28th Bethesda Conference. Task Force 5: Assessment, approval, and regulation of new technology.
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Biomedical subjects
Publications and source records attributed to D J Skorton.
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The ACC has affirmed its commitment to universal access to health care. Underserved populations exist in urban and rural centers. Common to each is a paucity of personnel trained in cardiovascular care and a lack of access to preventive and highly technologic services. These factors contribute to a poor health outcome (75). Part of the rural problem can be corrected by the transfer of information to local providers by the use of new information systems. Included would be real-time electronic consultation, on-site subspecialty visits and the appropriate use of nonphysician providers (15). The urban problem requires changes in priorities and responsibilities of the academic health centers toward the communities they serve. Curricula changes of cardiovascular specialists, internists, generalists and nonphysician health care personnel must include diversity in training, physician training of ethnically matched providers in addition to technical excellence and research into methods of patient education and motivation for a healthier life-style (51). Reimbursement must appropriately reward those caring for underserved patients and those providing evaluation and management services (43,52).
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Coronary artery bypass graft patency can be assessed using the indirect techniques of evaluating patients' symptoms and exercise tolerance, changes in stress electrocardiogram, radioisotope regional perfusion, and myocardial wall contraction. The direct techniques assess graft patency directly by visualizing grafts using conventional computed tomography (CT), ultrafast CT, magnetic resonance imaging, digital subtraction angiography, and echocardiography. The advantages and disadvantages of each of these modalities are reviewed. At the present time, ultrafast CT and possibly magnetic resonance imaging and Doppler appear to be the only techniques besides angiography that can consistently evaluate bypass graft patency. Although they have the advantage of being minimally invasive, they cannot show graft stenosis or sequential graft patency. These techniques are best used in following patients after coronary bypass graft surgery and ruling out graft closure as the source of chest pain.
Congenital pulmonary valve disease is often not discovered until adolescence or adulthood. Transthoracic two-dimensional echocardiography can provide detailed information regarding right ventricular outflow anatomy, although images are often less satisfactory than those obtained in infants and children. The more recent addition of biplanar transesophageal echocardiography has enhanced our ability to image the right ventricular outflow tract, pulmonary valve, and pulmonary artery noninvasively. Pulsed and continuous-wave Doppler estimates of subvalvular and transvalvular gradients have proved to be accurate. Doppler color flow mapping has proved useful in determining the location and direction of stenotic and regurgitant flow. With no accepted standard for comparison, quantification of regurgitation remains problematic. In many cases, echocardiography has replaced catheterization and angiography in the evaluation and long-term follow-up of congenital pulmonary valve disease before and after intervention.
Echocardiography is unique in its role as both a routine, mature technology and an expanding, innovative field. For the foreseeable future, ultrasound will remain one of the most important methods of diagnostic cardiac imaging.
The growing population of patients with congenital heart lesions surviving to adulthood necessitates a fresh look at the clinical training required to care for these patients. Physicians in pediatric and medical cardiology, general pediatrics, general medicine, family practice, obstetrics and gynecology and other specialities will all have a role in the care of these patients. Most likely, training will need to be incorporated into existing pathways with a clear delineation of a body of knowledge necessary to assimilate to complete the training program. The authors favor a certificate of added qualification for the treatment and management of adults with congenital heart disease to encourage excellence in preparation of physicians to care for this complex patient population.
Cyclic backscatter variation is useful in differentiating normal from ischemic and myopathic myocardium; however, there are few data on the reproducibility of clinical cyclic variation measurements. Therefore, a study using 2-dimensional and M-mode backscatter imaging was performed in 20 normal male subjects by 2 observers at an initial session and by 1 of the observers after 1 week. Cyclic variation on M-mode was calculated as the difference between the end-diastolic backscatter and the backscatter at the nadir. Two-dimensional determinations of backscatter were made using a single frame at end-diastole and one at end-systole. The cyclic change was the difference between backscatter measured in the end-diastolic and end-systolic frames. There were no statistically significant differences in analysis of variance among the grouped repeated measurements in either the interventricular septum or the posterior left ventricular wall. At the initial session, cyclic backscatter variation in the posterior wall using M-mode techniques was 5.9 +/- 1.8 dB (SD). The cyclic change in backscatter in the septal wall, using the 2-dimensional technique, was 4.3 +/- 2.4 dB. In the posterior wall, the cyclic change in backscatter was 5.7 +/- 1.7 dB. Pairwise observer correlations between repeated measurements ranged from -0.48 to 0.45. Thus, although there were no significant differences in group means on repeat measurements, repeated measurements in individual subjects were not reliably reproduced because of limited independent sampling of backscatter measurements at only 2 points in the heart cycle. Increased independent sampling and measurement from a backscatter waveform throughout the cardiac cycle may improve reproducibility of measurements.
Tissue changes known to occur with acute myocardial infarction include increases in tissue water and lipid content. We sought to evaluate the relative contribution of alterations in tissue water and fat content to the changes of T1 and T2 relaxation times with infarction. Nine mongrel dogs underwent coronary artery occlusion for 6-12 h. T1 and T2 at 20 MHz and tissue water and fat content of normal and infarcted tissue were measured. Tissue water content, T1, and T2 were significantly greater in infarcted myocardium compared to normal (P less than 0.05). Tissue fat content, while not significantly different, increased linearly in infarcted samples as a function of duration of ischemia (r = 0.77). Despite this increase in fat content, only tissue water content was significantly linearly related to T1 (r = 0.97) and T2 (r = 0.91). Increases in T1 and T2 of infarcted tissue appeared to be most significantly influenced by changes in tissue water content. While total tissue fat content increased with duration of ischemia, it did not appear to significantly alter T1 or T2.
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OBJECTIVES: The authors assessed the effects of varying one extracellular component (fibrinogen concentration) and one cellular component (hematocrit) on magnetic resonance (MR) T1 and T2 relaxation times of in vitro blood clots. METHODS: Blood from six male subjects was collected into sodium citrate anticoagulant (3.8%) and the whole blood was separated into platelet-rich plasma and packed erythrocytes. Subsequently, in vitro blood clots were made from varying concentrations of fibrinogen (1, 10, and 100 microM) in Tyrode's solution and washed, packed erythrocytes (hematocrit levels: 0%, 10%, 40%, and 80%). T1 and T2 measurements were completed at 20 MHz within 8 hours of initiating clotting. RESULTS: Significant shortening of MR relaxation times occurred with increasing fibrinogen concentration for hematocrit values of 0% and 10%. Extracellular fibrinogen concentration did not contribute significantly to variation in relaxation times at hematocrit values of 40% and 80%. For any given fibrinogen level, significant shortening occurred in T1 and T2 values for each successive increase in hematocrit values. CONCLUSIONS: Both extracellular (fibrinogen) and cellular (erythrocyte concentration) factors are significant determinants of thrombus T1 and T2 relaxation times.
BACKGROUND: Automated edge detection of endocardial borders in echocardiograms provides objective, reproducible estimation of cavity area; however, most methods have required off-line analysis. A recently developed prototype echocardiographic imaging system permits real-time automated edge detection during imaging and thus, the potential for measurement of cyclic changes in cavity area and the assessment of left ventricular function on-line. Our purpose was to compare measurements of endocardial area manually traced from conventional echocardiograms with those obtained with the real-time automated edge detection system in normal subjects. METHODS AND RESULTS: Two training sets of images were used to establish optimal methods of gain setting; the settings were then evaluated in a test set of images. In the high-gain training group (n = 8 subjects, 119 images), gain settings were adjusted sufficiently high to display at least 90% of the endocardial border. Manually drawn and real-time area measurements correlated at r = 0.92, but manually drawn areas were underestimated by computer. In the low-gain training group (n = 7 subjects, 104 images), gain settings were adjusted sufficiently low to avoid cavity clutter despite the presence of dropout of endocardial edges. Manually drawn and real-time areas again correlated (r = 0.79), but manually drawn areas were overestimated by computer. In the intermediate-gain test group (n = 7 subjects, 105 images), gain settings were balanced between maximal endocardial definition (greater than or equal to 90%) and minimal cavity clutter (less than or equal to 1 cm2). Manually drawn and real-time areas correlated at r = 0.91 for the group, and r ranged from 0.94 to 0.99 in individual subjects. Interobserver variability was 9.5% for manually traced areas and 10.6% for real-time area measurements. CONCLUSIONS: Real-time on-line automated edge detection provides accurate estimation of manually drawn cavity areas. Although the method is gain dependent, measurements are reproducible. The system should have clinical application in settings in which measurements of left ventricular function are important.
Phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy is able to identify alterations in myocardial high energy phosphate metabolism associated with acute infarction. It was hypothesized that the extent of acute myocardial infarction could be quantitated from changes in the tissue content of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) derived from P-31 NMR spectra. Nine isolated, perfused rat hearts were studied at 121.5 MHz. After baseline spectra were obtained, varying locations of either the right or the left coronary artery were occluded without removing the heart from the spectrometer. Spectra were then collected during regional ischemia at 15 and 45 min after occlusion. Phosphate metabolites were quantitated from the baseline and 45-min regional ischemia spectra, times at which the metabolites are at steady state for the normal and ischemic conditions. The heart was removed from the spectrometer, perfused for a total duration of 2 h and sectioned into 2-mm thick slices for triphenyltetrazolium chloride staining. Percent infarct was determined by manual tracing of magnified, digitized images of the stained sections. Coronary blood flow, heart rate and blood pressure were monitored throughout the experiment. Significant linear relations were found between percent infarct (by triphenyltetrazolium chloride staining) and the percent change of beta-ATP (r = -0.74), Pi (r = 0.83) and the PCr/Pi ratio (r = -0.71) at 45 min after coronary occlusion. Coronary flow was also found to correlate significantly with percent infarct (r = -0.70). These results are applicable to in vivo P-31 NMR studies of acute infarction where the volume of interest may include both normal and acutely infarcted myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to test the hypothesis that the increased myocardial collagen concentration in the older, spontaneously hypertensive (SH) rat is associated with altered T2 and T1, we performed in vitro studies of 70 left ventricles from 8-, 22-, and 33-week-old SH and Wistar-Kyoto (WKY) rats. We also measured the left ventricle/body weight (LV/BW) ratio (as a measure of hypertrophy), left ventricular water and fat content, and hydroxyproline concentration (as a measure of collagen). The LV/BW ration was not significantly different between 8-week-old SH rats and WKY rats but was significantly greater in SH rats than in WKY rats at 22 and 33 weeks of age. Comparing SH rats with WKY rats at 22 weeks of age, no significant difference existed in T1, T2, water content, or hydroxyproline concentration. However, at 33 weeks of age in SH rats compared with WKY rats, hydroxyproline concentration was significantly greater (4.3 +/- 0.6 mg/g, respectively; P less than .0005), water content was significantly greater (77.1% +/- 0.3% vs. 76.2% +/- 0.3%, respectively; P less than .0001), and T2 and T1 were significantly longer (T2: 52.6 +/- 2.1 msec vs. 48.6 +/- 2.2 msec, respectively; P less than .0001; T1: 656 +/- 14 msec vs. 619 +/- 12 msec, respectively; P less than .0001). In all SH rats combined, T2 and hydroxyproline concentration were significantly correlated (r = .63; P less than .0001). Thus, in SH rats, myocardial hypertrophy precedes increased collagen deposition. These data suggest that estimation of magnetic resonance relaxation times may permit noninvasive identification of increased myocardial collagen deposition independent from changes in myocardial hypertrophy.