Cost-effectiveness analysis of patient management alternatives after uncomplicated myocardial infarction: a model.

Quantitative decision analyses provide a means whereby the effectiveness, in terms of patient outcome, and costs of diverse clinical approaches to the care of patients with cardiovascular disease can be made explicit and understandable. Increasingly, the profession is being required to justify the costs of clinical care to society, government and third party payers. Such justifications can be effectively presented when structured in decision analytic format. To demonstrate the utility of decision analysis and its extension--cost-effectiveness analysis--as a technique for presenting the rationale for clinical practices and technology utilization, the Cardiovascular Norms Committee of the American College of Cardiology sponsored a model cost-effectiveness analysis. Alternative management options, 6 month mortality and costs for the post-myocardial infarction patient were compared. The options included exercise electrocardiography, exercise thallium scintigraphy and coronary angiography, followed by coronary artery bypass surgery for patients with left main coronary disease only or patients with left main disease, three vessel disease or single or double vessel disease and a significant amount of myocardium in jeopardy. Within the constraints of the model, proceeding directly to angiography for risk stratification was the most effective approach, lowering expected mortality from 8% to approximately 3%. The marginal costs for this strategy, however, were high. The most cost-effective approach was to screen patients initially with exercise electrocardiography.

Effects of dynamic and isometric exercise on the radionuclide-determined regurgitant fraction in aortic insufficiency.

Twenty-five patients with aortic insufficiency and eight asymptomatic control subjects underwent radionuclide ventriculography at rest and during dynamic and isometric exercise to clarify the mechanisms for preservation of exercise capacity in aortic insufficiency. Regardless of symptomatic state or severity of regurgitation, patients with aortic insufficiency had no significant increase in left ventricular ejection fraction or relative left ventricular end-diastolic volume during dynamic or isometric exercise. The radionuclide stroke count ratio (ratio of left ventricular to right ventricular stroke counts) progressively decreased in patients with aortic insufficiency from 2.98 +/- 1.14 (mean +/- 1 standard deviation) at a mean heart rate at rest of 69.6 beats/min to 2.48 +/- 0.59 (p = not significant [NS]) at a mean submaximal bicycle exercise heart rate of 129 beats/min and to 1.97 +/- 0.57 (p less than 0.005) at a mean maximal bicycle exercise heart rate of 145 beats/min. The decrease in stroke count ratio with bicycle exercise was significantly related to the severity of valvular regurgitation at rest (p less than 0.005). Although achieving lower bicycle exercise heart rates and comparable diastolic blood pressures, symptomatic patients had a lower mean stroke count ratio compared with asymptomatic patients with aortic insufficiency, suggesting that an elevation left ventricular diastolic pressure significantly decreased the regurgitant fraction in symptomatic patients during bicycle exercise. In patients with aortic insufficiency, the mean heart rate (92 beats/min) was significantly lower with isometric exercise than during the submaximal stage of bicycle exercise (129 beats/min). However, diastolic blood pressures, left ventricular diastolic counts and ejection fractions were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Intercomparison of myocardial imaging agents: 201Ti, 129Cs, 43K, and 81Rb.

Thallium-201, 129Cs, 43K, and 81Rb were evaluated as "static" myocardial-imaging agents. Optimal settings of the scintillation camera were determined for each agent. Accumulation for good-quality images can be started as early as 5 min after the dose with 43K, 10 min with 201T1, and 30 min with 129Cs. Imaging times were comparable for 43K, 129Cs, and 201T1 (using the 80-keV x-rays). High-energy photons from the 81Rb preparation, largely from 82mRb contaminant, made it impossible to obtain an interpretable image without the addition of more shielding. Absorbed radiation dose from 81Rb is lower than that from 43K, 129Cs, and 201T1. The highest background activity was observed with 81Rb, followed by 43K, 129Cs, and 201T1 in that order. Overall, 201T1 was best suited for imaging acute myocardial infarction with currently available equipment, and 129Cs was next best. However, because of instrument setting and commercially obtained preparations, 81Rb could not be properly compared with the other radionuclides in our study.

Cesium-129 myocardial scintigraphy to quantify myocardial infarction in dogs.

The sizes of surgically induced acute myocardial infarctions were quantified in a study of 28 dogs. Four projections (right and left anterior oblique, anterior, and left lateral) were obtained with 129Cs myocardial scintigraphy. Control images, taken before surgery, were compared with images taken 24-72 hr after coronary artery ligation. From postmortem examination the size of the infarct was determined and expressed as a percentage of the total left ventricle. On a standard diagram four independent observers marked the infarcted areas in each projection, expressed the severity of involvement in each area, and determined overall infarction size as a percentage of the total left ventricle. A nonlinear least-squares method was also employed to derive the size of the infarct, using the results from each observer's diagram. There were positive correlations between each observer's percentage estimate and the autopsy results. The overall accuracy of the least-squares method was similar to that of the individual observers. In this study, Observer 3 proved that acute myocardial infarcts can be quantified accurately from multiple scintigraphic projections of the myocardium, but the other three observers had difficulty in estimating infarct size. This difficulty probably resulted from the lack of well-validated criteria to aid the observer in determining the area of infarction, the severity of involvement within that area, or the total size of a myocardial infarct. Improvement in these estimates will require the development of definitive criteria, the use of optical scanners or computer processing, and combinations of radionuclides.

A comparison of technetium etidronate and pyrophosphate for acute myocardial infarct imaging.

Etidronate and pyrophosphate, labeled with Tc-95m and Tc-99m, were studied in experimentally infarcted mongrel dogs. A distribution study was conducted 2 hr after simultaneous administration of both agents in two groups of dogs. In one group, the injection was made 15 min after release of a 2-hr coronary arterial ligation. Another group was injected 48 hr after release of the ligation. The uptakes for each radiopharmaceutical and the ratio of uptakes for each sample were computed. The data show pyrophosphate to be a superior agent for the imaging of acute myocardial infarcts because of the higher uptake by infarcted myocardium and the greater contrast between infarcted myocardium and neighboring organs.

Effect of coronary blood flow on uptake and washout of Tc-99m DMPE and Tl-201.

After intravenous administration of Tc-99m DMPE the flow-dependent kinetics were studied in dogs during induced ischemia and during induced maximal reactive hyperemia. A control group was also studied. Mean time-activity curves obtained from the myocardial wall were compared within the same intervention group and also with other groups. During reactive hyperemia, there was a rapid and absolute increase in uptake followed by a rapid washout, whereas during ischemia there was a slow and decreased uptake followed by a slow washout. The magnitude of Tc-99m DMPE uptake during reactive hyperemia was slightly less than that of Tl-201, but the decreased uptake with ischemia was about equal for the two agents. Following maximal uptake in the myocardium the effective half-life of Tc-99m DMPE was one-third to one-fourth that of Tl-201. The similar kinetics of Tc-99m DMPE compared to Tl-201 suggests its usefulness in the evaluation of ischemic heart disease.

Collimator evaluation for Tl-201 myocardial imaging.

Three collimators--high-resolutions, converging, and pinhole--were evaluated for Tl-201 myocardial imaging. Line spread function, sensitivity measurements, and phantom and animal studies were used. Features common to all the collimators were: a) better resolution at a closer distance with higher count density, and b) higher infarct detection rate in the tangenital projection than in the en face view relative to the lesion. Furthermore, an infarct in the epicardial location was better visualized than one in the endocardial location. In terms of resolution and sensitivity, the high-resolution collimator was found to be satisfactory in most clinical imagings, but for visualization of an infarct, its size by weight must be over 10--12 g. The pinhole collimator could resolve an infarct as small as 7 g, and use of the pinhole yielded a diagnostic accuracy of over 90%, compared with 75-80% for the high-resolution collimator. Although the low sensitivity of the pinhole collimator precludes its routine clinical use, the selected view would increase diagnostic accuracy. The converging collimator performed poorly in terms of lesion detectability, and its routine clinical use is not encouraged. The conclusion drawn here is valid in the system we have studied, but the variety of converging collimators must be evaluated further for their specific purposes.

Basal kinetic studies of Tc-99m DMPE as a myocardial imaging agent in the dog.

Newly synthesized Tc-99m dichlorobis(1,2-dimethylphosphino)ethane (DMPE) was investigated as a myocardial imaging agent with respect to its kinetics (dependent on both time and regional coronary blood flow), its percent organ uptake, and its imaging characteristics in the anesthetized dog. Most of these data are compared with those of Tl-201. Blood clearance of the two agents is essentially the same. Compared with Tl-201, Tc-99m DMPE shows faster overall kinetics, higher heart-to-lung ratio, equally good correlation with a wide range of regional blood flows, and higher liver uptake. At the time of peak myocardial uptake, the mean heart uptake of Tl-201 is 4.3%, compared with 2.9% for Tc-99m DMPE, yet only 0.9% uptake of Tc-99m DMPE is found in the lung as compared with 3.3% for Tl-201. These differences result in a heart-to-lung ratio of 2:1 for Tc-99m DMPE and 1:1 for Tl-201, based on the data obtained from the time-activity curve. The quantitative findings are supported by the superior quality of Tc-99m DMPE images of both normal and infarcted dog heart. The high hepatic uptake of Tc-99m DMPE is not a serious problem if images are obtained within 5-60 min after dose. These basic kinetic studies suggest that Tc-99m DMPE is a promising myocardial imaging agent.

Nonobstructive hypertrophic cardiomyopathy mimicking mitral stenosis. Documentation by echocardiography, phonocardiography and intracardiac pressure and sound recordings.

The physical findings in hypertrophic cardiomyopathy with left ventricular outflow tract obstruction are well described. In the absence of outflow tract obstruction the findings are less distinctive. There have been several reported cases in which the cardiac findings have suggested the diagnosis of mitral stenosis, In this report we describe a patient whose auscultatory and roentgenographic findings more closely mimicked mitral stenosis. The patient had a loud first heart sound, mitral opening snap and an apical presystolic murmur; left atrial enlargement was present. Noninvasive studies, including phonocardiography, echocardiography and apex cardiography, strongly suggested the correct diagnosis of nonobstructive hypertrophic cardiomyopathy. The diagnosis and unusual auscultatory findings were confirmed by results of cardiac catheterization and intracardiac phonocardiography. The importance of recognizing this syndrome and the use of noninvasive methods to establish the diagnosis are stressed.

Effects of myocardial hypoxia and ischemia on myocardial scintigraphy.

The effect of regional myocardial ischemia and hypoxia on myocardial scintigraphy was studied in patients and dogs after intravenous administration of cesium-129. Seven men with angiographically proved ischemic heart disease underwent exercise testing and 129Cs was given immediately when ischemia was manifested in the electrocardiogram. Defects were not evident in the scintigrams of any patient. Failure to visualize a defect might be related to delayed uptake of 129Cs by the myocardium (maximal uptake in 45 minutes). The ischemic state was dissipated before the disparity in uptake between normal and ischemic myocardium could be visualized. Cesium-129 is useful for identifying acute myocardial infarcts but should not be used to visualize transient exercise-induced regional ischemia. Six dogs were given 129Cs after induction of regional myocardial hypoxia by perfusion of the anterior descending coronary artery with venous blood. In each, scintigraphy revealed a defect that resolved after reperfusion with arterial blood. Two other dogs were given 129Cs before perfusion with hypoxemic blood; neither dog manifested a defect. Since perfusion was maintained by a pump these results suggest that the major cause of the scintigraphically observed defect was inadequate cellular uptake of 129Cs rather than excessive cellular loss. Since regional myocardial hypoxia produced a reversible defect, scintigraphic studies might overestimate the size of an acute myocardial infarct in man by including the ischemic zone surrounding the infarct.

Myocarditis: unresolved issues in diagnosis and treatment.

Myocarditis is an enigmatic disease. Lymphocytic myocarditis is most commonly viral in origin. Considerable evidence suggests that myocardial damage is due to an immune-mediated mechanism rather than to direct effects of the virus itself. The presentation is variable, ranging from a clinically inapparent or relatively benign illness to acute progressive heart failure and death. Although examination of the endomyocardial biopsy specimen is the "gold standard" for the diagnosis of myocarditis there are problems with this technique, relating particularly to sampling error and histologic interpretation. Considerable evidence, both animal and human, suggests that a link between viral myocarditis and dilated cardiomyopathy does exist. There is a rational basis for the use of immunosuppressive therapy in myocarditis. Although many favorable responses have been reported with the use of these agents, the results of more definitive studies are awaited to determine the role of immunosuppressive therapy in myocarditis more clearly. Recommendations for the practical management of patients with myocarditis are made. Whenever possible, patients with this diagnosis should be entered into the ongoing NIH trial.