Radionuclide Imaging in Myocardial Sarcoidosis

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development intimal lesions. 14 In complete transposition of the great arteries, we also suggested that the factor responsible fOr the suppression laecliaI hyperbophy is the highly oxygenated blood within tbe pulmonary arteries.• It should be mentioned, howevei; that Wagenwort et al11 reported that the factor responsible i>r atrophy mthe media in complete transposition of the great arteries is the increased pulmonary blood Sow. In the present case, although the right pulmonary blood Sow was almost the same as the left, the media of small pulmonary arteries in the right lung was thinner than that in the left lung. TherefOre, we suggest that the cause ofthe difference in medial hypertrophy between the left and right lungs is not the increased pulmonary blood Sow, but the difference in the nature of the blood within the vessel, ie, difference in oxygen content. We would like to stress that the observation in the present case strongly suggests that the cause of suppressed medial hyperbophy which is characteristic in complete transposition mthe great arteries is the hyperoxic blood in the pulmonary circulation.

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REFERENCES

1 Grlfllths SP, Levine OR, Anderson DH. Aortic origin of right pulmonary artery. Cinlulation 1962; 25:73-84 ! Keane JF, Maltz D, Bernhard WF, Corwin RD, Nadas AS. Anomalous origin of one pulmonary artery from the ascending aorta: cliagnostic, physiological and surgical considerations. Circulation 1974; 50-.588-94 3 Yamaki s. 1ezuka F. QuantitatM analysis of pulmonary vascular disease in complete transposition of the great arteries. Circulation 1976; 54:805-9 4 Yamaki S, Horiuchi T. QuantitlltM analysis of postoperative changes in the pulmonary vucuJatme of patients with complete · transposition of the great arteries and pulmonary hypertension. Am J Cardiol 1979; 44:284-9 5 Yamaki S, 1ezuka F. Quantitatiw evaluation of hypertensive pulmonary arterial change. Acta Pathol Jap 1979; 29:61-6 6 Yamaki S, Horiuchi 'I; Ishimwa E, Mohri H, Fukuda M. Indialtion b total correction of complete transposition of the great arteries with pulmonary hypertension. JThone Cardiovasc Surg 1980; 70:890-S 7 Caudill DR, Helmsworth JA, Daoud G, Kaplan S. Anomalous origin of left pulmonary artery from ascending aorta. J Thone Cardiovasc Surg 1969; 57:493-505 8 \\'igenwort CA, Neufeld HN, Birge RF, Caffrey JA, Edwards JE. Origin of right pulmonary artery from ascending aorta. Cinlulation 1961; 23:84-90 9 Odell JE, Smith JC. Right pulmonary artery arising from ascending aorta. Am J Dis Child 1963; 105:5.l-62 10 Bosenberg HS, Halbnan GL, \\blfe BR, l..aston JR. Origin of the right pulmonary artery from the aorta. Am Heart J 1966; 72:106-15 11 KaidFman SL, YaoAC, Webber CB, Lyn&eldJ. Originoftheright pulmonary artery from the aorta. Am J Cardiol 1967; 19:741-48 U Caro C, Lermanda VC, Lyons HA. Aortic origin of the right pulmonary artery. Br Heart J 1957; 19:3415-52 13 Winshi~ WS, Beck W. Schrine AV. Congenital absence and anomalous origin of the main pulmonary arteries. Br Heart J 1967; 29:34-42 14 Yamaki S, \\'igenwort CA. Plemgenic pulmonary arteriopathy: signi&cance of medial thickness with respect to advanced pulmonary vascular lesions. Am J Pathol 1961; 105:70-5 15 \\'igenwort CA, Nauta J, van der Schaar PJ, Weeda HWH, \\'igenwort N. The pulmonary vucuJatme in complete transposition of the great vessels, judged from lung biopsies. Circulation 1968; 38:746-54

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Radlonucllde Imaging In Myocardial Sarcofdosls*

Damonsballon of Myocardial Uptake of Technellum PyrophOsphal8" and Galllum Met'f)fln B. Forman, M.D.; Marlin P. Sandler, M.D.; Sacb, M.D.; Maroin W. Kronenberg, M.D.; and 77aomaa A Powen, M.D. ~A

A patient had sewre congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was c:on-

&rmed by radionuclide ventriculography, thallium !01 <-0), gallium-61 (17Ga), and technetium-99m Mc) pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process. produces noncaseating granulomata, the morSarcoidosis phologic hallmark of the disease, and these may be

present in virtually every organ of the body. Autopsy studies have revealed myocardial involvement in approximately 25 percent of patients, 1 but cardiac involvement has been extremely difficult to diagnose clinically. Cardiac radionuclide imaging with both thallium and gallium have been used to diagnose myocardial sarcoidosis. M Abnormal technetium pyrophosphate (TcPYP) myocardial accumulation has not been reported previously in this disorder. Recently, we fOund TcPYP accretion in a patient with convincing evidence fOr sarcoid cardiomyopathy, and this patient is the subject of the present report. CASE REPORT

A2:9-yeap.old previously healthy black man presented in 1976with the sudden onset of dyspnea and generalized weakness. He had had no cardiorespiratory symptoms but had been exposed chronically to copper fumes and cigarette smoke. Physical examination was essentially within normal limits. A chest roentgenogram done at this time demonstrated a diffuse reticulaJ'.nodular pattern involving both lung fields, with some volume loss at the apices. No hilar lymphadenopathy was noted, and the cardiac silhouette was normal (Fig lA). Pulmonary function tests showed a moderate restrictive and obstructive wntilatory impairment with no response to bronchodilators. An open lung biopsy specimen revealed noncaseating granulomata compatible with sarcoidosis. Stains and cultures tor tubercle bacilli were negative. The patient was treated with prednisone, 10 mg daily b tour years. There was mild Improvement in the pulmonary function tests with some clearing of the pulmonary infiltrate. Steroids were discontinued, and he remained asymptomatic tor 18 months. Chest roentgenograms during this period always revealed a normal cardiac silhouette. At the age of 36, he noticed the gradual onset of symptoms consistent with biventricular cardiac &ilure. The jugular venous pressure was elevated withlarge "V'' waves, and third

the ])epartments of Medicine (Cardiologr) and Radiology, Veterans Administration Medical Center and Vanderbilt University Medical Center, Nashville, TN. Suooorted in~ by a National Research Service Award (5-1'3! HL 074111) froni the National Heart, Lung and Blood Institute, Bethesda, Maryland. Dr. Forman is a Merck Fell°"" the American College ii Cardiology. &print~: Dr. Kronenberg, Divfafon of Cardiology, Vande,.. blit Medical Center North, NashOllle 37.232 *F~

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F1cuu 1. Serial chest roentgenograms showing initially a ~nodular infiltrate in both lung fields with a normal cardiac silhouette (A), later cardiomegaly with residual lung fibrosis (B). and rourtb heart sounds were present. A pansystolic murmur loudest at the left parastemal border suggestive of tricuspid regurgitation was audible. The chest x-ray film showed marked biventricular enlargement with residual &brosis in the apical and hilar regions (Fig 18). The ECG revealed multifOcal ventricular ectopy, left atrial enlargement, and nonspecific ST-T wave changes. An echocardiogram revealed moderate enlargement of the left ventricle and left atrium. The interventricular septum and posterior left ventricular wall were both markedly hypokinetic. The right ventricle was normal in size. The pericardium appeared thin, and no pericardial effusion was visible. Sdntigraphic Studiea

Gated equilibrium radionuclide ventriculography was pemrmed at rest using in-oWo labeling of red blood cells with stannous pyrophosphate fi:>llowed by intravenous injection of 20 mCi of technetium 99m pertechnetate. Data were acquired using a small &eld-of-vlew camera, a parallel hole collimator; and a minicomputer. The left ventricular ejection fraction was determined using validated system software. Gallium scintigraphy was pemrmed 72 hours after the intravenous injection of 5 mCi of Ga 67 citrate. Images of the thorax were obtained in the anterior and posterior projections on a large &eld-of-vlew camera utilizing the 92 and 1&1 KeV photopeaks. Thallium images were collected immediately, 40 minutes and 2.5 houn after intravenous injection of2 mCi of••n tballous chloride. Anterior, 45° LAO and left lateral Images were obtained on a small field camera using a parallel hole collimator and a 25 pen:ent window centered on the 69-83 KeV mercury x-ray photopeak, stored in a minicomputer using a 64 x 64 matrix and displayed using background subtraction of 20 pen:ent. Myocardial TcPYP scintiphotos were obtained fi>ur hours fi:>llowing the intravenous injection of 20 mCi of-i"c-pyrophosphate with collection of 400,000-oount Images in the anterior; 15° RAO, 45° LAO and left lateral projections using a small field-of-view camera and a general all-purpose parallel hole collimator.

The sdntigraphic results con6rmed further the cliniail impression of a congestive cardiomyopathy secondary to sarooidosis. Radionuclide ventriculography demonstrated biventricular dilatation, diffuse left ventricular hypokinesis, and an ejection fraction of 12 pen:ent at rest. This unusual flndingwu ampli&ed by the myocardial sdntipbotos shown in Figure 2. The 17Ga image (Fig 2A) showed moderate, diffuse myocardial accumulation, and slight uptake in the lungs bilaterally. Both these findings are consistent with an active Inflammatory process. The •111 images revealed multiple Photo: penic defects in the left ventricle in the initial Images, particularly II\ the inferior wall (Fig 2C). There was considerable further uptake by 2.5 hours post-injection (Fig 20). The TcPYP sdntipbotos demonstrated 2 + diffuse myocardial activity consistent with accretion in both ventricles (Fig 28). A diagnosis of sarooid cardiomyopathy was made, and the patient was treated with prednisone, 40 to 60 mg daily. After two months of therapy, the radionuclide ejection fraction had risen to 20 pen:ent, and there was more homogenous uptake of ••n soon after injection. DISCUSSION

Cardiac sarcoidosis may cause congestive cardiomyopathy, heart block. anhythmias, and sudden death. In one study_ sudden death occurred in two-thirds of patients, some Of whom bad no cardiac symptoms. 1 Prior to the advent Of newer imaging modalities, myocardial sarcoidosis might be suspected but could be confirmed only at autopsy. While ecbocardiography and systolic time intervals remain relatively insensitive, radionuclide methods demonstrate great promise. 1 Recently, sarcoid heart disease has been shown to be associated with defects on 1111n scintiphotos, even in those patients without overt cardiac symptoms .... Our patient demonstrated numerous photopenic areas in the left ventricle, and in accordance with other studies, signi&cant improvement on the delayed 1111n images. The explanation i>r this &nding is unclear at present, but it may have high CHEST I 83 I 3 I MM:h, 11183

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F1cuRE 2. Scintigraphic studies demonstrating moderate diffuse 87Ga cardiac uptake (A), 2+ diffuse myocardial TcPYP accretion (B), and multiple photopenic areas soon after 1111n injection at rest (C) which resolve considerably on the delayed image (D). All images are anterior views.

specificity for sarcoidosis in the appropriate clinical setting. Gallium-67 citrate scintiphotos may be abnormal in a number ofcardiac disorders including bacterial endocarditis, pericarditis, tuberculosis, myocardial abscesses, idiopathic cardiomyopathy, myocarditis, and sarcoidosis.u Gallium tends to accumulate in the areas of active inflammation, and its accumulation in myocardial sarcoidosis strongly suggests active myocarditis. Myocardial TcPYP uptake has not been documented previously in myocardial sarcoidosis, but it was prominent in our patient. The precise mechanism of cardiac TcPYP accumulation is not well defined, and most data address myocardial infarction. In acute experimental myocardial infarction, Buja et al8 found that TcPYP accretion paralleled calcium deposition. However, Kronenberg et al' found little calcification in spite of large TcPYP accumulation. Dewanjee et al' documented TcPYP uptake by myocardial cells in the absence of calcium and postulated that it was due to denatured proteins. Myocardial calcification is uncommon in sarcoidosis, 3 and thus, the mechanism appears unrelated to calcium deposition. However, TcPYP uptake is not specific for sarcoidosis, as positive TcPYP images have recently been reported in amyloidosis, systemic sclerosis, and congestive cardiomyopathies of various causes. e.u Our patient had myocardial TcPYP uptake in the presence of sarcoidosis and congestive cardiac failure. Thus, the cause of TcPYP accretion in this instance may be due to either a specific myocardial process related to sarcoidosis or to a less specific process common to other patients with cardiomyopathies. Further studies will be necessary to define the sensitivity of TcPYP in this disorder and to judge the degree of TcPYP accretion in patients without cardiac failure . Nevertheless, a positive scan in the clinical setting of sarcoidosis would be strongly supportive of myocardial involvement, warranting further investigation. There are several potential advantages ofTcPYP scintigraphy compared to 87Ga imaging, since TcPYP images can be obtained rapidly, have high resolution due to using a low energy isotope, are readily available, and are inexpensive. Thus, TcPYP scintiphotos may be a useful screening test in patients with sarcoidosis to detect myocardial involvement, since the disorder occurs mainly in young adults without 580

underlying ischemic heart disease. The improved ejection fraction and thallium uptake after steroid therapy in our patient suggest that these methods may prove useful and convenient for assessing the response to treatment. Additional evaluation is needed to define the most useful methods for the diagnosis and serial follow-up of patients with cardiac sarcoid. REFERENCES 1 Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarooid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 1978; 58:1204-11 2 Kinney EL, Jackson GL, Reeves WC, Zelis R, Beers, E . Thallium-scan myocardial defects and echocardiographic abnol'malities in patients with sarooidosis without clinical cardiac dysfunction. Am J Med 1980; 68:497-503 3 Bulkley BH, Rouleau JR, Whitaker JQ, Strauss HW, Pitt B. The use of 1111Thallium fur myocardial perfusion imaging in sarooid heart disease. Chest 1977; 72:27-32 4 'lll.jima 'I: Naito 'I: Dohi Y, Miyamae T. GA-67 and n-201 imaging in sarooidosis involving the myocardium. Clin Nucl Med 1981; 6:120-21 5 O'Connel JB, Robinson JA, Henkin RE, Gunnar RM. Gallium-67 citrate scanning fur noninvasive detection of inflammation in pericardial diseases. Am J Cardiol 1980; 46:879-84 6 Buja LM, Parkey RW, Stokely EM, Bonte FJ, Willerson JT. Pathophysiology of technetium-99m stannous pyrophosphate and thallium 201 scintigraphy of acute anterior myocardial in&rcts in dogs. J Clin Invest 1976; 57:1508-22 7 Kronenberg MW, Ettinger UR, Wilson GA, Schenk EA, Cohen J. A comparison of radiotracer and biochemical methods fur the quantitation of experimental myocardial infarct weight: in vitro relationships. J Nucl Med 1979; 20:224-31 8 Dewanjee MK, Kahn PC. Mechanism of localization of-rclabeled pyrophosphate and tetracycline in infarcted myocardium. J Nucl Med 1976; 17:639-46 9 Sobol SM, Brown JM, Bunker SR, Patel J, Lull RJ. Noninvasive diagnosis of cardiac amyloidosis by technetium-99mpyrophosphate myocardial scintigraphy. Am Heart J 1982;

103:563-66 10 Duska F, Bradna P, Novak J, Kubicek J, Vizda J, Kafka P, et al. Pyrophosphate heart scan in patients with systemic sclerosis. Br Heart J 1972; 47:90-3 11 Ahmad M, Dubiel JP, Logan KW, Verdon TA, Martin RH. Limited clinical diagnostic specificity of technetium-99m stannous pyrophosphate myocardial imaging in acute myocardial infarction. Am J Cardiol 1977; 39:50-4 Rlldlonucllde Imaging In Myoc:ardlal San:oldolll (Forman et el)