MISCELLANEOUS

Thallium-201 Stress Scintigraphy in Takayasu Arteritis

Yuji Hashimoto, MD, Fuji0 Numano, MD, Yoshiaki Maruyama, MD, Toshiyuki Oniki, MD, Kenji Kasuya, MD, Tsunekazu Kakuta, MD,

Tomoko Wada, MD, Michiyoshi Yajima, MD, and Hidenori Maezawa, MD

Thirty-eight women with Takayasu arteritis were studied using thallium-201 stress myocar- dial scintigraphy to assess the prevalence and pathophysiology of the perfusion abnormality. Twenty (53%) had abnormal scintigraphic find- ings (group A). Abnormal scans were divided into 3 groups: permanent defects in 6, reversible defects in 7 and slow washout in 7. The remain- ing 18 patients had normal scintigrams (group N). Group A had a tendency to be older and to have a high prevalence of complicated significant aortic regurgitation. Interventricular thickness plus left ventricular posterior wall thickness (26 f 7 vs 17 f 2 mm, p <O.Ol) and left ventricular mass (267 f 121 vs 133 f 39 g, p <O.Ol) were all greater in group A on echocardiography. The mean value of the central aortic pressure in sys- tole was 170 f 15 mm Hg in the 7 catheterized patients in group A. Coronary ostial stenoses were present in 2 group A patients who showed reversible defects on scintigrams. These data in- dicate that the abnormal perfusion detected by imaging in patients with Takayasu arteritis was responsible for a decrease in coronary reserve or myocardial damage, or both, due to long-stand- ing systemic hypertension or aortic regurgita- tion. Coronary artery disease should be consid- ered if a reversible defect is present.

(Am J Cardiol 1991;67:879-662)

From the Third Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan. Manuscript re- ceived September 24, 1990; revised manuscript received and accepted January 2, 1991.

Address for reprints: Yuji Hashimoto, MD, the Third Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, l-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan.

T akayasu arteritis is a nonspecific vasculitis that affects the aorta and its major branches, includ- ing coronary and pulmonary arteries. l Epidemi-

ologic studies show that Takayasu arteritis is frequent in Asia and South America. This finding leads to the speculation that genetic or racial factors may be in- volved in Takayasu arteritis.2m4 In patients with Ta- kayasu arteritis, congestive heart failure or lethal ar- rhythmias and sudden death are the most frequent causes of death.‘J

It has recently been reported that, in addition to cor- onary artery disease, several other heart diseases may result in thallium perfusion abnormalities. Several in- vestigations have been conducted on cardiac involve- ment in Takayasu arteritis by using cardiac catheter- ization or echocardiography.6-s Our objective was to in- vestigate the myocardium of patients with Takayasu arteritis using thallium-201 stress scintigraphy.

METHODS Patients: Thirty-eight women ranging in age from

24 to 72 years comprised the group with Takayasu ar- teritis. In all patients, the diagnosis of Takayasu arteri- tis was established by clinical and angiographic data.9 Patients continued to receive their usual medical treat- ment throughout the study.

Thallium-201 imaging: Thirty-eight patients under- went thallium-201 stress myocardial scintigraphy.lOJ l Of these, 27 exercised on an upright bicycle ergometer. The remaining 11 older or “pulseless” patients received an infusion of dipyridamole.

EXERCISE: Exercise testing was performed with a multistage bicycle ergometer using the symptom-limit- ed method. The work load, which began at 2.5 W, was increased by 25 W every 3 minutes. Exercise continued for 1 minute after the intravenous injection of 111 MBq of thallium-201 at the end point. Exercise was discontinued when patients developed angina, ischemic ST depression on the electrocardiogram, serious ar- rhythmia, dyspnea or leg fatigue. The 12-lead electro- cardiogram was monitored during exercise and blood pressure recorded every 3 minutes.

THE AMERICAN JOURNAL OF CARDIOLOGY APRIL 15, 1991 879

DIPYRIDAMOLE: After the intravenous infusion of di- pyridamole (0.568 mg/kg) for 4 minutes, patients re- ceived an intravenous injection of 111 MBq of thalli- um-201. The electrocardiogram and blood pressure were monitored as during the previous exercise testing.

THALLIUM-201 EMISSION COMPUTED TOMOGRAPHY: Ac- quisition of thallium images was begun immediately af- ter exercise or 9 minutes after the dipyridamole infu- sion. Patients were imaged using a rotational gamma camera (Hitachi RC150DT) equipped with a low-ener- gy, all-purpose parallel hole collimator. A total of 32 projections were obtained for 30 seconds in a 180” arc extending from the 45’ right anterior oblique to the left posterior oblique projection. A 20% energy window was centered on the 80-keV x-ray peak. All projections were stored on a magnetic disk using a 64 X 64, 16-bit computer matrix.

After correction for nonuniformity and center of ro- tation, contiguous transaxial tomograms encompassing the entire heart were reconstructed after filtered back projection with a Chesler filter. Then, using the left ventricular long axis as a reference, the images were constructed into short-axis, horizontal long-axis and vertical long-axis tomograms (oblique images). Delayed images were acquired and constructed in the same pro- jections 3 hours later. Both during stress and at redistri- bution, each short-axis cut was divided into 60 seg- ments of 60 equidistant radii. Maximal count circum- ferential profiles for each cut were then generated from the apical to the basal cut. The values were then nor- malized to the highest value found in each slice and expressed as a circumferential profile curve to represent myocardial thallium distribution. Similarly, the thalli- um washout rate of each myocardial segment of the entire left ventricle was calculated and plotted as the washout rate curve: washout rate = (initial count-de- layed count/initial count) X 100. Permanent and re- versible defects were distinguished by evaluation of both visual inspection and the quantification of the cir- cumferential profiles. Slow washout was defined as fall- ing below the lower limit of normal without any defects on stress. Tomographic images were interpreted by consensus of 2 observers who had no knowledge of the clinical findings.

Scalar (124ead) electrocardiography: Supine, rest- ing 1Zlead electrocardiograms were examined in the 38 patients on the day of scintigraphy. Electrocardio- graphic left ventricular hypertrophy was defined by the Romhilt-Estes criteria. Myocardial ischemia was de- fined as >O.l mV of ST depression in Vs or Vg.

Echocardiographic studies: Echocardiographic data were obtained from a commercially available imaging system with Doppler capability (Toshiba SSH- 160A equipped with a 2.5- or 3.75-MHz transducer). Two-

880 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67

dimensional images oriented the ultrasonic beam for the best M-mode recordings of the left ventricles. Mea- surements of left ventricular end-diastolic and end-sys- tolic dimensions, and wall thickness (inter-ventricular septal thickness + left ventricular posterior wall thick- ness) were performed from M-mode echocardiograms. Technically adequate recordings were obtained in 33 of the 38 patients (87%). Left ventricular mass was ob- tained using the formula of Devereux et al. t2 The sever- ity of aortic regurgitation was assessed by the flow mapping technique on conventional pulsed and color Doppler echocardiography.

Cardiac catheterization: Cardiac catheterization and coronary cineangiography were performed in 9 pa- tients using standard techniques.

Statistical analysis: Data were compared using Fisher’s exact test or the unpaired t test. Statistical sig- nificance refers to a p value <0.05.

RESULTS Thallium-201 emission computed tomography:

Scintigraphic abnormalities were identified in 20 of the 38 patients (53%) with Takayasu arteritis. Permanent defects were observed in 6 patients (Figure 1 ), revers- ible defects in 7 (Figure 2) and slow washout in 7. The differences between patients with perfusion abnormali- ties (group A) and those with normal scintigrams (group N) were then compared.

Comparison of group A versus B (Table I): AGE: The mean age of group A was 48 f 13 (mean i standard deviation) years and that of group N was 41 f 8 years. Group A tended to be older but not to a statistically significant extent. There was no significant difference in body surface area between the 2 groups.

ELECTROCARDIOGRAMS: Left ventricular hypertrophy or ischemic ST depression was evident in 13 group A (65%) and in 2 group B (11%) patients. Electrocardio- graphic abnormalities were significantly more frequent in group A than in group N (p <O.Ol ).

M-MODE ECHOCARDIOGRAPHIC DATA: Wall thickness (26 f 7 vs 17 f 2 mm, p <O.Ol ) and left ventricular mass (267 z!= 121 vs 133 f 39 g, p <O.Ol) were signifi- cantly greater in group A than in group N (Figure 3). These echocardiographic data suggest that the group A patients had left ventricular hypertrophy with normal contractility.

PRESENCEOFAORTICREGURGITATION: Eight of the 20 group A patients (40%) had significant aortic regurgi- tation, whereas only 3 of the 18 group N patients (17%) had this complication. However, the difference was not statistically significant.

PRESSUREOFTHEASCENDINGAORTA(CENTRALAORTIC

PRESSURE): Cardiac catheterization was conducted in 7 group A patients, 5 of whom had significant aortic re-

gurgitation. The mean value of the central aortic pres- sure in group A was 170 f 15 mm Hg in systole and 60 f 13 mm Hg in diastole.

CORONARY ARTERY LESIONS: We were able to examine coronary artery stenoses in 8 group A and 2 group N patients. This lesion was diagnosed in 2 group A pa- tients at autopsy. Significant stenoses were present in only 2 of the subjects in group A. One, a 72-year-old woman, had a 99% diameter stenosis of the right coro-

FIGURE 1. Stress (leff] and redistribution (righfj images ob- tained in a 48-year-old woman with normal coronary arteries. The short-axis images and the cireumferentiil profile curves (bottom] obviously demonstrated a permanent defect in the anteroseptal wall.

--- FIGURE 2. Stress 1 ff) and r( isttibution (right) images ob- tained in a 72-year-old woman with a 99% diameter stenosis of the right coronary ostium. The short-axis images and the clrcumferentlal profile curves (bottom) show a typical revers- ible defect in the inferoposterior wall.

nary ostium and a 75% diameter stenosis of the left anterior descending artery. The other, a 53-year-old woman, had a 99% diameter stenosis of the right coro- nary ostium. These ostial stenoses were thought to re- flect the coronary involvement of Takayasu arteritis.

Mortality: The 2 patients in group A died suddenly during the study. The cause of death was thought to be ventricular arrhythmia.

DISCUSSION The usefulness of evaluating ischemic heart disease

by thallium-201 stress scintigraphy has been estab- lished. It has been reported that several heart diseases, in addition to coronary artery disease, have abnormal scintigraphic findings. I 3-1 *

Pfisterer et alI3 reported that 12 of 17 patients with predominant aortic regurgitation had distinct left ven- tricular apical defects during exercise despite normal coronary arteries. They concluded that changes in left ventricular geometry and contraction pattern by vol- ume overload might cause perfusion abnormalities. I9

Schulman et alI4 performed stress imaging in hyper- tensive patients, and found that 29% of those with a low risk of coronary disease had abnormal thallium-201

TABLE I Comparison of Group A and Group N

Group A Group N

LVH or ischemic STchange on ECG (n = 38)

13* 2

Echocardiographic parameters (n = 33) LVDd (mm) 46+6 4455 LVDs (mm) 28f6 27f4 %FS (%) 39i7 39f6

w(mm) 26 17f2

LVM @ 267f121’ 133f39 Aortlc regurgitation (n = 38) 8 3 Hemodynamics (n = 7)

sAoP (mm Hg) 170f15 - dAoP (mm Hg) 60f13 - LVEDP (mm Hg) 14f4 -

* p<o.o1. ECG = ekctrocardlogram; %FS = percent fractional shortening: LVDd = left ven-

tricular enddlastokc dimension: LVDs = left ventricular end-systolic dnnens!on; LVEDP = left ventricular enddlastolic pressure; LVH = left ventricular hypertrophy; LVM = left ventricular mass: sAoP & dAoP = central aorttc pressure in systole and in d!astok: Wf = interventricular thickness plus ventricular posterw wall thickness.

WT (..) LVM (9)

30- -P<O.O11 300 - r-P<O.Ol-

20 - 200 - 1

lo- loo-

Group A Group N Group A Group N

FIGURE 3. Wall thickness (WT) and left ventricular mass (LVM) were significantly greater in group A than in group N.

THE AMERICAN JOURNAL OF CARDIOLOGY APRIL 15, 1991 881

stress images. They considered the possibility that un- detected coronary artery disease, an increased oxygen demand caused by increased left ventricular mass and inadequate coronary reserve may be related. O’Gara et aIt5 found that 41 of 72 patients (57%) with hypertro- phic cardiomyopathy demonstrated abnormalities in myocardial perfusion on thallium-201 emission com- puted tomography. Their patients were considered to be free of coronary artery disease. They concluded that myocardial ischemia in hypertrophic cardiomyopathy may result from one or more mechanisms, including an inadequate capillary density relative to the increased myocardial mass, impaired left ventricular relaxation, or abnormalities of the small intramyocardial coronary arteries. Positive scintigraphic scans were demonstrated by von Dohlen et all6 in 11 of 28 subjects (38%) with hypertrophic cardiomyopathy, despite normal epicardi- al coronary arteries. In their patients, left ventricular wall thickness was greater, left ventricular ejection frac- tion was lower and ventricular tachycardia was more frequent in those with thallium perfusion abnormalities than in those with normal scans. These investigators confirmed that myocardial ischemia, myocardial fibro- sis, or both, were responsible for the abnormalities.

We observed that 20 of our 38 patients (53%) with Takayasu arteritis had a perfusion defect or a slow washout. Electrocardiographic abnormalities were more frequent in group A than group N. Wall thickness and left ventricular mass were greater in group A than group N. Complicated significant aortic regurgitation tended to be more common in group A than group N. The sites of the perfusion abnormalities are shown in the various portions of the left ventricle. We could not adequately examine the correlation between perfusion abnormalities and epicardial coronary artery disease, including ostial stenosis. It was reported that about 10% of patients with Takayasu arteritis had coronary artery involvement. l Coronary lesions were found in 2 of the 8 patients in group A: 1 had a 99% diameter stenosis of the right coronary ostium and the other had a 99% diameter stenosis of the right coronary ostium with a 75% diameter stenosis of the left anterior descending artery. Both patients had reversible defects in areas of the right coronary artery. Peripheral blood pressure of- ten cannot be measured adequately in patients with Ta- kayasu arteritis because of stenotic or occlusive lesions of the major aortic branches. One should obtain the central aortic pressure to evaluate the afterload to the left ventricle. Nevertheless, in our patients, we could not obtain adequate pressure data. The mean central aortic pressure in systole in the 7 group A patients was 170 mm Hg. We believe that systemic hypertension plays an important role in the development of left ven- tricular impairment.

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It is reasonable to think that abnormal scintigraphic findings are responsible for a decrease in coronary re- serve, myocardial damage, or both, due to long-stand- ing systemic hypertension or to aortic regurgitation. On the other hand, an epicardial or ostial coronary lesion should be considered when a typical reversible defect is revealed. There are a few cases of Takayasu arteritis with myocarditis. 2o In >10 cases autopsied, however, we have not seen any evidence of myocarditis.

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