 0.78 to 2.58 +/- 0.87 correspondingly (p < 0.001). Significant elevation of coronary flow parameters were also found in 132 patients with subsequent stent implantation (bAPV from 15.3 +/- 6.7 cm/s to 18.7 +/- 9.1 cm/s, hAPV from 28.7 +/- 14.4 cm/s to 44.3 +/- 17.7 cm/s and CFVR from 1.90 +/- 0.70 to 2.59 +/- 0.87, all p < 0.001). Reduction of CFVR (< 3.0) after intervention still existed in 46 (61.3%) of 80 patients after PTCA and 88 (66.7%) of 132 patients after stenting. Moreover, CFVR < 3.0 were found in 50 (45.9%) of 109 reference vessels in patients with single vessel disease. Significant improvement of coronary flow velocity and coronary flow velocity reserve could be obtained after successful angioplasty. However, microvascualr dysfunction existed in a large proportion of patients either in normal reference vessels or in target vessels after interventions.