Skip to main content

Advertisement

SpringerLink
Log in

Updates in Cardiac Amyloidosis Diagnosis and Treatment

  • Cardio-oncology (EH Yang, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Cardiac amyloidosis is an underrecognized cause of heart failure. We review clinical clues to the diagnoses, a rational approach to testing, and current and emerging therapies.

Recent Findings

Advances in the diagnosis of amyloid cardiomyopathy include (1) use of 99mtechnetium (99mTc) bone-avid compounds which allow accurate noninvasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in the context of a negative monoclonal light chain screen; and (2) the use of serum and urine immunofixation electrophoresis with serum free light chains as an accurate first diagnostic step for light chain cardiac amyloidosis (AL-CM). Advances in treatment include tafamidis for ATTR-CM and immunologic therapies for AL-CM.

Summary

With the advent of accurate noninvasive diagnostic modalities and effective therapies, early recognition of cardiac amyloidosis is paramount to implement a diagnostic algorithm and expeditiously institute effective therapies to minimize morbidity and mortality.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva MJM, Sekijima Y, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2018;25(4):215–9.

    Article  CAS  PubMed  Google Scholar 

  2. Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study. Ann Med. 2008;40(3):232–9.

    Article  CAS  PubMed  Google Scholar 

  3. Cornwell GG, Murdoch WL, Kyle RA, Westermark P, Pitkänen P. Frequency and distribution of senile cardiovascular amyloid: A clinicopathologic correlation. Am J Med. 1983;75(4):618–23.

    Article  PubMed  Google Scholar 

  4. Kyle RA, Larson DR, Kurtin PJ, Kumar S, Cerhan JR, Therneau TM, et al. Incidence of AL amyloidosis in Olmsted County, Minnesota, 1990 through 2015. Mayo Clin Proc. 2019;94(3):465–71.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lousada I, Comenzo RL, Landau H, Guthrie S, Merlini G. Patient experience with hereditary and senile systemic amyloidoses: a survey from the Amyloidosis Research Consortium. Orphanet J Rare Dis. 2015;10(Suppl 1):P22.

    Article  PubMed Central  Google Scholar 

  6. Muchtar E, Gertz MA, Kyle RA, Lacy MQ, Dingli D, Leung N, et al. A Modern primer on light chain amyloidosis in 592 patients with mass spectrometry-verified typing. Mayo Clin Proc. 2019;94(3):472–83.

    CAS  PubMed  Google Scholar 

  7. McCausland KL, White MK, Guthrie SD, Quock T, Finkel M, Lousada I, et al. Light Chain (AL) Amyloidosis: the Journey to Diagnosis. Patient. 2018;11(2):207–16.

    Article  PubMed  Google Scholar 

  8. 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(7):1817–22.

    Article  CAS  PubMed  Google Scholar 

  9. 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(12):1323–41.

    Article  PubMed  Google Scholar 

  10. Lane T, Fontana M, Martinez-Naharro A, Quarta CC, Whelan CJ, Petrie A, et al. Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis. Circulation. 2019;140(1):16–26.

    Article  CAS  PubMed  Google Scholar 

  11. 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(10):1014–20.

    Article  PubMed  Google Scholar 

  12. Shimazaki C, Hata H, Iida S, Ueda M, Katoh N, Sekijima Y, et al. Nationwide Survey of 741 Patients with systemic amyloid light-chain amyloidosis in Japan. Intern Med. 2018;57(2):181–7.

    Article  CAS  PubMed  Google Scholar 

  13. Rowczenio DM, Noor I, Gillmore JD, Lachmann HJ, Whelan C, Hawkins PN, et al. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum Mutat. 2014;35(9):E2403–12.

    Article  CAS  PubMed  Google Scholar 

  14. Jacobson DR, Alexander AA, Tagoe C, Buxbaum JN. Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African-Americans. Amyloid. 2015;22(3):171–4.

    Article  CAS  PubMed  Google Scholar 

  15. Gillmore JD, Damy T, Fontana M, Hutchinson M, Lachmann HJ, Martinez-Naharro A, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799–806.

    Article  CAS  PubMed  Google Scholar 

  16. 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(18):3751–7.

    Article  CAS  PubMed  Google Scholar 

  17. Lilleness B, Ruberg FL, Mussinelli R, Doros G, Sanchorawala V. Development and validation of a survival staging system incorporating BNP in patients with light chain amyloidosis. Blood. 2019;133(3):215–23.

    Article  CAS  PubMed  Google Scholar 

  18. Longhi S, Lorenzini M, Gagliardi C, Milandri A, Marzocchi A, Marrozzini C, et al. Coexistence of degenerative aortic stenosis and wild-type transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging. 2016;9(3):325–7.

    Article  PubMed  Google Scholar 

  19. Castano 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(38):2879–87.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585–94.

    Article  CAS  PubMed  Google Scholar 

  21. Maurer MS, Hanna M, Grogan M, Dispenzieri A, Witteles R, Drachman B, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Donnelly JP, Hanna M, Sperry BW, Seitz WH Jr. Carpal tunnel syndrome: a potential early, red-flag sign of amyloidosis. J Hand Surg [Am]. 2019;44(10):868–76.

    Article  Google Scholar 

  23. Connors LH, Sam F, Skinner M, Salinaro F, Sun F, Ruberg FL, et al. Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282–90.

    Article  CAS  PubMed  Google Scholar 

  24. 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. 2019;108(12):1324–30.

    Article  CAS  PubMed  Google Scholar 

  25. Milandri A, Farioli A, Gagliardi C, Longhi S, Salvi F, Curti S, et al. Carpal tunnel syndrome in cardiac amyloidosis: implications for early diagnosis and prognostic role across the spectrum of aetiologies. Eur J Heart Fail. 2020;22(3):507–15.

    Article  CAS  PubMed  Google Scholar 

  26. Geller HI, Singh A, Alexander KM, Mirto TM, Falk RH. Association between ruptured distal biceps tendon and wild-type transthyretin cardiac amyloidosis. JAMA. 2017;318(10):962–3.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223–8.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 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(17):2040–50.

    Article  PubMed  Google Scholar 

  29. Rubin J, Alvarez J, Teruya S, Castano A, Lehman RA, Weidenbaum M, et al. Hip and knee arthroplasty are common among patients with transthyretin cardiac amyloidosis, occurring years before cardiac amyloid diagnosis: can we identify affected patients earlier? Amyloid. 2017;24(4):226–30.

    Article  PubMed  Google Scholar 

  30. Rubin J, Maurer MS. Cardiac amyloidosis: overlooked, underappreciated, and treatable. Annu Rev Med. 2020;71:203–19.

    Article  CAS  PubMed  Google Scholar 

  31. Witteles RM, Liedtke M. AL Amyloidosis for the cardiologist and oncologist. J Am Coll Cardiol CardioOnc. 2019;1(1):117–30.

    Google Scholar 

  32. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014;114(7):1089–93.

    Article  PubMed  Google Scholar 

  33. 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(18):1840–9.

    Article  PubMed  Google Scholar 

  34. Towbin JA, McKenna WJ, Abrams DJ, Ackerman MJ, Calkins H, Darrieux FCC, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. 2019;16(11):e301–e72.

    Article  PubMed  Google Scholar 

  35. Aljaroudi WA, Desai MY, Tang WH, Phelan D, Cerqueira MD, Jaber WA. 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. 2014;21(2):271–83.

    Article  PubMed  Google Scholar 

  36. 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. 2012;98(19):1442–8.

    Article  PubMed  Google Scholar 

  37. Martinez-Naharro A, Treibel TA, Abdel-Gadir A, Bulluck H, Zumbo G, Knight DS, et al. Magnetic resonance in transthyretin cardiac amyloidosis. J Am Coll Cardiol. 2017;70(4):466–77.

    Article  CAS  PubMed  Google Scholar 

  38. Scully PR, Patel KP, Saberwal B, Klotz E, Augusto JB, Thornton GD, et al. Identifying cardiac amyloid in aortic stenosis. ECV Quantification by CT in TAVR Patients. JACC Cardiovasc Imaging. 2020;13(10):2177–89 3486.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 2 of 2-diagnostic criteria and appropriate utilization. J Card Fail. 2019;25(11):854–65.

    Article  PubMed  Google Scholar 

  40. Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, et al. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008;3(6):1684–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hanna M, Ruberg FL, Maurer MS, Dispenzieri A, Dorbala S, Falk RH, et al. Cardiac scintigraphy with technetium-99m-labeled bone-seeking tracers for suspected amyloidosis. J Am Coll Cardiol. 2020;75(22):2851–62.

    Article  CAS  PubMed  Google Scholar 

  42. Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, et al. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the american heart association. Circulation. 2020;142(1):e7–e22.

    Article  PubMed  Google Scholar 

  43. Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009;55(3):499–504.

    Article  CAS  PubMed  Google Scholar 

  44. Katzmann JA, Abraham RS, Dispenzieri A, Lust JA, Kyle RA. Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem. 2005;51(5):878–81.

    Article  CAS  PubMed  Google Scholar 

  45. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404–12.

    Article  CAS  PubMed  Google Scholar 

  46. Phull P, Sanchorawala V, Connors LH, Doros G, Ruberg FL, Berk JL, et al. Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR). Amyloid. 2018;25(1):62–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. 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(6):1076–84.

    Article  PubMed  Google Scholar 

  48. Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6(2):195–201.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1(8):880–9.

    Article  PubMed  Google Scholar 

  50. Singh V, Falk R, Di Carli MF, Kijewski M, Rapezzi C, Dorbala S. State-of-the-art radionuclide imaging in cardiac transthyretin amyloidosis. J Nucl Cardiol. 2019;26(1):158–73.

    Article  PubMed  Google Scholar 

  51. Chang ICY, Bois JP, Bois MC, Maleszewski JJ, Johnson GB, Grogan M. Hydroxychloroquine-mediated cardiotoxicity with a false-positive (99m)Technetium-labeled pyrophosphate scan for transthyretin-related cardiac amyloidosis. Circ Cardiovasc Imaging. 2018;11(1):e007059.

    Article  PubMed  Google Scholar 

  52. Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 1 of 2-evidence base and standardized methods of imaging. J Nucl Cardiol. 2019;26(6):2065–123.

    Article  PubMed  Google Scholar 

  53. Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, et al. Multicenter study of planar Technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1(8):880–9.

    Article  PubMed  Google Scholar 

  54. Galat A, Rosso J, Guellich A, Van Der Gucht A, Rappeneau S, Bodez D, et al. Usefulness of (99m)Tc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis. Amyloid. 2015;22(4):210–20.

    Article  CAS  PubMed  Google Scholar 

  55. Cappelli F, Gallini C, Di Mario C, Costanzo EN, Vaggelli L, Tutino F, et al. Accuracy of 99mTc-Hydroxymethylene diphosphonate scintigraphy for diagnosis of transthyretin cardiac amyloidosis. J Nucl Cardiol. 2019;26(2):497–504.

    Article  PubMed  Google Scholar 

  56. Musumeci MB, Cappelli F, Russo D, Tini G, Canepa M, Milandri A, et al. Low sensitivity of bone scintigraphy in detecting Phe64Leu mutation-related transthyretin cardiac amyloidosis. JACC Cardiovasc Imaging. 2020;13(6):1314–21.

    Article  PubMed  Google Scholar 

  57. Leung N, Nasr SH, Sethi S. How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing. Blood. 2012;120(16):3206–13.

    Article  CAS  PubMed  Google Scholar 

  58. Quarta CC, Gonzalez-Lopez E, Gilbertson JA, Botcher N, Rowczenio D, Petrie A, et al. Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. Eur Heart J. 2017;38(24):1905–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kastritis E, Dialoupi I, Gavriatopoulou M, Roussou M, Kanellias N, Fotiou D, et al. Primary treatment of light-chain amyloidosis with bortezomib, lenalidomide, and dexamethasone. Blood Adv. 2019;3(20):3002–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wechalekar AD, Hawkins PN, Gillmore JD. Perspectives in treatment of AL amyloidosis. Br J Haematol. 2008;140(4):365–77.

    Article  CAS  PubMed  Google Scholar 

  61. Manwani R, Cohen O, Sharpley F, Mahmood S, Sachchithanantham S, Foard D, et al. A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib. Blood. 2019;134(25):2271–80.

    Article  PubMed  Google Scholar 

  62. Kastritis E, Leleu X, Arnulf B, Zamagni E, Cibeira MT, Kwok F, et al. Bortezomib, melphalan, and dexamethasone for light-chain amyloidosis. J Clin Oncol. 2020;38(28):3252–60.

    Article  CAS  PubMed  Google Scholar 

  63. Comenzo RL, Reece D, Palladini G, Seldin D, Sanchorawala V, Landau H, et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis. Leukemia. 2012;26(11):2317–25.

    Article  CAS  PubMed  Google Scholar 

  64. Palladini G, Kastritis E, Maurer MS, Zonder J, Minnema MC, Wechalekar AD, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020;136(1):71–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 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. 2018;379(11):1007–16.

    Article  CAS  PubMed  Google Scholar 

  66. Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):11–21.

    Article  CAS  PubMed  Google Scholar 

  67. 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. 2018;379(1):22–31.

    Article  CAS  PubMed  Google Scholar 

  68. Dasgupta NR, Rissing SM, Smith J, Jung J, Benson MD. Inotersen therapy of transthyretin amyloid cardiomyopathy. Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2020;27(1):52–8.

    Article  CAS  Google Scholar 

  69. Benson MD, Dasgupta NR, Rissing SM, Smith J, Feigenbaum H. Safety and efficacy of a TTR specific antisense oligonucleotide in patients with transthyretin amyloid cardiomyopathy. Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2017;24(4):219–25.

    Article  Google Scholar 

  70. Solomon SD, Adams D, Kristen A, Grogan M, Gonzalez-Duarte A, Maurer MS, et al. Effects of patisiran, an RNA interference therapeutic, on cardiac parameters in patients with hereditary transthyretin-mediated amyloidosis. Circulation. 2019;139(4):431–43.

    Article  CAS  PubMed  Google Scholar 

  71. Minamisawa M, Claggett B, Adams D, Kristen AV, Merlini G, Slama MS, et al. Association of patisiran, an RNA interference therapeutic, with regional left ventricular myocardial strain in hereditary transthyretin amyloidosis: The APOLLO Study. JAMA Cardiol. 2019;4(5):466–72.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Judge DP, Kristen AV, Grogan M, Maurer MS, Falk RH, Hanna M, et al. Phase 3 multicenter study of revusiran in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with cardiomyopathy (ENDEAVOUR). Cardiovasc Drugs Ther. 2020;34(3):357–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sekijima Y, Dendle MA, Kelly JW. Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis. Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2006;13(4):236–49.

    Article  CAS  Google Scholar 

  74. 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(24):2658–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ikram A, Donnelly JP, Sperry BW, Samaras C, Valent J, Hanna M. Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center’s experience. Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2018;25(3):197–202.

    Article  CAS  Google Scholar 

  76. Sekijima Y, Tojo K, Morita H, Koyama J, Ikeda S. Safety and efficacy of long-term diflunisal administration in hereditary transthyretin (ATTR) amyloidosis. Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2015;22(2):79–83.

    Article  CAS  Google Scholar 

  77. Castano A, Helmke S, Alvarez J, Delisle S, Maurer MS. Diflunisal for ATTR cardiac amyloidosis. Congestive Heart Fail (Greenwich, Conn). 2012;18(6):315–9.

    Article  CAS  Google Scholar 

  78. Kazi DS, Bellows BK, Baron SJ, Shen C, Cohen DJ, Spertus JA, et al. Cost-effectiveness of tafamidis therapy for transthyretin amyloid cardiomyopathy. Circulation. 2020;141(15):1214–24.

    Article  PubMed  Google Scholar 

  79. Judge DP, Heitner SB, Falk RH, Maurer MS, Shah SJ, Witteles RM, et al. Transthyretin stabilization by AG10 in symptomatic transthyretin amyloid cardiomyopathy. J Am Coll Cardiol. 2019;74(3):285–95.

    Article  CAS  PubMed  Google Scholar 

  80. Judge DP. Long-term safety and efficacy of AG10 in ATTR-CM: phase 2 open label extension. Circulation. 2019;140:e966–e7.

    Google Scholar 

  81. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Wixner J, Pilebro B, Lundgren HE, Olsson M, Anan I. Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis. Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2017;24(sup1):78–9.

    Article  CAS  Google Scholar 

  83. 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: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2012;19(Suppl 1):34–6.

    Article  CAS  Google Scholar 

  84. Ferreira N, Cardoso I, Domingues MR, Vitorino R, Bastos M, Bai G, et al. Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity. FEBS Lett. 2009;583(22):3569–76.

    Article  CAS  PubMed  Google Scholar 

  85. Ferreira N, Saraiva MJ, Almeida MR. Epigallocatechin-3-gallate as a potential therapeutic drug for TTR-related amyloidosis: "in vivo" evidence from FAP mice models. PLoS One. 2012;7(1):e29933.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Aus dem Siepen F, Bauer R, Aurich M, Buss SJ, Steen H, Altland K, et al. Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study. Drug Des Devel Ther. 2015;9:6319–25.

    Article  CAS  PubMed  Google Scholar 

  87. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137–e61.

    Article  PubMed  Google Scholar 

  88. Longhi S, Quarta CC, Milandri A, Lorenzini M, Gagliardi C, Manuzzi L, et al. Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk factors and prognostic role. Amyloid. 2015;22(3):147–55.

    Article  CAS  PubMed  Google Scholar 

  89. Feng D, Syed IS, Martinez M, Oh JK, Jaffe AS, Grogan M, et al. Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis. Circulation. 2009;119(18):2490–7.

    Article  CAS  PubMed  Google Scholar 

  90. Feng D, Edwards WD, Oh JK, Chandrasekaran K, Grogan M, Martinez MW, et al. Intracardiac thrombosis and embolism in patients with cardiac amyloidosis. Circulation. 2007;116(21):2420–6.

    Article  PubMed  Google Scholar 

  91. 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(5):589–97.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Donnellan E, Elshazly MB, Vakamudi S, Wazni OM, Cohen JA, Kanj M, et al. No association between CHADS-VASc score and left atrial appendage thrombus in patients with transthyretin amyloidosis. JACC Clin Electrophysiol. 2019;5(12):1473–4.

    Article  PubMed  Google Scholar 

  93. Givens RC, Russo C, Green P, Maurer MS. Comparison of cardiac amyloidosis due to wild-type and V122I transthyretin in older adults referred to an academic medical center. Aging Health. 2013;9(2):229–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Pinney JH, Whelan CJ, Petrie A, Dungu J, Banypersad SM, Sattianayagam P, et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013;2(2):e000098.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Ruberg FL, Maurer MS, Judge DP, Zeldenrust S, Skinner M, Kim AY, 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. 2012;164(2):222–8 e1.

    Article  CAS  PubMed  Google Scholar 

  96. Donnellan E, Wazni OM, Saliba WI, Baranowski B, Hanna M, Martyn M, et al. Cardiac devices in patients with transthyretin amyloidosis: Impact on functional class, left ventricular function, mitral regurgitation, and mortality. J Cardiovasc Electrophysiol. 2019;30(11):2427–32.

    Article  PubMed  Google Scholar 

  97. Kim EJ, Holmes BB, Huang S, Lugo R, Al Aboud A, Goodman S, et al. Outcomes in patients with cardiac amyloidosis and implantable cardioverter-defibrillator. Europace. 2020;22(8):1216–23.

    Article  PubMed  Google Scholar 

  98. 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(5):563–8.

    Article  PubMed  Google Scholar 

  99. Kittleson MM, Cole RM, Patel J, Ramzy D, Passano E, Chang DH, et al. Mechanical circulatory support for cardiac amyloidosis. Clin Transpl. 2019;33(10):e13663.

    Article  Google Scholar 

  100. 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(5):611–8.

    Article  PubMed  Google Scholar 

  101. Davis MK, Kale P, Liedtke M, Schrier S, Arai S, Wheeler M, et al. Outcomes after heart transplantation for amyloid cardiomyopathy in the modern era. Am J Transplant. 2015;15(3):650–8.

    Article  CAS  PubMed  Google Scholar 

  102. Criteria requirements in adult heart allocation policy. Available from: https://optn.transplant.hrsa.gov/media/2413/adult_heart_criteria.pdf. Accessed 23 Oct 2020.

Download references

Author information

Author notes

  1. Michelle M. Kittleson

    Present address: , Los Angeles, USA

Authors and Affiliations

  1. Department of Cardiology, Smidt Heart Institute, Cedars-Sinai, Los Angeles, CA, USA

    Lily K. Stern & Michelle M. Kittleson

Authors
  1. Lily K. Stern
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michelle M. Kittleson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michelle M. Kittleson.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Cardio-oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stern, L.K., Kittleson, M.M. Updates in Cardiac Amyloidosis Diagnosis and Treatment. Curr Oncol Rep 23, 47 (2021). https://doi.org/10.1007/s11912-021-01028-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11912-021-01028-8

Keywords

Search

Navigation