Produção Nacional
Revisado por pares
Role of 99m Tc-DPD scintigraphy on discrimination of familial cardiac amyloidosis
2015; Elsevier BV; Volume: 203; Linguagem: Inglês
10.1016/j.ijcard.2015.11.002
ISSN1874-1754
AutoresSuzane Garcia Ferreira, Alexandre Marins Rocha, Osvaldo J. M. Nascimento, Cláudio Tinoco Mesquita,
Tópico(s)Medical Imaging and Pathology Studies
ResumoHereditary transthyretin-related amyloidosis (ATTR) is the most frequent form of familial systemic amyloidoses, a group of severe diseases with neurological and polyvisceral involvement [[1]Rapezzi C. Quarta C.C. Guidalotti P.L. Pettinato C. Fanti S. Leone O. et al.Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis.J. Am. Coll. Cardiol. Img. 2011; 4: 659-670Abstract Full Text Full Text PDF Scopus (229) Google Scholar]. Cardiac involvement is a major cause of morbidity and mortality [[2]de Haro-del Moral F.J. Sánchez-Lajusticia A. Gómez-Bueno M. García-Pavía P. Salas-Antón C. Segovia-Cubero J. Role of cardiac scintigraphy with 99mTc-DPD in the differentiation of cardiac amyloidosis subtype.Rev. Esp. Cardiol. 2012; 65: 440-446Crossref PubMed Scopus (46) Google Scholar]. The discovery of tests that allow early diagnosis of cardiac involvement in amyloidosis is very important because these patients require strict follow-up. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy has proved to be useful in differential diagnosis between TTR (both mutant and wild-type) and immunoglobulin light chain (AL) etiologies in patients with echocardiographically defined cardiac amyloidosis [[3]Hutt D.F. Quigley A.M. Page J. et al.Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis.Eur. Heart J. Cardiovasc. Imaging. 2014; 15: 1289-1298Crossref PubMed Scopus (149) Google Scholar]. 99mTc-MDP seems to have lower sensitivity than 99mTc-DPD for detecting cardiac amyloidosis, especially in the hereditary form related protein transthyretin [[2]de Haro-del Moral F.J. Sánchez-Lajusticia A. Gómez-Bueno M. García-Pavía P. Salas-Antón C. Segovia-Cubero J. Role of cardiac scintigraphy with 99mTc-DPD in the differentiation of cardiac amyloidosis subtype.Rev. Esp. Cardiol. 2012; 65: 440-446Crossref PubMed Scopus (46) Google Scholar]. Little is known whether the use of 99mTc DPD is superior to 99mTc-MDP in the detection of asymptomatic cardiac involvement in patients with familial amyloidosis. We conducted this comparative study in patients with proven amyloidosis and in their relatives to assess which of the two radiopharmaceuticals are more accurate in the early detection of cardiac amyloid involvement. The patients were recruited from the Neurology Outpatient Clinic in Antônio Pedro University Hospital and from the Brazilian Association of Amyloidosis by phone/electronic contact. Eligibility criteria involved (1) age ≥18 years, (2) signed consent form and (3) the status of amyloidosis or first-degree relatives' DNA mutation carriers. Diagnosis of familial TTR-related amyloidosis was defined by a documented TTR mutation at DNA analysis [[4]Kyle R.A. Spittel P.C. Gertz M.A. et al.The premortem recognition of systemic senile amyloidosis with cardiac involvement.Am. J. Med. 1996; 101: 395-400Abstract Full Text PDF PubMed Scopus (142) Google Scholar]. We excluded women who were pregnant or with suspected pregnancy. The patients were submitted to two separate scintigraphic images with a minimum interval of 72 h to evaluate cardiac amyloid deposit. Eligible patients provided a consent form after receiving verbal and written details regarding the procedures adopted in the study, which was approved by the Ethics Committee of the Federal Fluminense University (protocol approval number 384.150/2013). Preparation of 99mTc-MDP and 99mTc-DPD and quality control were made in accordance with instructions provided by the manufacturers in package inserts. Each patient was administered 740 MBq of 99mTc-DPD and 99mTc-MDP intravenously, and anterior and posterior whole-body images and selective images in anterior, 45° left anterior oblique, and left lateral projections were obtained 3 h later. Two observers from the nuclear medicine service with extensive experience in the evaluation of cardiology studies analyzed the resulting gray-scale images visually. Discrepancies were resolved by consensus. The intensity of the uptake was scored according to Rappezzi et al. seen using a semi-quantitative visual scale [[1]Rapezzi C. Quarta C.C. Guidalotti P.L. Pettinato C. Fanti S. Leone O. et al.Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis.J. Am. Coll. Cardiol. Img. 2011; 4: 659-670Abstract Full Text Full Text PDF Scopus (229) Google Scholar]. Cardiac amyloidosis was echocardiographically defined as end-diastolic thickness of the interventricular septum >1.2 cm (in the absence of any other plausible cause of ventricular hypertrophy) [[5]Falk R.H. Dubrey S.W. Amyloid heart disease.Prog. Cardiovasc. Dis. 2010; 52: 347-361Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar]. Independence of categorical variables was tested using Fisher exact test or Pearson chi-square test. Continuous variables were analyzed using Mann–Whitney U test. Values of p <0.05 were considered significant. We recruited 19 subjects (11 female), mean age of 41.3 ± 13.9 years. Eighteen patients underwent two scans; one patient underwent 99mTc-MDP but refused to carry on the 99mTc-DPD scintigraphy (Table 1). Neither 99mTc-DPD nor 99mTc-MDP scintigraphy revealed an appreciable deposition in the cardiac region (score of 0) in any of the patients who had a normal echocardiogram, except one that had abnormal strain rate (patient number 5 in Table 1). Two patients were diagnosed with cardiac amyloidosis defined by echo criteria: one had intense 99mTc-DPD uptake (score of 2–3) and mild 99mTc-MDP uptake in the cardiac region and the other had no uptake of any tracer. In Fig. 1 we depicted a patient with cardiac uptake of DPD Grade 3 and MDP Grade 0. There were three additional patients that had abnormal strain rate by echo but did not have radiotracer uptake in the cardiac region. Using traditional echocardiographic criteria for diagnosing cardiac amyloidosis the sensitivity of DPD was 50% and specificity was 94%. Interestingly, nuclear medicine was positive in one patient that did not have left ventricular hypertrophy but had atrioventricular block, suggesting an association of DPD uptake and conduction disturbances without hypertrophy.Table 1Demography and imaging findings in subjects studied.PatientSexAgeEcho positiveMutationScore 99mTc-MDPScore 99mTc-DPD1F41Nval122Ile002F64LVHval30met133M31Nval30met004F33LVHval30met005M54ASTval30met126F31Nval30met007M60Nval30met008F56NNA009F21NNA0010M38Nval30met0011F36Nval30met0012M39ASTval30met0013M45Nval30met0014F22Nval30met0015F59ASTval30met–016M52ASTNA0017F25NNA0018F31Nval30met0019M35Nval30met00Uptake intensity was graded according to a visual scale ranging from 0 to 3 points, in which the absence of uptake was assigned a value of 0 points: uptake less than that observed in bone (referred to as the adjacent rib), 1 point; uptake similar to that of bone, 2 points; and uptake greater than that of bone, 3 points. Open table in a new tab Uptake intensity was graded according to a visual scale ranging from 0 to 3 points, in which the absence of uptake was assigned a value of 0 points: uptake less than that observed in bone (referred to as the adjacent rib), 1 point; uptake similar to that of bone, 2 points; and uptake greater than that of bone, 3 points. Our findings suggest that 99mTc-DPD is a better imaging tracer for the diagnosis of ATTR because it binds preferentially to cardiac amyloid, with more avidity than 99mTc-DPD. However, 99mTc-DPD cannot replace echocardiography because of its low sensitivity, being complementary as demonstrated by the finding of abnormal uptake in a patient with normal echocardiographic exam. The first description involving the use of DPD in amyloidosis was performed by De Haro et al., where a patient with amyloidosis AL type (for immunoglobulin light chains) showed uptake in heart projection, parotid gland, uterus and gastrointestinal tract [[6]Haro D. Castejon I. Besada E. Berrocal J. Soft-tissue uptake of Tc-99 m DPD (dicarboxypropane diphosphonate) in amyloidosis.Clin. Nucl. Med. 1996; 21: 509Crossref PubMed Scopus (5) Google Scholar]. In 2002, Puille et al. [[7]Puille M. Altland K. Linke R.P. Steen-Müller M.K. Kiett R. Steiner D. et al.99mTc-DPD scintigraphy in transthyretin-related familial amyloidotic polyneuropathy.Eur. J. Nucl. Med. Mol. Imaging. 2002 Mar; 29: 376-379Crossref PubMed Scopus (91) Google Scholar] have shown for the first time in 8 patients with ATTR, abnormal uptake of DPD in the heart. These authors concluded that although not definitive, 99mTc-DPD uptake in the heart of a patient with systemic amyloidosis strongly suggests ATTR disease [[7]Puille M. Altland K. Linke R.P. Steen-Müller M.K. Kiett R. Steiner D. et al.99mTc-DPD scintigraphy in transthyretin-related familial amyloidotic polyneuropathy.Eur. J. Nucl. Med. Mol. Imaging. 2002 Mar; 29: 376-379Crossref PubMed Scopus (91) Google Scholar]. Hutt et al. [[3]Hutt D.F. Quigley A.M. Page J. et al.Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis.Eur. Heart J. Cardiovasc. Imaging. 2014; 15: 1289-1298Crossref PubMed Scopus (149) Google Scholar] studied the utility and limitations of 99mTc-DPD scintigraphy in the greatest series of patients with suspected cardiac amyloidosis (321 patients). All 158 patients with ATTR with clinical cardiac involvement had cardiac 99mTc-DPD uptake, with median Grade 2 intensity, however 18 of 35 (51%) AL patients with cardiac involvement had 99mTc-DPD cardiac uptake too (median Grade 1 intensity). Taken together these data suggest that 99mTc-DPD scintigraphy is a highly sensitive technique for imaging cardiac ATTR but it is not specific for ATTR in isolation [[3]Hutt D.F. Quigley A.M. Page J. et al.Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis.Eur. Heart J. Cardiovasc. Imaging. 2014; 15: 1289-1298Crossref PubMed Scopus (149) Google Scholar]. Our findings are in accordance with Hutt [[3]Hutt D.F. Quigley A.M. Page J. et al.Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis.Eur. Heart J. Cardiovasc. Imaging. 2014; 15: 1289-1298Crossref PubMed Scopus (149) Google Scholar] data because we found one patient with ATTR and 99mTc-DPD cardiac uptake but without echocardiographic hypertrophy. In their study 13 ATTR patients without clinical evidence of cardiac involvement also demonstrated 99mTc-DPD cardiac uptake [[3]Hutt D.F. Quigley A.M. Page J. et al.Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis.Eur. Heart J. Cardiovasc. Imaging. 2014; 15: 1289-1298Crossref PubMed Scopus (149) Google Scholar]. We may speculate that speckle tracking imaging may detect earlier cardiac involvement and can correlate better with DPD uptake in these patients [[8]Gustavsson S. Granåsen G. Grönlund C. Wiklund U. Mörner S. Henein M. et al.Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?.Amyloid. 2015 Jun; 24: 1-8Crossref Scopus (11) Google Scholar]. In conclusion, 99mTc-DPD is a better imaging tracer for the diagnosis of ATTR than 99mTc-MDP. The role of 99mTc-DPD scintigraphy on discrimination of familial cardiac amyloidosis is complementary to other imaging techniques, especially echocardiography. The authors report no relationships that could be construed as a conflict of interest. CAPES and FAPERJ (E-26/102.208/2009) supported this work.
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