Relationship between vascular calcification and bone mineral density in the Old-order Amish.

Vascular calcification and osteoporosis are common age-related processes that are influenced by both genetic and nongenetic factors. Whether common genes underlie these processes is not known. We measured coronary artery calcification (CAC), aortic calcification (AC), and bone mineral density (BMD) in 682 men and women from large Old-Order Amish families. We assessed the heritabilities of these traits and then evaluated, using variance decomposition procedures, whether variation in the traits was influenced by a common set of genes (i.e., pleiotropy). Significant heritabilities were detected for BMD of the femoral neck and spine (0.65, 0.63) and CAC and AC (0.43, 0.42). Mean BMD did not differ significantly across quartiles of either CAC or AC in either sex. In neither the total group nor any single subgroup (men, women, postmenopausal women) did any of the genetic or environmental correlations between BMD and vascular calcification achieve statistical significance. However, subjects with a history of cardiovascular disease (CVD) events had significantly lower BMD at the femoral neck compared to subjects who reported no prior history of CVD (age-, sex-, body mass index-, and family structure-adjusted P = 0.003). We detected no evidence for shared genes affecting the joint distribution of bone and vascular calcification. However, our results do reveal a lower BMD in subjects with a prior history of CVD in the Old-Order Amish.

Evaluation of the coronary venous system using electron beam computed tomography.

New therapeutic strategies in interventional cardiology and electrophysiology involve the coronary veins. This study examines the potential usefulness of electron beam computed tomography to obtain detailed noninvasive definition of the coronary venous anatomy and of arteriovenous relationships. Electron beam computed tomography allows acquisition and three-dimensional reconstruction of tomographic images of the beating heart with high spatial and temporal resolution. Contrast-enhanced, thin-section electron beam computed tomographic coronary arteriographic images of 34 patients (21 men and 13 women, age 60+/-10 years) were analyzed. The visibility of the coronary veins and their spatial relationship to the coronary arteries were assessed qualitatively on two- and three-dimensional displays. The coronary sinus was visible in 91%, the great cardiac vein in 100%, the middle cardiac vein in 88%, at least one vein overlying the lateral surface of the left ventricle in 97%, the anterior interventricular vein in 97%, and the small cardiac vein in 68%. A left marginal and a left posterior vein were seen in 44%, one of the two in 38%, and neither in 3%. The course of the anterior interventricular vein was parallel to the left anterior coronary artery in 79% and a crossover between the two vessels at an obtuse angle occurred in 12%. Contrast-enhanced electron beam computed tomography imaging of the heart noninvasively provides information on the coronary venous system and arteriovenous relationships that may help guide new interventional procedures.

Tomographic (plaque) imaging: state of the art.

Tomographic coronary artery plaque imaging is possible noninvasively using x-ray computed tomography (CT) and magnetic resonance imaging (MRI). The pathophysiology of coronary plaque disease is one of repeated inflammation and repair. Imaging of coronary artery calcium, a consequence of this process, is possible using CT, whereas MRI has the potential to examine the lipid and fibrous components of plaque acquisition and 3-dimensional slice registration. Quantitation of coronary artery calcium has been validated using electron-beam CT [EBCT], a unique device that images the entire heart in a single breathold from rapid [100 msec] tomographic scans done in synchrony with the heart cycle. Current mechanical CT devices require 300 to 500 msec per scan and acquire hundreds of tomographic images that then must be retrospectively separated to the required phase of the heart cycle. There are limited correlations with calcium scoring by EBCT versus mechanical CT and the later device has a limitation in situations of low plaque volume and necessitates increased radiation exposure to the patient. MRI has been shown to have the potential to define plaque composition ex vivo or in the aorta, but studies of the heart arteries are so far very limited. Widespread utilization of noninvasive plaque imaging requires that the studies be done consistently and reproducibly. The training of the interpreting physicians is of paramount concern.

Long-term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography.

BACKGROUND: Electron-beam CT (EBCT) quantification of coronary artery calcification (CAC) allows noninvasive assessment of coronary atherosclerosis. We undertook a follow-up study to determine whether CAC extent, measured at the time of angiography by EBCT, predicted future hard cardiac events, comprising cardiac death and nonfatal myocardial infarction (MI). We also assessed the potential of selected coronary artery disease (CAD) risk factors, prior CAD event history (MI or revascularization), and angiographic findings (number of diseased vessels and overall disease burden) to predict subsequent hard events. METHODS AND RESULTS: Two hundred eighty-eight patients who underwent contemporaneous coronary angiography and EBCT scanning were contacted after a mean of 6.9 years. Vital status and history of MI during follow-up were determined. Cox proportional hazards models were used to compare the predictive ability of CAC extent with selected CAD risk factors, CAD event history, and angiographic findings. Median CAC score was 160 (range 0 to 7633). The 22 patients who experienced hard events during follow-up were older and had more extensive CAC and angiographic disease (P<0.05). Only 1 of 87 patients with CAC score <20 experienced a subsequent hard event during follow-up. Event-free survival was significantly higher for patients with CAC scores <100 than for those with scores >/=100 (relative risk 3.20; 95% CI 1.17 to 8.71). When a stepwise multivariable model was used, only age and CAC extent predicted hard events (risk ratios 1.72 and 1.88, respectively; P<0.05). CONCLUSIONS: In patients undergoing angiography, CAC extent on EBCT is highly predictive of future hard cardiac events and adds valuable prognostic information.

Use of a new myocardial centroid for measurement of regional myocardial dysfunction by electron beam computed tomography: comparison with technetium-99m sestamibi infarct size quantification.

RATIONALE AND OBJECTIVES: The study compared the performance of conventional endocardial and epicardial centroid algorithms with the new "myocardial" centroid algorithm in patients with anterior myocardial infarction. "Floating" endocardial or epicardial centroid algorithms, commonly used in tomographic imaging methods to assess regional motion, may misrepresent left ventricular regional myocardial function in the presence of markedly asymmetric left ventricular contraction. METHODS: A new centroid algorithm based on regional myocardial mass distribution was tested in 29 patients with a first anterior myocardial infarction and was compared with conventional centroid algorithms. Direct comparisons in 60 equal sectors at one midventricular level per patient were performed between electron beam computed tomography and technetium-99m sestamibi single-photon emission computed tomography. The thresholds of regional myocardial function used to define infarction were varied for regional ejection fraction from 20% to 40% and for regional wall thickening from 0 to 4 mm. Regression and Bland-Altman analysis were used to compare infarct size by regional myocardial function with infarct size by sestamibi single-photon emission computed tomography. RESULTS: The new myocardial centroid showed the least shift toward infarcted myocardium from diastole to systole and had the highest amplitudes of the measurement curves for regional ejection fraction and regional wall thickening. The optimal regional myocardial function thresholds for each centroid algorithm for regional ejection fraction were endocardial, 30% (R = 0.62; mean difference to sestamibi, -0.5% +/- 22.1% tomographic infarct size points); epicardial, 30% (R = 0.79; mean difference, 2.2% +/- 13.1% tomographic infarct size points); and new myocardial, 25% (R = 0.88; mean difference, -0.6% +/- 9.5% tomographic infarct size points). The optimal thresholds for regional wall thickening were endocardial, 1 mm (R = 0.70; mean difference, -2.2% +/- 14.3% tomographic infarct size points); epicardial, 1 mm (R = 0.78; mean difference, -4.6% +/- 12.7% tomographic infarct size points); and new myocardial, 2 mm (R = 0.71; mean difference, 2.1% +/- 14.1% tomographic infarct size points). The best agreement (R = 0.88) between electron beam computed tomography infarct size and sestamibi single-photon emission computed tomography infarct size was achieved with regional ejection fraction and the new myocardial centroid algorithm. CONCLUSIONS: In asymmetrically contracting left ventricles, the new myocardial centroid algorithm is superior to conventional methods for tomographic analysis of regional myocardial function.

Coronary atherosclerosis in unheralded sudden coronary death under age 50: histo-pathologic comparison with 'healthy' subjects dying out of hospital.

AIM: sudden coronary death (SCD) in older individuals is generally associated with extensive coronary atherosclerosis, although it may be the first manifestation of ischaemic heart disease. In younger age-groups, SCD may occur in the presence of less severe disease. We sought to (1) examine the extent of coronary atherosclerosis in young victims of SCD compared with age- and sex-matched controls, (2) analyse the composition of atherosclerotic plaques in these patients, (3) identify the predominant mechanism of SCD, and (4) evaluate the possibility of detecting this mechanism on the basis of morphologic plaque features, in particular presence and amount of lipid accumulation and calcific deposits. METHODS AND RESULTS: coronary arteries were obtained at autopsy from 28 victims of SCD under age 50 with no prior clinical manifestation of ischaemic heart disease (IHD) and no myocardial scar formation and from 16 age- and sex-matched subjects dying of noncardiac causes out of hospital. Sections of all available major coronary arteries were cut in 5-mm intervals to yield a total of 1357 histologic sections, which were analysed using digitised planimetry. Victims of SCD had significantly more major coronary arteries per subject with luminal area narrowing > or = 75% than controls (on average, 2.1 vs. 0.2). Plaque area per histologic section was 5.1 +/- 2.1 mm(2) in SCD cases and 2.0 +/- 0.9 mm(2) in controls (P < 0.001). The major constituent of all plaques was fibrous tissue. Lipid core area per section was 0.49 +/- 0.59 mm(2) in SCD cases and 0.004 +/- 0.01 mm(2) in controls (P < 0.001), and calcified plaque area was 0.18 +/- 0.19 mm(2) in SCD cases and 0.02 +/- 0.05 mm(2) in controls (P < 0.001), both defining significant differences between SCD cases and controls. Arterial thrombosis, most often with underlying plaque rupture was the mechanism of SCD in > 80% of the cases. Considering histologic sections with > or = 50 and with > or = 75% area stenosis, plaque rupture was independently predicted by lipid core area. Calcific deposits were a frequent feature of plaque rupture but were only associated with it in univariate analysis. CONCLUSIONS: the extent and severity of coronary atherosclerosis in young victims of SCD as the first manifestation of IHD was substantially greater than in age-and sex-matched controls and comparable with that previously reported in SCD cases with a broader age range. Lipid core and calcified plaque areas provided for excellent separation between the two groups, which may have implications for identifying persons at increased risk for SCD by non invasive visualisation and assessment of the coronary arteries.

Use of electron beam tomography to quantify cardiac diastolic function.

The examples provided in this article indicate that EBT, in addition to allowing for detailed descriptions of cardiac anatomy and contraction characteristics in man, can also be used to evaluate global and regional LV diastolic function using an approach previously validated for applications in radionuclide angiography. EBT is an established imaging modality that has been shown to be highly applicable to quantitative determination of ventricular mass, RV and LV volumes, and global and regional ventricular systolic and diastolic function in a variety of cardiac pathologic states. The attractiveness of EBT lies not so much in a single determination of systolic function or diastolic filling in a given individual, but in the strength of an easily acquired, highly reproducible, and accurate serial imaging method in patients following pharmacologic or interventional therapy for a specific cardiac disease.

Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization.

Based on the reduction of ischemic cardiac events in clinical trials and experimental observations, inhibition of the effects of angiotensin II on coronary microcirculatory function may afford myocardial protection after injury. The immediate effects of intracoronary AT1 receptor blockade with irbesartan were examined in a pig model in the healthy myocardium and in acute ischemia induced by injection of 30-microm microspheres into the left anterior descending coronary artery (LAD). Electron-beam computed tomography was performed for in-vivo quantitative measurements of regional intramyocardial vascular blood volume (V(B)) and perfusion (F(M)), as well as left ventricular ejection fraction (LVEF) and muscle mass. Ratios of V(B) and F(M) in the anterior (LAD-supplied)/ inferior (control) myocardium were generated. At baseline, 0.2 mg/kg irbesartan injected into the LAD increased V(B) and F(M) ratios significantly by 27 +/- 8% and 51 +/- 13%, respectively. After anterior coronary microembolization, V(B) and F(M) ratios were 0.60 +/- 0.05 and 0.51 +/- 0.05, respectively, and were significantly increased by irbesartan (by 24 +/- 10% and by 36 +/- 11%, respectively). After 4 weeks of treatment with oral irbesartan (n = 7) or placebo (n = 7), an improved LVEF (56 +/- 4% v 44 +/- 4%, P = .046) was observed in irbesartan-treated animals, but no difference in LV end-diastolic volumes or muscle mass. Resting V(B) (0.95 +/- 0.06 v 0.76 +/- 0.06; P = .047) and F(M) (0.84 +/- 0.05 v 0.64 +/- 0.04; P = .016) ratios were significantly greater in irbesartan-treated animals. Using adenosine, there was a trend for higher V(B) and F(M) ratios in irbesartan- v placebo-treated animals. Therefore, in a pig model of acute myocardial ischemia, AT1 receptor blockade by irbesartan induced microvascular vasodilation and, ostensibly, conveyed myocardial protection. Long-term treatment with irbesartan resulted in moderate enhancements of resting V(B) and F(M) compared with placebo, suggesting a role for coronary microcirculatory effects of chronic AT1 receptor blockade in preserving LVEF.

Probabilistic model for prediction of angiographically defined obstructive coronary artery disease using electron beam computed tomography calcium score strata.

BACKGROUND: Electron beam CT (EBCT) is an accurate, noninvasive method to detect and quantify coronary artery calcification, a marker of coronary artery disease (CAD). This investigation examined the accuracy of EBCT to detect obstructive CAD (> or =50% stenosis) and determined the optimal strata for quantity of coronary artery calcification to facilitate clinical decision-making. METHODS AND RESULTS: Clinical research patients (n=213) were examined with coronary angiography and EBCT (angiography group), and 765 research participants were examined with only EBCT (nonangiography group). Of the angiography group, 53% had obstructive CAD. After adjustment for verification bias, the estimated sensitivity and specificity for calcium score > or =1 were 97.0% and 72.4%, respectively. Likelihood ratios for strata of calcium score associated with obstructive CAD were calculated in each sex and 2 age groups. Among those > or =50 years old, the same 4 strata of EBCT calcium scores were identified in each sex; likelihood ratios ranged from 0.03 (calcium score 0) to 12.85 (calcium score > or =200). The same 3 strata EBCT calcium scores were identified in each sex among those <50 years old; likelihood ratios ranged from 0.13 (calcium score 0) to 190 (calcium score > or =100). CONCLUSIONS: A calcium score > or =200 among those > or =50 years old and calcium score > or =100 among those <50 years old provided strong evidence that patients of either sex had obstructive CAD. A calcium score of 0 provided strong evidence that patients > or =50 years old did not have obstructive CAD.

[Economic aspects of using electron beam computerized tomography]. / Okonomische Aspekte bei der Anwendung der Elektronenstrahlcomputertomographie.

Electron beam computed tomography (EBCT) allows visualization and quantification of calcium in the coronary arteries. This has been demonstrated to correlate well with the overall plaque burden in the coronary arteries. EBCT is, therefore, well suited for the detection of early stages of coronary atherosclerosis. Especially in asymptomatic patients with several risk factors, staging coronary artery disease by coronary calcium, scanning may allow prognostic assessment and guide preventive and therapeutic interventions. To date, only scant data are available regarding the cost effectiveness and the economic impact of this imaging technique. In this manuscript we compare various methods for the diagnosis of coronary artery disease using a theoretical model and review the results of a prospective trial in our emergency room of coronary calcium scanning in patients with acute chest pain. Using Framingham data and prognostic data from long-term follow-up, we discuss the impact of coronary calcification scanning on primary preventive measures and its economical consequences. EBCT is a promising technique which has created a lot of attention due to its ease of application. It is currently undergoing critical appraisal in the medical literature. Further randomized prospective trials are needed (and underway, i.e., MESA, EDIC, CARDIA II) to better define its value and limitations in the clinical arena.

Cost effectiveness of coronary calcification scanning using electron beam tomography in intermediate and high risk asymptomatic individuals.

Pharmaceutical therapy of hyperlipidemia is clearly beneficial. In the patient without established heart disease however, conventional risk assessment is imprecise and determining which patients are at highest versus lowest risk is a common clinical conundrum. It is well established that the most powerful determinant to risk is the overall extent/severity of coronary disease. Electron beam tomography (EBT) and quantification of coronary artery calcium has been shown to provide a valid non-invasive surrogate to atherosclerotic plaque burden. Screening patients who are considered to be at traditional intermediate to high risk by first using EBT can refine the broad-based population risk to a more individual basis. Data that is based upon a model developed for application of EBT are presented, which discuss its potential as a cost effective application to guide statin therapy in intermediate and high-risk sub-groups.

Independent and incremental value of coronary artery calcium for predicting the extent of angiographic coronary artery disease: comparison with cardiac risk factors and radionuclide perfusion imaging.

OBJECTIVES: The study was done to test the ability to predict the extent of angiographically determined coronary artery disease (CAD) by quantification of coronary calcium using electron-beam computed tomography (EBCT) and to compare it with more conventional parameters for delineating the angiographic extent of CAD, that is, cardiovascular risk factors and radionuclide single-photon emission computed tomography (SPECT). BACKGROUND: The angiographic extent of CAD is a powerful predictor of subsequent events. Use of EBCT may be able to define it by virtue of its ability to determine plaque burden. METHODS: We examined 308 patients presenting with suspected but not previously known CAD who underwent selective coronary angiography. As measures of the angiographic extent of CAD, coronary artery greater even 20 (CAGE > or =20) and CAGE > or =50 scores represented the total number of coronary segments with > or =20% or > or =50% stenoses, respectively. The EBCT-derived total calcium scores were obtained in 291 patients, risk factors as defined by the National Cholesterol Education Program in 239 patients, and SPECT scans in 136 patients. RESULTS: Using multiple linear regression analysis, total calcium scores were better independent predictors of both CAGE > or =20 and CAGE > or =50 scores than either a SPECT-derived radionuclide perfusion score or the risk factors age, male gender and ratio of total/high-density lipoprotein (HDL) cholesterol. The association between EBCT and angiographic scores remained highly significant after excluding the influence of all interrelated risk factors and SPECT variables (r = 0.65; p < 0.001 for CAGE > or =20 scores, r = 0.50; p < 0.001 for CAGE > or =50 scores). CONCLUSIONS: Coronary calcium predicts the angiographic extent of CAD in symptomatic patients and provides independent and incremental information to the more conventional clinical parameters derived from SPECT or risk assessment.

Cardiac production of angiotensin II and its pharmacologic inhibition: effects on the coronary circulation.

Angiotensin II (AII), produced systemically as well as locally in the heart, affects the coronary circulation, as do consequences of its pharmacologic inhibition. AII is a powerful vasoconstrictor directly acting on vascular smooth muscle cells, modulating sympathetic innervation and calcium ion influx, and releasing other vasoconstrictor factors. In addition to these immediate actions, AII has longer-term biologic actions that influence cardiac endothelial function, vascular smooth muscle cell phenotype expression, and fibroblast proliferation. Moreover, the production of AII is interrelated with the vasodilator substances bradykinin, nitric oxide, and prostaglandins E2 and I2 (prostacyclin). Circulating hormonal actions of AII include fluid retention, direct vasoconstriction, and sympathetic neuromodulation, all resulting in increased left ventricular preload and afterload. Because of these local and hormonal characteristics, AII can immediately affect the myocardial balance of metabolic demand and supply and long term can induce structural vascular and myocardial alterations. Pharmacologic inhibition of AII production likely conveys myocardial and vascular protection in situations of acute myocardial oxygen debt. In the long term, inhibition of AII may attenuate structural changes in the coronary microcirculation related to various cardiomyopathies or acute tissue injury, and direct antiatherogenic effects may also occur.

Validation of minimally invasive measurement of myocardial perfusion using electron beam computed tomography and application in human volunteers.

OBJECTIVES: To measure myocardial perfusion using an estimate of intramyocardial vascular volume obtained by electron beam computed tomography (EBCT) in an animal model; to assess the feasibility and validity of measuring regional myocardial perfusion in human volunteers using the techniques developed and validated in the animal studies. METHODS: Measurements of myocardial perfusion with EBCT employing intravenous contrast injections were compared with radioactive microsphere measurements (flow 57 to 346 ml/100 g/min) in seven closed chest dogs. Fourteen human volunteers then underwent EBCT scans using intravenous contrast injections. RESULTS: Mean (SEM) global intramyocardial vascular volume by EBCT was 7.6 (1.1)%. The correlation between global EBCT (y) and microsphere (x) perfusion was y = 0.59x + 15.56 (r = 0.86) before, and y = 0.72x + 6. 06 (r = 0.88) after correcting for intramyocardial vascular volume. Regional perfusion correlation was y = 0.75x + 23.84 (r = 0.82). Corresponding improvements in agreement between the two techniques were also seen using Bland-Altman plots. In the human subjects, mean resting global myocardial flow was 98 (6) ml/100 g/min, with homogeneous flow across all regions. In 10 of these subjects, perfusion was studied during coronary vasodilatation using intravenous adenosine. Global flow increased from 93 (5) ml/100 g/min at rest to 250 (19) ml/100 g/min during adenosine (p < 0.001), with an average perfusion reserve ratio of 2.8 (0.2). Similar changes in regional perfusion were observed and were uniform throughout all regions, with a mean regional perfusion reserve ratio of 2.8 (0.3). CONCLUSIONS: Accounting for intramyocardial vascular volume improves the accuracy of EBCT measurements of myocardial perfusion when using intravenous contrast injections. The feasibility of providing accurate measurements of global and regional myocardial perfusion and perfusion reserve in people using this minimally invasive technique has also been demonstrated.

Comparison of measurement of left ventricular ejection fraction by Tc-99m sestamibi first-pass angiography with electron beam computed tomography in patients with anterior wall acute myocardial infarction.

The goal of this study was to compare measurements of left ventricular (LV) ejection fraction (EF) by first-pass radionuclide angiography ("first-pass angiography") using technetium-99m (Tc-99m) sestamibi with those by contrast-enhanced electron beam computed tomography ("electron beam tomography") as a reference technique in patients with an anterior wall acute myocardial infarction (AMI). Twenty-five patients with first Q-wave anterior wall AMI underwent paired electron beam tomographic and first-pass angiographic studies (mean, 1 day apart). Fourteen patients had 2 sets of measurements of the LVEF obtained by both methods (separated by at least 6 weeks), for a total of 39 paired measurements. LVEF by electron beam tomography was calculated from absolute systolic and diastolic LV chamber volumes. LV volumes by electron beam tomography were 199 +/- 51 ml at end-diastole and 111 +/- 42 ml at end-systole. Mean LVEF was 45 +/- 11% by first-pass tomography and 46 +/- 9% by electron beam tomography. The linear correlation coefficient between both methods was 0.82 (p <0.0001), with slope = 1.0, y-intercept = -1.1, and SEE = 6.1. The mean difference between the 2 methods was -0.7 +/- 6.0 EF units (p = 0.75). The correlation between the differences and means of both methods was 0.34 (p = 0.04), indicating a trend for first-pass angiography to overestimate LVEF in the higher range. LVEFs measured by first-pass angiography in patients with abnormal LV geometry and contraction patterns caused by anterior wall AMI agree well with those measured by electron beam tomography in the clinically relevant range.

Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons.

Coronary artery disease is the No. 1 cause of death in the developed world. Effective means of treatment such as drug therapy to lower cholesterol levels are available, but clinical application to patients at highest risk remains imprecise. Electron beam computed tomography (EBCT) has been suggested as a means to diagnose subclinical coronary disease and facilitate risk stratification, but no current interpretive consensus exists in clinical practice. We critically reviewed current, pertinent literature regarding EBCT coronary calcium scanning from a clinical perspective and, in particular, studies that evaluated it as a measure of atherosclerotic coronary disease. Additionally, we reviewed studies that quantified the EBCT "calcium score" in relationship to coronary heart disease events. The available data suggest that the EBCT calcium score can help identify persons at higher than anticipated risk of future coronary events: the greater the EBCT coronary calcium score, the greater the extent of atherosclerotic plaque disease. Based on the literature review, we offer EBCT interpretation guidelines as they relate to drug therapy and risk reduction in asymptomatic persons with borderline cholesterol levels. Considerable evidence shows that coronary calcium is specific for atherosclerotic plaque and that it can be sensitively detected and accurately quantified by using EBCT. The coronary calcium score can help guide initiation of clinical prevention programs as part of a risk stratification and management scheme aimed at improving outcomes in patients determined to be at highest risk of coronary disease for their respective age and gender.

An algorithm for noninvasive identification of angiographic three-vessel and/or left main coronary artery disease in symptomatic patients on the basis of cardiac risk and electron-beam computed tomographic calcium scores.

OBJECTIVES: We sought to model an algorithm for noninvasive identification of angiographically obstructive three-vessel and/or left main disease based on conventional cardiac risk assessment and site and extent of coronary calcium determined by electron-beam computed tomography (EBCT). BACKGROUND: Such an algorithm would greatly facilitate clinical triage in symptomatic patients with no previous diagnosis of coronary artery disease (CAD). METHODS: We examined 291 patients with suspected, but not previously diagnosed, CAD who underwent coronary angiography for clinical indications. Cardiac risk factors were determined as defined by the National Cholesterol Education Program. An EBCT scan was performed in all patients, and a coronary calcium score (Agatston method) was computed. Total per-patient calcium scores and separate scores for the major coronary arteries were generated. These scores were also analyzed for localization of coronary calcium in the more distal versus proximal tomographic sections. These parameters and the risk factors were considered for the model described in the following section. RESULTS: Sixty-eight patients (23%) had angiographic three-vessel and/or left main CAD. Multiple logistic regression analysis determined male sex, presence of diabetes and left anterior descending (LAD) and circumflex (LCx) coronary calcium scores, independent from more distal calcium localization, as independent predictors for identification of three-vessel and/or left main CAD. Based on this four variable model, a simple noninvasive index (NI) was constructed as the following: loge(LAD score) + log(e)(LCx score) + 2[if diabetic] + 3[if male]. Receiver operating characteristic curve analysis for this NI yielded an area under the curve of 0.88+/-0.03 (p < 0.0001) for separating patients with, versus without, angiographic three-vessel and/or left main CAD. Various NI cutpoints demonstrated sensitivities from 87-97% and specificities from 46-74%. The NI values >14 increased the probability of angiographic three-vessel and/or left main CAD from 23% (pretest) to 65-100% (posttest), and NI values <10 increased the probability of no three-vessel and/or left main CAD from 77% (pretest) to 95-100% (posttest). CONCLUSIONS: On the basis of a simple algorithm ("noninvasive index"), EBCT calcium scanning in conjunction with risk factor analysis can rule in or rule out angiographically severe disease, i.e., three-vessel and/or left main CAD, in symptomatic patients.

Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods.

OBJECTIVES: The purpose of this study was to determine if electron beam computed tomography (EBCT) has potential as a cost-effective approach to diagnosis of obstructive coronary disease. BACKGROUND: Coronary calcification quantified by EBCT is closely related to the extent of atherosclerosis. METHODS: A model based upon published sensitivities (Se)/specificities (Sp) for diagnosis in an ambulatory patient of obstructive coronary disease (> or =50% stenosis) and population prevalence was tested for angiography alone, or treadmill exercise, stress echocardiography, stress thallium or predetermined EBCT calcium score outpoints, followed by angiography if indicated. RESULTS: Total direct testing costs increased in proportion to disease prevalence whereas cost-effectiveness, direct costs/patient diagnosed correctly with disease, decreased as a function of prevalence. Using an EBCT calcium score of 168 (Se/Sp = 71%/90%) provided for the least costly and most cost-effective noninvasive pathway. Calcium scores of 80 (Se/Sp = 84%/84%) and 37 (Se/Sp = 90%/77%) were also cost-effective when prevalence of disease was < or =70%; but results for a >0 calcium score (Se/Sp = 95%/46%) cutpoint were not superior to conventional methods. Calcium score cutpoints of 37, 80 or 168 provided similar or superior overall negative and positive predictive values to conventional noninvasive testing pathways across all prevalence subgroups. CONCLUSIONS: In ambulatory patients evaluated for obstructive coronary disease, a testing pathway utilizing quantification of coronary calcium by EBCT as an initial noninvasive testing approach minimized direct costs, and maximized cost-effectiveness in population groups with low/ moderate disease prevalence (< or =70%); as expected, direct angiography as the first and only test proved most cost-effective in patients with a high prevalence (>70%) of disease.

Use of electron-beam computed tomography in the evaluation of chest pain patients in the emergency department.

STUDY OBJECTIVE: We sought to determine whether electron-beam computed tomography (EBCT) could be used as a triage tool in the emergency department for patients with angina-like chest pain, no known history of coronary disease, normal or indeterminate ECG findings, and normal initial cardiac enzyme concentrations. METHODS: We conducted a prospective observational study of 105 patients admitted between December 1995 and October 1997 to the ED of a large tertiary care hospital with 70,000 annual ED visits. The study group was comprised of women aged 40 to 65 years and men aged 30 to 55 years who presented with angina-like chest pain requiring admission to the hospital or chest pain observation unit. All patients underwent EBCT of the coronary arteries, along with other cardiac testing as deemed necessary by staff physicians. RESULTS: Of the 105 patients, 100 underwent other cardiac testing during hospitalization. Evaluation included treadmill exercise testing in 58, coronary angiography in 25, radionuclide stress testing in 19, and echocardiography in 11. Results of EBCT and cardiac testing were negative for both in 53 patients (53%), positive for both in 14 (14%), positive for tomography and negative for cardiac testing in 32 (32%), and negative for tomography and positive for cardiac testing in only 1 patient. This positive test result, on a treadmill exercise test, was ruled a false positive by an independent staff cardiologist. Two other female patients with normal exercise sestamibi or coronary angiography and EBCT findings also had false-positive treadmill exercise results. The sensitivity of EBCT was 100% (95% confidence interval, 77% to 100%), with a negative predictive value of 100% (95% confidence interval, 94% to 100%). Specificity was 63% (95% confidence interval, 54% to 75%). CONCLUSION: EBCT is a rapid and efficient screening tool for patients admitted to the ED with angina-like chest pain, normal cardiac enzyme concentrations, indeterminate ECG findings, and no history of coronary artery disease. Our study suggests that patients with normal initial cardiac enzyme concentrations, normal or indeterminate ECG findings, and negative results on EBCT may be safely discharged from the ED without further testing or observation. Larger studies are required to confirm this conclusion.