Scott F. DeBoe

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%.

Quantitative regional curvature analysis: An application of shape determination for the assessment of segmental left ventricular function in man

All traditional techniques of regional ventricular function analysis depend upon one or more assumptions about coordinate, reference, or indexing systems, idealized ventricular geometry, and the uniformity of ventricular contraction. Therefore, a method of shape analysis was developed that allows the quantitation of regional curvature and is independent of the assumptions outlined. This was implemented on a commercial image processing unit and applied to silhouettes of 30-degree right anterior oblique left ventriculograms. Three groups with abnormal wall motion (anterior abnormality, n = 23; inferior abnormality, n = 23; anterior and inferior abnormalities, n = 22) were analyzed and compared to a group with normal regional function (n = 22). Relatively few significant quantitative curvature differences were noted at end diastole among the groups. These few abnormalities described a slight increase in curvature or globularity of the anterior and inferior walls. More marked and extensive aberrations were detected at end systole. The group with anterior wall motion disturbances showed four distinct areas of curvature abnormality. Excessive curvature was present on either side of the apex (anterior and inferoapical regions) and apical curvature was less than normal. The fourth region was in the inferior zone, which showed curvature values that were less than normal, suggesting increased inward motion contralateral to the anterior abnormality. The group with inferior wall motion abnormalities also showed excessive end-systolic curvature on either side of the apex (diaphragmatic and anteroapical zones) and deficient curvature at the apex. A combination of these regional morphologic abnormalities was noted in the group with both anterior and inferior dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Tachycardia, contractility and volume loading alter conventional indexes of coronary flow reserve, but not the instantaneous hyperemic flow versus pressure slope index

OBJECTIVES AND BACKGROUND Because measurements of flow reserve are often made in the setting of fluctuating hemodynamic variables that cause alterations in basal or hyperemic coronary blood flow, traditional flow reserve indexes may be difficult to interpret. Prior work in this laboratory has suggested that the instantaneous hyperemic flow versus pressure slope index is a more hemodynamically stable alternative to measures of flow reserve. Although this index has no hemodynamic dependence on changes in aortic pressure, the extent to which it is affected by other factors that alter myocardial work is unknown. Therefore, the purpose of this investigation was to analyze the effects of tachycardia (induced by atrial pacing at 10 beats/min above the basal heart rate), dobutamine infusion (10 micrograms/kg per min) and saline solution volume loading (500 ml) on measurements of traditional coronary flow reserve, the resistance reserve ratio and the instantaneous hyperemic flow versus pressure slope index. METHODS Twenty-nine open chest anesthetized dogs were studied in four sequential stages: baseline, tachycardia, dobutamine infusion and saline solution volume loading. Traditional coronary flow reserve was defined as the ratio of hyperemic coronary blood flow to basal coronary blood flow, the resistance reserve ratio as the ratio of basal coronary resistance to hyperemic coronary resistance and the instantaneous hyperemic flow versus pressure slope index as the slope of the instantaneous relation between diastolic hyperemic coronary blood flow and diastolic aortic pressure normalized by perfusion bed weight. Hyperemia was induced by intravenous adenosine infusion (1 mg/kg per min). Mean aortic pressure was kept nearly constant during the interventions by manipulation of an aortic clamp or a vena caval snare. RESULTS The final study group comprised 18 open chest dogs. Coronary flow reserve was significantly decreased by tachycardia (3.7 +/- 1.2 to 3.0 +/- 1.2, p < 0.0001), decreased by saline solution volume loading (3.2 +/- 1.3 vs. 2.7 +/- 0.8, p = 0.06) and significantly increased by dobutamine infusion (3.2 +/- 1.3 to 4.3 +/- 1.5, p < 0.0005). In contrast, the instantaneous hyperemic flow versus pressure slope index was not affected by the three interventions (7.4 +/- 3.1 vs. 7.3 +/- 3.3, 7.4 +/- 3.2 vs. 7.4 +/- 3.4 and 7.5 +/- 3.1 vs. 7.3 +/- 3.4, respectively, all p = NS). The changes observed in the resistance reserve ratio were of similar or greater magnitude and significance to the changes in coronary flow reserve. CONCLUSIONS The instantaneous hyperemic flow versus pressure slope index offers a hemodynamically stable alternative to measures of vascular reserve because it is independent of moderate changes in heart rate, contractility and volume loading that may occur commonly in clinical situations.

Instantaneous hyperemic flow-versus-pressure slope index. Microsphere validation of an alternative to measures of coronary reserve.

BackgroundThe instantaneous hyperemic flow-versus-pressure (i-HFVP) slope index is a new method of assessing maximal coronary conductance and canbe used as an alternative to conventional measures of coronary reserve. The i-HFVP slope index is determined by measuring the slope of thelinear diastolic segment of the relation between instantaneous aortic pressure and hyperemic coronary flow. Methods and ResultsTo validate the i-HFVP slope index as a measure of maximal coronary conductance, we compared this method with a microsphere-derived measurement of maximal coronary conductance (m-HFVP slope index) by determining the slope of the least-squares regression line of the data points for coronary flow during maximal hyperemia and four or five steady-state alterations of aortic pressure in 43 dogs (open-chest, anesthetized preparations) with or without coronary stenoses. The i-HFVP slope index demonstrated no dependence on heart rate, left ventricular end-diastolic pressure, or mean aortic pressure and was highly reproducible within the groups studied (intraclass correlation coefficient, 0.86 for normal arteries, 0.87 for stenotic arteries, and 0.93 for combined groups; for all coefficients, p < 0.001). The i-HFVP slope index was significantly decreased in the presence of a stenosis (10.3 ± 3.9 for normal arteries versus 3.6 ± 1.6 for stenotic arteries, p < 0.001) as was the transmural m-HFVP slope index (8.9 ± 4.6 for normal arteries versus 5.3±3.1, p < 0.01). Of special importance, the i-HFVP slope index measurement for normal arteries was not significantly different from the transmural and subendocardial m-HFVP slope index measurements (10.3 ± 3.9 versus 8.9 ± 4.6 and 9.2 ± 5.7, respectively). For stenotic arteries, the i-HFVP slope index measurement was also not significantly different from the transmural and subendocardial m-HFVP slope index measurements (3.6 ± 1.6 versus 5.3±3.1 and 4.1 ± 2.3, respectively). The i-HFVP slope index correlated best with subendocardial m-HFVP slope index measurements (correlation coefficient, 0.57; p < 0.001). When the 95% confidence intervals for the transmural (or subendocardial) m-HFVP slope index in normal arteries were compared with the i-HFVP slope index values, the latter demonstrated a systematic trend to overestimate the m-HFVP slope index. In the presence of a stenosis, this effect was minimized, and the slope values were nearly identical. ConclusionsThe i-HFVP slope index correlates most closely with subendocardial coronary conductance; the index is a hemodynamically independent measure of coronary reserve that is reproducible over a broad range of aortic pressures; and the methodology is applicable to an intact circulation in experimental preparations and may with future developments also prove useful in humans.

Cardiac care unit admission criteria for suspected acute myocardial infarction in new-onset atrial fibrillation

Management of new-onset atrial fibrillation (AF) varies between institutions and individual physicians. Because AF often occurs in elderly patients and is associated with coronary artery disease, patients presenting for the first time are often selected for admission to the coronary care unit to exclude the possibility of acute myocardial infarction (AMI). A review of 245 patients with AF admitted to an intensive care unit revealed 45 cases that were of new onset. AMI was diagnosed in 5 (11%) on the basis of elevated serum creatine kinase-MB levels. Evaluation of 56 clinical variables available during initial assessment indicated that infarction patients could be distinguished from others by the presence of left ventricular hypertrophy (p less than 0.01), electrocardiographic evidence of old myocardial infarction (p less than 0.01), typical cardiac chest pain (p less than 0.01), and duration of cardiac symptoms less than 4 hours (p less than 0.05). The presence of 2 or more of these features identified all AMI patients and 7 others at high risk for serious cardiac complications. The findings indicate that new-onset AF in the absence of clinical predictors suggesting myocardial ischemia or AMI does not warrant routine admission to the coronary care unit.

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)