Diagnostic and Prognostic Value of Myocardial Scintigraphy With Thallium-201 and Gallium-67 in Cardiac Sarcoidosis

Kenichi Okayama, Chinori Kurata, Kei Tawarahara, Yasushi Wakabayashi, Kingo Chida and Atsuhiko Sato Chest 1995;107;330-334 DOI 10.1378/chest.107.2.330 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/107/2/330

Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1995by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

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Diagnostic and Prognostic Value of Myocardial Scintigraphy With Thallium201 and Gallium-67 in Cardiac Sarcoidosis*
Kenichi Okayama, MD; Chinori Kurata, MD; Kei Tawarahara, MD; Yasushi Wakabayashi, MD; Kingo Chida, MD; and Atsuhiko Sato, MD, FCCP Study objective: To examine the diagnostic and prognostic value of myocardial scintigraphy using thallium201 and gallium-67 in cardiac sarcoidosis. Patients: Twenty-five patients with sarcoidosis. Methods: All patients underwent myocardial thallium201 scintigraphy. Six patients with myocardial thallium201 defects were classified into group A and another 19 without defects were classified into group B. Between
group A and B, we compared the results of other noninvasive examinations, including standard 12-lead ECG, 24 h ambulatory ECG, chest radiography, measurements of serum angiotensin-converting enzyme (ACE) and lysozyme levels, and gallium-67 scintigraphy. Results: Proportions of subjects who had varying degrees of heart block, severe ventricular arrhythmias (more than or equal to third grade of Lown's classification), and high levels of serum ACE and lysozyme levels were not different between these two groups (p>0.05). Although an enlarged cardiothoracic ratio was more frequent in group A (p<0.05), bilateral hilar lymphadenopathy was more frequent in group B (p<0.01). Four patients of group A and 15 of group B underwent gallium-67 scintigraphy. Although no subjects of group B had

myocardial uptake of gallium-67, two of four group A patients showed cardiac uptake. These four group A patients were treated with corticosteroids. The therapy provided clinical and scintigraphic improvement in two patients with myocardial gallium-67 uptake, although it did no improvement in the other two patients without

gallium-67 uptake.
Conclusions: When cardiac sarcoidosis was diagnosed according to myocardial thallium-201 defects, other
noninvasive examinations were not useful to detect this disease. However, gallium-67 uptake may predict the efficacy of corticosteroids. Thus, the combination of thallium-201 and gallium-67 scintigraphy may be useful not only in diagnosis of cardiac sarcoidosis but also in prediction of effects of corticosteroids. (Chest 1995; 107:330-34)
ACE=angiotensin-converting enzyme; BHL=bilateral hilar lymphadenopathy; CTR=cardiothoracic ratio

Key words: cardiac sarcoidosis; gallium-67; myocardial scintigraphy; thallium-201

Sarcoidosis is a multisystem disorder of unknown etiology. Although the organ most frequently affected is the lung, all parts of the body can be affected. Overall the prognosis is good because organ involvement is usually asymptomatic and the disease is often self-limiting."12 Cardiac sarcoidosis, however, sometimes causes fatal ventricular tachyarrhythmias or conduction block,3'4 and retrospective studies have revealed myocardial involvement in approximately 25% of these patients.5 Diagnosis of myocardial involvement of sarcoidosis during life is difficult because clinical evidence of myocardial involvement is apparent in only 5% of the patients.3'4'5 It is particularly required to diagnose cardiac sarcoidosis within an asymptomatic stage because sudden death is the most common manifestation of this disease.4'6 Endomyocardial biopsy may be essential for establishing
*From the Third and Second Departments of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. Manuscript received April 29, 1994; revision accepted June 8. Reprint requests: Dr. Okayama, Third Dept. of Internal Medicine, Hamamatsu University, 3600 Handa-Cho, Hamamatsu, 431-31 Japan

the diagnosis of cardiac sarcoidosis. However, it is invasive and may lack sensitivity because myocardial involvement is not homogeneous. Negative biopsy findings therefore do not exclude cardiac sarcoidosis, although abnormal findings are diagnostic.3'4'7

sarcoidosis.11"2

Myocardial scintigraphy with thallium-201 has been used in patients with suspected cardiac sarcoidosis.3'4'8'9 Segmental areas with thallium-201 defects correspond to areas of fibrogranulomatous replacement.6 Gallium-67 imaging also has been used to detect organ involvements, including myocardium.1'10 Its uptake suggests myocardial infiltration by sarcoidosis. The combination of thallium-201 and gallium-67 myocardial scintigraphy may provide more information about myocardial involvement of

Myocardial involvement appears to be an indication for corticosteroid hormone therapy, regardless of the severity of the systemic disease.3 Effect of this therapy, however, varies from excellent to poor. Accumulation of gallium-67 is considered as an indicator of inflammatory change. A large dose of corti-

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Myocardial Scintigraphy With TI-201 and Ga-67 in Sarcoidosis (Okayama et al) Downloaded from chestjournal.chestpubs.org at Ohio State University on March 4, 2011 1995, by the American College of Chest Physicians

costeroids is approved to decrease the accumulation of gallium-67 in patients with pulmonary sarcoidosis.10 Patients with myocardial gallium-67 uptake may therefore be responsive to corticosteroid therapy. In this study, we examined whether myocardial thallium-201 scintigraphy can play a significant role independently of other noninvasive examinations in the diagnosis of myocardial sarcoidosis and whether gallium-67 scintigraphy can predict the effect of corticosteroids on myocardial sarcoidosis.
METHODS
A patient population consisted of 25 patients who underwent thallium-201 scintigraphy in our hospital between 1988 and 1992. Sarcoidosis was diagnosed by pulmonologists in all patients except one whose condition was diagnosed by dermatologists on skin biopsy specimen. All the patients had no history of ischemic heart disease and no evidence of previous myocardial infarction on resting ECG. Myocardial thallium-201 scintigraphy was performed in all patients. After an overnight fast, 111 MBq of thallium-201 was injected intravenously in an upright position and single photon emission computed tomography was begun 5 min later. The tomographic images of vertical long axis, horizontal long axis, and short axis were reconstructed. Segmental uptakes were graded visually as follows: grade 0, severely reduced; grade 1, moderately reduced; grade 2, mildly reduced; and grade 3, intact uptake. We regarded the uptake less than or equal to grade 2 as an abnormal myocardial defect. All patients with myocardial defects on thallium-201 scintigraphy underwent coronary angiography and showed normal coronary arteries. Noninvasive examinations, including chest radiography, ECG, ambulatory ECG, and measurements of serum angiotensin-converting enzyme (ACE) and lysozyme levels were evaluated. Myocardial imaging with 111 MBq of gallium-67 was performed in 21 patients. If myocardial gallium-67 uptake was found on planar image, myocardial single photon emission computed tomography was performed. Twenty-five patients were classified into two groups according to the presence or absence of defects of myocardial thallium-201 scintigraphy. Six patients showed thallium-201 defects (group A) and the other 19 showed no defects (group B). Between group A and B, we compared the frequencies of enlarged cardiothoracic ratio (CTR) (>50%) or bilateral hilar lymphadenopathy (BHL) on chest radiographs, any kind of ventricular arrhythmias and varying degree of heart block on ECG, severe ventricular arrhythmias more than or equal to third grade of Lown's classification on ambulatory ECG, myocardial gallium-67 uptake, and serum ACE and lysozyme levels. Four patients of group A were treated with prednisolone, 50 to 60 mg/d followed by gradual tapering to a maintenance dose of 20 to 30 mg every other day. Three or four months later, they had myocardial scintigraphy with thallium-201 and gallium-67 again. The procedure was exactly as for the earlier studies. Differences between these two groups were examined by Student's t test or x2 test. The ACE and lysozyme levels were expressed as mean standard deviation.

(p>0.05). The proportion of the patients with an enlarged CTR on chest radiographs was significantly higher in group A than in group B (p<0.05). Conversely, the proportion of BHL was significantly lower in group A than in group B (p<0.01) (Table 3). Two patients of group A had abnormal gallium-67 uptakes in the heart. On tomographic imaging, the myocardial regions with gallium-67 uptake corresponded to those with thallium-201 defects. Four of six patients of group A were treated with corticosteroids. Two patients with myocardial gallium-67 uptakes showed excellent clinical improvement associated with disappearance of myocardial gallium-67 uptakes and reduction of thallium-201 defects. The other two patients without myocardial gallium-67 uptake did not show any improvement despite high-dose corticosteroid therapy (Table 4).
DISCUSSION

In this study, when cardiac involvements of sarcoidosis were diagnosed according to the findings of myocardial thallium-201 scintigraphy, other findings of noninvasive examinations, including BHL, any kind of conduction block, ventricular arrhythmias, and serum ACE and lysozyme levels were not useful for detecting cardiac sarcoidosis. Although the freTab le 1-Patient Data (1)

Patient/
Age, yr/ Sex

Myocardial Defects of Thallium-201

Patchy Patchy Patchy
Anterior

Myocardial Uptakes of Gallium-67

Group A

1/80/F 2/71/F 3/66/F 4/58/F 5/65/F 6/34/F

Group B

Patchy
Anterior

Patchy
Anterior

RESULTS

A summary of the clinical findings is presented in Tables 1 and 2. The proportions of the patients with any kind of abnormalities on ECG and ambulatory ECg, and mean levels of serum ACE and lysozyme were not significantly different between two groups

7/71/F 8/71/F 9/56/F 10/69/M 11/45/M 12/30/F 13/53/F 14/34/M 15/51/F 16/37/F 17/42/M 18/29/F 19/42/M 20/52/M 21/30/M 22/69/F 23/58/F 24/28/M 25/36/M *NP=not performed.

NP*

NP NP NP

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331

Table 2-Patient Data (2)*

Patient Group A 1 2 3 4 5 6 Group B 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

CTR, %
58 72 56 <50 55 <50

BHL
+ + + + + + + + + + + + + + + + + +

ECG
Normal Normal Normal 3rd AVB VPC Normal
Ist AVB VPC Normal Normal Normal VPC Normal 2nd AVB VPC Normal Normal Normal Normal Normal VT Normal Normal Normal Normal

Lown's Grade 1 2 4 4 4 2
3 1 NP 1 NP 2 NP NP 2 1 1 NP 1 1 4 1 1 1 1

ACE, IU/L
14.6 20.5 18.1 51.4 19.8 23.0
37.1 31.3 103 12.1 11.5 19.5 26.6 35.7 76.3 25.4 15.0 12.2 21.2 73.0 16.6 23.9 31.6 25.6 19.5

Lysozyme, ,ug/L
9.0 13.6 14.9 15.4 23.5 50.7
NM 10.7 NM 13.4 10.5 10.4 14.3 NM 27.1 NM 14.2 10.6 NM NM 13.1 14.7 13.9 10.2 11.3

70 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50

*AVB=atrioventricular block; VPC=ventricular premature contraction; VT=ventricular tachycardia; NP=not performed; NM=not measured.

quency of an enlarged CTR was significantly higher in group A (consisting of patients with myocardial

thallium-201 defects), the findings of enlarged CTR enough to detect cardiac sarcoidosis in the early stage. Furthermore, myocardial gallium-67 uptake could predict the effects of corticosteroid
were not

therapy.
Usefulness of myocardial thallium-201 imaging in detection of myocardial involvement is already admitted in patients with suspected cardiac sarcoidosis.3'4,8'9,13 In this study, we classified the patients on the basis of myocardial thallium-201 scintigraphy. Thallium 201 defects in the myocardium are not specific to sarcoidosis and may occur with ischemic heart disease or other cardiomyopathies. It is necessary to exclude these diseases by history taking, ECG, echocardiography, or coronary angiography. No patients of group A had any evidence of these diseases and the sites of thallium-201 defects did not correspond to the anatomic structure of coronary arteries. The probability that other diseases except cardiac sarcoidosis might cause the defects, therefore, is very low. In consideration of the existence of systemic sarcoidosis and acute onset of their symptoms, we regarded group A as patients with cardiac sarcoidoSiS.

tions of the patients with enlarged CTR were higher in group A. Cardiomegaly, however, is considered to occur following broad cardiac involvement of sarcoid. In this study, four patients with patchy defects on myocardial thallium-201 imaging showed a CTR over 50%. Conversely, two patients with a single defect had a CTR under 50%. The diagnosis based on an enlarged CTR may be too late to prevent cardiac

accidents. The finding of BHL is the hallmark of sarcoidosis though it may be observed in lymphoma, tuberculosis, or bronchogenic carcinoma.1'2 In our study, all group B patients except one showed BHL while no group A patients had this manifestation. However, a patient with cardiac sarcoidosis with BHL was preTable 3-Comparison of Noninvasive Examinations of Patients Between Two Groups*
Group A (n=6)
Mean age, yr

Group B (n=19)
48 + 14.7

Difference NS

6214.3

Enlarged CTR (%)

BHL (%)

Chest radiography may show mild to moderate cardiomegaly in cardiac sarcoidosis.1'4"14 It is, however, a nonspecific finding. In our study, the propor332

Abnormal ECG (%) Severe VPC on AECG (%) Serum ACE Serum lysozyme

4/6 (66) 0/6 (0) 2/6 (33) 3/6 (50)

24.6 13.4 21.2+15.2

1/19 (5) 18/19 (95) 6/19 (32) 2/19 (11)

32.5 24.8 15.24.6

p<O.05 p<O.Ol
NS NS

NS NS

*VPC=ventricular premature contraction; AECG=ambulatory electrocardiogram; NS=not significant.

Myocardial Scintigraphy With TI-201 and Ga-67 in Sarcoidosis (Okayama et al) Downloaded from chestjournal.chestpubs.org at Ohio State University on March 4, 2011 1995, by the American College of Chest Physicians

Table 4-Effects of Corticosteroids

Before Steroid Therapy
Patient
Group A
3 4 5 6
+ + + +

After Steroid Therapy Myocardial Defects of Thallium-201

Myocardial Uptakes of Gallium-67
Clinical Course

Myocardial Defects of Thallium-201

Myocardial Uptakes of Gallium-67

+ + -

Reduced Reduced No change No change

Disappeared Disappeared

Improved Improved Dead No change

sented in a previous report.14 Further studies are needed to examine this tendency for the frequency of BHL to be decreased in patients with cardiac sarcoidosis. As many as 50% of patients with cardiac sarcoidosis have ECG abnormalities of rhythm, conduction, and repolarization.34 These abnormalities commonly occur without cardiac symptoms.3 In our study, the frequency of patients with any kind of conduction block or ventricular arrhythmias was not significantly different between two groups. Standard ECG may fail to detect these abnormalities because arrhythmias are often paroxysmal and conduction abnormalities may vary. Although serial ECG may show varying conduction abnormalities, it is still difficult to detect paroxysmal arrhythmias. If we diagnosed cardiac sarcoidosis on the basis of ECG, 2 group A patients might be regarded as abnormal (sensitivity: 33%) and 14 group B patients might be regarded as normal (specificity: 71%). The sensitivity is too low to detect cardiac sarcoidosis. Furthermore, it is desirable to detect this disease before appearance of these ECG abnormalities, because arrhythmias are often refractory to any medication and because atrioventricular block may require implantation of permanent pacemaker.3'4 A lesion of cardiac sarcoidosis might be too small to be detectable on thallium-201 scintigraphy in our group B patients. Although corticosteroids were not indicated in such patients with isolated, asymptomatic ECG abnormalities, these patients who had ECG abnormalities but no myocardial thallium-201 defects must be observed carefully. Ambulatory ECG is useful to detect paroxysmal arrhythmias and intermittent conduction block.3 In our study, we regarded ventricular arrhythmias of more than or equal to third grade of Lown's classification as "severe." In this case, the sensitivity and specificity were 50% and 89%, respectively. Half of group A patients did not show "severe" ventricular arrhythmias despite obvious defects on myocardial thallium-201 scintigraphy. These false-negative cases may give a negative assessment of this examination because of its low sensitivity. Measurement of serum ACE levels may be useful

in supporting the diagnosis of sarcoidosis and in assessing the results of corticosteroid therapy.12 In our study, mean levels of serum ACE and lysozyme were not different between the two groups. Measurement of these enzymes, therefore, may not be useful to detect myocardial involvements of sarcoidosis. Gallium-67 scintigraphy is also used to diagnose myocardial involvements of sarcoidosis.15 In our study, half the patients with cardiac sarcoidosis had no myocardial gallium-67 uptakes and they were not responsive to corticosteroid therapy. Such a lack of gallium-67 uptake in the region with thallium-201 defect may indicate the lesion of myocardial involvement of sarcoidosis without active inflammation and may therefore show a poor response to corticosteroids. Alberts et al'0 demonstrated that a large dose of corticosteroids decreased the accumulation of gallium-67 in the pulmonary parenchyma and hilum in patients with pulmonary sarcoidosis. O'Connell et al'6 showed that gallium-67 scintigraphy may be an indicator of inflammatory changes to guide the use of immunosuppressive agents such as prednisolone and azathioprine in patients with congestive cardiomyopathy. When these results apply to cardiac sarcoidosis, the patients with myocardial gallium-67 uptake may be responsive to corticosteroid therapy. These hypotheses were compatible with our results. Conversely, the patients without gallium-67 uptake may have no active inflammation and may not be responsive to corticosteroid therapy. Myocardial gallium-67 scintigraphy may therefore be useful to predict the effect of corticosteroid therapy. In conclusion, the diagnosis of cardiac sarcoidosis with enlarged CTR, ventricular arrhythmias, or heart block may be too late to prevent cardiac accidents, because these cardiac signs are based on the permanent myocardial derangements that often do not improve with corticosteroid therapy. Myocardial thallium-201 scintigraphy must therefore be performed whenever the diagnosis of cardiac sarcoidosis is suspected. Patients with myocardial gallium-67 uptake may be responsive to corticosteroid therapy. Thus, the combination of thallium-201 and gallium-67 myocardial scintigraphy is useful in the diagnosis of cardiac sarcoidosis and the prediction of re333

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sponse

to corticosteroid therapy.

9 Kinney EL, Jackson GL, Reeves WC, Zelis R, Beers E. Thallium

scan

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Diagnostic and Prognostic Value of Myocardial Scintigraphy With Thallium-201 and Gallium-67 in Cardiac Sarcoidosis Kenichi Okayama, Chinori Kurata, Kei Tawarahara, Yasushi Wakabayashi, Kingo Chida and Atsuhiko Sato Chest 1995;107; 330-334 DOI 10.1378/chest.107.2.330 This information is current as of March 4, 2011
Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/107/2/330 Cited Bys This article has been cited by 12 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/107/2/330#related-urls Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.

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