Effect of surgical versus medical therapy on return to work in patients with coronary artery disease.

The proportion of medically and surgically treated patients with coronary artery disease working full time 1 year after cardiac catheterization or surgery, respectively, was assessed by questionnaire in a registry of patients who had had coronary angiography. The proportion of medically and surgically treated patients working 3 months before catheterization or surgery was 74 percent (148 of 201) and 75 percent (899 of 1,198), respectively, whereas 62 percent (125 of 201) and 62 percent (747 of 1,198), respectively, were working full time 1 year after catheterization or surgery. Multivariate analysis identified five variables predictive of return to work. In order of significance these were: working status 3 months before surgery or catheterization, years of education, age, functional class before surgery or catheterization and period of not working before surgery or catheterization. Work status 3 months before surgery or catheterization was clearly the best predictor of continued employment 15 months later. Surgical therapy was not more effective than medical therapy in maintaining full-time employment in this registry of patients with coronary artery disease.     

Effect of aortocoronary saphenous vein bypass grafting on death and sudden death: Comparison of nonrandomized medically and surgically treated cohorts with comparable coronary disease and left ventricular function

The effect of saphenous vein bypass grafting on the incidence of sudden cardiac death and total cardiovascular death was studied by comparing the survival of subsets of surgically and medically treated patients with coronary disease who were similar in two major prognostic variables: extent of coronary disease and ejection fraction. Significant differences in some baseline variables existed between medical and surgical subgroups with similar ejection fraction and extent of coronary disease. Medically treated patients tended to be in a lower functional class, to have more extensive ventricular contraction abnormalities, to have a larger end-diastolic volume, and to have fewer distal vessels feasible for grafting. Surgically treated patients with two vessel disease and normal or moderately reduced election fraction had improved survival when compared with medically treated patients with two vessel disease and similar ejection fraction. Improved survival of borderline statistical significance was also seen in surgically treated patients with three vessel disease and moderately reduced ejection fraction. When categorized according to end-diastolic volume, surgically treated patients with two vessel disease and normal or moderately increased end-diastolic volume also had improved survival over similarly defined medically treated patients. The sudden death rates for subgroups of mecically treated patients were 1.8 to 10.9 times higher than the rates in subgroups of surgically treated patients with a comparable extent of coronary disease and ejection fraction.     

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

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.     

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 $\text{129 ±}\text{16}\text{80}\text{± 9}\text{to}\text{120 ±}\text{17}\text{75}\text{± 9}\text{mm Hg}\text{(P < 0.001)}$. 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.     

Assessment of coronary stenoses with myocardial perfusion imaging during pharmacologic coronary vasodilatation: IV. Limits of detection of stenosis with idealized experimental cross-sectional myocardial imaging

Because atherosclerosis may be reversible, a routine noninvasive screening test for the reliable diagnosis of mild coronary arterial lesions would allow potential prevention of coronary events in specific patients through intensive dietary management, drug therapy and physical training. To determine the minimal coronary stenosis detectable with myocardial perfusion imaging techniques, standardized stenoses ranging from 31.4 to 72.5 percent diameter narrowing were applied to the left circumflex coronary artery of 12 open chest dogs. Indium-113m-labeled human albumin microspheres were injected into the left atrium under control conditions and technetium-99m human albumin microspheres during maximal coronary vasodilatation induced with intravenous dipyridamole. Hearts were removed, sliced into 1 cm thick cross sections and imaged under a gamma camera. The results demonstrate that 40 percent diameter coronary stenoses can be identified by imaging relative subendocardial underperfusion during pharmacologic coronary vasodilatation. An imaging technique sensitive enough to identify mild coronary lesions for diagnostic screening purposes requires (1) a potent stimulus for coronary vasodilatation, such as intravenous dipyridamole; (2) an imaging agent taken up by the myocardium in proportion to coronary flow at flow rates up to four or more times resting coronary flow so that differences in regional maximal flows caused by mild stenoses can be identified; and (3) cross-sectional tomographic myocardial imaging to visualize relative endocardial-epicardial perfusion, the most sensitive indicator of the hemodynamic effects of coronary stenoses, and to exclude from the imaging field the interfering activity of lung, background and overlying heart structures.     

Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilatation. I. Physiologic basis and experimental validation

This study was undertaken to establish the basic hemodynamic conditions necessary to cause abnormalities in external myocardial perfusion images of thallium-201 and technetium-99M-labeled particles as a result of defined coronary stenoses ranging from mild to severe narrowing. Twenty dogs underwent long-term instrumentation with a flow transducer and adjustable constrictor on the left circumflex coronary artery. Catheters were implanted in the aortic root and distal left circumflex coronary artery to measure pressure loss across the stenosis and in the pulmonary artery and left atrium for the injection of drugs or radionuclides, or both. All data were obtained in intact unsedated trained animals. The results from 145 images obtained at rest, during exercise or after coronary vasodilators in dogs with mild to severe coronary stenoses demonstrate the following: (1) The ratio of maximal flow in a normal to stenotic coronary artery must be at least 2:1 before defects appear in the myocardial perfusion image of thallium-201. (2) A diagnostic technique that utilizes a maximal stimulus for increasing coronary flow and an imaging agent that is distributed to the myocardium in linear proportion to coronary flow at flow rates up to 4 or 5 times resting levels will be the most sensitive method for detecting mild coronary stenoses; a diagnostic technique utilizing a submaximal stimulus for coronary flow or an imaging agent whose distribution is not proportional to flow at high flow rates will be least sensitive. (3) Myocardial perfusion imaging during coronary vasodilatation induced with intravenously administered dipyridamole is a better method for identifying moderate coronary stenoses than perfusion imaging during exercise stress in experimental animals. (4) The effect of intravenously administered dipyridamole on the coronary circulation can be closely regulated by adjusting the dose rate of infusion and can be instantaneously reversed with intravenous administration of aminophylline, a dipyridamole antagonist; dipyridamole infusion does not increase myocardial oxygen demands as much as exercise and does not Invoke myocardial ischemia as a diagnostic end point. This stimulus may therefore be more readily controlled than exercise stress and is not subject to the effects on treadmill testing of motivation, chronic lung disease, peripheral vascular disease or musculoskeletal impairment.     

Left ventricular thrombi: In vivo detection by indium-111 platelet imaging and two dimensional echocardiography

Indium-111 platelet Imaging, which can Identify sites of active intravascular platelet deposition, and two dimensional echocardlography, which can identify intracardiac masses, can both be used to detect left ventricular thrombi noninvasively. We compared these techniques in 44 men at risk for thrombi from remote transmural myocardial infarction (31 patients) or cardiomyopathy (13 patients). All 44 patients underwent platelet imaging; 35 underwent echocardlography.On platelet imaging nine patients had thrombi and one had a possible thrombus. Of these 10 studies, none were positive at 2 hours, 5 were positive at 24 hours and all were positive 48 or 72 hours after platelet labeling. Nine of these patients underwent echocardlography, and all had an intraventricular mass. The findings on platelet scanning were negative in six patients who had positive (four patients) or equivocally positive (two patients) findings on echocardiography. All patients with thrombi detected by either noninvasive method had transmural anterior myocardial infarction with ventricular aneurysm. Of the seven patients who underwent cardiac surgery or autopsy, three had thrombi. Platelet imaging failed to Identify one thrombus in a patient in whom imaging was performed only at 24 hours after labeling. There were no false positive platelet images in this group. Five of these seven patients (two with thrombi, three without) underwent echocardiography; in all cases the echocardiographic findings agreed with the pathologic findings.Both platelet Imaging and echocardiography detect ventricular thrombi. Platelet imaging may detect only the most hematologically active thrombi. Both techniques may help define patients at risk of embolization and may be useful for in vivo assessment of antithrombotic drugs.     

Indium-111 platelet imaging for detection of platelet deposition in abdominal aneurysms and prosthetic arterial grafts

Thirty-four platelet imaging studies were performed in 23 patients to determine whether platelet deposition could be detected in patients with vascular aneurysms (18 patients) or in patients in whom Dacron prosthetic grafts had been placed (5 patients). In patients in whom abnormal platelet deposition was detected, the effect of administration of platelet-active drugs on platelet deposition was examined.Of the 18 patients with an aneurysm, 12 had positive studies on initial imaging and 2 had equivocally positive images. Of five patients with Dacron arterial grafts in place, four had diffuse platelet deposition in the grafts; the fifth patient had platelet deposition only in a pseudoaneurysm. Eight patients with an abdominal aneurysm and positive or equivocally positive baseline images were restudied during platelet-active drug therapy either with aspirin plus dipyridamole (seven patients) or with sulfinpyrazone (four patients). No patient studied during treatment with aspirin plus dipyridamole had detectably decreased platelet deposition compared with baseline determinations. In contrast, two of four patients studied while receiving sulfinpyrazone showed decreased platelet deposition. Thus, platelet imaging may be of value for studying platelet physiology in vivo and for assessing platelet-active drugs and the thrombogeniclty of prosthetic graft materials in human beings.     

Transaxial tomography with thallium-201 for detecting remote myocardial infarction: Comparison with planar imaging

Transaxial tomograhic imaging with thallium-201 was compared with standard, planar imaging in 38 patients with remote myocardial infarction and in 15 normal patients. Tomographic images were reconstructed from 64 views collected by a gamma camera that rotated about the anterior circumference of the patient's chest. A series of consecutive transverse-section images which encompassed the cardiac volume were reconstructed at a 6 mm plane spacing by filtered back-projection. No correction was made for attenuation losses. The set of transverse-section images was reformatted by 3-dimensional interpolation to obtain tomograms along the long and short axes of the myocardium. Tomographic and planar images were interpreted qualitatively.

Overall, tomography detected 33 of 38 (87%) prior infarctions whereas planar imaging detected 24 of 38 (63 %) (p = 0.01). Improvement of the tomographic imaging method occurred only in the combined subset of transmural inferior and subendocardial infarctions, and not in transmural anterior infarctions. Peak increases in creatinine phosphokinase were smaller in patients detected only by tomography compared with those detected by both the planar and the tomographic approach (3.1 × normal versus 10.4 × normal, p = 0.04). Five patients (13%) with prior infarction were not detected by either approach. For 6 of the 9 patients detected by tomography alone, realignment of the image data along the short and long axes of the heart was essential for making the diagnosis. Fourteen of 15 patients without infarction were normal on both planar and tomographic imaging. A single normal patient had a defect detected by both techniques, yielding a specificity of 93% for each.

We conclude that transaxial tomography significantly improves the detection of thallium-201 myocardial perfusion defects in patients with prior myocardial infarction.     

Effects of coronary stenoses on coronary flow reserve and resistance

Resting coronary flow and regional distribution are not affected by narrowing of up to 85 percent of arterial diameter and therefore provide little insight into the effects of stenoses on coronary hemodynamics. However, maximal coronary flow and coronary flow reserve are markedly reduced by constrictions that do not affect resting flow. Accordingly, coronary flow reserve and its relations to pressure-flow-resis-tance characteristics of 177 single (10 dogs) and 125 double coronary stenoses in series (7 dogs) were studied in open chest preparations. Coronary flow, aortic pressure and left circumflex coronary pressure distal to a single or to each of two separate adjustable coronary constrictors in series were simultaneously recorded while flow was varied from basal to maximum by intracoronary injections of contrast medium.The hyperemic response to contrast medium is a quantitative measure of coronary flow reserve which was closely related to, and predictive of, the following characteristics of single and double stenoses in series: (1) total pressure gradient and distal circumflex perfusion pressure at resting coronary flow; (2) total pressure gradient and distal circumflex pressure at hyperemic flow when effects of stenoses are greatest; and (3) coronary stenoses resistance. Thus, the hyperemic response after injection of contrast medium, or coronary flow reserve, is in itself a quantitative measure of the pressure-flow-resistance characteristics of coronary constrictions. In addition, resistances of coronary stenoses in series are shown to be additive; the flow effects of stenoses in series are not generally determined by the dominant or most severe lesion, contrary to common clinical precepts. These concepts are applicable to patients in assessing the effects of stenoses on coronary hemodynamics.     

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

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 ¹³¹iodine-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 ^99mtechnetium 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.     

Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects

Serial hemodynamic and plasma catecholamine responses were compared among 10 healthy men (27 +/- 3 years) (+/- 1 standard deviation) during symptom-limited handgrip (33% maximal voluntary contraction for 4.4 +/- 1.8 minutes), cold pressor testing (6 minutes) and symptom-limited supine bicycle exercise (22 +/- 5 minutes). Plasma catecholamine concentrations were measured by radioenzymatic assays: ejection fraction and changes in cardiac volumes were assessed by equilibrium radionuclide angiography. During maximal supine exercise, plasma norepinephrine and epinephrine concentrations increased three to six times more than during either symptom-limited handgrip or cold pressor testing. Additionally, increases in heart rate, systolic blood pressure, rate-pressure product, stroke volume, ejection fraction and cardiac output were significantly greater during bicycle exercise than during the other two tests. A decrease in ejection fraction of 0.05 units or more was common in young normal subjects during the first 2 minutes of cold pressor testing (6 of 10 subjects) or at symptom-limited handgrip (3 of 10), but never occurred during maximal supine bicycle exercise. The magnitude of hemodynamic changes with maximal supine bicycle exercise was greater, more consistent and associated with much higher sympathetic nervous system activation, making this a potentially more useful diagnostic stress than either handgrip exercise or cold pressor testing.     

Immediate hemodynamic effects of cardiac angiography in man

Changes in human circulatory physiology occurring in the minutes after intracardiac injection of angiographic contrast material have been well documented, but little information is available for the period of left ventricular opacification. The immediate and instantaneous effect on left ventricular function of the rapid intracardiac injection of 1 ml/kg body weight of 75 percent sodium-meglumine diatrizoate (Hypaque M®) into the pulmonary artery, left atrium or left ventricle in 43 adult patients was studied by measurement during angiography of (1) peak aortic root blood velocity in 28 patients, (2) instantaneous stroke volume (computed from the velocity tracing) in 28 patients, (3) heart rate in 41 patients, (4) left ventricular end-diastolic pressure in 17 patients, and (5) left ventricular end-diastolic and end-systolic volumes (calculated from the single-plane cineangiogram) in 14 patients.During left ventricular opacification, variables 1 through 4 differed only slightly from control values; the only statistically significant changes were in peak velocity after pulmonary arterial injection (114 percent of control, control = 100 percent), heart rate after left atrial injection (93 percent of control) and left ventricular end-diastolic pressure after left ventricular injection (110 percent of control). Sequential left ventricular end-diastolic and end-systolic volumes measured over 3 to 5 cardiac cycles demonstrated no significant change. We conclude that measurements based on angiographic left ventricular volumes should be valid and correspond closely to the control state. The major hemodynamic changes secondary to contrast injection occur later, beginning 15 to 30 seconds after injection.     

Natural history of platelet deposition on Dacron aortic bifurcation grafts in the first year after implantation

This study defined the dynamics of platelet deposition on Dacron arterial grafts up to 1 year after implantation in human subjects. Indium-111 platelet imaging was performed on 8 men 1 to 2 weeks after graft implantation and on 5 of these patients at a mean of 31 weeks (range 28 to 34) and again at 55 weeks (range 50 to 62). Serial imaging was performed at 24 to 96 hours after platelet labeling and injection in each study. Quantitative analysis was performed using a graft/blood ratio that compared background-corrected indium-111 platelet activity in the graft region to whole-blood indium-111 platelet activity. Additionally, blinded qualitative visual analysis of the images compared graft activity with the activity in adjacent native arteries. The mean of all graft/blood ratios (24, 48, 72, and 96 hours) progressively decreased from 4.4 +/- 2.1 (+/- 1 standard deviation) at 1 to 2 weeks to 3.0 +/- 1.8 at 31 weeks (p = 0.002). There was no further decrease at 55 weeks (2.8 +/- 2.0). For comparison, 12 normal subjects without grafts had a mean ratio of 1.8 +/- 0.7. Visual analysis detected platelet deposition in 7 of 8 grafts at 1 to 2 weeks, 4 of 5 at 31 weeks, and 4 of 5 at 55 weeks. Deposition decreased qualitatively in 2 of 5 patients at late study. It is concluded that there is consistent, early platelet deposition on Dacron grafts in man. Although deposition decreases over 31 weeks, it remains readily detectable in most patients at 1 year. These findings suggest absent or incomplete endothelialization of the graft flow surface in humans in the first year after implantation.     

Detection of left ventricular thrombi with radionuclide angiography

Apparent filling defects compatible with left ventricular thrombus are occasionally noted in equilibrium radionuclide angiocardlograms. To define the usefulness of the radionuclide angiogram in detecting left ventricular thrombus, the anterior and left anterior oblique radionuclide angiograms of 39 patients with proved presence or absence of thrombus were blindly interpreted. The presence of thrombus was proved at autopsy in 5 patients, at cardiac operation in 2, or on indium-111 platelet imaging in 6; the absence of thrombus was proved at autopsy in 24 or at cardiac operation in 2. Overall, 13 radionuclide angiograms were interpreted as posltive (n = 10) or equivocally positive (n = 3) for thrombus, and 26 studies were judged negative. The sensitivity of a positive or equivocally positive radionuclide angiogram for detection of thrombus was 77 percent (10 of 13 patients), the specificity 88 percent (23 of 26 patients), the positive predictive value 77 percent, the negative predictlve value 88 percent. If the three equivocal studies are instead considered negative for thrombus, the sensitivity was 62 percent, the specificity 92 percent, the positive predictive value 80 percent and the negative predictive value 93 percent. All thrombi were visualized in the anterior view in an area of akinetic or dyskinetic wall motion. A small group of 13 patients (8 with thrombus, 5 without) underwent two dimenslonal echocardiography, which was 100 percent sensitive and specific. The finding of a discrete filling defect or squared or cutoff ventricular apex in an area of abnormal wall motion in the anterior view of the radionuclide angiogram should suggest the diagnosis of ventricular thrombus, which may be confirmed by other noninvasive studies.