Progression of coronary atherosclerotic disease assessed by cinevideodensitometry: relation to clinical risk factors.

Progression of coronary artery stenosis was measured using a quantitative, computer-assisted cinevideodensitometric method in 144 arterial segments in 44 subjects undergoing coronary arteriography on two separate occasions at least 6 months apart. Projected coronary arteriograms were digitized into 512 X 512 pixel mode and percent stenosis was calculated by comparing background-corrected videodensitometric values over stenotic and normal segments. Subjects underwent repeat coronary arteriography because of worsening symptoms of angina or heart failure; subjects with renal failure, coronary artery bypass grafts or cardiac transplant were excluded. Clinical variables determined at the time of the first arteriogram included age, sex, serum cholesterol, systolic blood pressure and presence or absence of cigarette smoking, diabetes mellitus and left ventricular hypertrophy. The mean interval between arteriograms was 29.3 months. Overall progression of coronary stenosis was observed in 40 of the 44 subjects; the mean progression at 24 months was 39% (90% confidence interval, 33 to 45%) and at 36 months was 48% (40 to 56%). The degree of overall progression was related to the length of time between arteriograms (F = 5.81, p less than 0.05) and to serum cholesterol level (F = 4.37, p less than 0.05). These data indicate that using an accurate, quantitative method, it is possible to measure progression of coronary artery atherosclerosis within 2 to 3 years of the initial arteriogram. Serum cholesterol appears to be an important determinant of disease progression.

Left ventricular mechanical efficiency in coronary artery disease.

The effect of coronary artery disease and prior myocardial infarction on cardiac energetics was determined by measuring left ventricular myocardial blood flow, oxygen consumption (MVO2), efficiency and ejection phase indexes in 36 patients undergoing coronary arteriography. Eight control patients with normal coronary arteriograms and normal left ventricular function, 15 patients with coronary artery disease without prior myocardial infarction and 13 patients with coronary disease and prior myocardial infarction (greater than 6 months) were studied. Left ventricular efficiency was calculated from left ventricular work, myocardial blood flow (measured by clearance of intracoronary xenon-133), and aortic and coronary sinus oxygen content. Left ventricular volumes, mass and ejection phase indexes were measured by quantitative left ventriculography. Left ventricular myocardial blood flow per 100 g/min was reduced in patients with coronary artery disease (49.0 +/- 8; p less than 0.01) and in patients with myocardial infarction (51.6 +/- 10; p less than 0.05) compared with control subjects (62.4 +/- 16), but total left ventricular flow was not reduced because of increased left ventricular mass. As a result, MVO2 did not differ significantly for the three patient groups (control 13.3, coronary artery disease 14.0 and myocardial infarction 14.3 ml/min). In the patients with myocardial infarction, left ventricular work index was reduced (2.4 versus 4.0 kg X m/m2 per min in the control group; p less than 0.001), causing efficiency to be reduced (15.9 versus 28.8% in the control group; p less than 0.001). Decreased efficiency correlated with ejection fraction (r = 0.54), mean velocity of circumferential fiber shortening (MVcf) (r = 0.45) and mean percent chordal shortening (r = 0.43) (all p less than 0.01). These data indicate that in control patients with normal coronary arteriograms, left ventricular myocardial efficiency averages 29%; in patients with coronary disease without myocardial infarction, left ventricular MVO2 and efficiency are in the normal range; in patients with prior myocardial infarction, left ventricular efficiency is significantly reduced as a result of diminished left ventricular work and normal MVO2; and reduced efficiency after myocardial infarction correlates with reduced ejection phase indexes.

Effect of isolated proximal coronary stenotic lesions on distal myocardial perfusion during exercise.

This study tested the hypothesis that the absolute dimension of a coronary stenotic lesion is a more important determinant of its hemodynamic effect on regional myocardial perfusion during exercise than is relative percent stenosis. In 31 patients with an isolated lesion of the left anterior descending coronary artery, regional myocardial perfusion was determined from thallium-201 scans recorded in the left anterior oblique projection after symptom-limited treadmill exercise. Thallium-201 uptake in the distribution of the left anterior descending coronary artery was expressed as a ratio of thallium-201 uptake in the left circumflex artery distribution. Percent area stenosis, minimal cross-sectional area and mean diameter of each stenotic lesion were measured by computer-assisted cinevideodensitometric analysis of projected coronary arteriograms digitized in a 512 X 512 pixel matrix with 256 gray levels. Thallium-201 uptake in the left anterior descending coronary artery distribution, expressed as a ratio, correlated poorly (r = 0.65) with relative percent stenosis, but correlated significantly (r = 0.83; p less than 0.05) with absolute lesion area. For all 16 patients with reduced regional perfusion in the left anterior descending coronary artery distribution during exercise, lesion cross-sectional area was less than 1.8 mm2 (mean 0.9 +/- 0.6); for 13 of the 15 patients with normal distal perfusion, the area of the stenotic lesion was greater than 1.8 mm2 (mean 2.7 +/- 0.7; p less than 0.001). Percent coronary stenosis failed to predict flow-limiting lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation in the coronary circulation.

The effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation was investigated in seven patients with severe proximal lesions of the left anterior descending coronary artery to determine if acute ischemia activates the coagulation system. Fibrin formation was assessed from plasma levels of fibrinopeptide A. Platelet activation was assessed by levels of platelet factor 4, beta-thromboglobulin and thromboxane B2. Plasma levels were measured before, during and after acute myocardial ischemia induced by rapid atrial pacing. Blood samples were collected from the ascending aorta and from the great cardiac vein through heparin-bonded catheters. The occurrence of anterior myocardial ischemia was established by electrocardiography and by myocardial lactate extraction. No significant transmyocardial gradients in the levels of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 were found at rest, during ischemia or in the recovery period, and levels in the great cardiac vein did not change in response to ischemia. These data indicate that pacing-induced myocardial ischemia does not result in release of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 into the coronary circulation, and imply that acute ischemia does not induce platelet activation or fibrin formation in the coronary circulation.

Importance of balloon size in coronary angioplasty.

The effect of balloon size on the success of coronary angioplasty was studied to develop quantitative criteria for optimal selection of balloon size. Coronary dimensions of 165 stenotic lesions were measured by computer-assisted cinevideodensitometry in 120 patients who had undergone angioplasty with a balloon selected by visual estimates. Cross-sectional areas and diameters of normal and stenotic arterial segments were measured before and after angioplasty by a previously validated cinevideodensitometric technique. The diameter of the inflated balloon compared with that of the normal arterial segment was expressed as a ratio for sizing balloons. Oversized balloons with a ratio greater than 1.3 (n = 35) caused a high (37%) incidence of dissection, with three severely compromised arterial lumens. Undersized balloons with a ratio less than 0.9 (n = 29) often resulted in significant (greater than 50% diameter stenosis) residual stenotic lesions (21%) and a significantly (p less than 0.05) higher rate of repeat angioplasty for restenosis. Selection of balloon sizes with ratios in the 0.9 to 1.3 range (n = 101) resulted in a low (4%) incidence of dissection with few patients (3%) having significant residual stenosis. Mean residual stenosis (percent diameter reduction) was most severe for undersized (35.0 +/- 18%) or oversized (23.1 +/- 19%) balloons and least severe for balloons with a ratio of 0.9 to 1.3 (18.7 +/- 14%) (p less than 0.001). Repeat angioplasty for restenosis was more frequently required (p less than 0.05) for lesions dilated with undersized balloons. Thus, selection of angioplasty balloons that approximate or slightly exceed the diameter of the normal arterial diameter yields optimal angiographic results with minimal dissections and minimal residual stenotic lesions.

Exercise-induced myocardial ischemia in patients with coronary artery disease: lack of evidence for platelet activation or fibrin formation in peripheral venous blood.

The hypothesis that exercise-induced myocardial ischemia is associated with abnormal platelet activation and fibrin formation or dissolution was tested in patients with coronary artery disease undergoing upright bicycle stress testing. In vivo platelet activation was assessed by radioimmunoassay of platelet factor 4, beta-thrombo-globulin and thromboxane B2. In vivo fibrin formation was assessed by radioimmunoassay of fibrinopeptide A, and fibrinolysis was assessed by radioimmunoassay of thrombin-increasable fibrinopeptide B which reflects plasmin cleavage of fibrin I. Peripheral venous concentrations of these substances were measured in 10 normal subjects and 13 patients with coronary artery disease at rest and during symptom-limited peak exercise. Platelet factor 4, beta-thromboglobulin and thromboxane B2 concentrations were correlated with rest and exercise catecholamine concentrations to determine if exercise-induced elevation of norepinephrine and epinephrine enhances platelet activation. Left ventricular end-diastolic and end-systolic volumes, ejection fraction and segmental wall motion were measured at rest and during peak exercise by first pass radionuclide angiography. All patients with coronary artery disease had documented exercise-induced myocardial ischemia manifested by angina pectoris, ischemic electrocardiographic changes, left ventricular segmental dyssynergy and a reduction in ejection fraction. Rest and peak exercise plasma concentrations were not significantly different for platelet factor 4, beta-thromboglobulin, thromboxane B2, fibrinopeptide A and thrombin-increasable fibrinopeptide B. Peripheral venous concentrations of norepinephrine and epinephrine increased significantly (p less than 0.001) in both groups of patients. The elevated catecholamine levels did not lead to detectable platelet activation. This study demonstrates that enhanced platelet activation, thromboxane release and fibrin formation or dissolution are not detectable in peripheral venous blood of patients with coronary disease during exercise-induced myocardial ischemia.

Quantification of myocardial infarction by computer-assisted positron emission tomography.

The accuracy of three-dimensional transverse section positron emission imaging for quantification of myocardial infarction size was validated and compared with the accuracy of two dimensional planar positron imaging. After induction of acute anterior myocardial infarction in anaesthetised dogs, gallium-68 albumin microspheres were injected into the left atrium. Planar and transverse section images of the thorax were obtained with a multicrystal positron camera. After staining with tetrazolium tetrachloride injected intravenously, the hearts were excised, sectioned manually, and planar imaging repeated. Each myocardial infarction was clearly delineated by transverse section imaging with high contrast ratios (mean 0.68 +/- 0.02 SEM); planar imaging identified seven of nine infarcts but with lower contrast ratios (0.24 +/- 0.04; P < 0.001). The volume of infarcted myocardium determined from transverse section images correlated well with true infarct volume (r = 0.94); whereas planar images poorly predicted infarct size (r = 0.63). Thus, computer-assisted transverse section positron imaging provides in vivo localisation of microsphere distribution for improved radioisotopic quantification of myocardial infarction.

Daily nutritional intake and serum lipid levels. The Tecumseh study.

To determine the influence of diet on serum cholesterol and triglyceride levels among adults, 24-hr dietary recall interviews were conducted among 957 men and 1,082 women resident in the community of Tecumseh, Michigan. Trained interviewers obtained detailed description of all foods consumed during 24 hr before venipuncture for lipid determination. Using a list of nutritional composition of 2,706 foods prepared from standard references, nutritionists determined quantities of all nutrients common to the American diet which were consumed by each participant according to a 24-hr diet record. For analysis, men and women were grouped into lower middle, and upper tertiles according to serum cholesterol and triglyceride levels. The mean daily consumption of each dietary component was virtually identical in all tertiles for men and women but differed between sexes. Cholesterol and triglyceride levels were unrelated to quality, quantity, or proportions of fat, carbohydrate, or protein consumed in the 24-hr recall period.

Resolution rates of pulmonary embolism assessed by serial positron imaging with inhaled O-15-labeled carbon dioxide.

Embolic obstruction of pulmonary blood flow results in delayed regional clearance of inhaled C15O2. Focally retained C15O2 appears as zones of increased O-15 activity on serial positron scintigrams, which show the locations of occluded pulmonary segments. Inhalation of C15O2, with serial imaging by a multicrystal positron camera, was used to locate and assess the magnitude of occluded pulmonary segments in eight patients with arteriographically documented pulmonary emboli. The imaging with C15O2 inhalation was repeated after 1 wk of i.v. heparin therapy to evaluate the ability of this technique to determine resolution rates of pulmonary emboli during anticoagulant therapy. In all patients, zones of increased C15O2 activity corresponded with sites of emboli identified arteriographically. After 1 wk of continuous heparin therapy, zones of focally retained C15O2 were totally resolved in three patients, diminished in four, and unchanged in one. The regional pulmonary clearance rate of C15O2 was delayed over embolized pulmonary segments in all patients (men clearance half-time = 42.2 sec +/- 11.2 s.e.m.) and improved after heparin therapy (13.9 +/- 3.9 sec; p less than 0.05). Serial C15O2 inhalation imaging is a rapid noninvasive radionuclide technique for detection of pulmonary emboli. It can be repeated at frequent intervals to assess the resolution of emboli during anticoagulant therapy.

Validation of the angiographic accuracy of digital left ventriculography.

Digital subtraction angiography enhances the contrast to background signal, enabling the performance of angiography with reduced doses of contrast medium. The objectives of the present study were (1) to validate the accuracy of digital left ventriculography for measurement of left ventricular volumes and segmental contraction; and (2) to compare the hemodynamic effects resulting from low-and high-dose intraventricular contrast injections. Twenty-eight patients underwent digital left ventriculography, performed by intraventricular injection of 7 ml of contrast medium diluted in saline solution, followed by conventional cineangiography of the left ventricle performed with 45 ml of undiluted contrast medium. Left ventricular volumes calculated from digital ventriculograms correlated well with volumes calculated from conventional ventriculograms: end-diastolic volume (r = 0.97, standard error of estimate [SEE] 23.4 ml; end-systolic volume (r = 0.97, SEE 15.4 ml); stroke volume (r = 0.95, SEE 14.7 ml); and ejection fraction (r = 0.97, SEE 3.8%). Segmental left ventricular contraction, measured as percent chordal shortening of hemiaxes, correlated moderately well (r = 0.81, SEE 11.5%). After injection of undiluted contrast medium, left ventricular systolic pressure decreased (133 +/- 31 to 123.5 +/- 27 mm Hg; p less than 0.01) and left ventricular end-diastolic pressure increased (12.0 +/- 7 to 16.9 +/- 10 mm Hg; p less than 0.001). Left ventricular systolic and end-diastolic pressures did not change significantly after injection of diluted contrast medium, and patients had no discomfort. Thus, digital subtraction angiography permits the performance of left ventriculography with markedly reduced doses of contrast medium, obviating the hemodynamic effects resulting from injection of conventional doses of contrast medium. This new approach to left ventriculography provides high resolution ventriculograms for accurate measurement of left ventricular volumes, stroke volume, and ejection fraction.

Percutaneous intraaortic balloon insertion.

A new single chambered percutaneous intraaortic balloon has been constructed around a central guidewire. The balloon can be wrapped around the guidewire, enabling its insertion into the femoral artery through a 12F sheath inserted with the conventional Seldinger technique. Percutaneous intraaortic balloon insertion has been performed in 27 patients (mean age 58 years) for a variety of medical and surgical indications. Percutaneous balloons could not be advanced into the aorta in two patients (7.4 percent) with severe bilateral aortoiliac occlusive disease. In all 25 patients undergoing intraaortic balloon pumping satisfactory circulatory support was achieved, and 21 (84 percent) of the patients survived to be discharged from the hospital. The mean duration of intraaortic balloon pumping was 3.5 days. Percutaneous intraaortic balloon insertion requires less than 5 minutes and has been successfully performed in the cardiac catheterization laboratory, coronary care unit, operating room and recovery room. After direct balloon removal, external pressure was applied for 30 minutes. No patient experienced hematoma of the groin, aortic dissection, compromised distal pulses or late wound complications. Percutaneous balloon insertion permits the rapid institution of circulatory support and broadens the medical and surgical applications of intraaortic balloon pumping.

Detection of pulmonary emboli by positron imaging of inhaled 15O-labeled carbon dioxide.

A new radionuclide approach to the scintigraphic detection of pulmonary emboli is described. This method utilizes cyclotron-produced C15O2, administered by inhalation, for rapid labeling of pulmonary blood. Following clearance of oxygen-15 from the lungs by pulmonary blood flow, focal retention of activity results from stasis of blood distal to emboli. On serial positron imaging, focally retained activity delineates embolized pulmonary segments and identifies the location and extent of pulmonary emboli. In animal studies this positron scintigraphic method detected emboli as small as 2 mm in diameter. In patients with suspected pulmonary emboli, this approach appears to be both sensitive and specific. Clinically, C15O2 inhalation imaging is most useful for the detection of pulmonary emboli in patients with chronic lung disease or congestive heart failure. It is rapid and safe and can be easily repeated, with minimal radiation exposure, for determining resolution rates of emboli and for assessing residual blood flow distal to emboli.

Evaluation of a cinevideodensitometric method for measuring vessel dimensions from digitized angiograms.

A cinevideodensitometric method for measuring the dimensions of small vessels by computer analysis of digitized cineangiograms was developed and validated in radiographic phantom models. With this method, which is based on full-width-at-half-maximum analysis of videodensitometric profile curves, the diameters of contrast-filled plexiglass cylinders ranging from 1.78 mm to 4.14 mm in diameter were measured to within 2% mean error. The theoretical basis for this method of cinevideodensitometric analysis is provided.

Quantitative analysis of coronary arteriograms by microprocessor cinevideodensitometry.

A rapid microprocessor technique for measuring the cross-sectional area, diameter, and relative percentage stenosis of coronary atherosclerotic lesions by cinevideodensitometric analysis was developed and validated. Video images of projected 35-mm coronary arteriographic cine frames were analyzed from cinevideodensitometric profile curves recorded for the catheter shaft, normal artery, and stenotic segment. In radiographic phantom studies of calibrated, contrast-filled, plexiglass cylinders, cinevideodensitometric measurements correlated linearly with percentage relative stenosis (r = 0.98; SEE = 4.1%), diameter (r = 0.99; SEE = 0.12 mm), and cross-sectional area (r = 0.99; SEE = 0.32 mm2). In postmortem studies of two patients dying after coronary arteriography, cross-sectional areas of arterial segments measured by cinevideodensitometry correlated well (r = 0.99; SEE = 0.71 mm) with areas of acrylic resin casts of the coronary arteries. Intraobserver variability (r = 0.99; SEE = 2.6%) and interobserver variability (r = 0.96; SEE = 5.3%) of cinevideodensitometric measurements of coronary arteriograms were low. Additionally, percentage relative stenosis measured in the right anterior oblique projection correlated well with measurements in the left anterior oblique projection (r = 0.98; SEE = 0.11 mm2) of patients with eccentric stenotic lesions. Lastly, cinevideodensitometric measurements were significantly (p less than 0.05) more reproducible than caliper measurements. This inexpensive dedicated microprocessor system provides rapid cinevideodensitometric measurements of coronary arterial dimensions, without requiring manual tracing of arterial segments or the major expense of a main-frame computer system.

Effect of coronary stenotic lesions on regional myocardial blood flow at rest.

To determine the effect of atherosclerotic coronary lesions on myocardial blood flow in patients at rest, regional myocardial blood flow was measured distal to stenotic lesions in 29 patients with isolated proximal lesions of the left anterior descending artery. Severity of coronary stenosis was measured by computer-assisted cinevideodensitometric analysis of digitized coronary arteriograms. Regional myocardial blood flow was measured from the clearance rate of intracoronary 133Xe injected into the left main coronary artery and recorded with a multicrystal scintillation camera. In 21 patients with stenotic lesions ranging from 19% to 84% area reduction, distal regional myocardial blood flow was normal. In all eight patients with reduced regional myocardial blood flow distal to left anterior descending lesions, the minimum area of each stenotic lesion was less 0.80 mm2 (mean 0.34 +/- 0.2 mm2), minimum calculated diameter was less than 1 mm (mean 0.59 +/- 0.3 mm), and percent stenosis, based on the reduction in cross-sectional area, was greater than 85% (mean 94 +/- 4%). For all patients, distal flow, expressed as a fraction of normal flow, correlated with the lesion cross-sectional area (r = .84), minimum luminal diameter (r = .84), and percent area stenosis (r = -.70). Thus, resting myocardial blood flow distal to stenotic lesions of the proximal coronary arteries remains normal until the degree of narrowing is severe. The dimensions observed for critical coronary stenotic lesions correlate well with theoretical predictions based on fluid mechanics and with experimental preparations in laboratory animals.

Spatial calibration of digital scintigraphic images: work in progress.

Accurate scintigraphic determination of organ dimensions is often difficult because of the wide variety of camera-collimator combinations and display formats used for imaging. An algorithm (SPACE-CAL) was developed for digital spatial calibration of up to six large- or small-field gamma cameras using various collimators and magnification factors. The algorithm employs a master calibration file that can be used at multiple terminals. An interactive subroutine permits the operator to measure distances and areas directly from the images. Evaluation of three operators' measurements of a pine-tree phantom acquired at various magnifications showed that distances could be measured with a high degree of accuracy. Calculation of ejection fraction from end-diastolic and end-systolic areas determined by SPACE-CAL showed a high correlation with automatic count determinations (r = 0.96) and angiographic calculations (r = 0.93) of ejection fraction in 12 patients. SPACE-CAL provides an easily implemented, reproducible, and rapid method for accurate analysis of organ dimensions in digital images.

Detection of experimental pulmonary emboli in dogs by sequential positron imaging after inhalation of 15O-carbon dioxide.

After inhalation, C15O2 (T1/2 = 2 minutes) rapidly diffuses into pulmonary blood and is cleared from the lungs within 10 seconds. The purpose of this study was to determine whether impaired clearance of inhaled C15O2 from oligemic zones, distal to areas of obstructed pulmonary blood flow, could be detected by serial pulmonary imaging with a positron camera. Experimental obstruction of branches of the pulmonary artery was induced in 19 anesthetized dogs by inflation of balloon-tipped catheters (8-12 mm in diameter), injection of radiopaque silicone spheres (0.5-4.0 mm), and embolization with barium-impregnated autologous blood clots (1-5 mm) via the right external jugular vein. After a single bolus injection of 2 mCi of C15O2 into the endotracheal tube, serial lung images of 15O activity were obtained over 60-180 seconds. Obstruction of pulmonary arterial branches resulted in visualization of discrete zones of impaired 15O clearance which varied in area with catheter diameter. Location and size of these zones were confirmed by repeat imaging after direct injection of 15O-labeled blood through the distal catheter lumen. In dogs receiving autologous clots (n = 8), similar zones of impaired 15O clearance were consistently imaged, and single emboli as small as 2 mm in diameter produced regions of retained 15O activity. Zones of retained 15O activity corresponded to the location of radiopaque emboli on chest radiographs. This study introduces a new technique of radionuclide imaging for detection of pulmonary emboli that is noninvasive, safe, sensitive, and repeatable at short intervals.