Skip to main content

Advertisement

Log in

Cardiac amyloidosis: the heart of the matter

  • IM - REVIEW
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Amyloidosis comprises a unique group of diseases that share in common the extracellular deposition of insoluble fibrillar proteins in organs and tissue including the heart. Cardiac amyloidosis could be primary a part of systemic acquired amyloidosis, or a result of heredofamilial amyloidosis. Although the infiltration of the heart from different types of amyloid results in restrictive cardiomyopathy that manifests with refractory congestive heart failure and conduction abnormalities, unequivocal identification of the deposited amyloidogenic protein is mandatory in order to avoid misdiagnosis and inappropriate treatment. Recent developments in imaging techniques and extracardiac tissue biopsy have minimized the need for invasive endomyocardial biopsy for amyloidosis. Despite advances in treatment, the prognosis of a patient with amyloidosis is still poor and depends upon the underlying disease, and the type and degree of dysfunction of the involved organs. Thus, early diagnosis is mandatory because patients with advanced disease are usually too ill for intensive therapy. This review outlines current approaches to diagnosis, assessment of disease severity, and treatment of cardiac amyloidosis.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Assuero Giorgetti, Dario Genovesi, … Italian Group of Nuclear Cardiology (GICN)

References

  1. Dubrey SW, Cha K, Anderson J et al (1998) The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM 91:141–157

    Article  PubMed  CAS  Google Scholar 

  2. Kyle RA, Gertz MA (1995) Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 32:45–59

    PubMed  CAS  Google Scholar 

  3. Kyle RA, Linos A, Beard CM et al (1992) Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood 79:1817–1822

    PubMed  CAS  Google Scholar 

  4. Hazembergh BPC, Van Rijswisk MH (2000) Aspects cliniques de l’amylose AA. In: Grateau G, Benson MD, Delpech M (eds) Les Amyloses. Médicine-Sciences Flammarion, Paris, pp 377–427

  5. Magy-Bertrand N, Dupond JL, Mauny F, Dupond AS, Duchene F, Gil H, Kantelip B, The CRISAP Members (2008) Incidence of amyloidosis over 3 years: the AMYPRO study. Clin Exp Rheum 26:1074–1078

    CAS  Google Scholar 

  6. Obici L, Perfetti V, Palladini G, Moratti R, Merlini G (2005) Clinical aspects of systemic amyloid diseases. Biochem Biophys Acta 1753:11–22

    Article  PubMed  CAS  Google Scholar 

  7. Park MA, Mueller PS, Kyle RA et al (2003) Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine 82:291–298

    Article  PubMed  Google Scholar 

  8. Nestle FO, Burg G (2001) Bilateral carpal tunnel syndrome as a clue for the diagnosis of systemic amyloidosis. Dermatology 202:353–355

    Article  PubMed  CAS  Google Scholar 

  9. Pettersson T, Konttinen YT, Maury CPJ (2008) Treatment strategies for amyloid A amyloidosis. Expert Opin Pharmacother 9(12):2117–2128

    Article  PubMed  CAS  Google Scholar 

  10. Hawkins PN (2002) Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis. Curr Opin Nephrol Hypertens 11:649–655

    Article  PubMed  Google Scholar 

  11. Gertz MA, Kyle RA (1991) Secondary systemic amyloidosis: response and survival in 64 patients. Medicine 70:246–256

    Article  PubMed  CAS  Google Scholar 

  12. Benson MD, Kincaid JC (2007) The molecular biology and clinical features of amyloid neuropathy. Muscle Nerve 36:411–423

    Article  PubMed  CAS  Google Scholar 

  13. Cornwell GG III, Murdoch WL, Kyle RA, Westermark P, Pitkanen P (1983) Frequency and distribution of senile cardiovascular amyloid: a clinicopathologic correlation. Am J Med 75:618–623

    Article  PubMed  Google Scholar 

  14. Murtagh B, Hammill SC, Gertz MA et al (2005) Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol 95:535–537

    Article  PubMed  Google Scholar 

  15. Feng D, Edwards WD, Krishnaswamy JKO et al (2007) Intracardiac thrombosis and embolism in patients with cardiac amyloidosis. Circulation 116:2420–2426

    Article  PubMed  Google Scholar 

  16. Mueller PS, Edwards WD, Gertz MA (2000) Symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis. Am J Med 109:181–188

    Article  PubMed  CAS  Google Scholar 

  17. Chamarthi B, Dubrey SW, Cha K et al (1997) Features and prognosis of exertional syncope in light-chain associated AL cardiac amyloidosis. Am J Cardiol 80:1242–1245

    Article  PubMed  CAS  Google Scholar 

  18. Falk RH, Rubinow A, Cohen AS (1984) Cardiac arrhythmias in systemic amyloidosis: correlation with echocardiographic abnormalities. J Am Coll Cardiol 3:107–113

    Article  PubMed  CAS  Google Scholar 

  19. Falk RH, Plehn J, Deering T et al (1987) Sensitivity and specificity of the echocardiographic features of cardiac amyloidosis. Am J Cardiol 59:418–422

    Article  PubMed  CAS  Google Scholar 

  20. Klein AL, Hatle LK, Taliercio CP et al (1990) Serial Doppler echocardiographic follow-up of left ventricular diastolic function in cardiac amyloidosis. J Am Coll Cardiol 16:1135–1141

    Article  PubMed  CAS  Google Scholar 

  21. Rahman JE, Helou EF, Gelzer-Bell R et al (2004) Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 43:410–415

    Article  PubMed  Google Scholar 

  22. Bhandari AK, Nanda NC (1983) Myocardial texture characterization by two-dimensional echocardiography. Am J Cardiol 51:817–825

    Article  PubMed  CAS  Google Scholar 

  23. Simons M, Isner JM (1992) Assessment of relative sensitivities of noninvasive tests for cardiac amyloidosis in documented cardiac amyloidosis. Am J Cardiol 69:425–427

    Article  PubMed  CAS  Google Scholar 

  24. Hongo M, Kono J, Yamada H et al (1991) Doppler echocardiographic assessments of left ventricular diastolic filling in patients with amyloid heart disease. J Cardiol 21:391–401

    PubMed  CAS  Google Scholar 

  25. Koyama J, Ray-Sequin PA, Davidoff R et al (2002) Usefulness of pulsed tissue Doppler imaging for evaluating systolic and diastolic left ventricular function in patients with AL (primary) amyloidosis. Am J Cardiol 89:1067–1071

    Article  PubMed  Google Scholar 

  26. Porciani MC, Lilli A, Perfetto F et al (2009) Tissue Doppler and strain imaging: a new tool for early detection of cardiac amyloidosis. Amyloid 16:63–70

    Article  PubMed  Google Scholar 

  27. Koyama J, Ray-Sequin PA, Falk RH (2003) Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation 107:2446–2452

    Article  PubMed  Google Scholar 

  28. Porciani MC, Cappelli F, Perfetto F et al (2010) Rotational mechanics of the left ventricle in AL amyloidosis. Echocardiography 27:1061–1068

    Article  PubMed  Google Scholar 

  29. Notomi Y, Martin-Miklovic MG, Oryszak SJ, Shiota T, Deserranno D, Popovic ZB, Garcia MJ, Greenberg NL, Thomas JD (2006) Enhanced ventricular untwisting during exercise: a mechanistic manifestation of elastic recoil described by Doppler tissue imaging. Circulation 113:2524–2533

    Article  PubMed  Google Scholar 

  30. Rapezzi C, Merlini G, Quarta CC et al (2009) Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation 120:1203–1212

    Article  PubMed  CAS  Google Scholar 

  31. Maceira AM, Joshi J, Prasad SK, Moon JC, Perugini E et al (2005) Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 111:186–193

    Article  PubMed  Google Scholar 

  32. Perugini E, Rapezzi C, Piva T et al (2006) Non-invasive evaluation of the myocardial substrate of cardiac amyloidosis by gadolinium cardiac magnetic resonance. Heart 92:343–349

    Article  PubMed  CAS  Google Scholar 

  33. Perugini E, Guidalotti PL, Salvi F et al (2005) Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol 46:1076–1084

    Article  PubMed  Google Scholar 

  34. Dispenzieri A, Kyle RA, Gertz MA et al (2003) Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 361:1787–1789

    Article  PubMed  CAS  Google Scholar 

  35. Dispenzieri A, Gertz M, Kyle R et al (2004) Serum cardiac troponins and N-terminal probrain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol 22(18):3751–3757

    Article  PubMed  CAS  Google Scholar 

  36. Palladini G, Lavatelli F, Russo P et al (2006) Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 107:3854–3858

    Article  PubMed  CAS  Google Scholar 

  37. Kristen AV, Giannitsis E, Lehrke S, Hegenbart U, Konstandin M et al (2010) Assessment of disease severity and outcome in patients with systemic light-chain amyloidosis by the high-sensitivity troponin-T assay. Blood 116:2455–2461

    Article  PubMed  CAS  Google Scholar 

  38. Palladini G, Barassi A, Klersy C, Pacciolla R, Milani P et al (2010) The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis. Blood 116:3426–3430

    Article  PubMed  CAS  Google Scholar 

  39. Gertz MA, Merlini G (2010) Definition of organ involvement and response to treatment in AL amyloidosis: un updated consensus opinion (abstract). Amyloid 17(s1):48

    Google Scholar 

  40. Duston MA, Skinner M, Meenan RF, Cohen AS (1989) Sensitivity, specificity, and predictive value of abdominal fat aspiration for the diagnosis of amyloidosis. Arthritis Rheum 32:82–85

    Article  PubMed  CAS  Google Scholar 

  41. Lavatelli F, Perlman DH, Spencer B et al (2008) Amyloidogenic and associated proteins in systemic amyloidosis proteome of adipose tissue. Mol Cell Proteomics 7:1570–1583

    Article  PubMed  CAS  Google Scholar 

  42. Falk RH, Comenzo RL, Skinner M (1997) The systemic amyloidoses. N Engl J Med 337:898–909

    Article  PubMed  CAS  Google Scholar 

  43. Cueto-Garcia L, Reeder GS, Kyle RA et al (1985) Echocardiographic findings in systemic amyloidosis: spectrum of cardiac involvement and relation to survival. J Am Coll Cardiol 6:737–743

    Article  PubMed  CAS  Google Scholar 

  44. Klein AL, Hatle LK, Taliercio CP et al (1991) Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis. Circulation 83:808–816

    Article  PubMed  CAS  Google Scholar 

  45. Ghio S, Perlini S, Palladini G et al (2007) Importance of the echocardiographic evaluation of right ventricular function in patients with AL amyloidosis. Eur J Heart Fail 9:808–813

    Article  PubMed  Google Scholar 

  46. Koyama J, Falk RH (2010) Prognostic significance of strain Doppler imaging in light-chain amyloidosis. J Am Coll Cardiol Imag 3:333–342

    Google Scholar 

  47. Bellavia D, Pellikka PA, Al-Zahrani GB et al (2010) Independent predictors of survival in primary systemic (AL) amyloidosis, including cardiac biomarkers and left ventricular strain imaging: an observational cohort study. J Am Soc Echocardiogr 23:643–652

    Article  PubMed  Google Scholar 

  48. Gillmore JD, Lovat LB, Persey MR, Pepys MB, Hawkins PN (2001) Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet 358:24–29

    Article  PubMed  CAS  Google Scholar 

  49. Bergesio F, Ciciani AM, Manganaro M, Palladini G, Santostefano M, Brugnano R (2008) Renal involvement in systemic amyloidosis An Italian collaborative study on survival and renal outcome Nephrol. Dial Transplant 2:941–951

    Google Scholar 

  50. Lachmann HJ, Goodman HJB, Gilbertson JA et al (2007) Natural history and outcome in systemic AA amyloidosis. N Engl J Med 356:2361–2371

    Article  PubMed  CAS  Google Scholar 

  51. Rapezzi, C. Perugini E, Salvi F et al. (2006) Phenotypic and genotypic heterogeneity in transthyretin-related cardiac amyloidosis: towards tailoring of therapeutic strategies? Amyloid 13:143–153

    Google Scholar 

  52. Rapezzi C, Quarta CC, L Riva et al (2010) Transthyretin-related amyloidoses and the heart: a clinical overview. Nat Rev Cardiol 7:398–408

    Article  PubMed  CAS  Google Scholar 

  53. Ng B, Connors LH, Davidoff R, Skinner M, Falk RH (2005) Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med 165:1425–1429

    Article  PubMed  Google Scholar 

  54. Dubrey SW, Cha K, Skinner M, LaValley M, Falk RH (1997) Familial and primary (AL) cardiac amyloidosis: echocardiographically similar diseases with distinctly different clinical outcomes. Heart 78:74–82

    PubMed  CAS  Google Scholar 

  55. Pollak A, Falk RH (1993) Left ventricular systolic dysfunction precipitated by verapamil in cardiac amyloidosis. Chest 104:618–620

    Article  PubMed  CAS  Google Scholar 

  56. Rubinow A, Skinner M, Cohen AS (1981) Digoxin sensitivity in amyloid cardiomyopathy. Circulation 63:1285–1288

    Article  PubMed  CAS  Google Scholar 

  57. Dubrey S, Pollak A, Skinner M, Falk RH (1995) Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for atrial electromechanical dissociation. Br Heart J 74:541–544

    Article  PubMed  CAS  Google Scholar 

  58. Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H et al (2008) Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death heart rhythm. Heart Rhythm 5:235–240

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  60. Sanchorawala V, Wright DG, Seldin DC et al (2004) High-dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: results of a prospective randomized trial. Bone Marrow Transplant 33:381–388

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  62. Palladini G, Perfetti V, Perlini S et al (2005) The combination of thalidomide and intermediate dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL). Blood 105:2949–2951

    Article  PubMed  CAS  Google Scholar 

  63. Sanchorawala V, Finn KT, Fennessey S et al (2007) Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood 109:492–496

    Article  PubMed  CAS  Google Scholar 

  64. Moreau P, Jaccard A, Benboubker L et al (2010) Lenalidomide in combination with melphalan and dexamethasone in patients with newly-diagnosed AL amyloidosis: a multicenter phase 1/2 dose escalation study. Blood 116:4777–4782

    Article  PubMed  CAS  Google Scholar 

  65. Kumar S, Hayman SR, Buadi F et al. (2009) A phase II trial of lenalidomide, cyclophosphamide and dexamethasone (RCD) in patients with light chain amyloidosis. Blood (ASH Annual Meeting Abstracts) 114 (abstr 3853)

  66. Dispenzieri A, Gertz MA, Hayman SR et al (2010) Pomalidomide and dexamethasone for previously treated AL: a phase 2 study. Amyloid 17(s1):87

    Google Scholar 

  67. Reece D, Sanchorawala V, Hegenbart U et al (2009) Weekly and twice-weekly bortezomib in patients with systemic AL-amyloidosis: results of a phase 1 dose escalation study. Blood 114:1489–1497

    Article  PubMed  CAS  Google Scholar 

  68. Wechalekar AD, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD (2008) Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease. Haematologica 93:295–298

    Article  PubMed  CAS  Google Scholar 

  69. Kastritis E, Anagnostopoulos A, Roussou M et al (2007) Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. Haematologica 92:1351–1358

    Article  PubMed  CAS  Google Scholar 

  70. Kastritis E, Wechalekar AD, Dimopoulos MA et al (2010) Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol 28:1031–1037

    Article  PubMed  CAS  Google Scholar 

  71. Drewe E, Huggins ML, Morgan AG, Cassidy MJ, Powell RJ (2004) Treatment of renal amyloidosis with etanercept in tumour necrosis factor receptor-associated periodic syndrome. Rheumatology 43:1405–1408

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  73. Coelho T, Maia L, Martin da Silva A (2010) Tafamidis (Fx-1006A): a first-in-class disease-modifying therapy for transthyretin familial amyloid. Amyloid 17(S1):75–76

    Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Federico Perfetto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perfetto, F., Cappelli, F., Bergesio, F. et al. Cardiac amyloidosis: the heart of the matter. Intern Emerg Med 8, 191–203 (2013). https://doi.org/10.1007/s11739-011-0647-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-011-0647-y

Keywords

Navigation