Current Cardiology Reports

, 21:164 | Cite as

Amyloid and the Heart

  • Aaron M. Wolfson
  • Kevin S. Shah
  • Jignesh K. PatelEmail author
Heart Failure (HJ Eisen, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Heart Failure


Purpose of Review

While morbidity and mortality remain high for amyloid cardiomyopathy (AC), increased awareness, earlier diagnosis, and advances in treatment have improved patient outcomes. This review will discuss the pathophysiology, contemporary diagnostic strategies, and novel and investigational therapeutic strategies for light-chain (AL) and transthyretin (ATTR) AC.

Recent Findings

Diagnostic strategies for AC now include cardiac magnetic resonance imaging and bone scintigraphy. Proteosome inhibitor therapy is now front-line therapy for AL AC followed by autologous stem cell transplantation. Emerging disease-modifying strategies for ATTR AC include the recently FDA-approved TTR-stabilizer, tafamadis. ATTR gene-silencing therapy and amyloid fibril degradation therapy are two other strategies under investigation. Heart transplantation and durable mechanical circulatory support remain a final potential option; however, contemporary outcomes are improving with better patient selection.


Patient outcomes for AC are expected to improve as increased awareness leads to earlier diagnosis and prompt treatment with emerging pharmacotherapy or advanced heart therapies.


Cardiac amyloidosis Restrictive cardiomyopathy Endomyocardial biopsy 


Funding Information

Jignesh Patel reports grants from the National Institutes of Health (Grant number: 1UO1AI136816-01).

Compliance with Ethical Standards

Conflict of Interest

Aaron M. Wolfson and Kevin S. Shah declare that they have no conflict of interest.

Jignesh Patel reports grants, personal fees, non-financial support and other from Alnylam Pharmaceuticals; personal fees, non-financial support and other from Akcea Pharmaceuticals; grants, personal fees, non-financial support and other from Pfizer Inc.; grants from Ionis Pharmaceuticals; grants from Alexion Pharmaceuticals; grants from CareDx Inc., and grants from Genzyme Inc.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Sipe JD, Cohen AS. Review: history of the amyloid fibril. J Struct Biol. 2000;130:88–98.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126:1286–300.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Buxbaum JN, Chuba JV, Hellman GC, Solomon A, Gallo GR. Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Ann Intern Med. 1990;112:455–64.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Falk RH, Alexander KM, Liao R, Dorbala S. AL (light-chain) cardiac amyloidosis. J Am Coll Cardiol. 2016;68:1323–41.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Sipe JD, Benson MD, Buxbaum JN, Ikeda S-I, Merlini G, Saraiva MJM, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 nomenclature guidelines. Amyloid Int J Exp Clin Investig Off J Int Soc Amyloidosis. 2016;23:209–13.CrossRefGoogle Scholar
  6. 6.
    Sousa MM, Du Yan S, Fernandes R, Guimaraes A, Stern D, Saraiva MJ. Familial amyloid polyneuropathy: receptor for advanced glycation end products-dependent triggering of neuronal inflammatory and apoptotic pathways. J Neurosci. 2001;21:7576–86.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Mendes Sousa M, Cardoso I, Fernandes R, Guimarães A, Saraiva MJ. Deposition of transthyretin in early stages of familial Amyloidotic polyneuropathy. Am J Pathol. 2001;159:1993–2000.PubMedCentralCrossRefGoogle Scholar
  8. 8.
    Shi J, Guan J, Jiang B, Brenner DA, del Monte F, Ward JE, et al. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38α MAPK pathway. Proc Natl Acad Sci U S A. 2010;107:4188–93.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med. 1997;336:267–76.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    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;32:178–84.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Falk RH, Quarta CC. Echocardiography in cardiac amyloidosis. Heart Fail Rev. 2015;20:125–31.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Kyle RA, Linos A, Beard CM, Linke RP, Gertz MA, O’Fallon WM, et al. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992;79:1817–22.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Chamarthi B, Dubrey SW, Cha K, Skinner M, Falk RH. Features and prognosis of exertional syncope in light-chain associated AL cardiac amyloidosis. Am J Cardiol. 1997;80:1242–5.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Baker KR, Rice L. The Amyloidoses: clinical features, diagnosis and treatment. Methodist DeBakey Cardiovasc J. 2012;8:3–7.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Mussinelli R, Salinaro F, Alogna A, Boldrini M, Raimondi A, Musca F, et al. Diagnostic and prognostic value of low QRS voltages in cardiac AL amyloidosis. Ann Noninvasive Electrocardiol Off J Int Soc Holter Noninvasive Electrocardiol Inc. 2013;18:271–80.CrossRefGoogle Scholar
  16. 16.
    Phelan D, Collier P, Thavendiranathan P, Popović ZB, Hanna M, Plana JC, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart Br Card Soc. 2012;98:1442–8.Google Scholar
  17. 17.
    Pericardial tamponade, a new complication of amyloid heart disease - The American Journal of Medicine [Internet]. [cited 2019 Apr 29]. Available from:
  18. 18.
    Navarro JF, Rivera M, Ortuño J. Cardiac tamponade as presentation of systemic amyloidosis. Int J Cardiol. 1992;36:107–8.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Philippakis AA, Falk RH. Cardiac amyloidosis mimicking hypertrophic cardiomyopathy with obstruction: treatment with disopyramide. Circulation. 2012;125:1821–4.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Kwong RY, Heydari B, Abbasi S, Steel K, Al-Mallah M, Wu H, et al. Characterization of cardiac amyloidosis by atrial late gadolinium enhancement using contrast-enhanced cardiac magnetic resonance imaging and correlation with left atrial conduit and contractile function. Am J Cardiol. 2015;116:622–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Fontana M, Chung R, Hawkins PN, Moon JC. Cardiovascular magnetic resonance for amyloidosis. Heart Fail Rev. 2015;20:133–44.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Dungu JN, Valencia O, Pinney JH, Gibbs SDJ, Rowczenio D, Gilbertson JA, et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. JACC Cardiovasc Imaging. 2014;7:133–42.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30:989–95.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Kumar SK, Gertz MA, Dispenzieri A. Validation of Mayo Clinic staging system for light chain amyloidosis with high-sensitivity troponin. J Clin Oncol. 2018;37:171–3.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68:1014–20.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    24 Month Open Label Study of the Tolerability and Efficacy of Inotersen in TTR Amyloid Cardiomyopathy Patients - Full Text View - [Internet]. [cited 2019 Apr 24]. Available from:
  27. 27.
    Swiecicki PL, Zhen DB, Mauermann ML, Kyle RA, Zeldenrust SR, Grogan M, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22:123–31.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Quarta CC, Buxbaum JN, Shah AM, Falk RH, Claggett B, Kitzman DW, et al. The amyloidogenic V122I transthyretin variant in elderly black Americans. N Engl J Med. 2015;372:21–9.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Castaño A, Drachman BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20:163–78.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73:2872–91.PubMedCrossRefGoogle Scholar
  31. 31.
    Aus dem Siepen F, Hein S, Prestel S, Baumgärtner C, Schönland S, Hegenbart U, et al. Carpal tunnel syndrome and spinal canal stenosis: harbingers of transthyretin amyloid cardiomyopathy? Clin Res Cardiol Off J Ger Card Soc. 2019.Google Scholar
  32. 32.
    Maurer MS, Ruberg FL. Early diagnosis of cardiac amyloidosis by carpal tunnel surgery: is it all in the wrist? J Am Coll Cardiol. 2018;72:2051–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Sperry BW, Reyes BA, Ikram A, Donnelly JP, Phelan D, Jaber WA, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol. 2018;72:2040–50.PubMedCrossRefGoogle Scholar
  34. 34.
    Castaño A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A, et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017;38:2879–87.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Quarta CC, Solomon SD, Uraizee I, Kruger J, Longhi S, Ferlito M, et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation. 2014;129:1840–9.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133:2404–12.PubMedCrossRefGoogle Scholar
  37. 37.
    Damy T, Jaccard A, Guellich A, Lavergne D, Galat A, Deux J-F, et al. Identification of prognostic markers in transthyretin and AL cardiac amyloidosis. Amyloid Int J Exp Clin Investig Off J Int Soc Amyloidosis. 2016;23:194–202.CrossRefGoogle Scholar
  38. 38.
    Nativi-Nicolau J, Maurer MS. Amyloidosis cardiomyopathy: update in the diagnosis and treatment of the most common types. Curr Opin Cardiol. 2018;33:571–9.PubMedGoogle Scholar
  39. 39.
    Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004;22:3751–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Marianna F, Silvia P, Patricia R, Amna A-G. Treibel Thomas a., Banypersad Sanjay M., et al. prognostic value of late gadolinium enhancement cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2015;132:1570–9.CrossRefGoogle Scholar
  41. 41.
    Gertz MA, Falk RH, Skinner M, Cohen AS, Kyle RA. Worsening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents. Am J Cardiol. 1985;55:1645.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Griffiths BE, Hughes P, Dowdle R, Stephens MR. Cardiac amyloidosis with asymmetrical septal hypertrophy and deterioration after nifedipine. Thorax. 1982;37:711–2.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Pollak A, Falk RH. Left ventricular systolic dysfunction precipitated by verapamil in cardiac amyloidosis. Chest. 1993;104:618–20.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Gertz MA, Skinner M, Connors LH, Falk RH, Cohen AS, Kyle RA. Selective binding of nifedipine to amyloid fibrils. Am J Cardiol. 1985;55:1646.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Algalarrondo V, Dinanian S, Juin C, Chemla D, Bennani SL, Sebag C, et al. Prophylactic pacemaker implantation in familial amyloid polyneuropathy. Heart Rhythm. 2012;9:1069–75.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    González-López E, Gagliardi C, Dominguez F, Quarta CC, de Haro-del Moral FJ, Milandri A, et al. Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths. Eur Heart J. 2017;38:1895–904.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Varr BC, Zarafshar S, Coakley T, Liedtke M, Lafayette RA, Arai S, et al. Implantable cardioverter-defibrillator placement in patients with cardiac amyloidosis. Heart Rhythm. 2014;11:158–62.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the Management of Patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36:2793–867.CrossRefGoogle Scholar
  49. 49.
    Lin G, Dispenzieri A, Kyle R, Grogan M, Brady PA. Implantable cardioverter defibrillators in patients with cardiac amyloidosis. J Cardiovasc Electrophysiol. 2013;24:793–8.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H, Sack F-U, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008;5:235–40.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    El-Am EA, Dispenzieri A, Melduni RM, Ammash NM, White RD, Hodge DO, et al. Direct current cardioversion of atrial arrhythmias in adults with cardiac amyloidosis. J Am Coll Cardiol. 2019;73:589–97.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Alexander KM, Singh A, Falk RH. Novel pharmacotherapies for cardiac amyloidosis. Pharmacol Ther. 2017;180:129–38.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Kastritis E, Dimopoulos MA. Recent advances in the management of AL amyloidosis. Br J Haematol. 2016;172:170–86.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med [Internet]. 2018 [cited 2019 Apr 24]; Available from:
  55. 55.
    Adams D, Gonzalez-Duarte A, O’Riordan WD, Yang C-C, Ueda M, Kristen AV, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379:11–21.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    • Solomon SD, David A, Arnt K, Martha G, Alejandra G-D, Maurer Mathew S, et al. Effects of Patisiran, an RNA interference therapeutic, on cardiac parameters in patients with hereditary transthyretin-mediated amyloidosis. Circulation. 2019;139:431–43. This study reported on the significant improvement in several exploratory cardiovascular endpoints. PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    • Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J med [internet]. 2018 [cited 2019 Apr 16]; available from: This study lead to the eventual FDA-approval of the drug tafamadis for amyloid cardiomyopathy.
  58. 58.
    Commissioner O of the. FDA approves new treatments for heart disease caused by a serious rare disease, transthyretin mediated amyloidosis [Internet]. FDA. 2019 [cited 2019 May 6]. Available from: /news-events/press-announcements/fda-approves-new-treatments-heart-disease-caused-serious-rare-disease-transthyretin-mediated.Google Scholar
  59. 59.
    Long-term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy - Full Text View - [Internet]. [cited 2019 Apr 29]. Available from:
  60. 60.
    Judge DP, Falk RH, Maurer MS, Shah SJ, Witteles RM, Grogan M, et al. Transthyretin stabilization by AG10 in symptomatic transthyretin amyloid cardiomyopathy. J Am Coll Cardiol. 2019;74:285–95.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310:2658–67.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Cardoso I, Merlini G, Saraiva MJ. 4′-iodo-4′-Deoxydoxorubicin and tetracyclines disrupt transthyretin amyloid fibrils in vitro producing noncytotoxic species: screening for TTR fibril disrupters. FASEB J. 2003;17:803–9.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Cardoso I, Saraiva MJ. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J. 2006;20:234–9.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Macedo B, Batista AR, Ferreira N, Almeida MR, Saraiva MJ. Anti-apoptotic treatment reduces transthyretin deposition in a transgenic mouse model of familial Amyloidotic polyneuropathy. Biochim Biophys Acta. 1782;2008:517–22.Google Scholar
  65. 65.
    Cardoso I, Martins D, Ribeiro T, Merlini G, Saraiva MJ. Synergy of combined doxycycline/TUDCA treatment in lowering transthyretin deposition and associated biomarkers: studies in FAP mouse models. J Transl Med. 2010;8:74.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Obici L, Cortese A, Lozza A, Lucchetti J, Gobbi M, Palladini G, et al. Doxycycline plus tauroursodeoxycholic acid for transthyretin amyloidosis: a phase II study. Amyloid. 2012;19:34–6.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Tolerability and Efficacy of a Combination of Doxycycline and TUDCA in Patients With Transthyretin Amyloid Cardiomyopathy - Full Text View - [Internet]. [cited 2019 Apr 30]. Available from:
  68. 68.
    Hora M, Carballo-Pacheco M, Weber B, Morris VK, Wittkopf A, Buchner J, et al. Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains. Sci Rep. 2017;7:41515.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    aus dem Siepen F, Buss SJ, Andre F, Seitz S, Giannitsis E, Steen H, et al. Extracellular remodeling in patients with wild-type amyloidosis consuming epigallocatechin-3-gallate: preliminary results of T1 mapping by cardiac magnetic resonance imaging in a small single center study. Clin Res Cardiol Off J Ger Card Soc. 2015;104:640–7.CrossRefGoogle Scholar
  70. 70.
    Mereles D, Buss SJ, Hardt SE, Hunstein W, Katus HA. Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis. Clin Res Cardiol Off J Ger Card Soc. 2010;99:483–90.CrossRefGoogle Scholar
  71. 71.
    • Richards DB, Cookson LM, Berges AC, Barton SV, Lane T, Ritter JM, et al. Therapeutic clearance of amyloid by antibodies to serum amyloid P component. N Engl J Med. 2015;373:1106–14.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    • Richards DB, Cookson LM, Barton SV, Liefaard L, Lane T, Hutt DF, et al. Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis. Sci Transl Med. 2018;10:eaan3128. This study is notable because it provides additional proof-of-concept for removal of amyloid deposition from tissues; whether this improves outcomes in amyloid cardiomyopathy is not yet clear. PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Falk RH, Alexander KM, Liao R, Dorbala S. AL (light-chain) cardiac amyloidosis: a review of diagnosis and therapy. J Am Coll Cardiol. 2016;68:1323–41.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Huang X, Wang Q, Chen W, Ren G, Liu Z. Bortezomib with dexamethasone as first-line treatment for AL amyloidosis with renal involvement. Amyloid Int J Exp Clin Investig Off J Int Soc Amyloidosis. 2016;23:51–7.CrossRefGoogle Scholar
  75. 75.
    Milani P, Gertz MA, Merlini G, Dispenzieri A. Attitudes about when and how to treat patients with AL amyloidosis: an international survey. Amyloid Int J Exp Clin Investig Off J Int Soc Amyloidosis. 2017;24:213–6.CrossRefGoogle Scholar
  76. 76.
    Palladini G, Sachchithanantham S, Milani P, Gillmore J, Foli A, Lachmann H, et al. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood. 2015;126:612–5.PubMedCrossRefGoogle Scholar
  77. 77.
    Venner CP, Lane T, Foard D, Rannigan L, Gibbs SDJ, Pinney JH, et al. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood. 2012;119:4387–90.PubMedCrossRefGoogle Scholar
  78. 78.
    Landau H, Hassoun H, Rosenzweig MA, Maurer M, Liu J, Flombaum C, et al. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia. 2013;27:823–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Study of Dexamethasone Plus IXAZOMIB (MLN9708) or Physicians Choice of Treatment in Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis - Full Text View - [Internet]. [cited 2019 May 1]. Available from:
  80. 80.
    A Safety Study of Carfilzomib in Patients With Previously-Treated Systemic Light Chain Amyloidosis - Full Text View - [Internet]. [cited 2019 May 1]. Available from:
  81. 81.
    Kaufman GP, Schrier SL, Lafayette RA, Arai S, Witteles RM, Liedtke M. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood. 2017;130:900–2.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Sher T, Fenton B, Akhtar A, Gertz MA. First report of safety and efficacy of daratumumab in 2 cases of advanced immunoglobulin light chain amyloidosis. Blood. 2016;128:1987–9.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Daratumumab for the Treatment of Patients With AL Amyloidosis - Full Text View - [Internet]. [cited 2019 May 1]. Available from:
  84. 84.
    Kumar SK, Hayman SR, Buadi FK, Roy V, Lacy MQ, Gertz MA, et al. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012;119:4860–7.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Mahmood S, Venner CP, Sachchithanantham S, Lane T, Rannigan L, Foard D, et al. Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens. Br J Haematol. 2014;166:842–8.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012;119:5397–404.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Sanchorawala V, Shelton AC, Lo S, Varga C, Sloan JM, Seldin DC. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Blood. 2016;128:1059–62.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Sharpley FA, Manwani R, Mahmood S, Sachchithanantham S, Lachmann H, Gilmore J, et al. Real world outcomes of pomalidomide for treatment of relapsed light chain amyloidosis. Br J Haematol. 2018;183:557–63.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Yan T, Pereira Naveen L, Shah Dipesh K, Barry B, Schirger John A, Kushwaha Sudhir S, et al. Left ventricular assist device therapy in patients with restrictive and hypertrophic cardiomyopathy. Circ Heart Fail. 2011;4:266–75.CrossRefGoogle Scholar
  90. 90.
    Swiecicki PL, Edwards BS, Kushwaha SS, Dispenzieri A, Park SJ, Gertz MA. Left ventricular device implantation for advanced cardiac amyloidosis. J Heart Lung Transplant. 2013;32:563–8.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Grupper A, Park SJ, Pereira NL, Schettle SD, Gerber Y, Topilsky Y, et al. Role of ventricular assist therapy for patients with heart failure and restrictive physiology: improving outcomes for a lethal disease. J Heart Lung Transplant. 2015;34:1042–9.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Scully MS, Wessman DE, McKee JM, Francisco GM, Nayak KR, Kobashigawa JA. Total artificial heart implantation as a bridge to heart transplantation in an active duty service member with amyloid cardiomyopathy. Mil Med. 2017;182:e1858–60.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Gerosa G, Scuri S, Iop L, Torregrossa G. Present and future perspectives on total artificial hearts. Ann Cardiothorac Surg. 2014;3:595–602–602.Google Scholar
  94. 94.
    DePasquale EC, Nasir K, Jacoby DL. Outcomes of adults with restrictive cardiomyopathy after heart transplantation. J Heart Lung Transplant Off Publ Int Soc Heart Transplant. 2012;31:1269–75.CrossRefGoogle Scholar
  95. 95.
    Davis MK, Lee PHU, Witteles RM. Changing outcomes after heart transplantation in patients with amyloid cardiomyopathy. J Heart Lung Transplant. 2015;34:658–66.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Panhwar MS, Al-Kindi SG, Tofovic D, Oliveira GH, Ginwalla M. Waitlist Mortality of Amyloid Cardiomyopathy Patients Listed for Heart Transplantation and Implications for Organ Allocation. J Card Fail [Internet]. 2019 [cited 2019 Apr 27]; Available from:
  97. 97.
    • Kristen AV, Kreusser MM, Blum P, Schönland SO, Frankenstein L, Dösch AO, et al. Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era. J Heart Lung Transplant. 2018;37:611–8. This provides important evidence for improving outcomes in select patients undergoing heart transplantation for amyloid cardiomyopathy. PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Varr BC, Liedtke M, Arai S, Lafayette RA, Schrier SL, Witteles RM. Heart transplantation and cardiac amyloidosis: approach to screening and novel management strategies. J Heart Lung Transplant. 2012;31:325–31.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    • Trachtenberg BH, Kamble RT, Rice L, Araujo-Gutierrez R, Bhimaraj A, Guha A, et al. Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2019.Google Scholar
  100. 100.
    Grogan M, Gertz M, McCurdy A, Roeker L, Kyle R, Kushwaha S, et al. Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: the Mayo Clinic experience. World J Transplant. 2016;6:380–8.PubMedPubMedCentralCrossRefGoogle Scholar

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Authors and Affiliations

  • Aaron M. Wolfson
    • 1
  • Kevin S. Shah
    • 2
  • Jignesh K. Patel
    • 3
    • 4
    Email author
  1. 1.Sarver Heart Center, University of ArizonaTucsonUSA
  2. 2.University of Utah Health Sciences CenterSalt Lake CityUSA
  3. 3.Heart Transplant Program, Cardiac Amyloidosis ProgramBeverly HillsUSA
  4. 4.Smidt Cedars-Sinai Heart InstituteLos AngelesUSA

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