Mark J. McGillem

Automated quantitative coronary arteriography: morphologic and physiologic validation in vivo of a rapid digital angiographic method.

Quantitative coronary arteriography has been shown to be useful in assessing the extent of coronary disease, its functional significance, and its response to therapeutic interventions. Most current methods rely either on hand-drawn arterial contours or automatic edge-detection algorithms applied to 35 mm cineangiograms. To assess the performance in vivo of a new, fully automatic, rapid coronary quantitation program, dogs were instrumented with precision-drilled, plastic cylinders to create intraluminal stenoses in the left anterior descending and/or circumflex arteries, as well as with high-fidelity micromanometers and electromagnetic flow probes. Stenosis diameters ranged from 0.83 to 1.83 mm. Biplane, on-line, digital coronary angiograms and cineangiograms were recorded during standard selective coronary arteriography in the closed-chest preparation. The on-line digital images were analyzed in nonsubtracted and subtracted modes. Cineangiograms were digitized to allow coronary quantitation by the same computer program. There was an excellent correlation between known and measured minimal diameter stenoses (r = .87 to .98, SEE = 0.09 to 0.24 mm). Interobserver and intraobserver variability analysis showed high reproducibility (r = .90 to .97, SEE = 0.12 to 0.23 mm). The best results in both analyses were achieved by nonsubtracted digital imaging and the worst by cineradiography. Measures of percent diameter stenosis, percent area stenosis (geometric and videometric), and absolute minimal cross-sectional area (geometric and videometric) were all significantly correlated with independent measures of actual coronary flow reserve. This study provides direct anatomic and physiologic validation in vivo of a new and rapid coronary quantitation method suitable for analysis of both digital angiograms and cineangiograms.

The effects of dopamine and dobutamine on regional function in the presence of rigid coronary stenoses and subcritical impairments of reactive hyperemia

Intraluminal stenosing cylinders were inserted in the coronary arteries of open-chest, anesthetized dogs to assess the sensitivity of sympathomimetic infusion for detection of subcritical impairment of reactive hyperemia. Observations were made at rest and during steady-state infusions of dopamine and dobutamine (each 10 micrograms/kg/min) before and after placement of the cylinder. Each stenosis was associated with subcritical impairment of postocclusion reactive hyperemia at rest. The degree of impairment was used to stratify experiments into mild (group A) and moderate (group B) cohorts. In group A, reactive hyperemia was 217 +/- 55 cc/min prior to cylinder placement and 82 +/- 17 cc/min (p less than 0.002) after insertion. In group B, reactive hyperemia was 235 +/- 54 cc/min and 63 +/- 7 cc/min (p less than 0.001) before and after insertion. Both drugs resulted in a significant increase in regional shortening (ultrasonic crystal technique) in the absence of a stenosis. After creation of the stenoses, dopamine continued to cause a significant increase in shortening in both groups, whereas this increase was impaired in group B during dobutamine infusion (14.8 +/- 5.9% at rest vs 21.4 +/- 10.3% during infusion, p = NS). Thus, with subcritical lesions in a single vessel, dobutamine infusion was associated with depressed regional function when reactive hyperemia was impaired by more than 80%.

Comparison of automated quantitative coronary angiography with caliper measurements of percent diameter stenosis

Measurement of coronary artery stenosis is an invaluable tool in the study of coronary artery disease. Clinical trials and even day-to-day decision making should ideally be based on accurate and reproducible quantitative methods. Quantitative coronary angiography (QCA) using digital angiographic techniques has been shown to fulfill these requirements. Yet many laboratories have abandoned visual analysis in favor of the intermediate quantitative approach involving hand-held calipers. Thus, the purpose of this study was to determine the relation between QCA and the commonly used caliper measurements. Percent stenosis was assessed in 155 lesions using 3 techniques: QCA, caliper measures from a 35-mm cine viewer (cine) and caliper measures from a video display (CRT). Good overall correlation was noted among the 3 different techniques (r greater than or equal to 0.72). Both of the caliper methods underestimated QCA for stenosis greater than or equal to 75% (p less than or equal to 0.001) and overestimated stenosis less than 75% (p less than 0.05). Reproducibility assessed in 52 lesions by independent observers showed QCA to be superior (r = 0.95) to either of the caliper measurements (cine: r = 0.63; CRT: r = 0.73). Therefore, the commonly used caliper method is not an adequate substitute for QCA because overestimation of noncritical stenoses and underestimation of severe stenoses may occur and the measurements have poor reproducibility. These factors definitely preclude its use in rigorous clinical trials. Moreover, since they do not appear to overcome known deficiencies of visual analysis, caliper measurements for day-to-day clinical use must also be seriously questioned.

The diastolic hyperemic flow versus pressure relation. A new index of coronary stenosis severity and flow reserve.

The measurement of coronary flow reserve, traditionally calculated as the ratio of maximal hyperemic blood flow divided by basal flow, is difficult to interpret in serial studies because fluctuating hemodynamic parameters may affect either basal or hyperemic flow measurements. To determine the magnitude of this problem and to develop alternative approaches for measuring vascular reserve, 10 anesthetized dogs were instrumented with aortic and inferior vena cava occluders, electromagnetic coronary flow probes, and high-fidelity micromanometers in the left ventricle and aortic root. Coronary flow was measured in the basal state and during maximal hyperemia induced by a steady-state adenosine infusion. Observations were made in the absence of a stenosis and in the presence of two incremental degrees of subcritical stenosis produced by a rigid, external screw occluder. Several parameters of vascular reserve were determined: 1) coronary flow reserve (defined above), 2) mean hyperemic flow divided by mean aortic pressure, 3) mean hyperemic flow divided by the difference between mean aortic pressure and left ventricular end-diastolic pressure, and 4) the slope of the instantaneous relation between diastolic hyperemic flow versus pressure. Each parameter was measured during five steady-state pressure levels achieved by partial occlusion of either the inferior vena cava or the aorta and the levels ranged from 82 +/- 8 mm Hg (mean +/- SD) to 127 +/- 9 mm Hg during hyperemia. All measures of vascular reserve were found to be dependent on hemodynamic parameters such as heart rate and mean aortic pressure. The slope of the instantaneous relation between diastolic hyperemic flow and pressure, however, showed only minimal dependence on heart rate and, in contrast to coronary flow reserve measurements, distinguished between the normal and the two stenotic states. Further, this optimal performance of the hyperemic flow versus pressure slope index was shown in a model in which coronary flow and myocardial work were not independently controlled. This index provides a sensitive and reliable indication of subcritical stenosis severity that may have clinical applications.

Automated quantitation of indexes of coronary lesion complexity. Comparison between patients with stable and unstable angina.

Analysis of lesion morphology is becoming increasingly important in the study of coronary artery disease. Lesion irregularity has been shown to be one of the most important predictive features for development of myocardial infarction. Most studies to date have used only qualitative assessments of morphology and are thus subject to variability and lack of standardization inherent in subjective visual inspection. We describe a new approach that allows quantitation of lesion morphology. Fifty-nine patients with unstable angina and 17 patients with stable angina were compared. Five morphometric parameters were tested (peaks per centimeter, summed maximum error per centimeter, integrated error per centimeter, number of major features per centimeter, and scaled edge length ratio), four of which were significantly different between the two groups and indicated greater lesion complexity in unstable compared with stable angina patients. No correlation was found between the parameters tested and the degree of luminal narrowing, showing the methods independence from traditional assessments of lesion severity. Excellent intraobserver and interobserver reproducibility was found for all of the parameters. This technique provides a more rigorous approach for analysis of lesion morphology than has previously been available, may provide a method for premorbid detection of high-risk lesions amenable to interventional therapy, and is especially well suited to detect subtle changes in lesion morphology after therapeutic interventions because the parameters are derived on a continuous scale and are not categorical.

Effect of angioplasty-induced endothelial denudation compared with medial injury on regional coronary blood flow.

To determine the effect of angioplasty-induced arterial injury on regional coronary blood flow, resting and postocclusion reactive hyperemic flows were measured in the left anterior descending (LAD) and circumflex (LCx) coronary arteries of 32 dogs after one of four interventions in the LAD with a balloon angioplasty catheter: group A, no injury; group B, endothelial denudation; group C, medial injury; group D, pretreatment with 325 mg of aspirin 2 hr before medial injury. Resting flows did not change in any group. In group C, hyperemic flow decreased in both the LAD and LCx by 15% to 20% (p less than .001) over 30 to 90 min, suggesting that a circulating substance changed coronary resistance. Histologic and ultrastructural studies of the LADs demonstrated an intact endothelial cell layer in group A, endothelial disruption with a few adherent platelets in group B, medial injury with a dense layer of adherent platelets in group C, and medial injury with a few adherent platelets in group D. Thus endothelial denudation results in relatively mild platelet deposition and no change in resting or hyperemic coronary blood flow. In contrast, medial injury results in relatively marked platelet deposition and a significant decrease in hyperemic flow, both of which are prevented by platelet inhibition with aspirin.

Quantitative regional curvature analysis: A prospective evaluation of ventricular shape and wall motion measurements

To overcome the assumptions and approximations mandated by the use of traditional wall motion methodologies, a method was recently developed for measuring ventricular shape based on quantitative curvature analysis of ventricular outlines. This study was designed to assess prospectively the performance of this algorithm, to compare it to traditional wall motion measurements (centerline method), and to determine the comparative degree to which each method mimicked the interpretation of wall motion by clinical observers. Semiquantitative visual grading of regional function in 52 patients was performed by four independent observers on two occasions. Anterior, apical, or inferior segments were judged to be normal (0 points) or abnormal (1 point) based on viewing nonrealigned, end-diastolic and end-systolic ventricular silhouettes from cineventriculograms obtained in the 30-degree right anterior oblique projection. Each segment was assigned a collated score ranging from 0 (all observers felt the region was normal on both readings) to 8 (all observers felt the region was abnormal on both readings). Quantitative regional curvature analysis and wall motion analysis (centerline method) were performed. Quantitative shape and wall motion scores correlated equally well with the semiquantitative visual scores. When a visual score of greater than or equal to 4 was used to designate an abnormal segment, both quantitative approaches demonstrated comparable sensitivity, specificity, and concordance rates. Both methods achieved optimal performance when maximum and minimum deviations from normal were recorded. Under these circumstances, the shape analysis demonstrated a greater concordance with the clinical diagnosis than did wall motion analysis (99% vs-93%, p less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary extraction of immunoreactive atrial natriuretic factor in dogs

Abstract A trial natriuretic factor (ANF) is a hormone predominantly secreted by the cardiac atria. It stimulates the kidney to produce natriuresis and diuresis, and vasodilates vascular smooth muscle. The half-life of the hormone is a few minutes, suggesting that breakdown occurs in many tissues. 1 Significant extraction of ANF has been demonstrated across the capillary beds of liver, kidney and limb. 1–3 Pulmonary extraction of the hormone has not been shown in dogs 3 or man, 1,2 however, even though rat lung homogenates destroy ANF 4 and isolated rabbit lungs remove ANF, 5 perhaps because blood samples in the in vivo studies were obtained from systemic arteries instead of pulmonary veins. If ANF is released into the left atrial cavity through the thebesian veins, systemic arterial sampling could underestimate pulmonary extraction of ANF. The purpose of this study was to determine whether ANF is extracted across the canine pulmonary perfusion bed.

Effects of video frame averaging, smoothing and edge enhancement on the accuracy and precision of quantitative coronary arteriography

Digital analysis of cine film provides numerous options for altering images by frame averaging or filtering algorithms that either smooth or enhance edges. While these may subjectively enhance image quality, there is no uniformity in their use among laboratories and effects on quantitative coronary analysis may not be ideal. To determine which processing algorithms might help or hinder quantitative coronary arteriography, cine film images of precision drilled stenotic cylinders (0.83 to 1.83 mm diameter) implanted in dog coronary arteries were analyzed with and without such algorithms. Video frame averaging of 1 to 49 frames had no effect on measures of accuracy (mean differences) but precision (standard deviation of mean differences) was improved from 0.23 to 0.17 mm (p<0.05) with video averaging of ≥25 frames. Edge enhancement filtering algorithms resulted in slight deterioration of accuracy and precision and smoothing filtering algorithms caused modest improvements in these parameters; however, these changes were not significantly different from unprocessed images. Using edge enhancement filtering algorithms, accuracy was significantly worse (−0.27 mm) compared to a smoothing filter enhancement algorithm (−0.08 mm, p<0.001). The combination of video averaging and smoothing algorithms had no additional beneficial effects. Thus, precision of quantitative coronary analysis of cine film can be optimized by appropriate video averaging. Edge enhancement filtering algorithms should be avoided whereas smoothing filter enhancement algorithms may improve accuracy.

Induction of ventricular arrhythmia by high and low osmolarity ionic and nonionic contrast media

Studies that used prolonged contrast media infusion in canine arteries have generated controversy regarding the arrhythmogenic potential of low osmolarity, nonionic contrast agents. In order to establish the relative safety of these agents in the more typical setting of bolus injections, 4 ml intracoronary bolus injections of Hypaque-76 (n = 54), Iohexol-350 (n = 51), and Iohexol-140 (n = 51) were given in random order to 10 anesthetized, open-chest dogs undergoing programmed cardiac stimulation. Hemodynamics and electrocardiogram were monitored during stimulation, both during and for 2 minutes after the end of contrast infusion. Occurrence of evoked single and coupled premature ventricular contractions and nonsustained ventricular tachycardia did not differ statistically among agents. Sustained ventricular tachycardia (five episodes) and ventricular fibrillation (seven episodes) occurred only after Hypaque-76 injections (p less than 0.002). These results differ from those in studies that use continuous contrast infusion and suggest that low osmolarity nonionic contrast agents are as safe as high osmolarity nonionic contrast media. Both appear safer than ionic contrast material.