Clinical Appraisal Noninvasive

ALFRED

F. PARISI,

DONALD

E. TOW,

of Current Nuclear and Other

Cardiac Diagnostic

MD,

FACC

MD

ARTHUR A. SASAHARA, MD, FACC West Roxbury and Boston, Massachusetts

From the Departments of Medicine (Cardiology) and Radiology (Nuclear Medicine), West Roxbury Veterans Admjnistration Hospital, West Roxbury, and Peter Bent Brigham Hospital and Harvard Medical School, Boston, Mass. Address for reprints: Alfred F. Parisi, MD, Veterans Administration Hospital, 1400 VFW Parkway, West Roxbury, Mass. 02132.

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Techniques

At a time of rapid increases in the cost of medical care and the application of complex invasive procedures to cardiovascular diagnosis, the use of noninvasive methods has aroused interest. This report discusses the usefulness and limitations of various noninvasive diagnostic methods including nuclear medicine techniques, echocardiography, exercise electrocardiography and determination of systolic time intervals. Emphasis is placed on the applicability of these methods to specific disease processes (such as ischemic heart disease, cardiac valve disease, pulmonary embolic disease), their relative merits, future potential and present shortcomings.

During the past decade, a variety of noninvasive cardiac diagnostic techniques have been introduced and are receiving increasing attention and acceptance. Interest in these procedures has been aroused by their ease of application, ability to provide meaningful results, repeatability, relative lack of expense and high degree of patient safety. At a time of geometrically escalating costs of medical care and increasing awareness of the limitations of our resources, it is particularly important to have available noninvasive low risk inexpensive testing procedures for selecting patients who require or will significantly benefit from more costly invasive diagnostic and therapeutic procedures. If noninvasive techniques can provide adequate objective evidence that a person has no or only minimal cardiac disease, the savings realized through avoidance of further hospit,alization for invasive diagnostic studies and absence from work would be considerable. Noninvasive tests also have appeal to the referring physician provided he can feel assured that such procedures will yield important diagnoses with virtually no risk to the patient. Consequently, in applying these noninvasive procedures, we must carefulfy consider their usefulness in patient care as well as their inherent sensitivity and specificity as diagnostic tests. Unless the physician is aware of the diagnostic accuracy of each noninvasive test, he cannot justify the use of such testing simply because it is noninvasive. At times, a well chosen invasive investigation, even at some risk, may be preferable to a noninvasive “fishing expedition.” We have tried to highlight the developments in noninvasive diagnostic techniques over the past decade, emphasizing particularly their application to major problems in clinical cardiology. We have stressed the current usefulness and limitations of such procedures and their potential for solving problems in cardiovascular disease. Finally, we fully appreciate the clinical importance of older techniques such as the resting electrocardiogram and chest X-ray film. The value of these procedures to cardiovascular diagnosis has clearly been established and need not be considered here.

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lschemic

Heart Disease

Myocardial Infarction A striking development in the past several years has been the ability to delineate acutely infarcted myocardium with radioactive tracers. Utilizing technetium99m stannous pyrophosphate, Bonte and Parkey et al.1*2 have shown a high correlation between acute myocardial infarction confirmed by electrocardiographic changes and serum enzyme studies and the appearance of a radioisotopic “hot spot” within the involved region 3 to 5 days after the acute event. McLaughlin et al.” found similar positive results up to 20 days after acute transmural infarction. With 99mTc tetracycline, Holman et al.4 showed an excellent correlation of abnormal and normal myocardial scans with the presence or absence of documented myocardial infarction. They found peak activity within the heart 1 to 3 days after the clinical onset of chest pain. The scintigraphic site of the infarct correlated grossly with maximal serum creatine phosphokinase (CPK) activity in 16 patients. The method appears to be valuable for the recognition of acute myocardial infarction although more experience is needed to reach a consensus as to its sensitivity and specificity. Diagnostic value: To the clinical cardiologist, the majority of patients presenting with acute myocardial infarction do not represent a diagnostic problem. Thus, the routine application of nuclear imaging of the zone of infarcted myocardium is not necessary for the proper care of most patients with this condition. However, this technique may be extremely helpful in certain circumstances. For example, the incidence of myocardial infarction after coronary bypass surgery has been reported to range between 5 and 40 percent.” Under these circumstances, the development of a diagnostic “hot spot” may allow more objective assessment of myocardial damage in a setting in which electrocardiographic S-T and T wave changes and routine serum enzyme levels can yield confusing results.“,7 This technique should also prove helpful in diagnosing recurrent acute infarction in patients with preexisting Q wave abnormalities. Similarly, the test may be helpful in patients who are comatose or confused (due to trauma or alcoholism for example), and have nonspecific electrocardiographic and enzyme abnormalities for reasons other than acute infarction. Assessing infarct size: An exciting aspect of the ability to radiolabel the infarcted myocardium is the concept that this method is qualitatively different from the traditional approaches of recognizing myocardial infarction in the living patient. Because in-hospital survival of the majority of patients with acute myocardial infarction appears to relate to the amount of damaged myocardium,s+9 radiolabeling potentially affords the opportunity to derive quantitative assessment of the amount of injured tissue. This could provide an additional approach to the problem of infarct sizing, which is currently under intense investigation with other noninvasive studies such as serial CPK determinations and precordial S-T segment elevation mapping.*n-12

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Whether this approach will yield additional meaningf~ information in a quantitative sense will be the subject of intensive clinical study over the next few years, in view of the current interest in therapeutic procedures that may modify the extent of damage to the acutely infarcted myocardium. Diagnosis of Coronary Artery Disease Assessing atypical chest pain: Considerably more troublesome than recognizing acute myocardial infarction is the problem of diagnosing coronary artery disease in patients with recurrent chest pain. The specificity of the syndrome of “classic” angina pectoris leaves little room for improvement with noninvasive diagnostic tests.‘3T14Nevertheless, many patients have recurrent chest pain with one or more atypical features13; in this group it is often difficult to establish an objective diagnosis of ischemic heart disease without performing coronary arteriography. Electrocardiographic exercise testing: During the past 5 years, there has been renewed interest in exercise tests, particularly tests using graded protocols on a bicycle or treadmill to diagnose ischemic heart disease. The diagnosis is based on the appearance of 1 mm or more of horizontal or downsloping (“ischemic”) S-T segment depression during or immediately after exercise.’ 5 The method has been clearly helpful in separating patient populations with and without significant coronary artery disease, particularly in view of longterm prognosis, but its ability to indicate the presence of coronary disease in an individual patient has been less striking.16 It has long been recognizedI that as the degree of S-T segment depression increases to 2 or more mm, the test becomes considerably more specific but simultaneously less sensitive. Several reports16Js-24 correlating the results of exercise testing with coronary angiographic studies have yielded widely variable sensitivity and specificity levels for the procedure. The disparities appear to stem in part from the nature of the groups studied. Thus, in asymptomatic patients selected for angiography on the basis of a positive exercise test there is considerably less specificity than in patients with classic angina who are studied similarly.16~~)False positive tests often lead to coronary angiography. Properly executed, the risk of coronary arteriography is minimal and considerably outweighed by the reassuring evidence of a normal coronary circulation. More disturbing are independent reports of false negative electrocardiographic exercise tests in more than one half to two thirds of patients with arteriographically significant coronary lesions. 16~24 As a consequence, some investigators’s have seriously questioned the diagnostic application of exercise testing to the clinical problem of ischemic heart disease. Certainly the procedure of exercise testing in search of ischemic S-T segment depression is an imperfect method for examining a large number of patients, particularly in view of the wide prevalence of coronary artery disease. Myocardial perfusion imaging during exercise testing: It is in this context that recent studies by Zaret et a1.2.5J6using the isotope potassium-43 have attracted

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great interest. By injecting this tracer during exercise into patients with angina pectoris, they have shown the lack of uptake of the tracer in areas of the heart supplied by severely obstructed coronary arteries. These initial studies raised the possibility of localizing ischemic areas of myocardium on the basis of failure of uptake of a radiolabel in involved muscle. The method has great appeal because of its potential ability to quantify ischemit areas of myocardium. Because of its energy characteristics, potassium-43 is not an ideal tracer for such studies. For this reason, some groupC have been unable to confirm the original observations of Zaret et al. in localizing ischemic zones with this method. More recent experience in several institutio.ns, using thallium-201, has confirmed and extended the usefulness of this method. It now seems likely that myocardial perfusion imaging will prove to be an alternative or supplemental method of measuring S-T segment shifts. Despite its limitations, particularly with S-T segment depression of 1 mm, exercise electrocardiography currently appears to be the most practical available noninvasive means of objectively confirming the presence of ischemic heart disease. In the face of a history of “classic” angina pectoris, however, a negative exercise test must be regarded with considerable skepticism, and a thallium-201 study would seem indicated. The presence of coronary artery disease can also be inferred from detection of localized abnormalities of contraction. Such abnormally contracting segments are most prevalent in the distribution of significant coronary arterial lesions. Assessment

of Ventricular

Function

In the past 5 years, several noninvasive techniques have been advocated to reflect left ventricular performance. These techniques include determination of systolic time intervals, echocardiography and imaging of the systolic and diastolic left ventricular chamber with radioactive tracers. Systolic time intervals: The determination of systolic time intervals is a completely noninvasive procedure and rapid and simple to perform.ssso However, the technique is not widely used to assess ventricular function. In part, this is a result of the extensive evaluations of the technique in the setting of acute myocardial infarction.:31m:‘:4 In this situation, the hemodynamic variables upon which the values of preejection period and left ventricular ejection time depend are often rapidly and acutely changing in opposite directions so that changes in the intervals are not useful in individual patients. In addition, since the study of Garrard et al.:‘” there has been little confirmation of the diagnostic accuracy of systolic time intervals in predicting ventricular function in homogeneous patient groups. The technique is also further limited by its dependence on the presence of normal intraventricular conduction and sinus rhythm.:“’ Echocardiography: Measurements made with this technique have been shown to correlate with ventricular volumes and ejection fraction determined by invasive studies.:{” X+ However, the wisdom of predicting ven-

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tricular function in individual patients on the basis of transverse dimensional measurement of the left ventricle has been criticized.:jg The difficulties are particularly evident in coronary artery disease wherein localized disorders of left ventricular contractility can alter chamber dimensions in either direction depending on whether a hypocontractile or hypercontractile area of the ventricle is traversed by the echocardiographic beam. Nevertheless, the echocardiographic approach appears to have considerable potential for rapid noninvasive overall assessment of left ventricular function. The results of recent studies of Teichholz et al.40 accurately predicting ejection fraction using the B scan technique support this contention. With the development of multiscan and sector scan approaches to the left ventricle, echocardiography may eventually prove to be the most practical and quickest means of assessing left ventricular function.41,4’ Ventricular nuclear imaging: Utilizing the gamma camera and electrocardiographic gating, radionuclide evaluation of left ventricular function currently appears to be the best noninvasive means of approximating angiographic evaluation of left ventricular performance. Because the radioactive tracer technique can yield multiprojection planar images of the left ventricle throughout the cardiac cycle, this approach appears to be theoretically sound. Several independent studies4”45 have shown correlation coefficients of 0.9 or better for ejection fractions obtained with nuclear imaging and angiography. Thus the radionuclide technique appears to offer 80 to 90 percent accuracy in predicting left ventricular ejection fraction. The imaging achieved with nuclear techniques cannot be compared with the resolution obtainable with angiocardiographic evaluation of the left ventricle. In particular, the margins of the left ventricular cavity and areas of transition between poorly and normally functioning segments of ventricular myocardium are poorly resolved. To those versed in the traditional angiographic evaluation of left ventricular performance, a procedure required by most surgeons today, radionuclide evaluation of left ventricular contractility is suboptimal. However, such evaluation appears able to distinguish patients with grossly poor ventricular function (ejection fraction less than 30 percent) from those with fair or good overall ventricular function. In this regard the radionuclide approach should receive greater attention. There is general agreement that preoperative assessment of left. ventricular performance provides a meaningful index of the likelihood of survival after coronary bypass surgery. 5,46-48In view of the increasing readiness to perform coronary angiography and bypass surgery to relieve angina pectoris, it may be worthwhile to use the nuclear approach for initial evaluation of ventricular performance. In those with definitely poor ventricular function, it would be reasonable to defer consideration of angiography and surgery until the results of intensive medical therapy are known. Radionuclide imaging of the left ventricle also makes possible evaluation of segmental left ventricular dysfunction. Detection of abnormally contracting segments can provide an important clue to the presence of coroVolume 36

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nary artery disease.4g Because the resolution of image is not ideal, the method is probably less sensitive for this purpose than for evaluating overall ventricular function. However, it appears to be the best noninvasive means of recognizing ventricular aneurysms, to which more conventional techniques are relatively insensitive.50 Cardiac

Valve Disease

The clinical recognition of cardiac valve disease is less difficult than the recognition of coronary artery disease because physical examination usually gives important clues to the lesions present. In this condition, nuclear techniques have been less helpful than echocardiography or phonocardiography and pulse recordings for producing objective evidence of the presence and severity of a specific valve disorder. Echocardiography Hypertrophic subaortic stenosis: Echocardiography has been particularly useful in the recognition of the obstructive form of idiopathic hypertrophic subaortic stenosis, for which the systolic anterior motion of the anterior mitral leaflet apposing a hypertrophied ventricular septum is considered pathognomonic.51-5” The proximity of the anterior mitral leaflet to the interventricular septum at the onset of systole also distinguishes most patients with the obstructive from those with the nonobstructive form of the disease.54 Echocardiography has allowed a further appreciation of the spectrum of this disease since it has been shown that many relatives of patients with the obstructive form have asymmetric septal hypertrophy.55 In fact, asymmetric septal hypertrophy appears to be the fundamental pathologic abnormality in both obstructive and nonobstructive forms of the disease.56,57 More important, this lesion, which can be confused with mitral regurgitation, ventricular septal defect or even aortic stenosis, can objectively be defined without the need of cardiac catheterization. In many centers cardiac catheterization is no,longer routinely performed in patients when this diagnosis can be confirmed by echocardiographic findings. Mitral stenosis: The presence of mitral stenosis can usually be objectively confirmed echocardiographically with a specificity that approaches 100 percent. Although parallel anterior diastolic motion of the anterior and posterior leaflets of the mitral valve is not present in every case of mitral stenosis, considerably more than 90 percent of patients have this finding.5s-ac Although the presence of mitral stenosis is confirmed relatively easily with echocardiography, its severity is somewhat difficult to determine by the single beam technique. There have been no published prospective series evaluating the accuracy of M mode scans in grading the severity of mitral stenosis. There is considerable variability of the E-F slope and other indicators of anterior leaflet motion in relation to severity.“’ With the single beam technique, it has been reported recently that leaflet separation correlated with mitral valve area with a correlation coefficient of 0.81.s2 Although this measurement was superior to the E-F slope,

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the method still accounts for only 66 percent of the variability of mitral valve stenosis in the group studied. Using a sector scanner in the transverse position, Henry et al. fir3have shown that it is possible to visualize directly the mitral valve orifice. This approach appears to offer great promise as a sensitive noninvasive way of predicting accurately the severity of mitral stenosis. Aortic stenosis: Echocardiography is less helpful in defining the presence of other left-sided cardiac valve disease. Dense additional echoes within the aortic root in the area of the aortic leaflets favor the presence of aortic stenosis but the severity of the stenosis cannot be determined from this finding alone.64%“5The additional presence of concentric left ventricular hypertrophy strongly favors a severe degree of obstruction at the aortic valve. Simultaneous pulse tracings and phonocardiography can provide objective confirmation of severe aortic stenosis. In the absence of heart failure, the left ventricular ejection time is usually prolonged, the carotid upstroke slowed and the peak of the basal ejection murmur delayed. 66~68When these three findings were combined, Bonner et a1.67 reported a 96 percent specificity for the presence of severe aortic stenosis. The presence of only one of these findings usually indicates severe stenosis. but by itself is usually not sensitive enough to identify all patients with severe aortic obstruction. Aortic regurgitation: Mitral and aortic regurgitation can also be recognized with echocardiography but severity must once again be inferred from associated findings. High frequency diastolic vibration of the anterior mitral leaflet is commonly present in all degrees of aortic regurgitation. 6g In acute severe aortic regurgitation, early coaptation of the anterior and posterior mitral leaflets indicating premature mitral closure is a highly reliable sign of wide open regurgitation.7o,7i However, because this is not the most common form of aortic insufficiency encountered clinically, the sign is of limited value. In chronic aortic regurgitation, the amount of left ventricular dilatation determined from the left ventricular internal diastolic dimension provides an index to the severity of the regurgitant lesion.72 Mitral regurgitation: Mitral incompetence may or may not be directly recognized from the echocardiographic pattern of mitral leaflet motion, depending on the specific form of regurgitation present. Echocardiography has provided anatomic confirmation of late sfltolic prolapse of either or both mitral leaflets in the systolic click-murmur syndrome and has demonstrated flail leaflets in cases of ruptured chordae tendineae?m7s Although echocardiography has shown that mitral valve prolapse is more prevalent than previously appreciated, such prolapse is not found in the majority of patients with mitral regurgitation; moreover, the severity of regurgitation can only be inferred from the presence of combined left atria1 and left ventricular dilatation.78 In summary, echocardiography is extremely helpful in placing our assessment of cardiac valve disease on a more objective basis without the need for invasive studies. It would appear possible to avoid cardiac

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catheterization in patients with evidence of idiopathic hypertrophic subaortic stenosis unless they are clearly unresponsive to medical management. Similarly, there is hope that with more prospective studies and refinement of planar imaging techniques the severity of mitral stenosis will be accurately predicted, thus avoiding the need for cardiac catheterization completely or at least until the presence of moderately severe stenosis is confirmed. Further refinements in echocardiographic resolution and its systematic application in controlled prospective studies will be needed before the severity of aortic stenosis can be assessed accurately in large patient populations. Similarly, more specific criteria must be established for the assessment of regurgitant and combined valve lesions. PuImonary

Embolic

Disease

(Lung Scanning)

The lungs lend themselves well to study of regional function with radioactive tracer techniques. Indeed, the practice of pulmonary scanning is one of the well established areas where definitive action is often taken on the basis of the results of radionuclide imaging.7gm81 False negative lung scan: Several studies, including the Urokinase Pulmonary Embolism Trial, have shown that a normal lung scan makes it very likely (probability close to 100 percent) that no pulmonary embolism is present.*‘mss Theoretically, a large proximal embolus in the main pulmonary artery may affect equally the regional pulmonary circulation and hence yield a false negative scan. In practice, this has not been observed. In the Urokinase Pulmonary Embolism Trial, there were 10 patients with a large proximal embolus in the main pulmonary artery; no lung scan was falsely negative.8” In this setting the estimation of perfusion deficit, by scanning was usually less than expected on the basis of the angiographic finding. Specificity of positive lung scan: Abnormal lung scans are more problematical since all pulmonary diseases can lead to abnormal scans. How specific is lung scanning in diagnosing pulmonary embolism? This question can be examined in the following manner: First, patterns of perfusion as shown in lung scans in the various pulmonary diseases have certain characteristics s4-sg such as peripheral concave defects in pulmonar; embolism, redistribution of blood flow in pulmonary venous hypertension and the fissure sign in congestive failure. Second, the diagnostic specificity of lung scanning is enhanced by a chest roentgenogram performed in conjunction with the scan. A concave peripheral perfusion defect in the presence of a normal chest roentgenogram is most likely due to pulmonary embolism. In a recent studyTg in which the scan perfusion defects were classified according to high or low probability of having been caused by pulmonary embolism, interpretations indicating embolism were confirmed by angiogram in 75 percent of cases. When the scan interpretation was normal, the angiogram was also normal. Third, in combination wit,h the xenon-133 ventilation study, an abnormal lung scan in the presence

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of a normal ventilation study is virtually diagnostic of pulmonary embolism. On the other hand, in a patient with an abnormal perfusion lung scan and matchingly abnormal ventilation study, pulmonary embolism is less likely but cannot be absolutely excluded.e”-9” There may be underlying disease such as chronic obstructive lung disease not apparent in the plain chest X-ray film. More recent data also suggest that in patients with suspected pulmonary embolism who have an abnormal perfusion scan and evidence of deep leg vein thrombosis documented noninvasively with electrical impedance plethysmography, there is a 90 percent probability that they have acute pulmonary embolism.gs Diagnostic specificity: In virtually all patients, normal perfusion lung scan excludes pulmonary embolism, and no further pursuit of the diagnosis is required. Similarly, in patients who have an abnormal scan and objective confirmation of phlebitis, particularly in the absence of roentgenographic findings of chronic lung disease, the probability is greater than 90 percent that they have acute pulmonary embolism. When a xenon-133 ventilation study is available, diagnostic specificity may increase. With these factors in mind, it is possible now to limit the application of pulmonary angiography to patients who do not meet these criteria or who have coexisting pulmonary embolism and chronic obstructive lung disease. Congenital

Heart Disease

Both nuclear techniques and echocardiography can be used to detect many congenital heart lesions. A detailed description of these applications is given in another article in this seriesg4; some general principles will be outlined here. Nuclear techniques: These have been used successfully to detect intracardiac shunts. After intravenous injection of a radionuclide the early appearance of radioactivity in a detector located over the systemic circulation indicates the presence of a right to left shunt. For this purpose, many prefer to use substances completely excreted or trapped by the lung, such as radioactive xenon or microspheres. The appearance of radioactivity in the systemic circulation shortly after intravenous injection indicates a significant right to left intracardiac shunt.gs*Y” Similarly, early reappearance of radioactivity in the selectively monitored lung suggests left. to right shunting.~~.gs nuclear an~~ocur~iogr~~s can aid considerably in the definition of selective cardiac chamber enlargement as well as the recognition of complex interrelations of the great vessels and of intracardiac shunts.gaJOO This technique is particularly useful in evaluating cyanotic neonates, in whom the risk of cardiac catheterization is considerable. Echocardiography: This method plays an increasingly important role in the diagnosis of congenital heart lesions. Since the technique allows recognition of anatomic continuity of intracardiac structures, the relation of the great vessels with the ventricular chambers, valve

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during nuclear angiography or ventricular function studies with ggmT~ albumin. Dissecting aneurysm of the ascending aorta: This is an acute medical emergency. Recent reports] 12m1 I4 have shown that echocardiography can distinguish the cavity of the dissecting hematoma from the true aortic lumen. However, in none of these studies has the patient series from a single institution been large enough to establish definitely the diagnostic accuracy of the method. Moreover, false positive results have been reported.‘“’ Further evaluation is necessary before we can be certain of the reliability of ultrasound as a screening technique for the presence of this lesion. Left atria1 myxoma: The diagnosis of this tumor was virtually impossible to establish noninvasively before the advent of echocardiography. Such tumors, while rare in occurrence, have been repeatedly detected with this method by independent observers.‘16~‘1g The presence of a radiodense area within the left atrium, particularly prolapsing into the mitral funnel during diastole, appears to be pathognomonic for the presence of the tumor. With appropriate attention to proper instrumental settings, the false positive detection of this lesion by an experienced echocardiographer should be quite rare. False negative results can occur, but their true incidence may never be known in view of the relative infrequency with which this lesion is encountered. Right atria1 myxomas have also been recognized, particularly when prolapsing into the right ventricle.’ if Atria1 myxoma has also been detected with scintiphotographic imaging.120~1Z’ Intracardiac thrombosis: Left atria1 clots in mitral stenosis and left ventricular thrombi in ventricular aneurysm and cardiomyopathy have been detected by the use of iodine-131 fibrinogen as well as radiolabeled fibrinolytic agents. I22 Here too, the reported series are too small to make definitive statements at this time as to the clinical usefulness of such radionuclide screening techniques.

abnormalities and structural defects within the interventricular septum can be recognized by this means. To date, more than 30 distinct congenital abnormalities have been identified with echocardiography.lOl In an adult population the congenital lesion that most often passes unnoticed is the atria1 septal defect. Although such a lesion still requires right heart catheterization to confirm its presence, echocardiography appears to be extremely sensitive in detecting evidence of significant left to right shunting with this defect.io2m104 Thus, the presence of an enlarged right ventricular internal dimension with or without septal paradoxical motion should raise the question of right ventricular volume overload. This finding is not specific for an atria1 septal defect because it may occur with other conditions such as tricuspid regurgitation, anomalous pulmonary venous connection and, occasionally, pulmonary hypertension. However, the absence of a significantly increased right ventricular internal dimension would appear to exclude a clinically significant left to right shunt on the basis of an uncomplicated interatrial septal defect. Miscellaneous Problems Pericardial effusion: Both echocardiography and nuclear techniques lend themselves to the evaluation of an enlarged cardiac silhouette. Whereas the majority of patients with this roentgenographic finding have cardiomegaly, the presence of a pericardial effusion is a not uncommon differential diagnostic problem. Echocardiography appears particularly sensitive to this condition since the separation of a nonmoving posterior pericardium from a moving adjacent epicardium can be detected even with very small effusions if care is taken with proper instrumental settings and technique to discern the posterior pericardium at the appropriate anatomic level.lO”JOs By routinely performing echocardiography 24 hours before cardiac surgery, Horowitz et a1.1°7 recently showed that effusions as small as 15 ml could be detected The overlap of negative and positive patterns in their group of 41 patients was small, thus attesting to the specificity of the method as well. Recently, features of cardiac tamponade have been demonstrated with echocardiography.10s With inspiration there is an increased right ventricular dimension consistent with filling of this chamber. Concomitantly there is decreased excursion of the anterior mitral leaflet and diminished left ventricular dimension, indicating poor transmitral flow. These findings are in accord with the physical finding of a paradoxic pulse. Ry radiolabeling the intracardiac blood pool large effusions can also be inferred from the discrepancy of this blood mass with the apparent size of the cardiac silhouette as well as its separation from the liver.lOs Effusions have also been demonstrated by ggmT~ pertechnetate flow studies in which the cardiac blood pool is separated from the lungs by the fluid-filled pericardium to an abnormal degree. l lo Nuclear techniques are less sensitive’l’ and less versatile than echocardiographic techniques which can be performed at the patient’s bedside, but pericardial effusions may be observed

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Conclusions The past decade has seen considerable progress in the development of diagnostically accurate noninvasive cardiovascular procedures for recognition of major problems in adult medicine. Particularly notable is our ability to deal with pulmonary embolism in the majority of cases without resorting to pulmonary angiography. On the opposite end of the spectrum, we are just beginning to define methods that show significant impairment of myocardial perfusion or myocardial damage, or both, as a result of coronary artery disease. Between these two extremes, we are able to identify qualitatively, and in some cases semiquantitatively, the presence and severity of specific forms of cardiac valve disease. In light of this progress it is hoped that in the future our reliance on invasive means of cardiovascular diagnosis can be limited almost exclusively to patients who are most likely to benefit from cardiac surgery, toward which cardiac catheterization and angiography are integral steps.

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References 1. Bonte FJ, Parkey RW, Graham KD, et ai: A new method for radionuclide imaging of myocardiai infarcts. Radiology 110: 473-474, 1974 2. Parkey RW, Bonte FJ, Meyer SL, et al: A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 50540-546, 1974 3. McLaughlin P, Coates G, Wood D, et ak Detection of acute myocardial infarction by technetium-99m polyphosphate. Am J Cardiol 35:390-396, 1975 4. Holman BL, Lesch M, Zwelman FG, et al: Detection and sizing of acute myocardial infarcts with 99mTc (Sn) tetracycline. N Engl J Med 291:159-163, 1974 5. Mundth ED, A&en WG: Surgical measures for coronary heart disease. N Engl J Med 293:13-19, 75-80, 124-130, 1975 6. Platt MR, Parkey RW, Bonte FJ: Myocardial imaging to detect myocardial infarction after coronary revascularization (abstr). Circulation 5O:Suppl Ill: 199, 1974 7. Lowenthal IS, Parisi AF, Tow DE, et al: Detection of myocardial damage with ssmTc-pyrophosphateafter open hoart surgery. Clin Res 23:567A, 1975 8. Page DL, Caulfield JB, Kastor JA, et al: Myocardial changes associated with cardiogenic shock. N Engl J Med 285: 133-137, 1971 9. Harnarayan C, Bennett MA, Pentecost BL, et al: Quantitative study of infarcted myocardium in cardiogenic shock. Br Heart J 32:728-732, 1970 IO. Shell WE, Lavelle JF, Covell JW, .et al: Early estimation of myocardial damage in conscious dogs and patients with evolving acute myocardial infarction. J Clin Invest 52:2579-2590, 1973 11. Sobel BE, Bresnahan GF, Shell WE, et al: Estimation of infarct size in man and its relation to prognosis. Circulation 46:640-648, 1972 12. Maroko PR, Libby P, Covell JW, et af: Precordial S-T segment elevation mapping: an atraumatic method for assessing alterations in the extent of myocardial ischemic injury. Am J Cardiol 29: 223-229, 1972 13. Ross RS, Frteslnger GC: Coronary arteriography. Am Heart J 72:437-441.1966 14. Friesinger GC, Page EE, Ross RS: Prognostic significance of coronary arteriography. Trans Assoc Am Physicians 83:78-92, 1970 15. The Committee on Exercise, Albert A. Kattus, MD, Chairman: Exercise Testing and Training of Apparently Healthy Individuals: A Handbook for Physicians. New York, American Heart Association, 1972 16. Borer JS, Brensike JF, Redwood DR, et at: limitations of the electrocardiographic response to exercise in predicting coronary-artery disease. New Engl J Med 293:367-371, 1975 17. Friedberg CK, Jaffe HL, Pordy L, et al: The two-step exercise electrocardiogram. A double-blind evaluation of its use in the diagnosis of angina pectoris. Circulation 26: 1254-1260, 1962 18. k&Henry PL, Philllps JF, Knoebel SB: Correlation of computer-q~ntitated treadmill exercise electrocardiogram with arteriographic location of coronary artery disease. Am J Cardiol 301747-752, 7972 19. McConahay DR, McCallister BD, Smith RE: Postexercise electrocardiography: correlations with coronary arteriography and left ventricular hemodynamics. Am J Cardiol 28:1-g, 1971 20. Froelicher VF Jr, Yanowitr FG, Thompson AJ, et al: The correlation of coronary angiography and the electrocardiographic response to maximal treadmill testing in 76 asymptomatic men. Circulation 48:597-604, 1973 21. Keleman NH, Gillilan RE, Bouchard RJ, et al Diagnosis of obstructive coronary disease by maximal exercise and atrial pacing. Circulation 48:1227-1233, 1973 22. Martin CM, McConahay DR: Maximal treadmill exercise electrocardiography. Correlations with coronary arteriography and cardiac hemodynamics. Circulation 46:956-962, 1972 23. Cohn PF, Vokonas PS, Herman MV, et al: Postexercise electrocardiogram in patients with abnormal resting electrocardiograms. Circulation 43:648-654, 1971 24. Kassebaum DG, Sutherland Kl, Judkins MP: A comparison of hypoxemia and exercise electrocardiography in coronary artery

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disease. Am Heart J 75:759-776,1968 25. Zaret BL, Strauss HW, Marlin ND, et al: Noninvasive regional myocardial perfusion with radioactive potassium. N Engl J Med 288:809-812, 1973 26. &ret BL, Stenson RE, Martin ND, et al: Potassium43 myocardial perfusion scanning for the noninvasive evaluation of patients with false-positive exercise tests. Circulation 48: 1234-1241, 1973 27. Myers RW, Redwood DR, Johnston GS: Diagnostic accuracy of stress myocardial scintigraphy (SMS) (abstr). Circulation 5O:Suppl lll:lll-4, 1974 28. Weissler AM, Peeler RG, Roehll WH Jr: Relationships between left ventricular ejection time, stroke volume, and heart rate in normal individuals and patients with cardiovascular disease. Am Heart J 62:367-378, 1961 29. Weissler AM, Harris WS, Schoenfeld CD: Systolic time intervals in heart failure in man. Circulation 37:149-159, 1968 30. Weissler AM, Harris WS, Schoenfeld CD: Bedside technics for the evaluation of ventricular function in man. Am J Cardiol 23: 577-583, 1969 31. Diamant B, Klllip T: Indirect assessment of left ven~icular performance in acute myocardial infarction. Circulation 42:579-592, 1970 32. Hodges M, Halpern BL, Friesinger GC, et al: Left ventricular preejection period and ejection time in patients with acute myocardial infarction. Circulation 45933-942, 1972 33. Perloff JK, Reichek N: Value and limitations of systolic time intervals (preejection period and ejection time) in patients with acute myocardial infarction. Circulation 45929-932, 1972 34. Garrard CL Jr, Wefssler AM, Dodge HT: The relationship of alterations in systolic time intervals to ejection fraction in patients with cardiac disease. Circulation 42:455-462. 1970 35. Weissler AM, Garrard CL Jr: Systolic time intervals in cardiac disease (I). Mod Concepts Cardiovasc Dis 40: 1-8, 1971 36 POpp RL, Harrison DC: Ultrasonic cardiac echography for determining stroke volume and valvular regurgitation. Circulation 41:493-502. 1970 37. Pombo JF, Troy BL, Russell RO Jr: Left ventricular volumes and ejection fraction by echocardiography. Circulation 43:480-490, 1971 38. Fortuin N, Sherman ME, Hood WP Jr, et ak Determination of left ventricular volumes by ultrasound. Circulation 44575-584, 1971 39. Linhart JW, Mintz OS, Segal BL, et al: Left ventricular volume measurement by echocardiography: fact or fiction? Am J Cardiol 36:114-118.1975 40. Telchholr LE, Cohen NIV, Sonnenblick EH, et al: Study of left ventricular geometry and function by B-scan ultrasonography in patients with and without asynergy. N Engl J Med 291: 1220- 1226, 1974 41. Kloster FE, Roelandt J, Cate FJ ten, et al: Multiscan echocarbiography. II. Technique and initial clinical results. Circulation 48:1075-1084, 1973 42. Griffith JM, Henry WL: A sector scanner for real time two-dimensional echocardiography. Circulation 49:1147-l 152, 1974 43. Strauss HW, Zaret BL, Hurley PJ, et al: A scintiphotographic method for measuring left ventricular ejection fraction in man without cardiac catheterization. Am J Cardiol 28:575-580, 1971 44. Seeker-Walker RH, Resnick L, Kunz H, et ak Measurement of ieft ventricular ejection fraction. J Nucl Med 14:798-802, 1973 45. Kostuk WJ, Ehsani AA, Karliner JS, et al: Left ventricular per:ormance after myocardial infarction assessed by radioisotope ~ngiocardiography. Circulation 47:242-249, 1973 46. 3ldham HN Jr, Kong Y, Bartel AG, et al: Risk factors in coronary artery bypass surgery. Arch Surg 105918-923, 1972 47. .ea RE, Tector AJ, Flemma RJ, et al: Prognostic significance If a reduced left ventricular ejection fraction in coronary artery surgery (abstr). Circulation 46:Suppl ll:ll-49, 1972 48. Cohn PF, Gorlin R, Cohn LH, et al: Left ventricular ejection raction as a prognostic guide in surgical treatment of coronary wd valvular heart disease. Am J Cardiol 34: 136-l 41, 1974

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49. Zaret BL, Strauss HW, Huriey PJ, et al: A noninvasive scintiphotographic method for detecting regional ventricular dysfunction in man. N Engl J Med 284:1165-1170, 1971 50. Huriey PJ, Zaret BL, Pitt B, et al: Assessment of left ventricular wall movement in patients with ventricular aneurysm (abstr). J Nucl Med 12:369, 1971 51. Shah PM, Gramfak R, Kramer OH: Ultrasound localization of left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40:3-l 1, 1969 52. Popp RL, Harrison M”r: Ultrasound in the diagnosis and evaluation of therapy of idiopathic hypertrophic subaortic stenosis. Circulation 40:905-914, 1969 53. Shah PM, Gramiak R, Adefman AG, et ak Role of echooardiography in diagnostic and ~~~rnic assessment of hypertrophic subaortic stenosis. Circulation 44:891-898, 1971 54. Henry WL, Clark CE, Griffith JY, et al: Melanism of left ventricular outflow obstruction in patients with obstructive asymmetric septal hypertrophy (idiopathic hypertrophic subaortic stenosis). Am J Cardiol 35337-345, 1975 55. Clark CE, Henry WL, Epstein SE: Familial prevalence and genetic transmission of idiopathic hypertrophic subaortic stenosis. N Engl J Med 289:709-714, 1973 56. Henry WL, Clark CE, Epstein SE: Asymmetric septal hyportrophy. Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 47:225-233, 1973 57. Epstein SE, Henry WL, Clark CE, et al: Asymmetric septal hypertrophy. Ann Intern Med 81:650-680, 1974 58. Edier I: Ultrasoundcardiography in mitral valve stenosis. Am J Cardiol 19:18-31, 1967 59. Duchak JY Jr, Chang S, Feigenbaum H: The posterior mitral valve echo and tha echocardi~raphi~ diagnosis of mitral stenosis. Am J Cardiol 29:628-632, 1972 60. Levisman JA, Abtmel AS, Pearce ML: Posterior mitral leaflet motion in mitral stenosis. Circulation 51:51 l-514, 1975 61. Gustafson A: Correlation between ultrasoundcardiography, hemcdynamics and surgical findings in mitral stenosis. Am J Cardiol 19:32-41, 1967 62. Fisher ML, Pa&i AF, DeFeilce CE: Predicting mitral valve area from echocardiograms (abstr). Clin Res 22:679A, 1974 63. Henry WL, Grffffth JM, Michaeils LL, et al: Measurement of mitral orifice area in patients with mitral valve disease by real-time, two-dimensional echocardiography. Circulation 51:827-831. 1975 64. Gramlak R, Shah PM: Echocardiography of the normal and diseased aortic valve, Radiology 96: 1-8, 1970 65. Fefri 0, Symons C, Yacoub P& Echocardi~raphy of the aortic valve. I. Studies of normal aortic valve, aortic stenosis, aortic regurgitation, and mixed aortic valve disease. Br Heart J 36: 341-351,1974 66. Parisi AF, Sairman SH, Schechter E: Systolic time intervals in severe aortic valve disease. Circulation 44:539-547, 1971 67. Bonner AJ, Sacks HN, Tavei ME: Assessing the severity of aortic stenosis by phonocardiography and external carotid pulse recordings. Circulation 48:247-252, 1973 68. Bathe RJ, Wang Y, Greenfield JC: Left ventricular ejection time in valvular aortic stenosis. Circulation 47527-533, 1973 69. Winsberg F, Gabor GE, Her&erg JO, et al: Fluttering of the mitral valve in aortic insufficiency. Circulation 41:225-229, 1970 70. Pridie RB, Benham R, Oakley CM: Echocardiography of the mitral valve in aortic valve disease. Br Heart J 33:296-304, 1971 71. Mann T, McLaurin L, Grossman W, et al: Assessing the hemodynamic severity of acute aortic reg~gitation due to infective endocarditis. N Engl J Med 293:108-i 13, 1975 72. Gray KE, Barrftt DW: Echocardiographic assessment of severity of aortic regurgitation. Br Heart J 37:691-699, 1975 73. Kerber RE, isaeff GM, Hancock EW: Echocardiographic patterns in patients with the syndrome of systolic click and late systolic murmur. N Engl J Med 284:691-693. 1971 74. Dillon JC, Haine CL, Chang S, et al: Use of echocardiography in patients with prolapsed mitral valve. Circulation 43:503-507, 1971 75. Popp RL, Brown OR, Silverman JF, et al: Echocardiographic abnormalities in the mitral valve prolapse syndrome. Circulation 49:428-433, 1974

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76. DeMaria AN, King JF, Bogren HG, et at: The variable spectrum of echocardiographic manifestations of the mitral valve prolapse syndrome. Circulation 50:33-41, 1974 77. Duchak JM, Chang S, Feigenbaum H: Echocardiographic features of torn chordae tendineae (abstr). Am J Cardiol 29:260, 1972 78. Burgess J, Clark R, Kamigakl M, et al: Echocardiographic findings in different types of mitral regurgitation. Circulation 48:97-106, 1973 79. Giiday DL, Pouiose KP, DeLand FH: Accuracy of detection of pulmonary embolism by lung scanning correlated with pulmonary angiography. Am J Roentgen01 Radium Ther Nucl Med 115: 732-738, 1972 80. Daien JE, Banas JS, Brooks HL, et al: Resolution rate of acute pulmona~ embolism in man. N Engl J Med 280:1194-1199, 1969 81. Greenspan RH: Does a normal isotope perfusion scan exclude pulmonary embolism? Invest Radio1 9:44-45, 1974 82. Sasahara AA, Beiko JS, Simpson RG: Multiple-view lung scanning. J Nucl Med 9:187-191, 1968 83. Tow DE, Simon AL: Comparison of lung scanning and pulmonary angiography in the detection and follow-up of pulmonary embolism: The Urokinase Pulmonary Embolism Trial experience. Prog Cardiovasc Dis 17:239-245, 1975 84. Wagner HN Jr, Sabiston DC Jr, YcAfee JG, et al: Diagnosis of massive pulmonary embolism in man by radioisotope scanning. N Engl J Med 271:377-384, 1964 85. Tow DE, Wagner NH Jr: Recovery of pulmonary arterial blood flow in patients with pulmonary embolism. N Engl J Med 276: 1053-1059, 1967 86. Mfshkin FS, Tow DE, Wagner HN Jr: Regional distribution of pulmonary arterial blood flow in acute asthma. JAMA 203: 1019-1021, 1968 87. James AE Jr, Cooper M, White RI, et al: Perfusion changes on lung scan in patients with congestive heart failure. Radiology 100:99-106, 1971 88. Friedman WF, Braunwaid E: Alterations in regional pulmonary blood flow in mitral valve disease studied by radioisotope scanning. A simple nontraumatic technique for estimation of left atrial pressure. Circulation 34:363-376, 1986 89. Pouiose K, Reba RC, Wagner HN Jr: Characterization of the shaoe and location of perfusion defects in certain oulmonprv CA’ I diseases. N Engl J Med‘279: 1020- 1025, 1968 90. Medina JR, L’Heureux P. Liiiehei JP. et al: Reaional ventilation in the differential diagnosis of pulmonary embolism. Circulation 39:831-835, 1969 91 DeNardo GL, Goodwhr DA, Ravasini R, et at: The ventilatory lung scan in the diagnosis of pulmonary embolism. N Engl J Med 282:1334-1336, 1970 92 McNeil BJ, Hoiman BL, Adeistein SJ: The scintigraphic definition of pulmonary embolism. JAMA 227:753-756, 1974 93 Wheeler HB, Pearson D, O’Connell DJ, et al: Impedance phlebography: technique, interpretation and results. Arch Surg 104:164-169, 1972 94. Treves S, Collins-Nakai RL: Radioactive tracers in congenital heart disease. Am J Cardiol 38:71 i-721, 1976 95. Strauss HW, Huriey PJ, Rhodes BA, et al: Quantification of right-to-left transpulmonary shunts in man. J Lab Clin Med 74: 597-607,1969 96. Krfss JP, Enright LP, Hayden WG. et ai: Radioisotopic angiocardiography. Wide scope of applicability in diagnosis and evaluation of therapy in diseases of the heart and great vessels. Circulation 43:792-808, 1971 97. Foise R, Braunwaid E: Pulmonary vascular dilution curves recorded by external detection in the diagnosis of left-to-right shunts. Br Heart J 24:166-172, 1962 98. Rosenthal1 L, Mercer EN: Intravenous radionuclide cardiography for the detection of cardiovascular shunts. Radiology 106: 601-606,1973 99. Mason DT, Ashburn WL, Harbert JC, et al: Rapid sequential visualization of the heart and great vessels in man using the wide-field Anger scintillation camera. Circulation 39: 19-28, 1969 100. Wesselhoeft H, Huriey PJ, Wagner HN Jr, et al: Nuclear angio-

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104.

105.

106.

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cardiography in the diagnosis of congenital heart disease in infants Circulation 45:77-91, 1972 Tucker C, Williams R: Manual of Pediatric Echocardiography. Boston, Little, Brown, in press. Diamond MA, Dillon JC, Haine CL, et al: Echocardiographic features of atrial septal defect. Circulation 43:129-135, 1971 Tajik AJ, Gau GT, Ritter DG, et al: Echocardiographic pattern of right ventricular diastolic volume overload in children. Circulation 46:36-43, 1972 Kamigaki M, Goldschlager N: Echocardiographic analysis of mitral valve motion in atrial septal defect. Am J Cardiol 30: 343-348, 1972 Feigenbaum Ii, Zaky A, Waldhausen JA: Use of reflected ultrasound in detecting pericardial effusion. Am J Cardiol 19:84-90, 1967 Feigenbaum H: Echocardiographic diagnosis of pericardial effusion. Am J Cardiol 26:475-476, 1970

107. Horowitz MS, Schultz CS, Stinson EB, et al: Sensitivity and specificity of echocardiographic diagnosis of pericardial effusion. Circulation 50:239-247, 1974 108. D’Cruz IA, Cohen HC, Prabhu R, et al: Diagnosis of cardiac tamponade by echocardiography. Changes in mitral valve motion and ventricular dimensions, with special reference to paradoxical pulse. Circulation 52:460-465, 1975 109. Wagner HN Jr, MacAfee JG, Mozley JM: Diagnosis of pericardial effusion by radioisotope scanning. Arch Intern Med 108:679-684, 1961 110. Kriss JP: Diagnosis of pericardial effusion by radioisotopic angiocardiography. J Nucl Med 10:233-241, 1969

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111. Christensen EE, Bonte FJ: The relative accuracy of echocardiography. intravenous COs studies, and blood-pool scanning in detecting pericardial effusions in dogs. Radiology 91:265-270, 1968 112. Nanda NC, Gramiak R, Shah PM: Diagnosis of aortic root dissection by echocardiography. Circulation 48:506-513. 1973 113. Brown OR, Popp RL, Kloster FE: Echocardiographic criteria for aortic root dissection. Am J Cardiol 36: 17-20, 1975 114. Moothart RW, Spangler RD, Blount SG Jr: Echocardiography in aortic root dissection and dilatation. Am J Cardiol 36:1 l-16, 1975 115. Krueger SK, Starke H, Forker AD, et al: Echocardiographic mimics of aortic root dissection. Chest 67:441-444, 1975 116. Wolfe SB, Popp RL, Feigenbaum H: Diagnosis of atrial tumors by ultrasound. Circulation 39:615-622, 1969 117. Finegan RE, Harrison DC: Diagnosis of left atrial myxoma by echocardiography. N Engl J Med 282:1022-1023, 1970 118. Kostis JB, Moghadam AN: Echocardiographic diagnosis of left atrial myxoma. Chest 58:550-552, 1970 119. Lortscher RH, Toews WH, Nora JJ, et al: Left atrial myxoma presenting as rheumatic fever. Chest 66:302-303, 1974 120. Bonte FJ, Curry TS: Tc-99m human serum albumin blood pool scan diagnosis of an intracardiac myxoma. J Nucl Med 8:35-39, 1967 121. Zaret BL, Hurley PJ, Pitt B: Non-invasive scintiphotographic diagnosis of left atrial myxoma. J Nucl Med 13:81-84, 1972 122. Frisbie JH, Tow DE, Sasahara AA, et al: Noninvasive detection of intracardiac thrombosis-131-l fibrinogen cardiac survey. Circulation 53:988-991, 1976

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