CASE REPORT Annals of Nuclear Medicine Vol. 7, No. 4, 273-276, 1993 A patient with cardiac amyloidosis presenting a rapid increase in technetium-99m-hydroxymethylene diphosphonate accumulation Takamasa KOBAYASHI, Michihito SEKIYA, Yasushi FUJIWARA, Takumi SUMIMOTO, Hiroshi MATSUOKA, Mareomi HAMADA and Kunio HIWADA Second Department oflnternal Medicine, Ehime University School ofMedicine, Ehime, Japan We assessed the changes in cardiac condition in a patient with cardiac amyloidosis, by means of dual nuclei single photon emission computed tomographic (SPECT) images with technetium-99m-hydroxymethylene diphosphonate (99*Tc-HMDP) and thallium-201 (2ouT1). Dual SPECT showed a marked increase in myocardial 99*TC-HMDP accumulation along with deterioration of symptoms and signs, while 201Tl scintigraphy remained almost unchanges. Key words: cardiac amyloidosis, scintigraphy, 99mTc-HMDP, 201Tl INTRODUCTION THE CARDIAC manifestations in primary amyloidosis vary depending on the area and the severity of amyloid deposition into the heart.1 Echocardiogra-phy is usually used to diagnose cardiac amyloidosis noninvasively,2,3 but in patients with advanced cardiac amyloidosis there is no significant echo-cardiographic change during the follow-up study.4 Recently scintigraphy with technetium-99m-1abeled phosphates has been used for the diagnosis of cardiac amyloidosis.5~7 However, there are few reports on the progression of cardiac amyloidosis detected by technetium-99m-labeled phosphates scintigra phy. In this report, we present a patient with primary amyloidosis involving the heart. Myocardial accumu-lation of technetium-99m-hydroxymethylene diphos-phonate (99mTc-HMDP) increased as symptoms and signs deteriorated during a 3 month follow-up, while thallium-201 (201T1) scintigraphic and echocardiog-raphic findings remained unchanged in this period. CASE REPORT A 69-year-old man was admitted to our hospital because of dyspnea. One year before admission, he noticed edema in the lower extremities. Then short-ness of breath on exertion appeared and rapidly deteriorated. On admission he was in New York Heart Association functional stage 111. Biopsy specimens from the duodenal mucosa revealed abundant amyloid deposits, and Congo red staining after treatment of amyloid deposits with potassium permanganate suggested the amyloidosis related to AL protein. There were no relatives known to be affected with amyloidosis. He had not experienced myocardial infarction. Physical examination revealed a blood pressure of 80/60 mmHg and a heart rate of 85 beats/minute. The chest X-ray film showed enlargement of the heart (cardiothoracic ratio 63%) and bilateral pleural effusion. A routine electrocardiogram showed right bundle branch block, poor R progression in pre-cordial leads, and low QRS-voltages. The echo-cardiogram showed left ventricular hypertrophy (interventricular septal thickness, 18 mm ; posterior wall thickness, 12 mm) with highly refractile myo-cardial echoes, so-called granular sparkling appear-ance. The left ventricular wall motion was reduced (fractional shortening ,18%)¥ Echocardiographic find-ings remained unchanged during 3 months' hospital-ization (Fig. 1). Dual single photon emission computed tomog-raphic (SPEC.T) images of 99mTC-HMDP and 201Tl were examined on admission and then 3 months later. Three hours after the administration of 740 MBq of 99mTc-HMDP, 111 MBq of 201Tl was administered, and the scintillation camera (.GE Starcam 400 AC/T), equipped with a low-energy general purpose collimator, was rotated for 35 seconds in each projection of 32 slices over 360' circulation orbits. Energy discrimination was pro-vided by a 20% window centered on the 140-keV photopeak of 99~TC-HMDP and 72-keV photopeak of 201Tl. Images of 1.33 magnification were recorded at a digital resolution of 64x64 matrics with a dedicated computed system. 201Tl scintigraphy on admission revealed defects in the posterior region as shown in Fig. 2-A, but 99mTC-HMDP scintigraphy showed the intense accumulation in posterior and septal regions seen in Fig. 2-B. Dyspnea on exertion progressively deteriorated in spite of treatment with a cardiac inotropic agent and increases in doses of diuretics. After 3 months' hospitalization, dual SPECT showed a marked increase in the accumu-lation of 99mTC-HMDP in the septal region and a new accumulation in the lateral region, while 201Tl scintigraphy remained almost unchanged (Fig. 3). Just after three months imaging, he suddenly died. His autopsy revealed amyloid deposition in the accumulated area of 99mTc-HMDP. DISCUSSION We report a patient with cardiac amyloidosis whose cardiac involvement was assessed by SPECT with 99mTC-HMDP and 201Tl. Since the first report of the cardiac accumulation of 99m,Tc-diphosphonate in patients with cardiac amyloidosis by Kula et al.,5 scintigraphy with 99mTc-labeled phosphates has been used as a noninvasive procedure for the diag-nosis of cardiac amyloidosis. However, there are some reports indicating that this technique is not useful because of low incidence of positive scan.8,9 The exact mechanism of myocardial accumulation of 99mTc-labeled phosphates in amyloidosis still remains unclear. It possibly relates to the increased calcium concentration in tissues infiltrated with amyloid, as shown by the study in which there was a strong relation between tissue uptake of 99mTc-labeled phosphate and calcium accumulation.5,10 99mTC-HMDP showed a significantly higher uptake in infarct myocardium than 99mTc-methylene diphos-phonate and approximate equality with 99mTc-pyro-phosphate.n We used 99mTC-HMDP to evaluate the severity of cardiac involvement. On admission, 99mTc-HMDP scintigraphy showed an uneven positive accumulation, while 201Tl scintigraphy showed a regional defect. The region of accumulation of 99mTC-HMDP almost exactly corresponded to the defect seen in the 201Tl image, and 3 months after the initial scintigraphic study, the accumulation of 99mTC-HMDP markedly increased. Hongo et al.6 reported that myocardial accumulation of 99mTc-pyrophosphate was detected in cardiac amyloidosis, while no cardiac perfusion defect of 201Tl was observed. They7 also reported in cases with familial amyloidosis that no significant changes in the area and the degree of 99mTc-pyrophosphate accumu-lation in cardiac amyloidosis were observed at least in a 3-year follow-up period. Takezaki et al.12 reported that 99mTc-pyrophosphate accumulation and 201T1 defect were observed in cardiac amyloidosis, and the accumulation of 99mTc-pyrophosphate was observed in the same regions as the perfusion defect seen with 201T1, which is similar to our case. They suggested that 201Tl defect might reflect the myocyte damage due to amyloid deposits in connective tissue of the myocardium. Three months after the initial SPECT, the extension and increase in 99mTC-HMDP accumu-lation were observed, while the 201T1 defect remained unchanged. We supposed that amyloid deposits increase, as indicated by the increase in 99mTc-HMDP accumulation, followed by myocardial cells degeneration, resulting in the subsequent appearance of the 201Tl defect. Hongo et al.13 reported that the incidence and the degree of abnormalities in echocardiography in patients with amyloidosis were correlated with the duration of the illness. In our case, unlike the scintigraphic data, echocardiographic findings were unchanged during the 3-month follow-up period. Thus echocardiography might not be useful for defecting the progression of advanced cardiac amyloidosis in a short term.4 The combination of 201Tl and 99mTC-HMDP SPECT is of value in assessing the degree and distribution of the infiltrative process of amyloidosis in cardiac tissue. Serial examinations would permit the estimation of the progression of the disease, and they might aid in evaluating the efficacy of the treatment regimen for amyloidosis. REFERENCES 1. Kyle RA. Greipp PR : Amyloidosis (AL) : Clinical and laboratory features in 229 cases. Mayo Clin Proc 58: 665-683, 1983 2. Siqueira-Filho AG. Cunha CLP. Tajik AJ, et al : M-mode and two-dimensional echocardiographic features in cardiac amyloidosis. Circulation 63 : 188-196, 1981 3. Sivaram CA, Jugdutt BI, Amy RWM, et al : Cardiac amyloidosis : Combined use of two-dimensional echocardiography and electrocardiography in non-invasive screening before biopsy. Clin Cardiol 8 : 511-518, 1985 4. Klein AL, Hatle LK, Taliercio CP, et al : Serial Doppler echocardiographic follow-up of left ventri-cular diastolic function in cardiac amyloidosis. J Am Col/ Cardiol 16: 1135-1141, 1990 5. Kula RW, Engel WK, Line BR : Scanning for soft-tissue amyloid. Lancet I : 92-93, 1977 6. Hongo M, Yamada H, Okubo S, et al: Cardiac involvement in systemic amyloidosis : Myocardial scintigraphic evaluation. J Cardiogr 1 5 : 1 63-180, 1985 (in Japanese) 7. Hongo M, Hirayama J, Fujii T, et al : Early identi-fication of amyloid heart disease by technetium-99m-pyrophosphate scintigraphy : A study with familial amyloid polyneuropathy. Am Heart J 1 13 : 651~662, 1987 8. Rossello R, Lomena F, Pons F, et al : Bone scan in systemic amyloidosis. Nucl Med Commun 9 : 879-890, 1988 9. Hartmann A, Frenkel J, Hopf R, et al : Is technetium-99m-pyrophosphate scintigraphy valuable in the diagnosis of cardiac amyloidosis ? Int J Card Imag 5 : 227-231, 1990 10. Willerson JT, Parkey RW, Bonte FJ, et al : Patho-physiologic considerations and clinicopathological correlates of technetium-99m stannous pyrophos-phate by myocardial scintigraphy. Semin Nucl Med 10: 54-69, 1980 11. Bevan JA, Tofe AJ, Benedict JJ, et al: Tc-99m HMDP (Hydroxymethylene Diphosphonate) : A radiopharmaceutical for skeletal and acute myo-cardial infarct imaging. II. Comparison of Tc-99m hydroxymethylene diphosphonate (HMDP) with other technetiurn-labeled bone-imaging agents in a canine model. J Nucl Med 21 : 967-970, 1980 12. Takezaki M, Ishida Y, Morozumi T, et al : Non-invasive diagnosis of cardiac involvement by tech-netium-99m-pyrophosphate (Tc-99m PYP) myocar-dial scintigraphy in 2 cases with fami]ial amyloid polyneuropathy and I case with secondary amy-loidosis. Kaku lgaku 26 : 1537-1 543, 1989 (in Japanese) 13. Hongo M, Ikeda S : Echocardiographic assessment of the evolution of amyloid heart disease : A study with familial amyloid polyneuropathy. Circulation 73 : 249-256, 1986