David J. Skorton

The effect of coronary angioplasty on coronary flow reserve.

To determine the effects of coronary angioplasty on coronary flow reserve (CFR), we studied 32 patients before and immediately after single-vessel coronary angioplasty and 31 patients evaluated late after angioplasty (7.5 +/- 1.2 months, mean +/- SEM). The geometry (percent area stenosis and minimal cross-sectional area) of each lesion was determined by quantitative coronary angiography (Brown/Dodge method) and the integrated optical density was measured by videodensitometry. CFR was measured with a No. 3F coronary Doppler catheter placed immediately proximal to the lesion and a maximally vasodilating dose of intracoronary papaverine. The translesional pressure gradient was obtained in all lesions before and immediately after angioplasty and in 18 of 31 vessels late after angioplasty. CFR immediately after angioplasty returned to normal levels (greater than 3.5 peak/resting velocity ratio) in 14 of 31 patients and was improved, although not normalized, in the remaining 17 patients. CFR immediately after dilation was not significantly correlated with any of the angiographic variables of arterial stenosis nor the resting pressure gradient. Moreover, the pressure gradient and absolute distal coronary pressure at peak hyperemia were not significantly different in vessels with normal and those with abnormal flow reserve immediately after dilation, suggesting that the residual stenosis did not significantly limit hyperemia. Late after angioplasty, however, a significant relationship emerged between CFR and all four indexes of residual arterial stenosis (percent area stenosis r = .70, p less than .01; minimum arterial cross-sectional area r = .70, p less than .01; integrated optical density r = .60, p less than .01; and translesional pressure gradient r = .77, p less than .01). Furthermore, in the absence of restenosis, CFR eventually normalized in all patients. These findings demonstrate that in one-half of patients there is a transient reduction in coronary flow reserve immediately after angioplasty. In the absence of restenosis, coronary flow reserve later normalizes. Consequently, measurements of coronary flow reserve immediately after angioplasty may not reflect the eventual success of the procedure in removing physiologic obstruction to coronary blood flow.

Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions.

We tested the hypothesis that lesion rethrombosis after streptokinase reperfusion is related to luminal size of the residual stenosis. Two independent techniques of analyzing coronary angiograms, quantitative coronary angiography and computer-based videodensitometry, were used to estimate the size of the residual lumen immediately after discontinuation of streptokinase. These techniques were selected because they provide independent estimates of cross-sectional area of a lesion with high degrees of reproducibility and minimal observer variability. Twenty-four patients who had undergone successful reperfusion with streptokinase were studied. Seven patients had lesion rethrombosis documented either on a repeat angiogram, at autopsy, or, in one case, by the fact that the patient had an acute transmural infarction resulting in death. Vessel patency was documented by repeat coronary angiography 8 to 14 days after initial streptokinase reperfusion in the other 17 patients. As assessed by quantitative coronary angiography, seven of 13 patients (54%) with minimal luminal cross-sectional areas of less than 0.4 mm2 had rethrombosis. None of the 11 patients with lumens greater than 0.4 mm2 had rethrombosis. In the 17 patients with vessels that remained patent the size of the residual lesion at repeat catheterization was compared with its size immediately after reperfusion with streptokinase. Over the intervening 8 to 14 day interval, an average percentage increase in minimal cross-sectional area of 116 +/- 34% was observed. In seven patients minimal luminal cross-sectional area more than doubled. Integrated optical density, an index of the severity of coronary stenosis derived from computer-based videodensitometry, was also useful in identifying a subgroup of patients at high risk for rethrombosis of lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneity of left ventricular segmental wall thickening and excursion in 2-dimensional echocardiograms of normal human subjects☆

Abstract Regional abnormalities of left ventricular (LV) wall thickening and excursion have been demonstrated by 2-dimensional (2-D) echocardiography. However, the variability of normal segmental contraction has not previously been defined. We performed 2-D echocardiography in 12 normal men aged 19 to 27 years. We obtained short-axis images at the level of the mitral valve, chordae tendineae, papillary muscles, and apex at end-diastole and end-systole. A computer-based system divided each short-axis image into 12 cavity and wall segments, and analyzed percent systolic wall thickening along each radius and percent area change of each cavity segment. Overall variability of contraction as well as the contributions of several sources of variability were determined. The overall range of cavity segment area change was 0 to 100% and of segmental wall thickening was 0 to 150% in these normal subjects. Average contraction was similar at different ventricular levels. Significant differences were found between adjacent segments at each level as well as between subjects. Intrathoracic cardiac rotation and motion were minimal; correction for these movements did not significantly alter the variability of contraction as calculated from 2-D echocardiograms. Temporal asynergy of contraction did contribute to variability; correction resulted in a significant alteration in mean segmental area change (from 59 ± 20% [standard deviation] uncorrected to 66 ± 16% corrected, p

Quantitative texture analysis in two-dimensional echocardiography: application to the diagnosis of experimental myocardial contusion.

We postulated that the analysis of regional image texture in two-dimensional (2D) echocardiograms would be an accurate method to differentiate normal from abnormal myocardial structure. We tested this hypothesis with quantitative texture measures to study the regional, spatial distribution of echo amplitudes in 2D echocardiograms performed before and immediately after blunt left chest trauma was induced in six anesthetized dogs. After trauma the contused region of myocardium appeared brighter and exhibited an altered myocardial texture. By use of a set quantitative texture measures, we found no significant differences in pretrauma images when normal regions were compared with regions to be contused. Also, we found no difference when we compared the normal regions in each animal in pretrauma vs posttrauma images. Twelve measures, however, differentiated normal from contused regions within the posttrauma images (p values ranged from .0057 to .0001 by multivariate analysis of variance). These texture measures were capable of differentiating normal from abnormal tissue only when texture along the azimuthal (lateral) direction was calculated. We conclude that regions of myocardial contusion exhibit visibly altered local echo-amplitude patterns (altered image texture) and that these image texture alterations may be quantified with digital image analysis techniques. These findings suggest that quantitative texture calculations may be a useful approach to ultrasound tissue characterization.

Detection of acute myocardial infarction in closed-chest dogs by analysis of regional two-dimensional echocardiographic gray-level distributions.

We hypothesized that acute myocardial infarction could be detected in standard two-dimensional echocardiograms of closed-chest dogs by evaluating regional echo amplitude distribu-tions using computerized image analysis. We tested this hypothesis by performing standard, 2.4 MHz two-dimensional echoes before and 2 days after circumflex coronary occlusion in seven closed-chest dogs. Control and infarcted regions of interest were studied in digitized stop-frame images. Average gray level was calculated for each region of interest, and the shape of the gray-level distribution was analyzed by calculation of skewness and kurtosis and by qualitative features of shape. Average gray level increased significantly from the pre-to postocclusion images in the infarcted regions (16.7 ± 4.2 vs. 32.4 ± 4.4 units, P < 0.01), but not in the control regions (17.4 ± 4 vs. 22.3 ± 5.5., P = NS). Average gray level could not distinguish between infarcted and normal regions within the postocclusion images (36 ± 5.2 vs. 33.6 ± 5.8, P = NS). Three independent observers qualitatively evaluated histogram shape and correctly identified 7/7 MI regions (100% sensitivity) and 14/20 normal regions (70% specificity). Quantitatively, infarct regions exhibited a significant decrease in kurtosis (2.8 ± 0.9 to 0.44 ± 0.5, P < 0.01); the normal regions showed no significant change in kurtosis from pre-to postocclusion images (7.1 ± 4.0 vs. 5.2 ± 2.9, P = NS). Within postocclusion images, infarcted regions displayed a significantly lower kurtosis than did normal regions (0.27 ± .47 vs. 2.5 ± 1.0, P < .01).

Measurement of left ventricular mass in vivo using gated nuclear magnetic resonance imaging

Alterations of left ventricular mass occur in a variety of congenital and acquired heart diseases. In vivo determination of left ventricular mass, using several different techniques, has been previously reported. Problems inherent in some previous methods include the use of ionizing radiation, complicated geometric assumptions and invasive techniques. We tested the ability of gated nuclear magnetic resonance imaging to determine in vivo left ventricular mass in animals. By studying both dogs (n = 9) and cats (n = 2) of various sizes, a broad range of left ventricular mass (7 to 133 g) was examined. With a 0.5 tesla superconducting nuclear magnetic resonance imaging system the left ventricle was imaged in the transaxial plane and multiple adjacent 10 mm thick slices were obtained. Endocardial and epicardial edges were manually traced in each computer-displayed image. The wall area of each image was determined by computer and the areas were summed and multiplied by the slice thickness and the specific gravity of muscle, providing calculated left ventricular mass. Calculated left ventricular mass was compared with actual postmortem left ventricular mass using linear regression analysis. An excellent relation between calculated and actual mass was found (r = 0.95; SEE = 13.1 g; regression equation: magnetic resonance mass = 0.95 X actual mass + 14.8 g). Intraobserver and interobserver reproducibility were also excellent (r = 0.99). Thus, gated nuclear magnetic resonance imaging can accurately determine in vivo left ventricular mass in anesthetized animals.

Assessment of fibrosis in infarcted human hearts by analysis of ultrasonic backscatter.

In animal hearts, the magnitude of integrated ultrasonic backscatter is increased in fibrotic myocardium. Our purpose in this study was to quantitate the relationship between ultrasonic backscatter and collagen deposition in 10 excised human hearts with old infarcts. A 2.25 MHz, 50% fractional bandwidth transducer was positioned at the transducer focal distance from the epicardium of each specimen. The radio frequency backscatter signal was digitized, squared, and integrated to yield the integrated ultrasonic backscatter, which was referenced to the backscatter from a water/steel interface. The interrogated myocardium was then excised and divided into two portions. One portion was assayed for hydroxyproline, a marker for collagen. A second portion was sectioned, stained with Massons trichrome, and studied with the use of a computer-assisted image analysis system. There was a linear correlation between the magnitude of integrated backscatter and myocardial collagen content estimated by hydroxyproline assay (r = .78). Quantitative histologic analysis revealed a variable relationship between the transmural distribution of collagen and the corresponding transmural pattern of the backscatter signal. In two specimens exhibiting a discrete layer of subendocardial fibrosis, the backscatter amplitude was also increased in the subendocardial region. In specimens with other patterns of fibrosis, the local backscatter amplitude did not correspond to the transmural pattern of collagen distribution. We conclude that the quantitative analysis of ultrasonic backscatter shows promise for the noninvasive evaluation of myocardial fibrosis after infarction.

Ultrasonic backscatter and collagen in normal ventricular myocardium.

Integrated ultrasonic backscatter has been related to collagen deposition in fibrotic myocardium. The purpose of our study was to measure the integrated ultrasonic backscatter in the right and left ventricles of 10 normal freshly excised canine hearts and five normal formalin-fixed human hearts. A 2.25 MHz, 50% fractional bandwidth transducer was positioned at the transducer focal distance from the epicardium. The radio frequency backscatter signal, excluding specular reflections, was digitized, squared, and integrated to yield the integrated ultrasonic backscatter (in decibels down from a 100% reflector). The segment of myocardium corresponding to the integrated ultrasonic backscatter sample volume was excised and assayed for hydroxyproline, a marker for collagen. A second purpose of our study was to evaluate the influence of fixation with formalin on the backscatter. Regional integrated ultrasonic backscatter was therefore measured in 10 freshly excised canine left ventricles, which were fixed in 10% formalin for 2 weeks. Integrated ultrasonic backscatter measurements were then repeated. In freshly excised canine hearts, the integrated ultrasonic backscatter from right ventricle was higher than that from left ventricle (-60.4 +/- 1.6 [SEM] vs -66.9 +/- 1.0 dB; p less than .001). The collagen content of right ventricle was also higher than that of left ventricle (4.40 +/- 0.26 [SEM] vs 3.58 +/- 0.13 micrograms/mg dry weight; p less than .005). Similar results were obtained in human hearts. There were no correlations between integrated ultrasonic backscatter and collagen content (r = .28 and .32 for dogs and humans, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

In vivo quantitation of regional myocardial blood flow by positron-emission computed tomography.

The potential of positron-emission computed tomography (PCT) for external quantitation of myocardial indicator concentrations and regonal myocardial blood flow (RMBF) and the effect of left ventricular wall thickness on tracer concentration recovery by PCT was examined in seven open-chest dogs. RMBF was determined by the arterial reference technique in vivo and in vitro. Together with gamma-emitting Ce-141 microspheres, positron-emitting Ga-68-labeled microspheres were injected into the left atrium and their myocardial concentrations determined in vivo from gated and ungated cross-sectional PCT images. It is concluded that (1) myocardial indicator tissue concentrations, and thus, RMBF, can be accurately measured by PCT provided corrections are made for the effect of wall thickness on count recovery; (2) these corrections can be made using in vivo echocardiography; and (3) gated PCT imaging can be used to evaluate regional myocardial systolic wall thickening as an index of regional function and combined with measurements of RMBF or regional metabolism. The results represent a framework for the noninvasive measurement of RMBF and metabolism by PCT in the experimental animal and in man.