Pathophysiology and treatment of cardiac amyloidosis

Key Points

  • Cardiac amyloidosis should be suspected in any patient with heart failure and preserved ejection fraction or infiltrative cardiomyopathy

  • Histological diagnosis of amyloid requires further investigation to determine the protein subunit type, because the therapies vary widely

  • Preferred therapies for immunoglobulin light-chain amyloidosis involve standard-dose or high-dose chemotherapy with stem-cell rescue

  • Investigational therapies for transthyretin-related cardiomyopathy are diflunisal or tafamidis, and multiple new therapies for transthyretin-related amyloidosis and antibody therapy for immunoglobulin light-chain amyloidosis are being developed


Amyloid cardiomyopathy should be suspected in any patient who presents with heart failure and preserved ejection fraction. In patients with echocardiographic evidence of ventricular thickening and without a clear history of hypertension, infiltrative cardiomyopathy should be considered. If imaging suggests the presence of amyloid deposits, confirmation by biopsy is required, although endomyocardial biopsy is generally not necessary. Assessment of aspirated subcutaneous fat and bone-marrow biopsy samples verifies the diagnosis in 40–80% of patients, dependent on the type of amyloidosis. Mass spectroscopy can be used to determine the protein subunit and classify the disease as immunoglobulin light-chain amyloidosis or transthyretin-related amyloidosis associated with mutant or wild-type TTR (formerly known as familial amyloid cardiomyopathy and senile cardiac amyloidosis, respectively). In this Review, we discuss the characteristics of cardiac amyloidosis, and present a structured approach to both the assessment of patients and treatment with emerging therapies and organ transplantation.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Endomyocardial biopsy specimen.
Figure 2: Algorithm for diagnosis in patients with suspected amyloidosis.
Figure 3: Algorithm for diagnosis in patients with amyloidosis established by biopsy.


  1. 1

    Gertz, M. A. 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. 79, 319–328 (2005).

  2. 2

    Monge, M. et al. Localized amyloidosis of the genitourinary tract: report of 5 new cases and review of the literature. Medicine (Baltimore) 90, 212–222 (2011).

  3. 3

    Sommer, P., Kumar, G., Lipchik, R. J. & Patel, J. J. Tracheobronchial amyloidosis managed with multimodality therapies. Ther. Adv. Respir. Dis. 8, 48–52 (2014).

  4. 4

    Gertz, M. A. Immunoglobulin light chain amyloidosis: update on diagnosis, prognosis, and treatment. Am. J. Hematol. 88, 416–425 (2013).

  5. 5

    Sikkink, L. A. & Ramirez-Alvarado, M. Cytotoxicity of amyloidogenic immunoglobulin light chains in cell culture. Cell Death Dis. 1, e98 (2010).

  6. 6

    Levinson, R. T. et al. Role of mutations in the cellular internalization of amyloidogenic light chains into cardiomyocytes. Sci. Rep. 3, 1278 (2013).

  7. 7

    Ramirez-Alvarado, M. Amyloid formation in light chain amyloidosis. Curr. Top. Med. Chem. 12, 2523–2533 (2012).

  8. 8

    Pinney, J. H. et al. Systemic amyloidosis in England: an epidemiological study. Br. J. Haematol. 161, 525–532 (2013).

  9. 9

    Bhole, M. V., Sadler, R. & Ramasamy, K. Serum-free light-chain assay: clinical utility and limitations. Ann. Clin. Biochem. 51, 528–542 (2014).

  10. 10

    Kourelis, T. V. et al. Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J. Clin. Oncol. 31, 4319–4324 (2013).

  11. 11

    Kyle, R. A. & Gertz, M. A. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin. Hematol. 32, 45–59 (1995).

  12. 12

    Anrade, C. A peculiar form of peripheral neuropathy: familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 75, 408–427 (1952).

  13. 13

    Azevedo, E. M., Scaff, M., Canelas, H. M. & Spina-Franca, A. Type I primary neuropathic amyloidosis [Portuguese]. Arq. Neuropsiquiatr. 33, 105–118 (1975).

  14. 14

    Rowczenio, D. & Wechalekar, A. Mutations in hereditary amyloidosis [online], (2010).

  15. 15

    Saraiva, M. J. Transthyretin mutations in health and disease. Hum. Mutat. 5, 191–196 (1995).

  16. 16

    Rapezzi, C. et al. Gender-related risk of myocardial involvement in systemic amyloidosis. Amyloid 15, 40–48 (2008).

  17. 17

    Zeldenrust, S. R. Genotype–phenotype correlation in FAP. Amyloid 19 (Suppl. 1), 22–24 (2012).

  18. 18

    Sattianayagam, P. T. et al. Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant. Eur. Heart J. 33, 1120–1127 (2012).

  19. 19

    Arruda-Olson, A. M. et al. Genotype, echocardiography, and survival in familial transthyretin amyloidosis. Amyloid 20, 263–268 (2013).

  20. 20

    Ruberg, F. L. et al. Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS). Am. Heart J. 164, 222–228.e1 (2012).

  21. 21

    Reddi, H. V. et al. Homozygosity for the V122I mutation in transthyretin is associated with earlier onset of cardiac amyloidosis in the African American population in the seventh decade of life. J. Mol. Diagn. 16, 68–74 (2014).

  22. 22

    Pukitis, A. et al. Effect of infliximab induction therapy on secondary systemic amyloidosis associated with Crohn's disease: case report and review of the literature. J. Gastrointestin. Liver Dis. 22, 333–336 (2013).

  23. 23

    Kristen, A. V. et al. Transthyretin valine-94-alanine, a novel variant associated with late-onset systemic amyloidosis with cardiac involvement. Amyloid 14, 283–287 (2007).

  24. 24

    Pinney, J. H. et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J. Am. Heart Assoc. 2, e000098 (2013).

  25. 25

    Swiecicki, P. L. et al. Hereditary amyloidosis: a single-institution experience with 284 patients [abstract OP-53]. Presented at the XIVth International Symposium on Amyloidosis.

  26. 26

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

  27. 27

    Takeda, M. et al. MRI differentiation of cardiomyopathy showing left ventricular hypertrophy and heart failure: differentiation between cardiac amyloidosis, hypertrophic cardiomyopathy, and hypertensive heart disease. Jpn. J. Radiol. 31, 693–700 (2013).

  28. 28

    Mookadam, F., Haley, J. H., Olson, L. J., Cikes, M. & Mookadam, M. Dynamic left ventricular outflow tract obstruction in senile cardiac amyloidosis. Eur. J. Echocardiogr. 7, 465–468 (2006).

  29. 29

    Potysova, Z. et al. Renal AA amyloidosis: survey of epidemiologic and laboratory data from one nephrology centre. Int. Urol. Nephrol. 41, 941–945 (2009).

  30. 30

    Girnius, S., Dember, L., Doros, G. & Skinner, M. The changing face of AA amyloidosis: a single center experience. Amyloid 18 (Suppl. 1), 226–228 (2011).

  31. 31

    Browning, M. J. et al. Ten years' experience of an amyloid clinic: a clinicopathological survey. Q. J. Med. 54, 213–227 (1985).

  32. 32

    Louros, N. N. et al. An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone' segment involved in isolated atrial amyloidosis. FEBS Lett. 588, 52–57 (2014).

  33. 33

    Podduturi, V., Armstrong, D. R., Hitchcock, M. A., Roberts, W. C. & Guileyardo, J. M. Isolated atrial amyloidosis and the importance of molecular classification. Proc. (Bayl. Univ. Med. Cent.) 26, 387–389 (2013).

  34. 34

    Millucci, L. et al. Prevalence of isolated atrial amyloidosis in young patients affected by congestive heart failure. ScientificWorldJournal 2012, 293863 (2012).

  35. 35

    Ariyarajah, V. et al. The association of atrial tachyarrhythmias with isolated atrial amyloid disease: preliminary observations in autopsied heart specimens. Cardiology 113, 132–137 (2009).

  36. 36

    Steensma, D. P. “Congo” red: out of Africa? Arch. Pathol. Lab. Med. 125, 250–252 (2001).

  37. 37

    Benson, M. D., Breall, J., Cummings, O. W. & Liepnieks, J. J. Biochemical characterisation of amyloid by endomyocardial biopsy. Amyloid 16, 9–14 (2009).

  38. 38

    Arbustini, E. et al. Cardiac immunocyte-derived (AL) amyloidosis: an endomyocardial biopsy study in 11 patients. Am. Heart J. 130, 528–536 (1995).

  39. 39

    Sloan, K. P., Bruce, C. J., Oh, J. K. & Rihal, C. S. Complications of echocardiography-guided endomyocardial biopsy. J. Am. Soc. Echocardiogr. 22, 324.e1–324.e4 (2009).

  40. 40

    Gertz, M. A. Immunoglobulin light chain amyloidosis: update on diagnosis, risk-stratification, and management. Am. J. Hematol. 86, 180–186 (2011).

  41. 41

    Fine, N. M. et al. Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis. Am. J. Cardiol. 113, 1723–1727 (2014).

  42. 42

    Brambilla, F., Lavatelli, F., Merlini, G. & Mauri, P. Clinical proteomics for diagnosis and typing of systemic amyloidoses. Proteomics Clin. Appl. 7, 136–143 (2013).

  43. 43

    Chee, C. E., Lacy, M. Q., Dogan, A., Zeldenrust, S. R. & Gertz, M. A. Pitfalls in the diagnosis of primary amyloidosis. Clin. Lymphoma Myeloma Leuk. 10, 177–180 (2010).

  44. 44

    Maleszewski, J. J. et al. Relationship between monoclonal gammopathy and cardiac amyloid type. Cardiovasc. Pathol. 22, 189–194 (2013).

  45. 45

    Paueksakon, P., Fogo, A. B. & Sethi, S. Leukocyte chemotactic factor 2 amyloidosis cannot be reliably diagnosed by immunohistochemical staining. Hum. Pathol. 45, 1445–1450 (2014).

  46. 46

    Mollee, P., Renaut, P., Gottlieb, D. & Goodman, H. How to diagnose amyloidosis. Intern. Med. J. 44, 7–17 (2014).

  47. 47

    Hoshii, Y., Nanbara, H., Cui, D., Takahashi, M. & Ikeda, E. Immunohistochemical examination of Aκ amyloidosis with antibody against adjacent portion of the carboxy terminus of immunoglobulin kappa light chain. Med. Mol. Morphol. 45, 124–128 (2012).

  48. 48

    Satoskar, A. A. et al. Strong transthyretin immunostaining: potential pitfall in cardiac amyloid typing. Am. J. Surg. Pathol. 35, 1685–1690 (2011).

  49. 49

    Vrana, J. A. et al. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 114, 4957–4959 (2009).

  50. 50

    Nasr, S. H. et al. The diagnosis and characteristics of renal heavy-chain and heavy/light-chain amyloidosis and their comparison with renal light-chain amyloidosis. Kidney Int. 83, 463–470 (2013).

  51. 51

    Laffer, U. Intra-portal chemoprevention and therapy of liver metastases [German]. Z. Gastroenterol. Verh. 24, 189–191 (1989).

  52. 52

    Theis, J. D. et al. Proteome of amyloidosis: Mayo Clinic experience in 4139 cases [abstract OP-19] [online], (2014).

  53. 53

    Guan, J. et al. Stanniocalcin1 is a key mediator of amyloidogenic light chain induced cardiotoxicity. Basic Res. Cardiol. 108, 378 (2013).

  54. 54

    Shi, J. et al. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38α MAPK pathway. Proc. Natl Acad. Sci. USA 107, 4188–4193 (2010).

  55. 55

    Mohammed, S. F. et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2, 113–122 (2014).

  56. 56

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

  57. 57

    Mohty, D. et al. Cardiac amyloidosis: updates in diagnosis and management. Arch. Cardiovasc. Dis. 106, 528–540 (2013).

  58. 58

    Russo, C., Green, P. & Maurer, M. The prognostic significance of central hemodynamics in patients with cardiac amyloidosis. Amyloid 20, 199–203 (2013).

  59. 59

    Wittich, C. M., Neben-Wittich, M. A., Mueller, P. S., Gertz, M. A. & Edwards, W. D. Deposition of amyloid proteins in the epicardial coronary arteries of 58 patients with primary systemic amyloidosis. Cardiovasc. Pathol. 16, 75–78 (2007).

  60. 60

    Seward, J. B. & Casaclang-Verzosa, G. Infiltrative cardiovascular diseases: cardiomyopathies that look alike. J. Am. Coll. Cardiol. 55, 1769–1779 (2010).

  61. 61

    Bellavia, D. et al. Detection of left ventricular systolic dysfunction in cardiac amyloidosis with strain rate echocardiography. J. Am. Soc. Echocardiogr. 20, 1194–1202 (2007).

  62. 62

    Buss, S. J. et al. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers. J. Am. Coll. Cardiol. 60, 1067–1076 (2012).

  63. 63

    Bellavia, D. et al. Evidence of impaired left ventricular systolic function by Doppler myocardial imaging in patients with systemic amyloidosis and no evidence of cardiac involvement by standard two-dimensional and Doppler echocardiography. Am. J. Cardiol. 101, 1039–1045 (2008).

  64. 64

    Al-Zahrani, G. B. et al. Doppler myocardial imaging compared to standard two-dimensional and Doppler echocardiography for assessment of diastolic function in patients with systemic amyloidosis. J. Am. Soc. Echocardiogr. 22, 290–298 (2009).

  65. 65

    Nesbitt, G. C. & Mankad, S. Strain and strain rate imaging in cardiomyopathy. Echocardiography 26, 337–344 (2009).

  66. 66

    Bellavia, D. et al. 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 (2010).

  67. 67

    Bellavia, D. et al. Comparison of right ventricular longitudinal strain imaging, tricuspid annular plane systolic excursion, and cardiac biomarkers for early diagnosis of cardiac involvement and risk stratification in primary systematic (AL) amyloidosis: a 5-year cohort study. Eur. Heart J. Cardiovasc. Imaging 13, 680–689 (2012).

  68. 68

    Lee, G. Y. et al. Cardiac amyloidosis without increased left ventricular wall thickness. Mayo Clin. Proc. 89, 781–789 (2014).

  69. 69

    Suresh, R. et al. Advanced cardiac amyloidosis associated with normal interventricular spetal thickness: an uncommon presentation of infiltrative cardiomyopathy. J. Am. Soc. Echocardiogr. 27, 440–447 (2014).

  70. 70

    Hazenberg, B. P. et al. Diagnostic performance and prognostic value of extravascular retention of 123I-labeled serum amyloid P component in systemic amyloidosis. J. Nucl. Med. 48, 865–872 (2007).

  71. 71

    Hawkins, P. N. et al. Scintigraphic imaging and turnover studies with iodine-131 labelled serum amyloid P component in systemic amyloidosis. Eur. J. Nucl. Med. 25, 701–708 (1998).

  72. 72

    Sachchithanantham, S. & Wechalekar, A. D. Imaging in systemic amyloidosis. Br. Med. Bull. 107, 41–56 (2013).

  73. 73

    Bokhari, S. et al. 99mTc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ. Cardiovasc. Imaging 6, 195–201 (2013).

  74. 74

    Gertz, M. A., Brown, M. L., Hauser, M. F. & Kyle, R. A. Utility of technetium Tc 99m pyrophosphate bone scanning in cardiac amyloidosis. Arch. Intern. Med. 147, 1039–1044 (1987).

  75. 75

    Aljaroudi, W. A. et al. Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: state of the art review and focus on emerging nuclear techniques. J. Nucl. Cardiol. 21, 271–283 (2014).

  76. 76

    Storandt, M., Mintun, M. A., Head, D. & Morris, J. C. Cognitive decline and brain volume loss as signatures of cerebral amyloid-β peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition. Arch. Neurol. 66, 1476–1481 (2009).

  77. 77

    Antoni, G. et al. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J. Nucl. Med. 54, 213–220 (2013).

  78. 78

    Wang, J. et al. Noninvasive diagnosis of cardiac amyloidosis by MRI and echochardiography. J. Huazhong Univ. Sci. Technolog. Med. Sci. 30, 536–540 (2010).

  79. 79

    Cheng, A. S., Banning, A. P., Mitchell, A. R., Neubauer, S. & Selvanayagam, J. B. Cardiac changes in systemic amyloidosis: visualisation by magnetic resonance imaging. Int. J. Cardiol. 113, E21–E23 (2006).

  80. 80

    Aquaro, G. D. et al. Myocardial signal intensity decay after gadolinium injection: a fast and effective method for the diagnosis of cardiac amyloidosis. Int. J. Cardiovasc. Imaging 30, 1105–1115 (2014).

  81. 81

    Pouchot, J. & Arlet, J. B. Biological treatment in adult-onset Still's disease. Best Pract. Res. Clin. Rheumatol. 26, 477–487 (2012).

  82. 82

    Rubinshtein, R. et al. Comparison of magnetic resonance imaging versus Doppler echocardiography for the evaluation of left ventricular diastolic function in patients with cardiac amyloidosis. Am. J. Cardiol. 103, 718–723 (2009).

  83. 83

    Syed, I. S. et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc. Imaging 3, 155–164 (2010).

  84. 84

    Giesbrandt, K. J., Bolan, C. W., Shapiro, B. P., Edwards, W. D. & Mergo, P. J. Diffuse diseases of the myocardium: MRI-pathologic review of cardiomyopathies with dilatation. Am. J. Roentgenol. 200, W274–W282 (2013).

  85. 85

    Harvey-Taylor, J., Zhang, Y., Kuderer, V. & Cooke, D. T. Diagnosis of systemic amyloidosis and amyloidosis mediated cardiomyopathy by VATS pleural biopsy for chronic pleural effusion. J. Thorac. Dis. 5, E112–E114 (2013).

  86. 86

    Finocchiaro, G. et al. Long term survival in patients with cardiac amyloidosis: prevalence and characterisation during follow-up. Heart Lung Circ. 22, 647–654 (2013).

  87. 87

    Chaulagain, C. P. & Comenzo, R. L. New insights and modern treatment of AL amyloidosis. Curr. Hematol. Malig. Rep. 8, 291–298 (2013).

  88. 88

    Dispenzieri, A. et al. Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 104, 1881–1887 (2004).

  89. 89

    Gertz, M. A. et al. Clinical outcome of immunoglobulin light chain amyloidosis affecting the kidney. Nephrol. Dial. Transplant. 24, 3132–3137 (2009).

  90. 90

    Park, M. A. et al. Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine (Baltimore) 82, 291–298 (2003).

  91. 91

    Rajkumar, S. V., Gertz, M. A. & Kyle, R. A. Prognosis of patients with primary systemic amyloidosis who present with dominant neuropathy. Am. J. Med. 104, 232–237 (1998).

  92. 92

    Dispenzieri, A. et al. High sensitivity cardiac troponin T in patients with immunoglobulin light chain amyloidosis. Heart 100, 383–388 (2014).

  93. 93

    Kumar, S. et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J. Clin. Oncol. 30, 989–995 (2012).

  94. 94

    Halwani, O. & Delgado, D. H. Cardiac amyloidosis: an approach to diagnosis and management. Expert Rev. Cardiovasc. Ther. 8, 1007–1013 (2010).

  95. 95

    Nash, K. L., Brij, S. O. & Clesham, G. J. Cardiac amyloidosis and the use of diuretic and ACE inhibitor therapy in severe heart failure. Int. J. Clin. Pract. 51, 384–385 (1997).

  96. 96

    Bouhour, J. B., Haddak, M. & Lefevre, M. Risks of beta-blockers and calcium inhibitors in amyloid cardiopathy [French]. Presse Med. 15, 981 (1986).

  97. 97

    Desport, E. et al. AL amyloidosis. Orphanet J. Rare Dis. 7, 54 (2012).

  98. 98

    Lin, G., Dispenzieri, A., Kyle, R., Grogan, M. & Brady, P. A. Implantable cardioverter defibrillators in patients with cardiac amyloidosis. J. Cardiovasc. Electrophysiol. 24, 793–798 (2013).

  99. 99

    Hess, E. P. & White, R. D. Out-of-hospital cardiac arrest in patients with cardiac amyloidosis: presenting rhythms, management and outcomes in four patients. Resuscitation 60, 105–111 (2004).

  100. 100

    Swiecicki, P. L. et al. Left ventricular device implantation for advanced cardiac amyloidosis. J. Heart Lung Transplant. 32, 563–568 (2013).

  101. 101

    Feng, D. et al. Intracardiac thrombosis and embolism in patients with cardiac amyloidosis. Circulation 116, 2420–2426 (2007).

  102. 102

    Zubkov, A. Y., Rabinstein, A. A., Dispenzieri, A. & Wijdicks, E. F. Primary systemic amyloidosis with ischemic stroke as a presenting complication. Neurology 69, 1136–1141 (2007).

  103. 103

    Feng, D. et al. Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis. Circulation 119, 2490–2497 (2009).

  104. 104

    Kumar, S. K. et al. Recent improvements in survival in primary systemic amyloidosis and the importance of an early mortality risk score. Mayo Clin. Proc. 86, 12–18 (2011).

  105. 105

    Gertz, M. A. How to manage primary amyloidosis. Leukemia 26, 191–198 (2012).

  106. 106

    Nelson, M. R. et al. Histologic remission of cardiac amyloidosis: a case report. Amyloid 19, 106–109 (2012).

  107. 107

    Palladini, G. et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J. Clin. Oncol. 30, 4541–4549 (2012).

  108. 108

    Merlini, G., Seldin, D. C. & Gertz, M. A. Amyloidosis: pathogenesis and new therapeutic options. J. Clin. Oncol. 29, 1924–1933 (2011).

  109. 109

    Kumar, S. K. et al. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood 119, 4860–4867 (2012).

  110. 110

    Tapan, U. et al. Increases in B-type natriuretic peptide (BNP) during treatment with lenalidomide in AL amyloidosis. Blood 116, 5071–5072 (2010).

  111. 111

    Mikhael, J. R. et al. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood 119, 4391–4394 (2012).

  112. 112

    Landau, H. et al. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia 27, 823–828 (2013).

  113. 113

    Gertz, M. et al. Troponin T level as an exclusion criterion for stem cell transplantation in light-chain amyloidosis. Leuk. Lymphoma 49, 36–41 (2008).

  114. 114

    Gertz, M. A. et al. Trends in day 100 and 2-year survival after auto-SCT for AL amyloidosis: outcomes before and after 2006. Bone Marrow Transplant. 46, 970–975 (2011).

  115. 115

    Gertz, M. A. et al. Trend toward improved day 100 and two-year survival following stem cell transplantation for AL: a comparison before and after 2006. Amyloid 18 (Suppl. 1), 137–138 (2011).

  116. 116

    Bellavia, D. et al. Utility of Doppler myocardial imaging, cardiac biomarkers, and clonal immunoglobulin genes to assess left ventricular performance and stratify risk following peripheral blood stem cell transplantation in patients with systemic light chain amyloidosis (AL). J. Am. Soc. Echocardiogr. 24, 444–454 (2011).

  117. 117

    Singla, A. et al. Incidence of supraventricular arrhythmias during autologous peripheral blood stem cell transplantation. Biol. Blood Marrow Transplant. 19, 1233–1237 (2013).

  118. 118

    Bleeker, J. S. et al. Evaluation of pretransplant factors predicting cardiac dysfunction following high-dose melphalan conditioning and autologous peripheral blood stem cell transplantation. Eur. J. Haematol. 89, 228–235 (2012).

  119. 119

    Madan, S. et al. High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement. Blood 119, 1117–1122 (2012).

  120. 120

    Gertz, M. A. et al. Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transplant. 48, 557–561 (2013).

  121. 121

    Jimenez-Zepeda, V. H. et al. Autologous stem cell transplant is an effective therapy for carefully selected patients with AL amyloidosis: experience of a single institution. Br. J. Haematol. 164, 722–728 (2014).

  122. 122

    Dispenzieri, A. et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 109, 465–470 (2007).

  123. 123

    Dispenzieri, A. et al. Discordance between serum cardiac biomarker and immunoglobulin-free light-chain response in patients with immunoglobulin light-chain amyloidosis treated with immune modulatory drugs. Am. J. Hematol. 85, 757–759 (2010).

  124. 124

    Dispenzieri, A. et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood 119, 5397–5404 (2012).

  125. 125

    Liedtke, M. et al. Preliminary cardiac biomarker responses demonstrated in an ongoing phase I study of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction [abstract PB-48] [online], (2014).

  126. 126

    Gertz, M. A. & Dispenzieri, A. Immunoglobulin light-chain amyloidosis: growing recognition, new approaches to therapy, active clinical trials. Oncology (Williston Park) 26, 152–161 (2012).

  127. 127

    Lacy, M. Q. et al. Autologous stem cell transplant after heart transplant for light chain (AL) amyloid cardiomyopathy. J. Heart Lung Transplant. 27, 823–829 (2008).

  128. 128

    Gray Gilstrap, L. et al. Predictors of survival to orthotopic heart transplant in patients with light chain amyloidosis. J. Heart Lung Transplant. 33, 149–156 (2014).

  129. 129

    Varr, B. C. et al. Heart transplantation and cardiac amyloidosis: approach to screening and novel management strategies. J. Heart Lung Transplant. 31, 325–331 (2012).

  130. 130

    Raichlin, E. et al. Combined heart and liver transplantation: a single-center experience. Transplantation 88, 219–225 (2009).

  131. 131

    Merlini, G. et al. Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. J. Cardiovasc. Transl. Res. 6, 1011–1020 (2013).

  132. 132

    Coelho, T. et al. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J. Neurol. 260, 2802–2814 (2013).

  133. 133

    Merlini, G. et al. Survival in patients with transthyretin familial amyloid polyneuropathy receiving tafamidis treatment [abstract OP-65]. Presented at the XIVth International Symposium on Amyloidosis.

  134. 134

    Maurer, M. S., Judge, D. P., Rosas, G. R., Mandel, F. S. & Aarts, J. Interim analysis of long-term, open-label tafamidis treatment in transthyretin amyloid cardiomyopathy after up to 5 years of treatment [abstract OP-66]. Presented at the XIVth International Symposium on Amyloidosis.

  135. 135

    Coelho, T. et al. Familial amyloid polyneuropathy treatment with tafamidis: evaluation of one year treatment at Porto, Portugal [abstract OP-67]. Presented at the XIVth International Symposium on Amyloidosis.

  136. 136

    Obici, L. et al. A phase II study of doxycycline plus tauroursodeoxycholic acid in transthyretin amyloidosis [abstract OP-68]. Presented at the XIVth International Symposium on Amyloidosis.

  137. 137

    Quarta, C. C. et al. The prevalence of cardiac amyloidosis in familial amyloidotic polyneuropathy with predominant neuropathy: the Diflunisal Trial [abstract OP-69]. Presented at the XIVth International Symposium on Amyloidosis.

  138. 138

    Berk, J. L. et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA 310, 2658–2667 (2013).

  139. 139

    Ackermann, E. J., Hughes, S., Yamashita, M. & Monia, B. P. Clinical development of ISIS-TTRRx: a second generation antisense therapy for the treatment of transthyretin-associated diseases [abstract OP-71]. Presented at the XIVth International Symposium on Amyloidosis.

  140. 140

    Suhr, O. et al. Further analysis of phase II trial of patisiran, a novel RNAi therapeutic for the treatment of familial amyloidotic polyneuropathy [abstract OP-72]. Presented at the XIVth International Symposium on Amyloidosis.

Download references

Author information

M.A.G. researched data for the article, discussed its content, and wrote, reviewed, and edited the manuscript before submission. A.D. and T.S. also wrote the manuscript, and reviewed and edited it before submission.

Correspondence to Morie A. Gertz.

Ethics declarations

Competing interests

M.A.G. declares that he has received honoraria from Celgene, ISIS, Millennium, Neotope, Novartis, and Onyx. A.D. declares that she has received research funding from Celgene, Janssen, Millennium, and Pfizer. T.S. declares no competing interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gertz, M., Dispenzieri, A. & Sher, T. Pathophysiology and treatment of cardiac amyloidosis. Nat Rev Cardiol 12, 91–102 (2015).

Download citation

Further reading