Advertisement

Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy

  • Claudio Rapezzi
  • Candida Cristina Quarta
  • Pier Luigi Guidalotti
  • Simone Longhi
  • Cinzia Pettinato
  • Ornella Leone
  • Alessandra Ferlini
  • Fabrizio Salvi
  • Pamela Gallo
  • Christian Gagliardi
  • Angelo Branzi
Original Article

Abstract

Purpose

We previously reported in a small series of patients that 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC.

Methods

We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of 99mTc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h.

Results

Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late 99mTc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing 99mTc-DPD uptake in terms of both HR [β 2.5, 95% confidence interval (CI) 1.5–3.5; p < 0.0001] and H/WB (β 3.5, 95% CI 2.1–4.9; p < 0.0001).

Conclusion

While 99mTc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. 99mTc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score.

Keywords

Amyloid Cardiomyopathy 99mTc-DPD scintigraphy Differential diagnosis Accuracy 

Notes

Conflicts of interest

None.

References

  1. 1.
    Falk RH, Dubrey SW. Amyloid heart disease. Prog Cardiovasc Dis 2010;52:347–61.CrossRefPubMedGoogle Scholar
  2. 2.
    Shah KB, Inoue Y, Mehra MR. Amyloidosis and the heart: a comprehensive review. Arch Intern Med 2006;166:1805–13.CrossRefPubMedGoogle Scholar
  3. 3.
    Gertz MA, Lacy MQ, Dispenzieri A. Amyloidosis: recognition, confirmation, prognosis, and therapy. Mayo Clin Proc 1999;74:490–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Sun JP, Stewart WJ, Yang XS, Donnell RO, Leon AR, Felner JM, et al. Differentiation of hypertrophic cardiomyopathy and cardiac amyloidosis from other causes of ventricular wall thickening by two-dimensional strain imaging echocardiography. Am J Cardiol 2009;103:411–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Selvanayagam JB, Hawkins PN, Paul B, Myerson SG, Neubauer S. Evaluation and management of the cardiac amyloidosis. J Am Coll Cardiol 2007;50:2101–10.CrossRefPubMedGoogle Scholar
  6. 6.
    Arbustini E, Verga L, Concardi M, Palladini G, Obici L, Merlini G. Electron and immuno-electron microscopy of abdominal fat identifies and characterizes amyloid fibrils in suspected cardiac amyloidosis. Amyloid 2002;9:108–14.PubMedGoogle Scholar
  7. 7.
    Benson MD, Breall J, Cummings OW, Liepnieks JJ. Biochemical characterisation of amyloid by endomyocardial biopsy. Amyloid 2009;16:9–14.CrossRefPubMedGoogle Scholar
  8. 8.
    Perugini E, Guidalotti PL, Salvi F, Cooke RM, Pettinato C, Riva L, et al. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol 2005;46:1076–84.CrossRefPubMedGoogle Scholar
  9. 9.
    Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18–22 April 2004. Am J Hematol 2005;79:319–28.CrossRefPubMedGoogle Scholar
  10. 10.
    Rapezzi C, Merlini G, Quarta CC, Riva L, Longhi S, Leone O, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation 2009;120:1203–12.CrossRefPubMedGoogle Scholar
  11. 11.
    Lachmann HJ, Booth DR, Booth SE, Bybee A, Gilbertson JA, Gillmore JD, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med 2002;346(23):1786–91.CrossRefPubMedGoogle Scholar
  12. 12.
    Ferlini A, Fini S, Salvi F, Patrosso MC, Vezzoni P, Forabosco A. Molecular strategies in genetic diagnosis of transthyretin-related hereditary amyloidosis. FASEB J 1992;6:2864–6.PubMedGoogle Scholar
  13. 13.
    Kyle RA, Spittell PC, Gertz MA, Li CY, Edwards WD, Olson LJ, et al. The premortem recognition of systemic senile amyloidosis with cardiac involvement. Am J Med 1996;101:395–400.CrossRefPubMedGoogle Scholar
  14. 14.
    Palladini G, Perfetti V, Merlini G. Therapy and management of systemic AL (primary) amyloidosis. Swiss Med Wkly 2006;136:715–20.PubMedGoogle Scholar
  15. 15.
    Ng B, Connors LH, Davidoff R, Skinner M, Falk RH. Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med 2005;165:1425–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Glaudemans AW, Slart RH, Zeebregts CJ, Veltman NC, Tio RA, Hazenberg BP, et al. Nuclear imaging in cardiac amyloidosis. Eur J Nucl Med Mol Imaging 2009;36:702–14.CrossRefPubMedGoogle Scholar
  17. 17.
    Hazenberg BP, van Rijswijk MH, Lub-de Hooge MN, Vellenga E, Haagsma EB, Posthumus MD, et al. Diagnostic performance and prognostic value of extravascular retention of 123I-labeled serum amyloid P component in systemic amyloidosis. J Nucl Med 2007;48:865–72.CrossRefPubMedGoogle Scholar
  18. 18.
    Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component. N Engl J Med 1990;323:508–13.CrossRefPubMedGoogle Scholar
  19. 19.
    Hawkins P. Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis. Curr Opin Nephrol Hypertens 2002;11:649–55.CrossRefPubMedGoogle Scholar
  20. 20.
    Aprile C, Marinone G, Saponaro R, Bonino C, Merlini G. Cardiac and pleuropulmonary AL amyloid imaging with technetium-99m labelled aprotinin. Eur J Nucl Med 1995;22:1393–401.CrossRefPubMedGoogle Scholar
  21. 21.
    Han S, Chong V, Murray T, McDonagh T, Hunter J, Poon FW, et al. Preliminary experience of 99mTc-aprotinin scintigraphy in amyloidosis. Eur J Haematol 2007;79:494–500.CrossRefPubMedGoogle Scholar
  22. 22.
    Schaadt BK, Hendel HW, Gimsing P, Jønsson V, Pedersen H, Hesse B. 99mTc-aprotinin scintigraphy in amyloidosis. J Nucl Med 2003;44:177–83.PubMedGoogle Scholar
  23. 23.
    Hongo M, Urushibata K, Kai R, Takahashi W, Koizumi T, Uchikawa S, et al. Iodine-123 metaiodobenzylguanidine scintigraphic analysis of myocardial sympathetic innervation in patients with AL (primary) amyloidosis. Am Heart J 2002;144:122–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Tanaka M, Hongo M, Kinoshita O, Takabayashi Y, Fujii T, Yazaki Y, et al. Iodine-123 metaiodobenzylguanidine scintigraphic assessment of myocardial sympathetic innervation in patients with familial amyloid polyneuropathy. J Am Coll Cardiol 1997;29:168–74.CrossRefPubMedGoogle Scholar
  25. 25.
    Leinonen H, Tötterman KJ, Korppi-Tommola T, Korhola O. Negative myocardial technetium-99m pyrophosphate scintigraphy in amyloid heart disease associated with type AA systemic amyloidosis. Am J Cardiol 1984;53:380–1.CrossRefPubMedGoogle Scholar
  26. 26.
    Eriksson P, Backman C, Bjerle P, Eriksson A, Holm S, Olofsson BO. Non-invasive assessment of the presence and severity of cardiac amyloidosis. A study in familial amyloidosis with polyneuropathy by cross sectional echocardiography and technetium-99m pyrophosphate scintigraphy. Br Heart J 1984;52:321–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Worsley DF, Lentle BC. Uptake of technetium-99m MDP in primary amyloidosis with a review of the mechanisms of soft tissue localization of bone seeking radiopharmaceuticals. J Nucl Med 1993;34:1612–5.PubMedGoogle Scholar
  28. 28.
    Ak I, Vardareli E, Erdinĉ O, Kasapoğlu E, Ata N. Myocardial Tc-99m MDP uptake on a bone scan in senile systemic amyloidosis with cardiac involvement. Clin Nucl Med 2000;25:826–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Puille M, Altland K, Linke RP, Steen-Müller MK, Kiett R, Steiner D, et al. 99mTc-DPD scintigraphy in transthyretin-related familial amyloidotic polyneuropathy. Eur J Nucl Med Mol Imaging 2002;29:376–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Kulhanek J, Movahed A. Uptake of technetium 99m HDP in cardiac amyloidosis. Int J Cardiovasc Imaging 2003;19:225–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Falk RH, Lee VW, Rubinow A, Hood Jr WB, Cohen AS. Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis. Am J Cardiol 1983;51:826–30.CrossRefPubMedGoogle Scholar
  32. 32.
    Willerson JT, Parkey RW, Bowe TJ, Lewis SE, Corbett J, Buja LM. Pathophysiologic considerations and clinicopathological correlates of technetium-99m stannous pyrophosphate myocardial scintigraphy. Semin Nucl Med 1980;10:54–69.CrossRefPubMedGoogle Scholar
  33. 33.
    Yood RA, Skinner M, Cohen AS, Lee VW. Soft tissue uptake of bone seeking radionuclide in amyloidosis. J Rheumatol 1981;8:760–6.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Claudio Rapezzi
    • 1
  • Candida Cristina Quarta
    • 1
  • Pier Luigi Guidalotti
    • 2
  • Simone Longhi
    • 1
  • Cinzia Pettinato
    • 2
  • Ornella Leone
    • 3
  • Alessandra Ferlini
    • 4
  • Fabrizio Salvi
    • 5
  • Pamela Gallo
    • 1
  • Christian Gagliardi
    • 1
  • Angelo Branzi
    • 1
  1. 1.Institute of CardiologyUniversity of Bologna and Policlinico S. Orsola-Malpighi HospitalBolognaItaly
  2. 2.Nuclear Medicine UnitS. Orsola-Malpighi HospitalBolognaItaly
  3. 3.Department of PathologyUniversity of Bologna and S. Orsola-Malpighi HospitalBolognaItaly
  4. 4.Department of Diagnostic and Experimental Medicine, Section of Medical GeneticsUniversity of FerraraFerraraItaly
  5. 5.Department of NeurologyOspedale BellariaBolognaItaly

Personalised recommendations