Glen W. Hamilton

Physiologic basis for assessing critical coronary stenosis: Instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve

Abstract Quantitative hemodynamic assessment of coronary stenosis has not been previously reported. Resting coronary blood flow and its regional distribution are insensitive indexes for determining critical stenosis, but flow response to a hyperemic stimulus quantifies restrictions on maximal flow due to coronary arterial lesions. Coronary flow responses to temporary occlusion and to selective main coronary arterial injection of sodium diatrizoate (Hypaque-M 75 percent) were studied in 12 consecutive dogs with a surgically implanted electromagnetic flowmeter and separate micrometer constrictor on the left circumflex coronary artery. Selective Hypaque injection adequate for coronary cineangiography increased coronary flow to four times the resting base-line value, peaking at 6 seconds and lasting 3 minutes, a response equivalent to hyperemia after 10 seconds of circumflex arterial occlusion. With progressive micrometer constriction, resting flow measurements did not decrease until there was 85 percent stenosis. Hyperemia after intracoronary injection of Hypaque decreased when there was 30 to 45 percent stenosis and disappeared when there was 88 to 93 percent stenosis. Myocardial images obtained by gamma camera after left atrial injection of 131 iodine-macroaggregated albumin demonstrated uniform regional distribution of resting flow in spite of severe constriction. However, 6 seconds after selective Hypaque injection, left atrial injection of 99m technetium macroaggregates demonstrated distinct perfusion abnormalities in the region of circumflex stenosis. Thus, flow distribution with a severe lesion was normal at rest but showed marked differences due to restricted circumflex versus normal anterior descending hyperemic response after injection of Hypaque. Flow response and regional distribution during coronary hyperemia caused by Hypaque are quantitative measures for physiologically assessing critical coronary stenosis and flow reserve with potential applicability to patients.

Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilatation. III. Clinical trial

Thallium-201 myocardial imaging was performed at rest, after maximal treadmill exercise and during coronary vasodilatation induced by the intravenous administration of dipyridamole in 62 patients undergoing coronary angiography. Myocardial images after dipyridamole infusion were compared with rest and exercise thallium-201 images to determine the utility of pharmacologic stress for detecting coronary artery disease. Dipyridamole, 0.142 mg/min, was infused for 4 minutes with electrocardiographic and blood pressure monitoring, and thallium-201 was injected intravenously 4 minutes after infusion. Myocardial/background count ratios of 2.3 ± 0.5 (mean ± 1 standard deviation) after the administration of dipyridamole were higher than similar ratios for exercise images (2.1 ± 0.5; P < 0.001). The sensitivity of thallium-201 imaging for detecting significant coronary artery disease was equal for dipyridamole and exercise stress. In 51 patients with a 50 percent or greater stenosis of one or more coronary arteries, image defects were identified in 34 of 51 (67 percent) exercise and dipyridamole images. Twenty of 51 patients (39 percent) had abnormal rest images; in 17 of 20 patients, new or increased image defects were present after exercise and the infusion of dipyridamole. One of 11 patients (9 percent) with no stenosis of 50 percent or greater had a defect on exercise and dipyridamole images. Six of seven patients with new or enlarged image defects after the intravenous administration of dipyridamole also had new or enlarged defects after the oral administration of dipyridamole. After the infusion of dipyridamole, the heart rate increased from 64 ±10 beats/min supine to 88 ± 13 beats/min standing (P < 0.001), and blood pressure decreased from 129 ± 1680 ± 9 to 120 ± 1775 ± 9 mm Hg (P < 0.001). Angina and S-T depression occurred more frequently with exercise than with dipyridamole. S-T depression occurred in only two patients (3 percent) with dipyridamole, suggesting that diagnostic images were often obtained without significant ischemia. This study demonstrates that pharmacologic coronary vasodilatation is as effective as maximal treadmill exercise in creating myocardial perfusion abnormalities detectable with thallium-201 imaging in man.

Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilatation: II. Clinical methodology and feasibility

Abstract A noninvasive method has been developed utilizing myocardial imaging of thallium-201 injected intravenously at rest and during coronary vasodilatation induced with intravenously administered dipyridamole, a potent selective coronary vasodllator. The method has been validated in experimental animals and shown to be more sensitive than exercise imaging in identifying moderate experimental coronary stenoses. This report describes the clinical feasibility and methodology of applying the technique to man. Study of a total of 162 myocardial perfusion images in 62 patients revealed the following: (1) The quality of myocardial perfusion images of thallium-201 injected during coronary vasodilatation induced with intravenously administered dipyridamole was equal to or better than that of myocardial images of thallium-201 injected during treadmill stress. (2) Myocardial uptake of thallium-201 measured with external imaging was considerably greater during dipyridamole-induced coronary vasodilatation than during treadmill stress. (3) The optimal dose rate of intravenously administered dipyridamole for this imaging technique was 0.142 mg/kg per min for 4 minutes with the thallium injected in the 3rd to 4th minute after completion of infusion while the patient was upright, walking in place. (4) With this dose rate regimen, side effects were minimal except for the occasional development of angina pectoris; the latter was eliminated by intravenous administration of aminophylline, a complete and virtually instantaneous antagonist of dipyridamole, after thallium had been taken up by the myocardium. This new method is therefore applicable to man and the initial results warrant a larger clinical study in order to define the diagnostic sensitivity and specificity of the technique.

Myocardial imaging with thallium-201: A multicenter study in patients with angina pectoris or acute myocardial infarction

A multicenter study of rest and exercise thallium-201 myocardial imaging in 190 patients from five centers was performed. Exercise images were obtained after graded treadmill or bicycle stress with use of five different gamma camera models and were interpreted by the originating investigator without knowledge of other clinical data. Of 42 patients with less than 50 percent coronary stenosis, 4 (10 percent) had a resting image defect, 1 (2 percent) a new exercise defect and 5 (12 percent) either a resting or an exercise image defect, or both. Of 148 patients with coronary stenosis of 50 percent or greater, 64, (45 percent) had an image defect in the study at rest, 90 (61 percent) had new or increased defects after exercise, and 115 (78 percent) had resting or exercise defects, or both. New exercise image defects were more common than exercise S-T depression (90 of 148 [61 percent] versus 62 of 148[42 percent]; P less than 0.01). In a second group of 111 patients with acute myocardial infarction studied at three centers, 90 patients (81 percent) had image defects compared with 71 (64 percent) two had new electrocardiographic Q waves (P less than 0.01). Smaller infractions, as assessed with serum enzyme values, and diaphragmatic infarctions were less commonly detected than larger or anterior infarctions. These findings suggest that myocardial imaging complements the electrocardiographic identification of acute myocardial infarction of exericse-induced myocardial ischemia.

Relation of left ventricular shape, function and wall stress in man

Abstract The relations among left ventricular hypertrophy, equatorial and meridional wall stresses, ventricular chamber shape and performance are described for the first time on the basis of data from 122 patients with valvular, coronary or primary myocardial heart disease. Patients were studied by biplane anglocardiograms; pressure-volume data were processed by computer. The results Indicate that if the left ventricle dilates because of myocardial injury, the following changes occur: Ventricular shape becomes more spherical, circumferential shortening and wall thickening diminish, myocardial fiber orientation changes, meridional stress increases and equatorial stress remains within normal limits. However, If the ventricle dilates because of volume overload with intact myocardial function, then ventricular shape, circumferential shortening, wall thickening and fiber orientation remain relatively intact compared with findings in impaired hearts of equivalent size; both meridional and equatorial wall stresses increase, and to the same degree, but the alterations may not reflect increased force per myocardial fiber If shape and fiber orientation are taken into consideration.

Myocardial imaging with intravenously injected thallium-201 in patients with suspected coronary artery disease: Analysis of technique and correlation with electrocardiographic, coronary anatomic and ventriculographic findings

Myocardial imaging was performed after intravenous injection of thallium-201 at rest in 50 patients with suspected coronary artery disease and the results were compared with electrocardiographic, ventriculographic and coronary arteriographic findings. The thallium-201 myocardial images were of good quality and compared favorably with images previously obtained with intracoronary particle injection. Myocardial to background ratios averaged 2:1, a considerable improvement over ratios reported with potassium-43. There was complete intra- and interobserver agreement in the interpretation of images in 90 and 82 percent of cases, respectively. Major disagreement occurred in less than 5 percent of cases. Overall, 15 (30 percent) had an abnormal, 10 patients (20 percent) a borderline abnormal and 25 patients (50 percent) a normal myocardial image. Of patients with electrocardiographic Q waves, 91 percent had an image defect. Of 39 patients without Q waves, 13 percent had an image defect. All 30 patients with a normal or borderline abnormal thallium-201 image had a normal ventricular contraction pattern. All patients with a segmental ventriculographic abnormality had an image defect. In all cases, the area of electrocardiographic or ventriculographic abnormality corresponded to the area of the thallium-201 image defect. The systolic ejection fraction was depressed (0.49 +/- 0.18 [mean +/- standard deviation]) in patients with an image defect compared with that in patients with a normal image (0.64 +/- 0.06, P less than 0.005). Coronary arterial lesions were present and usually of high grade in all patients with an abnormal image; however, the presence of high grade coronary stenosis or occlusion as such correlated with image defects only to the extent that prior myocardial infraction was associated. Thus, satisfactory myocardial images at rest appear to be obtained with intravenously administered thallium-201 and electrocardiographic, ventriculographic and coronary arteriographic data suggest that image defects denote regions of prior myocardial infarction.

Quantitative Angiocardiography in Ischemic Heart Disease

Appropriate surgical and medical management of the patient with ischemic heart disease depends upon a thorough assessment of the clinical and pathophysiologic derangements in left ventricular function. This study examined the spectrum of abnormalities in ventricular function found in 66 patients with documented coronary artery lesions.Catheterization and biplane angiocardiography were used to measure end-diastolic and end-systolic volume (EDV, ESV), systolic ejection fraction (SEF), ventricular mass (LVM), end-diastolic pressure (LVEDP), peak systolic and end-diastolic stress (PSS, EDS), and stroke work (SW). The pattern of ventricular contraction was assessed for hypokinesis, akinesis, and dyskinesis and graded according to severity.The SEF, SW, and contractile pattern were sensitive and interrelated indicators of left ventricular contractile dysfunction or fiber shortening. Measurements of ventricular filling or fiber lengthening (EDV, LVEDP, EDS) were related but less sensitive parameters of dysfunction. However, when contractile function was reduced to about one half of normal, there was an associated marked increase in EDV, EDS, and LVEDP.A wide spectrum of derangements was found ranging from virtually normal function in 18 patients with angina alone to severe dysfunction in 18 patients with myocardial infarction, mitral regurgitation, or heart failure.Abnormalities in ventricular function were uniformly associated with myocardial infarction. Angina alone was associated with minimal or no ventricular dysfunction. Most patients with mitral regurgitation and all patients with heart failure had severe ventricular dysfunction manifested by an increase in EDV, LVM, and PSS, a marked decrease in SEF and SW, and a severe abnormality in contractile pattern.

Serial exercise radionuclide angiography. Validation of count-derived changes in cardiac output and quantitation of maximal exercise ventricular volume change after nitroglycerin and propranolol in normal men.

R–wave–synchronous radionuclide angiography provides time–activity curve information that is assumed to be proportional to ventricular volumes. We performed serial 2-minute time–activity curves and simultaneous Fick cardiac outputs before and during graded, maximal, supine exercise in nine normal subjects; each subject exercised without drug intervention, after nitroglycerin and after intravenous propranolol. Imaging was performed using an R–wave–synchronized gamma camera–computer system, a high–sensitivity collimator and autologous 99mTc–labeled red blood cells. Fick cardiac output was determined from pulmonary and radial artery blood samples and oxygen consumption. Changes in count–derived cardiac output, expressed as percent change from baseline, closely paralleled changes in Fick output at all levels of exercise for nondrug and nitroglycerin studies. After propranolol, agreement was maintained between both methods for low–tomoderate levels of exercise. Changes in count–defined end–diastolic volume, end–systolic volume and stroke volume agreed well with simultaneous heart rate, wedge pressure and Fick measurements and were in accord with known hemodynamic effects of exercise, nitroglycerin and propranolol. We conclude that radionuclide count data accurately reflect true hemodynamic change as determined by the Fick technique and may aid in defining the mechanisms of ventricular dysfunction in coronary and valvular heart disease, thereby providing a better understanding of the effects of interventions in these disorders.

The detection of coronary artery disease with radionuclide techniques: a comparison of rest-exercise thallium imaging and ejection fraction response.

Fifty–two patients with suspected coronary artery disease underwent coronary angiography, thallium-201 myocardial imaging, and ECG–gated blood pool ventriculography at rest and at maximal exercise. In 11 patients without coronary artery disease, all thallium images were normal. The resting ejection fraction (EF) was normal in all 11 patients and increased during exercise in six, was unchanged in three, and decreased in two. Of the 41 patients with coronary artery disease, the thallium image was normal at rest and at exercise in six (15%), whereas the exercise EF was abnormal in these six. A new (18 patients) or enlarged (11 patients) defect appeared on the thallium image in 29 of 41 patients (71%) with coronary disease. Six of 41 patients (15%) had an abnormal rest thallium image that was unchanged with exercise. An abnormal rest and/or exercise image defect identified 35 of 41 patients (85%) with coronary artery disease. The resting EF was normal in 26 of the 41 patients (63%) and in 24 patients demonstrated an abnormal response to exercise. Fifteen patients (37%) had an abnormal resting EF, and 14 of these 15 demonstrated persistent abnormalities. Thus, an abnormal exercise EF response identified 38 of 41 (93%) patients with coronary disease. The specificity of the thallium image was 100% and for the exercise EF determination, 54% (p < 0.02). We conclude that an abnormal exercise EF response and the rest–exercise thallium image have similar sensitivities for detecting coronary disease; however, an abnormal exercise ejection fraction was significantly more sensitive than was a new thallium abnormality alone (93% vs 71%). Combined, the two studies detected all patients with coronary disease.

Method for assessing stress-induced regional malperfusion during coronary arteriography. Experimental validation and clinical application.

Abstract Resting myocardial regional perfusion may be normal in spite of severe coronary stenosis. Accordingly, regional perfusion was evaluated during coronary hyperemia in order to quantify maldistribution occurring at high flow rates but not at rest. In eight open chest dogs quantitative regional distribution of left coronary flow was determined by electromagnetic flowmeters on the anterior descending and circumflex coronary arteries and simultaneously by double radionuclide studies. Coronary flow was varied from basal to maximum by intracoronary injection of Hypaque-M, 75 percent, previously shown to be a potent, repeatable stimulus for maximal hyperemia. Malperfusion due to coronary stenoses quantified with the gamma camera correlated closely with results obtained by electromagnetic flowmeters ( r = 0.96). In the presence of balanced lesions on the circumflex and anterior descending arteries, hyperemic responses were equally reduced in these branches, and regional perfusion by gamma camera and electromagnetic flowmeters was normal. To demonstrate the applicability of this approach in man, patients were studied by intracoronary injection of 113m indium-macro-aggregated albumin in the resting state and 99m technetium-macro-aggregated albumin during the hyperemia following intracoronary injection of contrast medium. Scintiphotographs from patients whose angiograms revealed moderate coronary lesions demonstrated normal regional distribution at rest but maldistribution during hyperemia. The results in patients also demonstrated that collateral vessels failed to maintain normal distribution during hyperemia despite normal regional perfusion at rest.