Technetium-99m Pyrophosphate Scintigraphic Finding in Cardiac Amyloidosis: A Case Report
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1 Technetium- Pyrophosphate Scintigraphic Finding in Cardiac Amyloidosis: A Case Report Pei-Ying Hsu 1,2, Yen-Wen Wu 2,3, Lung-Chun Lin 3, Su-Rong Hung 2, Kai-Yuan Tzen 2, Ruoh-Fang Yen 2 1 Division of Nuclear Medicine, National Taiwan University Hospital Yun-Lin Branch, Douliou City, Taiwan 2 Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 3 Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Amyloidosis is a rare systemic disorder caused by extracellular deposition of insoluble fibrils in a wide spectrum of tissues and organs. Among the variety of affected organs, cardiac involvement contributes to the majority of death. Echocardiography and technetium- pyrophosphate ( Tc-PYP) scintigraphy are the common non-invasive imaging modalities in the evaluation of cardiac amyloidosis. In this case report, we present a 65-year-old man with symptoms and signs of congestive heart failure. Cardiac amyloidosis was suspected from his family history. Echocardiography revealed diffuse myocardial hypertrophy and hyperechoic granular sparkling texture in the myocardium. Tc-PYP scintigraphy showed diffuse and intense Tc-PYP uptake in bilateral ventricular myocardium. The pathological result from a biopsy of subcutaneous fat from the chest wall later confirmed the diagnosis. Key words: amyloidosis, heart, Tc-PYP, scintigraphy Ann Nucl Med Sci 2009;22: Introduction Amyloidosis, a rare systemic disorder caused by extracellular deposition of insoluble fibrils in a wide spectrum of tissues and organs, results in various clinical manifestations [1,2] one of which is cardiac involvement, a devastating process with significant morbidity and mortality [1,2]. For the detection of cardiac amyloidosis, many noninvasive tests such as echocardiography, CT, MRI and technetium- pyrophosphate ( Tc-PYP) scintigraphy are available, although definitive diagnosis lies in tissue biopsy with special stain [3-5]. Tc-PYP is a bone seeking agent and has been observed to induce uptake in tissue with amyloid deposition. The precise mechanism of amyloid affinity for Tc-PYP is not understood. One commonly accepted proposal for this mechanism is that the increase of calcium content in the amyloid deposition tissue leads to the increase of Tc-PYP uptake [6]. In this report, we present a case with suspicious cardiac amyloidosis and with Tc-PYP scintigraphy revealing significant uptake in the myocardium. Amyloidosis for this case was later confirmed by subcutaneous fat biopsy of the chest wall. Received 12/23/2008; revised 1/6/2009; accepted 2/10/2009. For correspondence and reprints contact: Ruoh-Fang Yen, M.D., Department of Nuclear Medicine, National Taiwan University Hospital. 7 Chung-Shan South Road, Taipei 100, Taiwan. Tel: (886) ext , Fax: (886) , rfyen@ntu.edu.tw Case Report A 65-year-old male patient had suffered from progressive shortness of breath and leg edema for four months. Paroxysmal nocturnal dyspnea, orthopnea and dizziness were noted as well. This patient had already received endocardial
2 Hsu PY et al biopsy at Tri-Service General Hospital with negative Congo red stain in pathology. The patient s younger brother had also experienced congestive heart failure, which was suspected to be amyloidosis related but with inconclusive evidence from endocardial biopsy. The physical examination for this patient gave the result of low blood pressure (82/60 mmhg) and pedal edema. Hemogram and biochemistry, including cardiac enzymes, liver function and renal function, were all within normal ranges. Chest X ray showed normal heart size. 24-h Holter revealed sinus rhythm with 1st degree atrioventricular block. Sick sinus syndrome was noted during hospitalization and pacemaker was placed. Echocardiography revealed fair ejection fraction (55%), moderate mitral regurgitation, diffuse myocardial hypertrophy and hyperechoic granular sparkling texture in the myocardium (Figure 1). But other diagnostic workups of serum and urine immunofixation electrophoresis for possible disorder associated with amyloidosis were all negative. Tc-PYP scintigraphy was then arranged and the resulting images taken at 3 h after injection of 925 MBq (25 mci) Tc-PYP showed diffuse intense tracer uptake (greater than sternum) in the myocardium of both right and left ventricles. This result further enhanced the possibility of cardiac amyloidosis and led to a subcutaneous fat biopsy from the Figure 1. Echocardiography shows typical granular sparkling texture in the hypertrophic ventricular myocardium, especially in the interventricular and interatrial septums. chest wall. The pathological result showed amorphorous eosinophilic deposition in the perivascular region and positive apple green birefringence in Congo red staining from polarized microscope. Amyloidosis was then confirmed. The patient was thus treated symptomatically for heart failure only, and discharged afterwards upon improvement of general condition. Discussion Amyloidosis is caused by deposition of amyloid fibrils in multiple organs, and can be classified according to the protein precursors [1,2]. Each type has different probabilities of cardiac involvement, extracardiac manifestations and median survival. It is also suggested that amyloidosis may be hereditary. About one third of the patients with amyloidosis are known to have overt heart disease [3]. Amyloid infiltration to the heart may interrupt contractile function and lead to mild diastolic dysfunction at the beginning stage of the disease and then to deteriorating restrictive cardiomyopathy and diastolic heart failure (rightside predominant). In addition, coronary blood flow is likely to be hindered due to microvascular involvement with amyloid so that patients may experience anginal chest pain. Furthermore, chance of arrhythmia is increased because amyloid infiltration may interrupt the conduction of heart [2]. Histological result from biopsy is generally used for the final verdict in diagnosing amyloidosis. However, the biopsy procedure bares the risk of bleeding from vascular integrity disruption in amyloid-laden tissue, and sometimes insufficiently sampling of myocardial biopsy occurs and leads to false negative result [7]. The subcutaneous abdominal fat aspirate is a safe and sensitive procedure for the confirmation of amyloidosis [4]. But, it lacks the important function of providing extent of the disease. Echocardiography is a non-invasive modality for diagnosing cardiac amyloidosis. The amyloid deposits in the ventricular myocardium may show granular sparkling texture in echocardiography to signal the occurrence of cardiac amyloidosis [1,3,4]. Other echocardiographical readings such as increased ventricular mass, biartrial dilatation, and thickening of the interventricular/interatrial septum and valve Ann Nucl Med Sci 2009;22: Vol. 22 No. 2 June
3 Tc-PYP Tc-PYP imaging on cardiac amyloidosis Figure 2. Tc-PYP scintigraphic images taken at 3 h after injection of 925 MBq (25 mci) Tc-PYP show diffuse intense Tc-PYP uptake (4+) in the myocardium of bilateral ventricles. (A) Planar images of anterior and left anterior oblique 60 degrees (LAO 60) views. (B) SPECT images of axial, coronal and sagittal views. leaflets are typical findings of cardiac amyloidosis [1,3]. In radionuclide scintigraphy, Tc-PYP is bound to calcium phosphate complex known to accumulate in severely damaged myocardial cells [3,4]. Usually, image acquisition is performed at 2 to 4 h after tracer injection for avoiding false positive interpretation of tracer activity in the blood pool early after tracer administration [8]. According to Holman classification of visual assessment of Tc-PYP uptake in the myocardium, the intensity of myocardial tracer activity is graded as 1+: minimal or equivocal uptake; 2+: definite uptake but intensity less than sternum; 3+: uptake activity equal in density to the sternum; and 4+: uptake activity greater in intensity than the sternum [9]. Diffuse and intense uptake of Tc-PYP (3+ or 4+) in the heart is likely to be attributed to the involvement of cardiac amyloidosis [3,4,8,10]. Tc-PYP scintigraphy used in conjunction with echocardiography is able to provide noninvasive evidence of cardiac amyloidosis for the suspected patients. Furthermore, the uptake maps in extra-cardiac organs such as liver, spleen or thyroid gland constructed from whole-body Tc-PYP scintigraphy should also conveniently provide valuable 2009;22:
4 Hsu PY et al informations regarding the localization and extent of amyloidosis infiltration [5,11]. References 1. Selvanayagam JB, Hawkins PN, Paul B, Myerson SG, Neubauer S. Evaluation and management of the cardiac amyloidosis. J Am Coll Cardiol 2007;50: Shah KB, Inoue Y, Mehra MR. Amyloidosis and the heart: a comprehensive review. Arch Intern Med 2006; 166: Sueyoshi E, Sakamoto I, Okimoto T, Hayashi K, Tanaka K, Toda G. Cardiac amyloidosis: typical imaging findings and diffuse myocardial damage demonstrated by delayed contrast-enhanced MRI. Cardiovasc Intervent Radiol 2006;29: Lee VW, Caldarone AG, Falk RH, Rubinow A, Cohen AS. Amyloidosis of heart and liver: comparison of Tc- pyrophosphate and Tc- methylene diphosphonate for detection. Radiology 1983;148: Hongo M, Hirayama J, Fujii T, et al. Early identification of amyloid heart disease by technetium--pyrophosphate scintigraphy: a study with familial amyloid polyneuropathy. Am Heart J 1987;113: Pepys MB, Dyck RF, de Beer FC, Skinner M, Cohen AS. Binding of serum amyloid P-component (SAP) by amyloid fibrils. Clin Exp Immunol 1979;38: Chen SD, Kao CH, Poon SK. Radionuclide imaging in primary amyloidosis with liver involvement. Clin Nucl Med 1998;23: Falk RH, Lee VW, Rubinow A, Hood WB Jr, Cohen AS. Sensitivity of technetium--pyrophosphate scintigraphy diagnosing cardiac amyloidosis. Am J Cardiol 1983; 51: Wynne J, Holman BL. Acute myocardial infarct sinctigraphy with infact-avid radiotracers. Med Clin North Am 1980;64: Schiff S, Bateman T, Moffatt R, Davidson R, Berman D. Diagnostic considerations in cardiomyopathy: unique scintigraphic pattern of diffuse biventricular technetium- -pyrophosphate uptake in amyloid heart disease. Am Heart J 1982;103: Rao BK, Padmalatha C, Au-Buchon J, Lieberman LM. Hepatic and splenic scintigraphy in idiopathic systemic amyloidosis. Eur J Nucl Med 1981;6: Ann Nucl Med Sci 2009;22: Vol. 22 No. 2 June
5 Tc-PYP Tc-PYP imaging on cardiac amyloidosis -- 1,2 2, ;22: (02) : (02) : rfyen@ntu.edu.tw 2009;22:
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