Christopher J. Wolfkiel

Ultrafast Computed Tomography as a Diagnostic Modality in the Detection of Coronary Artery Disease: A Multicenter Study

BACKGROUND Ultrafast computed tomography (CT), by acquiring images of the proximal coronary arteries, detects coronary calcifications and has been demonstrated to be highly sensitive for the detection of coronary artery disease in many small studies. The aim of this study was to determine the relationship between ultrafast CT scanning and coronary angiography in a large number of symptomatic patients. METHODS AND RESULTS The study population consisted of 710 patients from six participating centers. A multivariate logistic regression model was used to evaluate the individual contributions of age, number of calcified vessels, and the calcium score for the probability of angiographically significant disease. Of the 710 patients enrolled, 427 patients had significant angiographic disease, and coronary calcification was detected in 404, yielding a sensitivity of 95%. Of the 23 patients without calcifications, 19 (83%) had single-vessel disease at angiography. Of the 283 patients without angiographically significant disease, 124 had negative ultrafast CT coronary studies, for a specificity of 44%. An increasing number of vessels with calcification present on ultrafast CT was found to increase specificity for the presence of obstructive coronary artery disease in at least one vessel (P < .0001). As the log of the calcium score increases, the probability of multivessel obstructive disease increases (P < .0001). CONCLUSIONS Ultrafast CT scanning is an noninvasive, non-exercise-dependent test with an excellent sensitivity for the detection of coronary artery disease. The presence of calcifications in multiple vessels and in younger populations correlates with higher specificities for obstructive disease, making ultrafast CT coronary scanning a very useful diagnostic test.

Reproducibility of the measurement of coronary calcium with ultrafast computed tomography

The differences observed in repeated coronary calcium measurements underscores the importance of considering reproducibility issues when evaluating the significance of serial calcium scores. Furthermore, reproducibility data have important implications for planning intervention trials in which ultrafast computed tomography is used to monitor the evolution of atherosclerotic disease.

Measurement of myocardial blood flow by ultrafast computed tomography.

Myocardial blood flow was analyzed by radioisotope-labeled microspheres and ultrafast computed tomography (CT) in 16 closed-chest, anesthetized dogs. The first set of 10 dogs had CT and microsphere measurements before and after chromonar-induced increases in myocardial blood flow. A second set of six dogs had flows measured at control and during temporary reductions in regional flow produced by balloon cuff occlusion of the left anterior descending coronary artery. All dogs had four-slice, 20-instance CT scans after injection of a medium bolus (0.35 ml/kg) of contrast medium into a femoral vein simultaneous with injection of microspheres into the left atrium. CT myocardial flow was calculated as the change in myocardial CT numbers divided by the area from a blood pool time-density curve. A wide range of myocardial blood flows was produced as determined by microspheres (0 to 6.7 ml/min/g). Global flow of the first set of dogs was shown to have excellent correlation (r = .95, n = 17) for a limited range (.4 less than X less than 1.4 ml/min/g) of flows. Regional flows of these measurements demonstrated less correlation (r = .63, n = 110) but extended the range of flow to 1.7 ml/min/g. At higher flows (greater than 2.5 ml/min/g) the correlation for global and regional flows was not significantly different than zero. Regional ischemic flow correlation extended the linear range of flow to 0 ml/min/g (r = .62, n = 17). These results show that CT can measure myocardial blood flow over a limited but clinically relevant range of flows defined as slightly above normal to ischemic. These results indicate that another preparation of CT flow measurement must be sought for quantification of myocardial perfusion values significantly above normal.

Influence of Age and Gender on the Presence of Coronary Calcium Detected by Ultrafast Computed Tomography

OBJECTIVES This study sought to determine the relation between coronary calcification detected with ultrafast computed tomography and lumen narrowing defined with angiography and evaluated whether this relation is influenced by age and gender. BACKGROUND Ultrafast computed tomography has been shown to be a sensitive method for detection of coronary calcification associated with atherosclerotic disease, but the relation between the extent of coronary calcification and degree of lumen narrowing and the possible influence of gender or age, or both, on this relation have not been clarified. METHODS Seventy men and 70 women were studied with ultrafast computed tomography for analysis of coronary calcification and coronary angiography. Coronary atherosclerosis was considered present if any lumen irregularity was noted on angiography, and obstructive coronary artery disease was defined as a lumen diameter narrowing > or = 70%. RESULTS Coronary calcification had a sensitivity of 88% for identification of patients with atherosclerotic disease and 97% for those with obstructive disease, with corresponding specificities of 55% and 41%, respectively. The sensitivity of coronary calcium for detection of atherosclerotic disease in women < 60 years old was 50%, significantly less than the 97% sensitivity in women > 60 years old and the 87% sensitivity in men < 60 years old (p < 0.05 for each comparison). Logistic regression analysis revealed a 1.81-fold increase in the likelihood of detecting coronary calcification in the atherosclerotic lesions of men compared with those in women (95% confidence interval 1.12 to 2.93, p = 0.016) when controlled for age and severity of coronary disease by angiography. CONCLUSIONS Atherosclerotic lesions in women are less likely to have coronary calcium than lesions with a similar degree of lumen narrowing in men. Differences in the pattern of coronary calcification between men and women may provide insight into the gender differences observed in the clinical development of symptomatic coronary artery disease.

Understanding Right and left Ventricular Systolic Function and Interactions at Rest and With Exercise in Primary Pulmonary HyPertension

The effort limitation in primary pulmonary hypertension (PPH) is thought to result from an inability to increase cardiac output with exercise. The precise mechanism, however, is unknown. We studied right ventricular (RV) and left ventricular (LV) function and interactions in 16 patients with PPH with electron beam computed tomography (EBCT) at rest and during supine bicycle exercise. RV and LV volumes and masses were measured at systole and diastole, and ejection fraction and cardiac index computed. Resting RV end-diastolic volume (215 +/- 72 ml) and mass (110 +/- 45 g) were increased, whereas stroke volume (65 +/- 26 ml) and ejection fraction (31 +/- 8%) were decreased. LV end-diastolic volume (80 +/- 31 ml) was decreased, whereas ejection fraction remained normal (66 +/- 9%). Cardiac index was at the lower limit of normal (2.26 +/- 0.72 L/min/m2). During exercise, RV end-diastolic volume was unchanged (196 +/- 63 ml, p = NS) but stroke volume (52 +/- 29 ml, p < 0.05) and ejection fraction (26 +/- 10%, p = 0.08) decreased. LV end-diastolic (52 +/- 22 ml, p < 0.001), end-systolic (17 +/- 8 ml, p < 0.001), and stroke volumes (35 +/- 20 ml, p < 0.001) decreased, whereas ejection fraction (65 +/- 15%, p = NS) and cardiac index remained unchanged (2.17 +/- 0.93 L/min/m2, p = NS). the ratio of RV/LV stroke volume at rest (1.21 +/- 1.06) increased with exercise (1.74 +/- 1.13, p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of regional pulmonary enhancement in dogs by ultrafast computed tomography

Measurement of regional pulmonary enhancement was made in five anesthetized dogs with intravenous contrast material-enhanced ultrafast computed tomography (CT). Three or four electrocardiogram-gated flow scans were performed in each dog in the prone and supine positions. Immediately after each flow scan was acquired at four levels (8-mm thick slices), 20 times per level, 0.5 mL/kg (10 mL/second) ionic contrast medium was injected into the inferior vena cavae. Each level of each lung was divided into anterior, middle, and posterior regions for time density curve analysis and regional flow estimation. Images were transferred to an off-line workstation for lung pixel colorization and subjective interpretation. There was a statistically significant gravity-related enhancement gradient in both the supine and prone positions; however, the gradient was much greater in the supine position. This study shows that gravity-related contrast medium enhancement gradients in the lung can be demonstrated by ultrafast CT.

Reproducibility of left ventricular myocardial volume and mass measurements by ultrafast computed tomography.

Ultrafast computed tomography has been reported to be an accurate method of measuring left ventricular mass in dogs. To assess the interstudy, intraobserver and interobserver variability of left ventricular myocardial mass measurements in humans, left ventricular myocardial volume was measured three times within 24 h in 16 patients with ischemic heart disease. The mean percent difference of the mean of the three studies performed was -0.01 +/- 1.4% (range -2.9% to 3.6%). The regression analysis for the intraobserver variability at baseline was: Y = -4.33 + 1.03X; r = 0.99, SEE = 3.5 ml. The mean percent difference of the mean of the two sets of measurements performed by two independent observers was 0.28 +/- 2.1% (range -4.35% to 4.35%). The interobserver variability excluding papillary muscles at baseline study was: Y = -4.34 + 1.06X; r = 0.99, SEE = 1.5 ml. The regression analysis with versus without papillary muscles showed: Y = -8.72 + 0.97X; r = 0.96, SEE = 2.6 ml. Regression analysis to assess the variability of 24-h studies at end-systole versus end-diastole revealed: Y = 3.07 + 0.94X; r = 0.97, SEE = 1.8 ml. In conclusion, ultrafast computed tomography is a minimally invasive technique, with very low interstudy, intraobserver and interobserver variability for left ventricular myocardial volume and mass determinations in serial studies.

VALIDATION OF ULTRAFAST COMPUTED TOMOGRAPHIC LEFT VENTRICULAR VOLUME MEASUREMENT

Left ventricular volume has been measured with ultrafast computed tomography. However, the accuracy with which this can be done is unknown. We therefore imaged with ultrafast computed tomography 11 rectangular phantoms, 20 to 225 ml, and 17 left ventricular casts, 15 to 112 ml. Two observers planimetered serial tomographic images and computed volume from sequential tomograms. There was no significant inter- or intraobserver difference in measurement of phantoms. Deviation of ultrafast computed tomographic volume from true phantom volume was -0.1 +/- 3.5% SD, range 9.0 to -7.6%. Correlation of true phantom volume with ultrafast computed tomographic volume was 0.99, SEE = 1.9 ml. No significant difference was observed between merged and single ultrafast computed tomographic scanning sequences. Left ventricular cast volume determined by ultrafast computed tomography deviated from true volume by 6% +/- 20%, range 54% to -45%. Correlation of true volume with ultrafast computed tomographic volume was 0.99, SEE = 5.1 ml. There was no interobserver significant difference in measurement of left ventricular cast volume. Correlation between ultrafast computed tomographic volume and cineradiographic volume of the same left ventricular casts was 0.99, SEE = 4.4 ml. Thus, phantom volumes can be measured accurately without significant intra- or interobserver variation. Merged scanning sequences did not influence volume determination. Left ventricular cast volume determination was comparable to that obtained with cineradiography.

Measurement of myocardial blood flow by UFCT: towards clinical applicability.

This review is designed to be a summary of the research conducted towards establishing ultrafast CT as a clinically appropriate tool for measuring myocardial blood flow. The methods and techniques used in the animal validation studies are presented. The results will be critically analyzed and the conclusions discussed. The proposed improvements to flow calculation algorithms will also be addressed. Technical improvements and experimental research needed will also be addressed.

Acute hemodynamic effects of pindolol and propranolol in patients with dilated cardiomyopathy: Relevance of intrinsic sympathomimetic activity

The administration of beta-blocking agents to patients with poor left ventricular (LV) function may result in clinical and hemodynamic deterioration. The beta antagonist pindolol has intrinsic sympathomimetic activity (ISA) and therefore may be better tolerated. To test this hypothesis 30 patients with a precatheterization diagnosis of dilated cardiomyopathy were randomly assigned to three groups to receive intravenous injections of placebo, propranolol, or pindolol. The baseline ejection fraction and hemodynamics were similar for all groups. For propranolol 1 mg, 2 mg, 3 mg, and 4 mg doses were given 5 minutes apart until a maximum dose of 10 mg was reached, until a 25% reduction in the heart rate or mean arterial pressure occurred, or until clinical deterioration developed. For pindolol, 0.1 mg, 0.2 mg, 0.3 mg, and 0.4 mg boluses were used with the same end points. Baseline hemodynamics were measured and repeated 15 minutes after the last dose of each drug was administered. The mean number of doses given was similar for both groups: 3.3 doses for the propranolol group and 3.4 for the pindolol group. Compared to propranolol, pindolol caused less of a reduction in heart rate, cardiac output, cardiac index, stroke volume index, and stroke work index and less of an increase in the mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, and pulmonary vascular resistance; there was a decrease in systemic vascular resistance. These differences were statistically significant for changes in heart rate, right atrial pressure, cardiac index, and systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)