David K. Blood

Assessment of cardiac function by three-dimensional echocardiography compared with conventional noninvasive methods.

BACKGROUND Reliable, serial, noninvasive quantitative estimation of left ventricular ejection fraction is essential for selecting and timing therapeutic interventions in patients with heart disease. Equilibrium radionuclide angiography is widely used for this purpose but has well-recognized limitations. Advantages of echocardiography over equilibrium radionuclide angiography include assessment of wall motion, valvular pathology, and cardiac hemodynamics, in addition to portability, lack of radiation exposure, and substantially lower cost. However, conventional echocardiographic techniques are limited by geometric assumptions, image positioning errors, and use of subjective visual methods. To overcome these limitations, a three-dimensional echocardiographic method was developed. This study compares ejection fraction by three-dimensional echocardiography, quantitative two-dimensional echocardiography, and subjective two-dimensional echocardiographic visual estimation with that by equilibrium radionuclide angiography. METHODS AND RESULTS Fifty-one unselected patients with suspected heart disease underwent left ventricular ejection fraction determination by equilibrium radionuclide angiography and three-dimensional echocardiography using an interactive line-of-intersection display and a new algorithm, ventricular surface reconstruction, for volume computation. In 44 patients, ejection fractions were also estimated visually by experienced observers from two-dimensional echocardiography and by quantitative two-dimensional echocardiography using an apical biplane summation-of-disks algorithm. An excellent correlation was obtained between three-dimensional echocardiography and equilibrium radionuclide angiography (r = .94 to .97, SEE = 3.64% to 5.35%; limits of agreement, 10.3% to 13.3%) without significant underestimation or overestimation. SEE values and limits of agreement were twofold to threefold lower than corresponding values for all two-dimensional echocardiographic techniques. In addition, interobserver variability was significantly lower for the three-dimensional echocardiographic method (10.2%) than for the apical biplane summation-of-disks method (26.1%) and subjective visual estimation (33.3%). CONCLUSIONS Determination of ejection fraction by three-dimensional echocardiography yields results comparable to those obtained by equilibrium radionuclide angiography and is substantially superior to all two-dimensional echocardiographic methods. Therefore, three-dimensional echocardiography may be used for accurate serial quantification of left ventricular function as an alternative to equilibrium radionuclide angiography.

Comparison of single-dose and double-dose thallium-201 myocardial perfusion scintigraphy for the detection of coronary artery disease and prior myocardial infarction.

SUMMARY Thallium-201 myocardial perfusion scintigraphy was performed after exercise, 4 hours after exercise (redistribution) and after a separate rest injection in 87 patients undergoing coronary arteriography. Significant coronary lesions were present in 62 of the patients.Interpretation of the rest and redistribution scintiscans was the same in 69 patients, 45 of whom had coronary artery disease (CAD). In 16 of the 17 patients with CAD and differing interpretations, defects were present on redistribution scintiscans but not on rest scintiscans; 11 of these patients had evidence of prior transmural myocardial infarction and the other five had an occluded coronary artery supplying the region of the defect.Redistribution scintiscans were more sensitive than rest scintiscans for the detection of prior myocardial infarction (93% vs 54%; P < 0.01). The increased sensitivity was confined to the detection of prior inferior myocardial infarctions. In 36 of 38 patients with persistent perfusion defects on 4-hour redistribution scintiscans, either a prior infaretion or an occluded coronary vessel was present.Exercise scintiscans were compared with rest scintiscans or with redistribution scintiscans for the detection of CAD. The sensitivity was not significantly different with either technique (90% and 89%, respectively), but both scintigraphic techniques were more sensitive than exercise electrocardiography (66%, P < 0.01).These data demonstrate that redistribution thallium-201 scintiscans may be substituted for conventional rest scintiscans, resulting in reduced cost and radiation exposure to the patient.

Single dose myocardial perfusion imaging with thallium-201: application in patients with nondiagnostic electrocardiographic stress tests.

Abstract The rote of the single dose technique of myocardial perfusion imaging with thallium-201 in evaluating patients with suspected coronary artery disease was studied in 128 patients undergoing diagnostic coronary arteriography. Significant coronary disease (70 percent or more luminal stenosis) was present in 95 patients. Exercise scans were compared with 4 hour redistribution scans for the presence of new defects with exercise. Myocardial perfusion imaging was significantly more sensitive (85 versus 64 percent, P P The patients were classified into two groups: group I,89 patients with diagnostically adequate stress electrocardiograms (that is, positive for ischemia or negative at 85 percent or more predicted maximal heart rate), and group II, 39 patients with nondiagnostic stress electrocardiograms (that is, uninterpretable because of intraventricular conduction disturbance or inadequate because of absence of ischemic S-T depression but failure to achieve 85 percent of predicted maximal heart rate). The sensitivity (87 percent), specificity (85 percent) and accuracy (87 percent) of myocardial perfusion imaging in detecting coronary disease in group I were not significantly different from the results of stress electrocardiography alone (88 percent sensitivity, 85 percent specificity and 88 percent accuracy). in group II scintigraphy was 81 percent sensitive, 69 percent specific and 77 percent accurate in detecting coronary disease; these results were not significantly different from those in group I. These data indicate that myocardial perfusion imaging with thallium-201 is more sensitive and more accurate than stress electrocardiography in detecting coronary artery disease but offers no advantage for this purpose in patients with diagnostically adequate stress electrocardiograms.

Discriminant function analysis using thallium-201 scintiscans and exercise stress test variables to predict the presence and extent of coronary artery disease☆

Abstract The ability to predict the presence and extent (number of affected vessels) of coronary artery disease objectively from an exercise treadmill test and thallium-201 myocardial perfusion scintiscans was evaluated using linear discriminant function analysis. Exercise and redistribution scans in the 30 ° left anterior oblique view were characterized by their two dimensional Fourier transforms. The analysis was performed in 141 persons, including 110 patients with coronary artery disease (70 percent or greater stenosis of luminal diameter) and 31 control subjects. There were 43 patients with single vessel and 67 patients with multivessel disease. Input to the discriminant analysis included age, sex, 18 variables from the exercise treadmill test and 36 Fourier frequency coefficients from each scan (exercise and redistribution). Two analyses were performed. In the first, a discriminant function was constructed to detect the presence of coronary artery disease. Seven input variables were chosen: maximal exercise pressure-rate product, sex, anginal pain, change in S-T segment slope with exercise, two Fourier coefficients from the exercise scan and one Fourier coefficient from the redistribution scan. The function correctly classified 103 of 110 patients with coronary artery disease and 27 of 31 control subjects; the estimated sensitivity of the technique is 94 percent, with 87 percent specificity and an overall accuracy of 92 percent for the detection of coronary artery disease. The discriminant function was significantly more sensitive and accurate than qualitative scan interpretation (p In the second analysis, two discriminant functions were developed to predict the extent of disease. In addition to the preceding variables, the duration of exercise, change in systolic blood pressure during the last two stages of exercise, and another Fourier coefficient from the exercise scan were chosen. Using two functions, the method detected the presence of coronary artery disease in 104 of 110 patients (95 percent sensitivity) and correctly classified 28 of 31 control subjects (90 percent specificity). Multivessel disease was correctly predicted in 53 of 67 patients (79 percent accuracy); another 11 patients with multivessel disease were predicted to have single vessel disease. Twenty-nine (67 percent) of 43 patients with single vessel disease were correctly classified; of the remaining 14 patients, 12 were predicted to have multivessel disease and 2 were judged to have normal vessels. The data demonstrate that numerical functions derived from the exercise treadmill test variables and Fourier coefficients of thallium-201 scans can be used to detect the presence of coronary artery disease with 92 percent accuracy. The predictive accuracy for the number of diseased vessels was 78 percent (110 of 141 patients classified correctly).

Effect of left ventricular hypertrophy on myocardial blood flow and ventricular performance in systemic hypertension.

SUMMARY The effect of myocardial hypertrophy resulting from chronic pressure overload upon myocardial blood flow (MBF) and left ventricular (LV) performance was studied in 17 hypertensive patients, nine of whom had left ventricular hypertrophy (LVH), and nine normotensive controls. Mean LV MBF was measured at cardiac catheterization using the regional xenon-133 washout technique. In hypertensive patients with LVH, LV MBF was reduced at rest (35.0 ± 5.4 ml/100 g/min) compared with controls (64.8 ± 7.6 ml/100 g/min, p < 0.01) and hypertensive patients without LVH (62.6 ± 14.5 ml/ 100 g/min, p < 0.01). Coronary vascular resistance was also elevated in the hypertensive patients with LVH (37.6 ± 6.6 dyn * cm−5g−1, p < 0.01). In contrast, ejection fraction, mean velocity of circumferential fiber shortening(MVcf) and end-systolic and end-diastolic volumes were not significantly different among the three groups. Peak systolic stress was significantly lower (p < 0.01) in the hypertensive patients with LVH (225 ± 45 dyn * cm−2 X 10−8) than in the controls (385 ± 114 dyne cm−2 X 10−8) and the hypertensive patients without LVH (395 ± 39 dyn. cm−2 X 10−8). A multivariate regression equation was developed relating MBF to heart rate (HR), MVcf, and peak LV wall stress: MBF = 22.2 MVcf + 10.6 stress + 0.38 HR- 48.2 (r = 0.89, p < 0.01). When MBF was adjusted for differences in stress among patients using the regression equation, there was no significant difference in MBF between hypertensive patients with and without LVH. These results indicate that (1) resting LV myocardial blood flow is normal in hypertensive patients without LVH; (2) resting MBF Is redSuced in controlled hypertensive patients with LVH as a consequence of reduced wall stress; and (3) resting LV performance measured by ejection phase indexes is well preserved in hypertensive patients with and without LVH. These results also provide additional evidence that resting MBF in patients with normal coronary arteriograms is related to hemodynamic indexes of the major determinants of myocardial oxygen consumption.

Prognostic significance of silent myocardial ischemia on a thallium stress test

The clinical significance of silent ischemia is not fully known. The purpose of this study was to determine whether the presence or absence of angina during a thallium stress test positive for ischemia was independently predictive of an adverse outcome. Two hundred thirty-four consecutive patients with ischemia on a thallium stress test were identified. Ischemia was defined as the presence of defect(s) on the immediate postexercise scans not in the distribution of prior infarctions that redistributed on 4-hour scans. During the test 129 patients had angina, defined as characteristic neck, jaw, arm, back or chest discomfort, while the remaining 105 patients had no angina. Follow-up ranged from 2 to 8.2 years (mean 5.2 +/- 2.1) and was successfully obtained in 156 patients. Eighty-two of the 156 patients had angina (group A) and 74 had silent ischemia (group S). Group A patients were significantly older (62 +/- 8 vs 59 +/- 8 years, p less than 0.05). There was no significant difference between the 2 groups in terms of sex, history of prior infarction or presence of left main/3-vessel disease. A larger percentage of patients in group A were receiving beta blockers (60 vs 41%, p less than 0.05) and nitrates (52 vs 36%, 0.05 less than p less than 0.10). There was a large number of cardiac events (myocardial infarction, revascularization and death) in both groups (37 of 82 [45%] in group A; 28 of 72 [38%] in group S) but no statistically significant difference between the groups. Similarly, life-table analysis revealed no difference in mortality between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between segmental thallium-201 uptake and regional myocardial blood flow in patients with coronary artery disease.

The relationship between the spatial distribution of thallium-201 in myocardial perfusion scintigrams and the distribution of left ventricular regional myocardial blood flow was examined in 25 patients undergoing coronary arteriography. Thallium-201 myocardial scintigrams were obtained after symptom-limited exercise and after a 4 hr delay. Regional myocardial blood flow was measured by the xenon-133 clearance method in patients at rest and during rapid atrial pacing to a double product comparable with that achieved during exercise stress testing. Patterns of regional thallium-201 activity and regional myocardial blood flow, recorded in similar left anterior oblique projections, were compared for left ventricular segments supplied by the left anterior descending (LAD) and left circumflex (CIRC) arteries. In 11 patients without significant lesions of the left coronary artery (group 1), thallium-201 was homogeneously distributed in the LAD and CIRC distributions in scintigrams taken during peak exercise; these scintigrams correspond to homogeneous regional myocardial blood flow in the LAD and CIRC regions during pacing-induced stress. In 14 patients with significant lesions of the left coronary artery (group 2), ratios of regional thallium-201 activity in the LAD and CIRC distributions of exercise scintigrams correlated well (r = .84) with ratios of regional myocardial blood flow measured during rapid pacing. Background subtraction altered the relationship between relative thallium-201 uptake and regional myocardial blood flow, causing overestimation of the magnitude of flow reduction on exercise scintigrams. These data indicate that: (1) in patients with normal left coronary arteries, thallium-201 is homogeneously distributed to the left ventricle, reflecting the homogeneous distribution of regional myocardial blood flow over a wide range of mean left ventricular flow rates and (2) in patients with significant lesions of the left coronary artery, the relative spatial distribution of thallium-201 activity in exercise perfusion scintigrams reflects the distribution of regional myocardial blood flow.

Feasibility of a two-dimensional echocardiographic method for the clinical assessment of right ventricular volume and function in children.

The relative ease of acquisition and safety of two-dimensional echocardiography has established it as the mainstay for routine cardiac imaging. Translation of imaging data into useful quantitative information, however, requires fitting the ventricle to a specific geometric model. Because of its complex shape and anterior position, many attempts at right ventricular quantitation by two-dimensional echocardiography have been criticized as impractical and not reproducible. A simple method incorporating subcostal and apical imaging was introduced in 1984. This approach appeared to combine accuracy and practicability but was never validated in a clinical setting because of the difficulties of subcostal imaging in adults. This study assessed the feasibility and accuracy of this technique in the pediatric population. Results of volume comparison to values derived by magnetic resonance imaging were r = 0.96, standard error of the estimate (SEE) = 19.3 ml, and mean difference = 15 +/- 19.4 ml and r = 0.97, SEE = 12.3 ml, and bias = 5 +/- 11.8 ml for diastolic and systolic volumes, respectively. Comparison of estimates of ejection fraction with magnetic resonance imaging demonstrated r = 0.90, SEE = 5.9%, and bias = 3% +/- 5.7%. Interobserver and intraobserver variability was 9.9% and 8.2%, respectively, for systolic volumes and 11.5% and 8.9%, respectively, for diastolic volumes. Evaluation of right ventricular size and function by this approach is comparable to determinations by magnetic resonance imaging and may be clinically useful in the management of pediatric patients.

Thallium-201 lung uptake and peak treadmill exercise first-pass ejection fraction

Increased thallium-201 lung uptake immediately after exercise has been shown (1) to be a marker for extensive coronary artery disease, (2) to correlate with low rest and exercise left ventricular ejection fraction by supine gated blood pool scintigraphy, and (3) to be a powerful independent predictor of future cardiac events. Exercise left ventricular ejection fraction measured during upright exercise by the first-pass technique has also been shown to be a powerful independent prognostic variable. Combined perfusion and exercise left ventricular ejection fraction can be acquired by using the technetium 99m-based myocardial perfusion agents and offers an alternative protocol to stress/redistribution thallium imaging. It is therefore clinically important to understand the relation between exercise lung heart thallium uptake and exercise left ventricular ejection fraction. Accordingly, both these measurements were acquired in 38 patients with documented coronary artery disease who underwent two treadmill exercise studies. Parameters obtained from the first-pass study that are known to affect lung thallium uptake were correlated with exercise lung/heart thallium ratios; lung/heart ratios were used in a model to predict exercise left ventricular ejection fraction values. Exercise left ventricular ejection fraction and peak filling rate showed significant negative correlations with thallium lung/heart ratio, but the first-pass variables examined were not independently predictive of thallium lung uptake. The chance of finding an abnormal thallium lung/heart ratio at exercise LVEF of 40% is only 52%, whereas the chance of finding an abnormal ratio at exercise LVEF of 30% is 74%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of isolated proximal coronary stenotic lesions on distal myocardial perfusion during exercise

This study tested the hypothesis that the absolute dimension of a coronary stenotic lesion is a more important determinant of its hemodynamic effect on regional myocardial perfusion during exercise than is relative percent stenosis. In 31 patients with an isolated lesion of the left anterior descending coronary artery, regional myocardial perfusion was determined from thallium-201 scans recorded in the left anterior oblique projection after symptom-limited treadmill exercise. Thallium-201 uptake in the distribution of the left anterior descending coronary artery was expressed as a ratio of thallium-201 uptake in the left circumflex artery distribution. Percent area stenosis, minimal cross-sectional area and mean diameter of each stenotic lesion were measured by computer-assisted cinevideodensitometric analysis of projected coronary arteriograms digitized in a 512 X 512 pixel matrix with 256 gray levels. Thallium-201 uptake in the left anterior descending coronary artery distribution, expressed as a ratio, correlated poorly (r = 0.65) with relative percent stenosis, but correlated significantly (r = 0.83; p less than 0.05) with absolute lesion area. For all 16 patients with reduced regional perfusion in the left anterior descending coronary artery distribution during exercise, lesion cross-sectional area was less than 1.8 mm2 (mean 0.9 +/- 0.6); for 13 of the 15 patients with normal distal perfusion, the area of the stenotic lesion was greater than 1.8 mm2 (mean 2.7 +/- 0.7; p less than 0.001). Percent coronary stenosis failed to predict flow-limiting lesions.(ABSTRACT TRUNCATED AT 250 WORDS)