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Rapid left-ventricular (LV) diastolic filling assessed by radionuclide ventriculography is reevaluated in patients with coronary artery disease and normal LV systolic function considering the effects of age and heart rate. Thirty normal subjects were studied along with 44 patients with coronary artery disease and normal LV ejection fractions. The peak filling rate was not quite significantly different between the controls and patients (2.67 +/- 0.95 EDV/sec versus 2.25 +/- 0.65 EDV/sec, p = 0.08), and the time to peak filling rate was not different. When an inappropriate young control group was compared with coronary disease patients aged 40-65 yr, large differences in peak filling rate were seen. Sensitivity for detection of disease was very low (0%-9%) except when the inappropriate young control group was used. Thus, analysis of rapid diastolic filling cannot detect individual patients with coronary disease who have normal LV ejection fractions. Previous reports to the contrary may have suffered from failure to include the effects of age and heart rate.

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To define effects of nifedipine on regional metabolism in jeopardized myocardium we quantified accumulation of carbon-11 labeled palmitate ([11C]palmitate) in patients with acute myocardial infarction by positron emission tomography in a randomized, double-blind, placebo controlled study. Tomographic studies were performed prior to treatment as soon as possible after hospital admission. Subsequent studies were performed seven days later. Twenty-two patients with acute myocardial infarction were randomized to treatment with nifedipine (n = 13) or placebo (n = 9). The dosage of active medication was guided by a "third party observer" to avoid iatrogenic hypotension. Treatment was initiated within 9.6 +/- 1 hours after the onset of symptoms of infarction. The extent of the zone of abnormal accumulation of [11C]palmitate was similar in pre-treatment positron emission tomograms from patients subsequently given nifedipine compared with those given placebo. In subsequent positron emission tomography studies, patients treated with nifedipine exhibited improved metabolism of [11C]palmitate (by 16 +/- 10%, SE, P less than 0.05) compared with no change in patients given placebo. Neither enzymatic estimates of infarct size nor scintigraphic estimates of left ventricular ejection fraction differed in the two groups. Patients given nifedipine and manifesting substantial improvement in accumulation of [11C]palmitate had a high incidence of chest pain and recurrent infarction compared with those given placebo in whom no improvement was evident. These observations suggest that some regions of myocardium were benefited transiently by nifedipine but that they remained at high risk for recurrent injury. Thus, patients benefited transiently by drugs early after the onset of infarction may require aggressive intervention such as angioplasty or early coronary bypass surgery. Accordingly, they should be evaluated angiographically early for identification of lesions with unusually high risk.

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Thirty normal subjects, aged 22 to 80 years, were studied by radionuclide ventriculography to determine the age dependence of cardiac ventricular diastolic function and to evaluate the association of other factors with ventricular diastolic performance. A strong negative correlation was found between peak diastolic filling rate and age (r = -0.82, p less than 0.0001). Partial correlation analysis was used to factor out the strong age dependence and yielded additional significant correlations of peak filling rate with heart rate (r = 0.48, p less than 0.01) and time to peak filling rate (r = -0.48, p less than 0.01). Time to peak filling rate is also correlated with heart rate but not definitely with age. Analysis by multiple linear regression yields an equation predicting peak filling rate from age and heart rate. Thus, the rate of rapid diastolic filling declines markedly with age in normal subjects. The association of peak filling rate with age and with other factors indicates the need for careful consideration of these factors in the interpretation of scintigraphic findings in patients with heart disease.

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To determine whether prolonged, intense exercise training can improve left ventricular function in patients with coronary artery disease, we studied 25 patients, 52 +/- 2 years old (mean +/- SE), who completed a 12 month program of endurance exercise training and 14 additional patients with comparable maximal exercise capacities and ejection fractions who did not exercise. The training program consisted of endurance exercise of progressively increasing intensity, frequency, and duration. During the last 3 months the patients were running an average of 18 miles/week, or doing an equivalent amount of exercise on a cycle ergometer. Maximal attainable VO2 increased 37% (p less than .001). Of the 10 patients with effort angina, five became asymptomatic, three experienced less angina, and two were unchanged after training. Ejection fraction was determined by equilibrium radionuclide ventriculography. At rest, ejection fraction was 53 +/- 3% before and 54 +/- 3% after training (p = NS). Ejection fraction did not change during maximal supine exercise before training (52 +/- 3%), but after training it increased to 58 +/- 3% (p less than .01). During maximal exercise, systolic blood pressure and the rate-pressure product were higher after training. The systolic blood pressure-end-systolic volume relationship was shifted upward and to the left, with an increase in maximal systolic blood pressure (p less than .001) and a smaller end-systolic volume (p less than .05), providing evidence for an improvement in contractile state after training. In patients who did not participate in training neither this relationship nor the ejection fraction response to exercise was changed after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

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Circulatory abnormalities are common during the adult respiratory distress syndrome and contribute importantly to the high mortality seen with this illness, but what causes them is not well characterized. Oleic acid-induced acute lung injury is an experimental model of the human syndrome in which hemodynamic changes are also common. To characterize a possible link between lung injury and cardiac dysfunction in this model, we evaluated cardiac function in mongrel dogs after oleic acid administration. Stroke volume index decreased, the radionuclide ventriculographically determined ejection fraction decreased, and end-diastolic volume increased after oleic acid. These results suggested a decrease in myocardial contractility, a conclusion confirmed when other experiments demonstrated a consistent rightward displacement of the end-systolic pressure-diameter relationship after oleic acid. Histologic examination of the myocardium showed little evidence of vascular injury, and myocardial tissue wet-to-dry weight ratios were normal. Thus, although the pulmonary effects of oleic acid are due to microvascular injury, similar mechanisms are not responsible for the depression in myocardial contractility.

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Exercise-induced increases in pulmonary uptake of thallium-201 (201Tl) have been associated with exercise-induced myocardial dysfunction. To evaluate this phenomenon more replicably, a quantitative semi-automated computer program was used to generate, from anterior exercise and delayed views, lung-myocardial ratios (LMR) of 201Tl uptake in 78 patients [40 normal, 38 with coronary artery disease (CAD)]. Patients with CAD had a significantly higher mean exercise lung myocardial ratio (EXLMR) than normals (30.8 vs. 27.3; P less than 0.003). In patients with adequate exercise (greater than or equal to 85% of an age-adjusted maximal heart rate), the EXLMRs of CAD patients were significantly higher than those of normals (29.7 vs. 25.5; P = 0.003). However, this difference between CAD and normal patients was not apparent in a patient subgroup with submaximal exercise levels (less than 85% of an age-adjusted maximal heart rate). In both normal and CAD patients, EXLMR decreased with increasing exercise levels (r = -0.555; P = 0.007). In patients with 201Tl scans lacking visually defined perfusion defects (visually normal), an elevated LMR detected 60% of CAD cases with 81% specificity. A considerably elevated EXLMR in patients achieving adequate exercise should suggest the presence of CAD, even if there are no visually apparent cardiac perfusion defects. With submaximal exercise, however, the EXLMR is not a useful discriminator between CAD patients and normals.

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To assess the contribution of coronary vasospasm to chest pain in patients with nontransmural myocardial infarction, we performed a controlled trial of prophylactic antivasospastic therapy. Fifty patients with nontransmural infarction received either nifedipine or placebo in a double-blind randomized trial. Chest pain occurred in 52% of treated patients (38 episodes on 35 days) compared to 48% of control patients (42 episodes on 33 days). Concurrent therapy was comparable in the two groups. Recurrent infarction occurred in 12% and was comparable between groups. Ejection fraction was similar and was unchanged throughout the study in both groups. Logistic regression failed to identify predictors for recurrent chest discomfort. These data indicate that potent antivasospastic therapy does not reduce the incidence of recurrent chest pain or infarction. Thus, remediable coronary vasospasm is not likely to be a major cause of post infarction ischemia in patients with nontransmural infarction.

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To evaluate the reliability of "low probability" ventilation-perfusion (V-P) scintigrams in excluding pulmonary embolism (PE), we reviewed the clinical records of 99 consecutive patients (74 in-patients and 25 outpatients) whose V-P studies had been interpreted as indicative of a low probability of PE. None of the 99 patients were referred for pulmonary angiography. Venography was performed in four patients and was positive in three. No patients were treated specifically for pulmonary embolism, but five received full treatment with anticoagulants for other reasons (three for venous thrombosis, one for a history of venous thrombosis, and one for a ventricular aneurysm). Seven of the hospitalized patients died during the index admission and seven additional hospitalized patients (including one treated with anticoagulants) died 1-5 months after discharge from the hospital. None were thought clinically to have died as a result of PE, and autopsy disclosed no PE in two. Follow-up information was obtained for 69 surviving patients (49 inpatients and 20 outpatients) not treated with anticoagulants. None of these patients were thought clinically to have had PE during follow-up of at least 2 weeks duration (greater than 2 months in 93% and greater than 6 months in 75%). Our results suggest that major short-term morbidity or death attributable to PE are quite infrequent in patients with low-probability V-P scintigrams.

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The results of Kr-81m/Tc-99m ventilation-perfusion (VP) lung scintigraphy were correlated with the results of pulmonary angiography for 74 patients suspected of having pulmonary embolism (PE). Among patients having a diagnostic scan, the sensitivity and specificity of scintigraphy were 91% and 94%, respectively. Also, 157 consecutive cases of Kr-81m/Tc-99m VP lung scintigraphy were reviewed, and the frequency of an indeterminate scan was found to be 22%. A similar frequency was found for VP scintigraphy with xenon-133. Of eight patients who had indeterminate scans due to the presence of a single VP mismatch, four were demonstrated to have PE by angiography. Kr-81m is an excellent agent for VP scanning in cases of suspected PE, offering accuracy in diagnosis as well as favorable physical properties.

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To evaluate the clinical utility of improved methods for radioaerosol inhalation imaging, we obtained preperfusion radioaerosol images in 107 patients (mean age = 62 years), who were referred for evaluation of suspected pulmonary embolism (PE). For each patient, we compared six-view aerosol images with accompanying perfusion scans and chest radiographs and with Xenon-133 (Xe-133) or Krypton-81m (Kr-81m) studies. Four observers at four different institutions independently evaluated aerosol-perfusion and gas-perfusion pairs, classifying the probability of PE as low, high, or indeterminate. The radioaerosol images were good to excellent in quality; excessive central deposition of activity was infrequent and did not interfere with image interpretation. The aerosol-perfusion studies showed 86% agreement with Xe-133 perfusion interpretations (n = 299) and 80% agreement with Kr-81m perfusion interpretations (n = 99). These rates of agreement were comparable with those of intraobserver agreement for gas-to-gas and aerosol-to-aerosol comparisons, and higher than interobserver agreement rates. In a limited number (n = 9) of angiographically documented cases, aerosol-perfusion and gas-perfusion studies provided accurate and equivalent diagnoses. The results suggest that radioaerosol inhalation studies, performed with improved nebulizers, are diagnostically equivalent to ventilation imaging as an adjunct to perfusion scintigraphy in evaluating patients with suspected PE.

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The authors describe a digital filter that greatly enhances the quality of gated cardiac blood-pool images. Spatial filtering is accomplished with a minimum-mean-square-error (Wiener) filter incorporating measured camera blur and Poisson noise statistics. A low-pass temporal filter is then applied to each pixel, with the cutoff frequency determined from measurements of frequency spectra in 20 patients. This filter was evaluated in routine clinical use for nearly one year and found to significantly improve chamber definition, delineate wall motion abnormalities better, and reduce noise. To quantitatively assess the effect of the filter on image interpretation, four experienced observers evaluated wall motion in a series of mathematically simulated left ventricular images. ROC analysis revealed that accuracy in assessing wall motion was significantly greater with the filtered images.

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Pairs of sequential perfusion lung scans and pulmonary angiograms obtained in 45 patients were reviewed to investigate the utility of short-term, sequential scintigraphy in the diagnosis of pulmonary embolism (PE). Forty-six sequential scan pairs were reviewed; 13 were ventilation-perfusion (V-P) pairs. Angiograms were obtained within 48 hours of either the first (65%) or second (35%) perfusion scan in each pair. Sequential scintigraphic patterns were classified as showing change (i.e., improvement in defects, new defects), no change, or as being indeterminate. A changing perfusion pattern was associated with a high (20/23) likelihood of PE, but seven of 16 patients with stable perfusion patterns also had PE. The sensitivity of a changing perfusion pattern for PE was 0.74 (20/27) and its specificity was 0.75 (9/12). In two of six patients who had serial V-P studies that showed changing perfusion defects, there were matched changes in regional ventilation and angiograms were negative. The findings suggest that short-term serial perfusion lung scanning may aid the scintigraphic diagnosis of PE in certain circumstances. Serial V-P imaging is needed, however, to maximize diagnostic specificity.

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Separation of systolic and diastolic parameters in gated cardiac blood-pool imaging (RVG) was achieved with the retention of two harmonics in the Fourier-series representation of the time-activity curve. Regional and global analysis of left-ventricular peak filling rate (PFR) and time to peak filling (TPF) was performed in 18 control subjects, 20 patients with coronary artery disease (CAD) but with normal RVG (normal regional wall motion and ejection fraction, and 16 CAD patients with abnormal RVG. In regional analysis of CAD patients, the standard deviation of the TPF histogram identified 13/20 (65%) of normal RVG patients and 12/16 (75%) of abnormal RVG patients as abnormal. In global analysis of CAD patients, PFR values identified 10/20 (50%) of normal RVG patients and 11/16 (69%) of abnormal RVG patients as abnormal. Thus, left-ventricular systolic and diastolic parameters can be separately measured with retention of higher-order harmonics in the Fourier transform, and regional inhomogeneity of diastolic filling can be detected in CAD patients with normal resting ejection fraction and wall motion.

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Two diagnostic schemes for detection of pulmonary embolism by ventilation-perfusion (V-P) scintigraphy were compared for relative accuracy by two groups of observers interpreting 70 V-P scintiscans. Observers in Group B, who used the criteria recently proposed by Biello et al., had a significantly smaller average number of "indeterminate" interpretations (41%) than did the observers in Group A (55%), who used a simpler scheme (p less than 0.05). In addition, Group B showed a slight improvement in positive predictive value without a deterioration in the negative predictive value compared with Group A. Along with this improvement in diagnostic performance, Group B achieved a significant reduction in interobserver variability compared with Group A for patients without pulmonary embolism (p less than 0.05). There was no significant difference in interobserver variability between the two groups for patients with pulmonary embolism. The diagnostic scheme introduced by Biello et al. represents a useful improvement for the diagnosis of pulmonary embolism by V-P imaging.

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Considerable controversy surrounds the optimal management of symptomatic infants with anomalous origin of the left coronary artery from the pulmonary artery; this includes the timing and type of surgical intervention. Long-term follow-up was obtained on three patients who had simple ligation of the anomalous left coronary artery at or before 8 months of age; long-term follow-up on an adolescent treated with a saphenous vein bypass graft from the aorta to the coronary artery was available for comparison. Remarkable increase in left ventricular contractility was observed in the three patients treated only by simple ligation of the anomalous left coronary artery during infancy. Thallous chloride T1 201 exercise studies disclosed no perfusion abnormalities in any of the patients despite angiographically demonstrable wall-motion abnormalities in two of the four patients. Our study suggests that simple ligation of the anomalous left coronary artery near its origin in patients with angiographically detectable left-to-right shunting can provide long-term survival with good left ventricular function and minimal clinical complaints.

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Gated radionuclide imaging with 99mTc-labeled red blood cells was employed to assess changes in right atrial (RA) volume in 17 subjects. Studies were repeated within two hours in five of 12 normal subjects and at two and ten days after infarction in five patients. Time-activity curves were generated for the RA and right ventricle (RV) from variable regions of interest defined by automatic edge detection. The RA time-activity curve exhibited four phases: filling, early emptying, equilibration, and late emptying. Repeated measurements of RA early emptying rates correlated closely in normals (r = 0.93). Early RA emptying and RV filling rates corresponded closely (r = 0.89). In four patients with infarction, the RA emptying rate was slowed on the first study but had normalized by 10 days. In a patient with inferior infarction and suspected RV infarction, the RA emptying rate was depressed and remained so for 10 days. Thus, relative changes in right atrial volume can be assessed reproducibly by a radionuclide technique, which is relatively independent of geometric assumptions. This technique offers great promise as a method to assess atrial function in health and disease.

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