Skip to main content
SpringerLink
Log in

Current treatment in cardiac amyloidosis

  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

Involvement of the heart is a common finding in amyloidosis. The heart is usually infiltrated by amyloid fibrils in primary amyloidosis and age-related forms of amyloidosis, less commonly in transthyretin familial amyloidosis, and rarely in secondary amyloidosis. The most common clinical presentation is restrictive cardiomyopathy with right-sided heart failure. The second most frequent presentation is congestive heart failure due to systolic dysfunction, followed by arrhythmias and orthostatic hypotension. The diagnosis of amyloidosis requires tissue sample confirmation; at present, Congo red staining in polarized light is the diagnostic method of choice. The characterization of protein fibril type by immunohistochemistry or biochemistry is essential for patient prognosis and treatment. The therapeutic approach consists of specific treatment of amyloidosis and supportive treatment for cardiac-related symptoms. The treatment depends on the type of amyloidosis and the stage of disease. The mainstay of supportive treatment of cardiac failure is diuretic therapy. Primary amyloidosis treatment protocol includes melphalan and prednisone chemotherapy. Heart transplantation is only a palliative treatment. Stem cell transplantation is an emerging treatment alternative. Combination therapy of melphalan and stem cell transplantation has been shown to be a promising treatment strategy. Secondary amyloidosis requires aggressive treatment of the associated inflammatory and neoplastic process. Age-related (senile) amyloidosis benefits from supportive cardiac treatment when applicable. Transthyretin amyloidosis, the most common cardiac hereditary amyloidosis, is treated by liver or combined liver-heart transplantation. New therapies based on chemical and immunologic reaction with amyloid or its precursor are under intensive development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Merlini G, Bellotti V: Molecular mechanisms of amyloidosis. N Engl J Med 2003, 349:583–596.

    Article  PubMed  CAS  Google Scholar 

  2. Kholová I, Niessen HW: Amyloid in cardiovascular system: a review. J Clin Pathol 2005, 58:125–133.

    Article  PubMed  Google Scholar 

  3. Westermark P, Benson MD, Buxbaum JN, et al.: Amyloid fibril protein nomenclature—2002. Amyloid 2002, 9:197–200.

    PubMed  CAS  Google Scholar 

  4. Hassan W, Al-Sergani H, Mourad W, Tabbaa R: Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management. Tex Heart Inst J 2005, 32:178–184.

    PubMed  Google Scholar 

  5. Falk RH: Diagnosis and management of the cardiac amyloidoses. Circulation 2005, 112:2047–2060.

    Article  PubMed  Google Scholar 

  6. Röcken C, Peters B, Juenemann G, et al.: Atrial amyloidosis. An arrhythmogenic substrate for persistent atrial fibrillation. Circulation 2002, 106:2091–2097.

    Article  PubMed  Google Scholar 

  7. Steiner I, Hájková P, Kvasnicka P, Kholová I: Myocardial sleeves of pulmonary veins and atrial fibrillation: a postmortem histopathological study of 100 subjects. Virchows Arch 2006, 449:88–95.

    Article  PubMed  Google Scholar 

  8. Kushwaha SS, Fallon JT, Fuster V: Restrictive cardiomyopathy. N Engl J Med 1997, 336:267–276.

    Article  PubMed  CAS  Google Scholar 

  9. Dingli D, Utz JP, Gertz MA: Pulmonary hypertension in patients with amyloidosis. Chest 2001, 120:1735–1738.

    Article  PubMed  CAS  Google Scholar 

  10. Buxbaum JN: The systemic amyloidoses. Curr Opin Rheumatol 2004, 16:67–75.

    Article  PubMed  CAS  Google Scholar 

  11. O’Hara CJ, Falk RH: The diagnosis and typing of cardiac amyloidosis. Amyloid 2003, 10:127–129.

    PubMed  Google Scholar 

  12. Gertz MA: Diagnosing primary amyloidosis. Mayo Clin Proc 2002, 77:1278–1279.

    PubMed  Google Scholar 

  13. Prochorec-Sobieszek M, Bilinska ZT, Grzybowski J, et al.: Cardiac amyloidosis diagnosed by endomyocardial biopsy. Clinical, histopathological, immunohistochemical and ultrastructural studies. Kardiol Pol 2005, 63:20–35.

    PubMed  Google Scholar 

  14. Hunt SA, Baker DW, Chin MH, et al.: ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Circulation 2001, 104:2996–3007.

    PubMed  CAS  Google Scholar 

  15. Murphy CL, Eulitz M, Hrncic R, et al.: Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens. Am J Clin Pathol 2001, 116:135–142.

    Article  PubMed  CAS  Google Scholar 

  16. Kaplan B, Shtrasburg S, Pras M: Micropurification techniques in the analysis of amyloid proteins. J Clin Pathol 2003, 56:86–90.

    Article  PubMed  CAS  Google Scholar 

  17. Röcken C, Sletten K: Amyloid in surgical pathology. Virchows Arch 2003, 443:3–16.

    Article  PubMed  CAS  Google Scholar 

  18. Parikh S, De Lemos JA: Current therapeutic strategies in cardiac amyloidosis. Curr Treat Options Cardiovasc Med 2005, 7:443–448.

    Article  PubMed  Google Scholar 

  19. Gertz MA, Lacy MQ, Dispenzieri A: Therapy for immunoglobulin light chain amyloidosis: the new and the old. Blood Rev 2004, 18:17–37. This paper summarizes the treatment of primary amyloidosis and reviews a wide range of clinical trials and studies.

    Article  PubMed  Google Scholar 

  20. Gertz MA, Lacy MQ, Dispenzieri A: Immunoglobulin light chain amyloidosis and the kidney. Kidney Int 2002, 61:1–9.

    Article  PubMed  Google Scholar 

  21. Kylle RA, Gertz MA, Greipp PR, et al.: A trail of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone and melphalan, prednisone and colchicine. N Engl J Med 1997, 336:1202–1207.

    Article  Google Scholar 

  22. Sanchorawala V, Wright DG, Seldin DC, et al.: Low-dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis. Br J Haematol 2002, 117:886–889.

    Article  PubMed  CAS  Google Scholar 

  23. Palladini G, Perfetti V, Obici L, et al.: Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood 2004, 103:2936–2938.

    Article  PubMed  CAS  Google Scholar 

  24. Gertz MA, Merlini G, Treon SP: Amyloidosis and Waldenstrom’s macroglobulinemia. Hematology Am Soc Hematol Educ Program 2004, 257–282.

  25. Seldin DC, Choufani EB, Dember LM, et al.: Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis. Clin Lymphoma 2003, 3:241–246.

    Article  PubMed  CAS  Google Scholar 

  26. Kelly JW: Attacking amyloid. N Engl J Med 2005, 352:722–723.

    Article  PubMed  CAS  Google Scholar 

  27. Avramovich Y, Amit T, Youdim MBH: Non-steroidal anti-inflammatory drugs stimulate secretion of nonamyloidogenic precursor protein. J Biol Chem 2002, 277:31466–31773.

    Article  PubMed  CAS  Google Scholar 

  28. Oza VB, Smith C, Raman P, et al.: Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors. J Med Chem 2002, 45:321–332.

    Article  PubMed  CAS  Google Scholar 

  29. Miller SR, Sekijima Y, Kelly JW: Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variant. Lab Invest 2004, 84:545–552.

    Article  PubMed  CAS  Google Scholar 

  30. Dubrey SW, Burke MM, Khaghani A, et al.: Long-term results of heart transplantation in patients with amyloid heart disease. Heart 2001, 85:202–207.

    Article  PubMed  CAS  Google Scholar 

  31. Dubrey SW, Burke MM, Hawkins PN, Banner NR: Cardiac transplantation for amyloid heart disease: the United Kingdom experience. J Heart Lung Transplant 2004, 23:1142–1153. This study deals with heart transplantation in cardiac amyloidosis and summarizes the center and literature experience.

    Article  PubMed  Google Scholar 

  32. Gillmore JD, Goodman HJ, Lachmann HJ, et al.: Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis. Blood 2006, 107:1227–1229.

    Article  PubMed  CAS  Google Scholar 

  33. Suhr OB, Svendsen IH, Andersson R, et al.: Hereditary transthyretin amyloidosis from a Scandinavian perspective. J Intern Med 2003, 254:225–235.

    Article  PubMed  CAS  Google Scholar 

  34. Grazi GL, Cescon M, Salvi F, et al.: Combined heart and liver transplantation for familial amyloidotic neuropathy: considerations from the hepatic point of view. Liver Transpl 2003, 9:986–992.

    Article  PubMed  Google Scholar 

  35. Gillmore JD, Stangou AJ, Tennent GA, et al.: Clinical and biochemical outcome of hepatorenal transplantation for hereditary systemic amyloidosis associated with apolipoprotein AI Gly26Arg. Transplantation 2001, 71:986–992.

    Article  PubMed  CAS  Google Scholar 

  36. Jonsen E, Suhr OB, Tashima K, Athlin E: Early liver transplantation is essential for familial amyloidotic polyneuropathy patients’quality of life. Amyloid 2001, 8:52–57.

    PubMed  CAS  Google Scholar 

  37. Arpesella G, Chiappini B, Marinelli G, et al.: Combined heart and liver transplantation for familial amyloidotic polyneuropathy. J Thorac Cardiovasc Surg 2003, 125:1165–1166.

    Article  PubMed  Google Scholar 

  38. Zeldenrust S, Gertz M, Uemichi T, et al.: Orthotopic liver transplantation for hereditary fibrinogen amyloidosis. Transplantation 2003, 75:560–561.

    Article  PubMed  CAS  Google Scholar 

  39. Comenzo RL, Gertz MA: Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002, 99:4276–4282.

    Article  PubMed  CAS  Google Scholar 

  40. Gertz MA, Lacy MQ, Dispenzieri A, et al.: Stem cell transplantation for the management of primary systemic amyloidosis. Am J Med 2002, 113:549–555.

    Article  PubMed  CAS  Google Scholar 

  41. Skinner M, Sanchorawala V, Seldin DC: High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med 2004, 140:85–93.

    PubMed  CAS  Google Scholar 

  42. Kumar S, Dispenzieri A, Lacy MQ, et al.: High incidence of gastrointestinal bleeding after autologous stem cell transplant for primary systemic amyloidosis. Bone Marrow Transplant 2001, 28:381–385.

    Article  PubMed  CAS  Google Scholar 

  43. Oran B, Wright DG, Seldin DC, et al.: Spontaneous rupture of the spleen in AL amyloidosis. Am J Hematol 2003, 74:131–135.

    Article  PubMed  CAS  Google Scholar 

  44. Chow LQ, Bahlis N, Russell J, et al.: Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: the Calgary BMT Program experience. Bone Marrow Transplant 2005, 36:591–596.

    Article  PubMed  CAS  Google Scholar 

  45. Schonland SO, Perz JB, Hundemer M, et al.: Indications for high-dose chemotherapy with autologous stem cell support in patients with systemic amyloid light chain amyloidosis. Transplantation 2005, 80:S160-S163.

    Article  PubMed  CAS  Google Scholar 

  46. Kolstoe S, Wood S: Perspectives for drug intervention in amyloid diseases. Curr Drug Targets 2004, 5:151–158.

    Article  PubMed  CAS  Google Scholar 

  47. Pepys MB, Herbert J, Hutchinson WL, et al.: Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 2002, 417:254–259.

    Article  PubMed  CAS  Google Scholar 

  48. Ohno S, Yoshimoto M, Honda S, et al.: The antisense approach in amyloid light chain amyloidosis: identification of monoclonal Ig and inhibition of its production by antisense oligonucleotides in in vitro and in vivo models. J Immunol 2002, 169:4039–4045.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland

    Ivana Kholová MD, PhD

Authors
  1. Ivana Kholová MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Josef Kautzner MD, PhD, FESC
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kholová, I., Kautzner, J. Current treatment in cardiac amyloidosis. Curr Treat Options Cardio Med 8, 468–473 (2006). https://doi.org/10.1007/s11936-006-0035-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11936-006-0035-5

Keywords

Search

Navigation