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.

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.

Serial changes in regional right ventricular free wall and left ventricular septal wall lengths during the first 4 to 5 years after index anterior wall myocardial infarction.

OBJECTIVES: This study investigated serial changes in regional right ventricular free wall and interventricular septal wall lengths during the first 4 to 5 years after an index anterior wall myocardial infarction. BACKGROUND: We previously demonstrated that remodeling after anterior wall myocardial infarction was a biventricular process; however, regional changes in biventricular topology were not investigated. METHODS: Serial electron beam computed tomographic scanning was performed in 19 patients at five times (hospital discharge and at 6 weeks, 6 months, 1 year and 4 to 5 years) after an index anterior wall myocardial infarction, and global and regional right ventricular free wall and interventricular septal wall lengths were quantified. RESULTS: At a mean (+/- SD) of 1,642 +/- 171 days (4 to 5 years) after infarction, global end-diastolic and end-systolic right ventricular free wall and interventricular septal wall lengths increased in parallel by 13% to 23% as global left and right ventricular volumes increased 22% to 29% from hospital discharge to 4 to 5 years after infarction. When global right ventricular free wall was compared with interventricular septal wall lengths, percent increases at end-diastole and end-systole were not statistically different at any time during the study period. Distinct regional changes in both right ventricular free wall and interventricular septal wall lengths after infarction were most dramatic during the first 6 weeks and primarily confined to the most apical levels. However, further and significant increases in both were observed by 4 to 5 years after infarction. CONCLUSIONS: Changes in both right ventricular free wall and interventricular septal wall lengths were apparent during the 4 to 5 years after the index anterior wall infarction, and the combination of both contributed to global increases in right and left ventricular chamber volumes. Regional changes in both right ventricular free wall and interventricular septal wall lengths were almost exclusively confined to their respective apices and progressed generally in parallel; however, the cause-and-effect relation remains speculative at the present time.

Serial changes in left and right ventricular systolic and diastolic dynamics during the first year after an index left ventricular Q wave myocardial infarction.

OBJECTIVES: This study quantified serially biventricular emptying and filling after infarction and related these to changes in volume, muscle mass, wall stress and contractility. BACKGROUND: There are limited data on serial changes in ventricular dynamics after infarction. METHODS: Forty patients had serial electron beam computed tomographic examinations during the first year after index Q wave infarction (21 anterior, 19 inferior), and global biventricular volumes, peak rates of emptying and filling and left ventricular muscle masses were quantified. Mean mid-left ventricular end-systolic wall stresses, rate-corrected velocities of circumferential shortening and two indexes of left ventricular contractility--the end-systolic wall stress/volume ratio and the end-systolic wall stress/rate-corrected velocity of circumferential shortening relation--were estimated in each instance. RESULTS: Patients with anterior infarction had an increase in biventricular chamber volume of 15% to 35% by 1 year. Global biventricular peak rates of emptying and filling were decreased by 20% to 30% from hospital discharge to 6 weeks but thereafter remained unchanged. Despite a significant increase in mean wall stresses, the end-systolic wall stress/volume ratio remained unchanged during the year. The rate-corrected velocities of circumferential shortening declined serially after anterior infarction but did so in proportion to the increase in mean wall stresses, consistent with no net change in left ventricular contractility. Patients with inferior infarction showed a trend toward similar changes, but the magnitudes did not reach significance. CONCLUSIONS: Left (and right) ventricular global peak rates of emptying and filling during the first year after infarction can be altered in the absence of additional ischemic injury but are more consistent with responses to changes in left ventricular afterload than changes in intrinsic ventricular performance or contractility. Serial changes in left ventricular afterload after infarction are largely due to progressive chamber enlargement and limited development of compensatory hypertrophy during the first year. Intrinsic global left ventricular contractile performance was not altered by postinfarction cardiac remodeling in the patients examined.

Electron beam computed tomographic coronary calcium score cutpoints and severity of associated angiographic lumen stenosis.

OBJECTIVES: We sought to determine a range of cutpoints for coronary calcium scores measured by electron beam computed tomography (EBCT) in predicting the likely severity of associated angiographic coronary artery stenoses. BACKGROUND: EBCT can quantify coronary calcium and allow the estimation of atherosclerotic plaque burden, but use of the calcium score to define lumen narrowing is controversial. METHODS: A total of 213 patients (mean [+/- SD] age 50 +/- 9 years) underwent coronary angiography and EBCT. Maximal percent diameter stenosis in any artery was paired with total coronary calcium score. Receiver operating characteristic (ROC) curve analysis was done using definitions of "disease" for maximal stenosis from > or = 20% to 100%, and the corresponding score cutpoints were determined for 90% sensitivity, 90% specificity or "optimal" sensitivity and specificity. RESULTS: ROC curve areas ranged from a mean (+/- SE) of 0.91 +/- 0.02 for > or = 20% stenosis to 0.83 +/- 0.03 for 100% stenosis. Optimal calcium score cutpoints consisted of nonoverlapping values ranging from 15 for > or = 20% stenosis to 327 for 100% stenosis, whereas sensitivities and specificities ranged from 78% to 84%, depending on maximal stenosis severity. Calcium score cutpoints for 90% sensitivity and 90% specificity were also nonoverlapping and ranged from 3 and 27, respectively, for > or = 20% stenosis to 154 and 945, respectively, for 100% stenosis; corresponding specificities and sensitivities ranged from 40% to 78%. CONCLUSIONS: These data define the ranges for EBCT coronary calcium score cutpoints that predict the likely severity of associated maximal angiographic stenosis severity to a high sensitivity, high specificity or optimal sensitivity/specificity. These cutpoints potentially can be used in conjunction with clinical variables to predict the severity of lumen narrowing in patients undergoing assessment for coronary artery disease.

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.

Intravenous electron-beam computed tomographic coronary angiography for segmental analysis of coronary artery stenoses.

OBJECTIVES: We sought to identify and localize significant coronary stenoses on a segmental basis by electron-beam computed tomography (EBCT) and intravenous administration of a contrast agent. BACKGROUND: The clinical applicability and limitations of intravenous EBCT coronary angiography have not been defined. METHODS: EBCT was performed within 24 h of selective coronary angiography (SCA) in 28 patients (19 men and 9 women, mean [+/-SD] age 60 +/- 10 years). After examination for coronary calcium, EBCT coronary angiography was performed using overlapping slices (in-plane resolution 0.34 to 0.41 mm) with a nominal slice thickness of 1 mm. Based on quantitative analysis of SCA, lumen diameter narrowing > or = 50% (i.e., significant stenoses) was evaluated in 8 (major) or 12 (including side branches) coronary artery segments, using both two-dimensional (tomographic) and three-dimensional (volume) data sets. RESULTS: Of the 330 segments assessable by SCA, 237 (72%) were visualized by EBCT. The sensitivity (+/-SE) for detection of significant stenoses was 82 +/- 6%; specificity was 88 +/- 2%; positive and negative predictive values were 57 +/- 7% and 96 +/- 2%, respectively; and overall accuracy was 87 +/- 2%. If only eight (major) coronary artery segments were considered, 194 (88%) of 221 segments were visualized, and the overall accuracy was 90 +/- 2%. Seven (18%) of 38 significantly stenotic segments were classified as having < 50% stenoses by EBCT. Six of these segments (86%), but only 9 (29%) of the 31 correctly classified stenotic segments, were severely calcified (area > 20 mm2, p = 0.02). In 23 (12%) of 199 nonstenotic segments falsely classified as having > or = 50% stenosis by EBCT, the lumen diameter was significantly smaller than that of the segments correctly classified as negative (mean [+/-SD] 1.5 +/- 0.8 vs. 2.9 +/- 1.1 mm, p < 0.001). CONCLUSIONS: Intravenous EBCT coronary angiography allows for accurate segmental evaluation of significant disease in the major coronary arteries and may be of value for ruling out significant disease. The main determinant of false negative results is substantial segmental calcification, whereas the main determinant of false positive results is small vessel size.

Nonparallel changes in global left ventricular chamber volume and muscle mass during the first year after transmural myocardial infarction in humans.

OBJECTIVES: This study was designed to serially assess time-dependent changes in both chamber volume and myocardial muscle mass after infarction in humans. BACKGROUND: Dilation of the left ventricular chamber has been previously described after transmural myocardial infarction. METHODS: Global left ventricular chamber volumes and muscle mass were quantified by using cine computed tomographic scanning in 18 patients at hospital discharge and 6 weeks, 6 months and 1 year after an initial transmural myocardial infarction (12 anterior and 6 inferior). No patient had heart failure during the initial hospital stay or on any subsequent follow-up visit. RESULTS: The patients with anterior myocardial infarction (estimated infarct extent 27 +/- 2% of left ventricle) demonstrated a progressive increase in left ventricular end-diastolic volume from 148 +/- 9 ml (mean +/- SEM) at hospital discharge to 180 +/- 9 ml at 1 year after infarction (p < 0.001). However, global left ventricular muscle mass decreased significantly during the 1st 6 weeks after infarction but returned by 1 year to nearly the value determined at hospital discharge (177 +/- 13 vs. 165 +/- 10 g, p = NS). The changes in global muscle mass did not parallel the steady and progressive increases in chamber end-diastolic volume. The end-diastolic chamber volume to muscle mass ratio, an index of global left ventricular wall tension, increased steadily after hospital discharge but remained level by 1 year after infarction. The time course of changes in global end-systolic chamber volume was roughly proportional to the concomitant changes in end-diastolic volume. During this same time period, left ventricular stroke volume remained constant or improved from that determined at baseline. Global left ventricular end-diastolic and end-systolic volumes remained relatively static during the 1st year in the patient subgroup with inferior wall myocardial infarction (estimated infarct extent 10 +/- 1% of left ventricle), but global muscle (myocardial) mass initially decreased and then increased in a pattern similar, although of smaller magnitude, to that observed in patients with anterior wall myocardial infarction. CONCLUSIONS: Overall, left ventricular end-diastolic and end-systolic chamber volumes increase progressively from hospital discharge to 1 year after an initial transmural myocardial infarction in patients with a moderately large anterior wall infarction but remain stable in patients with a small inferior wall infarction. Concurrently, total left ventricular muscle mass decreases significantly during the initial 6 weeks after infarction (presumed largely secondary to changes in the necrotic segments) but then returns to the hospital discharge baseline values by 1 year. These data are consistent with the late development of, at most, limited ventricular hypertrophy in the noninfarcted myocardium that occurs well after the early and progressive left ventricular chamber dilation observed in patients with a moderate to large myocardial infarction. These data, in particular as applied to patients with anterior infarction, suggest that ventricular wall tension is significantly elevated at least during the 1st year after an initial transmural myocardial infarction. These observations may explain the potential utility of agents aimed at reducing afterload or ventricular wall tension during the early convalescent phase after myocardial infarction.

Relation of initial infarct size to extent of left ventricular remodeling in the year after acute myocardial infarction.

OBJECTIVES: This study attempted to determine the relation between infarct size after acute myocardial infarction and subsequent left ventricular remodeling using precise clinical measurements. BACKGROUND: Animal studies have demonstrated that the degree of left ventricular remodeling after myocardial infarction is linearly related to infarct size. Clinical studies have not clearly replicated these results because of imprecise measurements and failure to adjust for patency of the infarct-related artery. METHODS: Infarct size was measured from technetium-99m (Tc-99m) sestamibi perfusion images in 14 patients (12 with an anterior, 2 with an inferior infarction) by a threshold method previously described and expressed as percent of the left ventricle (32 +/- 17% left ventricle [mean +/- SD], range 6% to 58%). Absolute end-systolic volume, end-diastolic volume and ejection fraction were determined by electron beam computed tomographic images performed at discharge and at 6 weeks, 6 months and 1 year after myocardial infarction. All patients had documented infarct-related artery patency after reperfusion therapy. RESULTS: At hospital discharge, there was no correlation between infarct size and end-systolic and end-diastolic volumes or ejection fraction. There was significant left ventricular dilation in the study group over the next year. As remodeling progressed, there was closer correlation between infarct size and ejection fraction and end-systolic volume measures (infarct size vs. end-systolic volume, from r = 0.43 at discharge to r = 0.80 at 1 year; infarct size vs. ejection fraction, from r = -0.39 at discharge to r = -0.84 at 1 year). There was a strong inverse correlation between infarct size at discharge and subsequent changes over the next year in end-systolic volume (r = 0.63, p = 0.02) and ejection fraction (r = -0.66, p = 0.01). CONCLUSION: Infarct size as measured by Tc-99m sestamibi at hospital discharge after an index infarction is predictive of subsequent change in left ventricular volume and function in the year after myocardial infarction. Patients with a large infarct demonstrated the greatest degree of dilation in the setting of patency of the infarct-related artery.

Quantification of coronary artery calcium by electron beam computed tomography for determination of severity of angiographic coronary artery disease in younger patients.

OBJECTIVES: This study attempted to 1) evaluate five quantitative measures of coronary artery calcium and determine which best agreed with coronary artery disease severity at angiography; and 2) determine optimal quantity cutpoints to distinguish among no, mild and significant disease. BACKGROUND: Coronary artery calcium identified noninvasively by electron beam computed tomography is a sensitive marker for atherosclerosis. Quantitative assessments of calcium could distinguish among patients with no, mild and significant disease in clinical, screening and research settings. METHODS: One hundred sixty patients, 23 to 59 years old, underwent coronary angiography and electron beam computed tomography. Coronary artery calcium was defined as dense (> 130 Hounsfield units) foci > or = 2 mm2 on the tomogram. Regression and receiver operating characteristic analyses were used to evaluate five quantitative measures of calcium as predictors of the largest stenosis in the coronary arteries and to identify optimal cutpoints for distinguishing among disease categories. No disease was defined as no stenosis, mild disease as 10% to 49% diameter stenosis in one or more major branches and significant disease as > or = 50% diameter stenosis in one or more major branches. RESULTS: All measures evaluated performed well. With calcific area as the quantitative measure, the best cutpoint for discriminating between patients with and without disease was the presence of calcium: sensitivity 81%, specificity 86% and overall accuracy 83%. The best cutpoint for discriminating between patients with and without significant disease was 18 mm2: sensitivity 86%, specificity 81% and accuracy 83%. CONCLUSIONS: Because the ranges of calcium quantity overlapped across disease categories, no cutpoints would distinguish among categories with absolute certainty. However, selected cutpoints could rule out disease in most healthy subjects and identify most patients with significant disease.

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.

Use of ultrafast computed tomography to quantitate regional myocardial perfusion: a preliminary report.

The purpose of this study was to assess the potential for rapid acquisition computed axial tomography (Imatron C-100) to quantify regional myocardial perfusion. Myocardial and left ventricular cavity contrast clearance curves were constructed after injecting nonionic contrast (1 ml/kg over 2 to 3 seconds) into the inferior vena cava of six anesthetized, closed chest dogs (n = 14). Independent myocardial perfusion measurements were obtained by coincident injection of radiolabeled microspheres into the left atrium during control, intermediate and maximal myocardial vasodilation with adenosine (0.5 to 1.0 mg/kg per min, intravenously, respectively). At each flow state, 40 serial short-axis scans of the left ventricle were taken near end-diastole at the midpapillary muscle level. Contrast clearance curves were generated and analyzed from the left ventricular cavity and posterior papillary muscle regions after excluding contrast recirculation and minimizing partial volume effects. The area under the curve (gamma variate function) was determined for a region of interest placed within the left ventricular cavity. Characteristics of contrast clearance data from the posterior papillary muscle region that were evaluated included the peak myocardial opacification, area under the contrast clearance curve and a contrast clearance time defined by the full width/half maximal extent of the clearance curve. Myocardial perfusion (microspheres) ranged from 35 to 450 ml/100 g per min (mean 167 +/- 125). Two flow algorithms derived from characteristics of the contrast clearance curves showed a good correlation with regional myocardial flow determined by microspheres: the ratio of the peak myocardial opacification from baseline to the area under the left ventricular cavity curve (r = 0.7, p less than 0.001, SEE = 44.4 ml/min), and the ratio of the left ventricular cavity to posterior papillary muscle curve areas divided by the full width/half maximal contrast transit time in the region of the posterior papillary muscle (r = 0.82, p less than 0.001, SEE = 52.2 ml/100 g per min). The form of these two flow algorithms was derived from classical indicator dilution theory. In conclusion, indices derived from these data correlated well with regional myocardial perfusion in the posterior papillary muscle region of the dog as assessed by microspheres. This approach offers promise for the quantitation of regional myocardial perfusion and myocardial flow reserve in patients.

Sectional and segmental variability of left ventricular function: experimental and clinical studies using ultrafast computed tomography.

In this study, ultrafast computed tomography, a new high spatial and temporal resolution imaging system, was employed to define the range of sectional (tomographic) and segmental left ventricular function in 11 normal anesthetized dogs and 11 normal human volunteers. After intravenous infusion of contrast agent, multilevel tomographic images of the left ventricle (apex to base) were acquired at a rate of 17 frames/s. Analysis of these studies demonstrated substantial but predictable heterogeneity in left ventricular contraction from apex to base. In dogs and humans, for example, the average tomographic ejection fraction of the most basal level of the left ventricle was 40% less than that of the most apical level (p less than 0.05). In humans, circumferential segmental cavity contraction at the mid-papillary muscle level was relatively homogeneous (range 50 to 92% for 12 wedge-shaped segments around the tomographic circumference) if the reference system employed an endocardial centroid, but was less uniform if it used an epicardial centroid (range 22 to 98%). It is concluded that contraction of the normal left ventricle in dogs and humans is heterogeneous both between levels (apex to base) and within a single level (circumferential cavity contraction). However, the patterns of cavity contraction from apex to base and circumferential segmental cavity contraction within a given level as defined by ultrafast computed tomography are sufficiently narrow and predictable in normal individuals that these variables may be useful to define regional contraction abnormalities in pathologic conditions.

Patterns of regional diastolic function in the normal human left ventricle: an ultrafast computed tomographic study.

The detailed evaluation of regional diastolic filling at multiple ventricular levels in the normal human left ventricle has not previously been reported. Ultrafast computed tomography was used to characterize global and regional early diastolic filling in the left ventricle of 11 normal male volunteers. Regional early diastolic filling data from six distinct ventricular levels (apex to base) were fit to a third-order polynomial curve, and the peak rate of diastolic filling and time of peak filling were determined. Peak filling rate was 259 +/- 17 ml/s (+/- SEM) as a global average, where peak filling rate referenced to end-diastolic volume and stroke volume across the levels examined was 3.78 +/- 0.17 s-1 and 4.83 +/- 0.20 s-1, respectively. Average filling fraction was 39 +/- 1%, and time to peak filling from end-systole was 145 +/- 5 ms. Regional (tomographic) peak filling rates, except for the most apical level examined, were not statistically different across the ventricle. Filling fraction and time to peak filling were remarkably constant from one level to another. However, reference of regional peak filling rate to regional end-diastolic volume demonstrated significant nonuniformity from apex (120% of average for all levels) to base (87% of average for all levels). Peak filling rate referenced to tomographic stroke volume was less variable and not statistically different across the ventricle as a whole.(ABSTRACT TRUNCATED AT 250 WORDS)

Measuring the effect of risk factors on coronary atherosclerosis: coronary calcium score versus angiographic disease severity.

OBJECTIVES: This study sought to determine whether noninvasive quantification of coronary calcium is comparable to selective coronary angiography in measuring the effect of cardiovascular risk factors on coronary atherosclerosis. BACKGROUND: Electron beam computed tomography (EBCT) allows the delineation of anatomic coronary atherosclerotic disease and may be useful for noninvasively defining the role of established and new cardiovascular risk factors in selected patient groups. METHODS: A total of 211 consecutive patients, 26 to 79 years old, referred for evaluation of suspected or recently diagnosed coronary artery disease were examined. Selective coronary angiography was used to define five angiographic disease categories: normal coronary arteries, nonobstructive disease and one-, two- or three-vessel disease. EBCT was used to calculate coronary calcium scores, and cardiovascular risk, including lipid variables and fibrinogen levels, was assessed. RESULTS: Coronary calcium score and angiographic disease severity categories were largely predicted by identical risk factors (i.e., age, male gender, total/high density lipoprotein cholesterol ratio, fibrinogen) and, to a lesser degree, hypertension. Only smoking predicted angiographic disease severity but not calcium scores. The risk factors together explained a comparable proportion of the variability in angiographic disease categories and in calcium score quintiles (33% vs. 41%, p=0.16 by bootstrap analysis). An overall risk score composed of these risk factors separated angiographic disease categories and calcium score quintiles with a similar area under the receiver operating characteristic curve ([mean+/-SE] 0.81+/-0.03 vs. 0.83+/-0.03, p=NS). CONCLUSIONS: Quantification of coronary calcium is comparable to selective coronary angiography in measuring the effect of established cardiovascular risk factors on coronary atherosclerosis. Thus, EBCT may be useful for the noninvasive evaluation of the relations between conventional or developing cardiovascular risk factors and coronary atherosclerosis.

Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: a quantitative pathologic comparison study.

OBJECTIVES: The aim of this study was to determine the relation between coronary artery calcification detected by ultrafast computed tomographic scanning and histopathologic coronary artery disease. BACKGROUND: Recent studies suggest that discrete coronary artery calcification as visualized by ultrafast computed tomographic scanning may facilitate the noninvasive detection or estimation, or both, of the in situ extent of coronary disease. Such quantitative relations have not been established. METHODS: Thirteen consecutive perfusion-fixed autopsy hearts (from eight male and five female patients aged 17 to 83 years) were scanned by ultrafast computed tomographic scanning in contiguous 3-mm tomographic sections. The major epicardial arteries were dissected free, positioned longitudinally and scanned again in cross section. Coronary artery calcification in a coronary segment was defined as the presence of one or more voxels with a computed tomographic density > 130 Hounsfield units. Each epicardial artery was sectioned longitudinally, stained and measured with a planimeter for quantification of cross-sectional and atherosclerotic plaque areas at 3-mm intervals, corresponding to the computed tomographic scans. A total of 522 paired coronary computed tomographic and histologic sections were studied. RESULTS: Direct relations were found between ultrafast computed tomographic scanning coronary artery calcium burden and atherosclerotic plaque area and percent lumen area stenosis. However, the range for plaque area or percent lumen stenosis, or both, associated with a given calcium burden was broad. Three hundred thirty-one coronary segments showed no calcification by computed tomography. Although atherosclerotic disease was found in several corresponding pathologic specimens, > 97% of these noncalcified segments were associated with nonobstructive disease (< 75% area stenosis); if no calcification was determined in an entire coronary vessel, all corresponding coronary disease was found to be nonobstructive. To determine the relation between arterial calcification and any atheromatous disease, computed tomographic calcium burden for each segment was paired with the histologic absence or presence of disease. Ultrafast computed tomographic scanning had a sensitivity and specificity of 59% and 90% and a negative and positive predictive value of 65% and 87%, respectively. A direct correlation was found (r = 0.99) between total calcium burden calculated from tomographic scans of the heart as a whole and scans of the arteries obtained in cross section. CONCLUSIONS: The detection of coronary calcification by ultrafast computed tomographic scanning is highly predictive of the presence of histopathologic coronary disease, but the use of this technique to define the extent of coronary disease may be limited. However, the absence of coronary calcification at any site is highly specific for the absence of obstructive disease.

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.

Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology.

OBJECTIVES: This study was designed to evaluate whether calcium deposition in the coronary arteries is related to atherosclerotic plaque burden and narrowing of the arterial lumen. BACKGROUND: Many studies have recently documented the feasibility of electron beam computed tomography to detect and quantify coronary artery calcification in patients. Although these studies suggest a general relation between calcification and severity of coronary artery disease, the value of coronary calcium in defining atherosclerotic plaque and coronary lumen narrowing is unclear. Previous pathologic comparisons have failed to detail such a relation in identical histologic sections. This finding may be due to atherosclerotic remodeling. METHODS: A total of 37 nondecalcified coronary arteries were processed, sectioned at 3-mm intervals (723 sections) and evaluated by computer planimetry and densitometry. RESULTS: A significant relation between calcium area and plaque area was found on a per-heart basis (n = 13, r = 0.87, p < 0.0001), per-artery basis (left anterior descending coronary artery [LAD]: n = 13, r = 0.89, p < 0.0001; left circumflex coronary artery [LCx]: n = 11, r = 0.7, p < 0.001; right coronary artery [RCA]: n = 13, r = 0.89, p < 0.0001) and per-segment basis (n = 723, r = 0.52, p < 0.0001). In contrast, a poor relation existed between residual histologic lumen area and calcium area for individual hearts (r = 0.48, p = NS), individual coronary arteries (LAD: r = 0.59, p = NS; LCx: r = 0.10, p = NS; RCA: r = 0.59, p = NS) and coronary segments (r = 0.07, p = NS). Longitudinal changes in external elastic lamina areas were highly correlated with changes in plaque area values (r = 0.60, p < 0.0001), whereas lumen area did not correlate with plaque size change (r = 0.01, p = NS). CONCLUSIONS: Coronary calcium quantification is an excellent method of assessing atherosclerotic plaque presence at individual artery sites. Moreover, the amount of calcium correlates with the overall magnitude of atherosclerotic plaque burden. This study suggests that the remodeling phenomenon is the likely explanation for the lack of a good predictive value between lumen narrowing and quantification of mural calcification.

Coronary artery pressure development and wave transmission characteristics in the horse.

Measurements of the pressure waveform development and the wave transmission characteristics in the left extramural coronary arteries of the horse have been carried out. Near the ostium the left coronary pressure waveforms are seen to be virtually identical to the corresponding aortic root waveforms; however, the present of low frequency, relatively large amplitude pressure oscillations (on the order of 5 to 10 Hz) gradually become the dominant diastolic feature as one proceeds distally from the left ostium, and these eventually completely mask the incisura. In a limited number of experiments, these oscillations have been simultaneously observed on both centerline velocity and phasic flow signals. These are felt to be primarily due to wave reflection phenomena, but may represent a combined effect of wave reflections and the natural oscillatory motion of the heart mass. Peak systolic pressures were found to remain relatively unchanged as one proceeds distally; however, the end-diastolic pressures were found to decrease steadily, thus giving rise to an increasing pulse pressure and a gradually decreasing mean pressure. Wave speeds in the coronary arteries were found to range between 4 and 11 m.s-1, and the data obtained indicate the wave speed to be highly dependent on both local intralumenal pressure and spatial location.

Hot film coronary artery velocity measurements in horses.

Coronary velocity measurements have been carried out in anaesthetized, open-chest horses using a constant-temperature, hot-film anemometer system. L-shaped needle probes inserted by direct vessel puncture have been used to measure velocity profiles in the left common, left anterior descending (LAD), and left circumflex coronary arteries. The flow conditions were characterized by peak Reynolds numbers from approximately 200 to 1500 and values of the unsteadiness parameter from 3 to 10. These measurements indicate that in the left common coronary artery the profile is in general skewed towards the outer wall as would be expected for fully viscous flow in a curved tube. In the left anterior descending and left circumflex coronary arteries just distal to the bifurcation, the skewing was found in general to be away from the flow divider. However, in regions of the LAD and left circumflex 5-6 diameters downstream of the bifurcation, the peak systolic and diastolic profiles were indicative of a more fully developed, Poiseuille type flow with only slight skewing observed. The results of this study indicate that the flow in the coronary system, though in general laminar and disturbance free, is extremely varied in character and may exhibit large amplitude, low frequency flow oscillations. Furthermore, for these vessels which all lie on the surface of the myocardium, large systolic flows were observed to be present, even though the major portion of the volume flow was reserved for the diastolic period.