Skip to main content
Have a personal or library account? Click to login
Clinical Clues and Diagnostic Workup of Cardiac Amyloidosis Cover

Clinical Clues and Diagnostic Workup of Cardiac Amyloidosis

Open Access
|Mar 2022

References

  1. Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021 Apr 21;42(16):15541568. doi: 10.1093/eurheartj/ehab072
  2. Hasserjian RP, Goodman HJB, Lachmann HJ, Muzikansky A, Hawkins PN. Bone marrow findings correlate with clinical outcome in systemic AL amyloidosis patients. Histopathology. 2007 Apr;50(5):56773. doi: 10.1111/j.1365-2559.2007.02658.x
  3. Muchtar E, Buadi FK, Dispenzieri A, Gertz MA. Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy. Acta Haematol. 2016;135(3):17290. doi: 10.1159/000443200
  4. Eirin A, Irazabal MV, Gertz MA, et al. Clinical features of patients with immunoglobulin light chain amyloidosis (AL) with vascular-limited deposition in the kidney. Nephrol Dial Transplant. 2012 Mar;27(3):1097101. doi: 10.1093/ndt/gfr381
  5. McCausland KL, White MK, Guthrie SD, et al. Light Chain (AL) Amyloidosis: The Journey to Diagnosis. Patient. 2018 Apr;11(2):207216. doi: 10.1007/s40271-017-0273-5
  6. Nienhuis HLA, Bijzet J, Hazenberg BPC. The Prevalence and Management of Systemic Amyloidosis in Western Countries. Kidney Dis (Basel). 2016 Apr;2(1):109. doi: 10.1159/000444206. Epub 2016 Feb 25. doi: 10.1159/000444206
  7. Purkey HE, Dorrell MI, Kelly JW. Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma. Proc Natl Acad Sci U S A. 2001 May 8;98(10):556671. doi: 10.1073/pnas.091431798
  8. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003 Aug 7;349(6):58396. doi: 10.1056/NEJMra023144
  9. Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):5863. doi: 10.3109/13506129.2015.1135792
  10. Aus dem Siepen F, Hein S, Prestel S, et al. Carpal tunnel syndrome and spinal canal stenosis: harbingers of transthyretin amyloid cardiomyopathy? Clin Res Cardiol. 2019 Dec;108(12):13241330. doi: 10.1007/s00392-019-01467-1
  11. Parman Y, Adams D, Obici L, et al. Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP. Curr Opin Neurol. 2016 Feb;29 Suppl 1(Suppl 1):S3S13. doi: 10.1097/WCO.0000000000000288
  12. Mariani L-L, Lozeron P, Théaudin M, et al. Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France. Ann Neurol. 2015 Dec;78(6):90116. doi: 10.1002/ana.24519
  13. Waddington-Cruz M, Ackermann EJ, Polydefkis M, et al. Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial. Amyloid. 2018 Sep;25(3):180188. doi: 10.1080/13506129.2018.1503593
  14. Russo M, Obici L, Bartolomei I, Cappelli F, Luigetti M, Fenu S, et al. ATTRv amyloidosis Italian Registry: clinical and epidemiological data. Amyloid. 2020 Dec;27(4):259265. doi: 10.1080/13506129.2020.1794807
  15. Chandrashekar P, Alhuneafat L, Mannello M, et al. Prevalence and Outcomes of p.Val142Ile TTR Amyloidosis Cardiomyopathy: A Systematic Review. Circ Genom Precis Med. 2021 Oct;14(5):e003356. doi: 10.1161/CIRCGEN.121.003356
  16. Shah KB, Mankad AK, Castano A, et al. Transthyretin Cardiac Amyloidosis in Black Americans. Circ Heart Fail. 2016 Jun;9(6):e002558. doi: 10.1161/CIRCHEARTFAILURE.115.002558
  17. Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018 Jan;28(1):1021. doi: 10.1016/j.tcm.2017.07.004
  18. Perlini S, Mussinelli R, Salinaro F. New and Evolving Concepts Regarding the Prognosis and Treatment of Cardiac Amyloidosis. Curr Heart Fail Rep. 2016 Dec;13(6):267272. doi: 10.1007/s11897-016-0311-y
  19. Ihne S, Morbach C, Sommer C, Geier A, Knop S, Störk S. Amyloidosis-the Diagnosis and Treatment of an Underdiagnosed Disease. Dtsch Arztebl Int. 2020 Mar 6;117(10):159166. doi: 10.3238/arztebl.2020.0159
  20. Martinez-Naharro A, Hawkins PN, Fontana M. Cardiac amyloidosis. Clin Med (Lond). 2018 Apr 1;18(Suppl 2):s30s35. doi: 10.7861/clinmedicine.18-2-s30
  21. Dispenzieri A, Gertz MA, Buadi F. What do I need to know about immunoglobulin light chain (AL) amyloidosis? Blood Rev. 2012 Jul;26(4):13754. doi: 10.1016/j.blre.2012.03.001
  22. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):10071016. doi: 10.1056/NEJMoa1805689
  23. Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005 Sep 27;112(13):204760. doi: 10.1161/CIRCULATIONAHA.104.489187
  24. Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012 Sep 4;126(10):1286300. doi: 10.1161/CIRCULATIONAHA.111.078915
  25. Pennell DJ, Maceira AM. Magnetic resonance imaging in cardiac amyloidosis. JACC Cardiovasc Imaging. 2009 Dec;2(12):137880. doi: 10.1016/j.jcmg.2009.10.001
  26. Dispenzieri A, Merlini G. Immunoglobulin Light Chain Systemic Amyloidosis. Cancer Treat Res. 2016;169:273318. doi: 10.1007/978-3-319-40320-5_15
  27. Rahman JE, Helou EF, Gelzer-Bell R, et al. Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol. 2004 Feb 4;43(3):4105. doi: 10.1016/j.jacc.2003.08.043
  28. Papathanasiou M, Carpinteiro A, Rischpler C, Hagenacker T, Rassaf T, Luedike P. Diagnosing cardiac amyloidosis in every-day practice: A practical guide for the cardiologist. Int J Cardiol Heart Vasc. 2020 Apr 27;28:100519. doi: 10.1016/j.ijcha.2020.100519
  29. Pagourelias ED, Mirea O, Duchenne J, et al. Echo Parameters for Differential Diagnosis in Cardiac Amyloidosis: A Head-to-Head Comparison of Deformation and Nondeformation Parameters. Circ Cardiovasc Imaging. 2017 Mar;10(3):e005588. doi: 10.1161/CIRCIMAGING.116.005588
  30. Castaño A, Narotsky DL, Hamid N, 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 Oct 7;38(38):28792887. doi: 10.1093/eurheartj/ehx350
  31. Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982 Jan;49(1):913. doi: 10.1016/0002-9149(82)90270-3
  32. Murtagh B, Hammill SC, Gertz MA, Kyle RA, Tajik AJ, Grogan M. Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol. 2005 Feb 15;95(4):5357. doi: 10.1016/j.amjcard.2004.10.028
  33. 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 Oct 1;114(7):108993. doi: 10.1016/j.amjcard.2014.07.026
  34. Mussinelli R, Salinaro F, Alogna A, et al. Diagnostic and prognostic value of low QRS voltages in cardiac AL amyloidosis. Ann Noninvasive Electrocardiol. 2013 May;18(3):27180. doi: 10.1111/anec.12036
  35. Dungu JN, Papadopoulou SA, Wykes K, et al. Afro-Caribbean Heart Failure in the United Kingdom: Cause, Outcomes, and ATTR V122I Cardiac Amyloidosis. Circ Heart Fail. 2016 Sep;9(9):e003352. doi: 10.1161/CIRCHEARTFAILURE.116.003352
  36. Treibel TA, Fontana M, Gilbertson JA, et al. Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement. Circ Cardiovasc Imaging. 2016 Aug;9(8):e005066. doi: 10.1161/CIRCIMAGING.116.005066
  37. Rosenblum H, Masri A, Narotsky DL, et al. Unveiling outcomes in coexisting severe aortic stenosis and transthyretin cardiac amyloidosis. Eur J Heart Fail. 2021 Feb;23(2):250258. doi: 10.1002/ejhf.1974
  38. Nitsche C, Scully PR, Patel KP, et al. Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis. J Am Coll Cardiol. 2021 Jan 19;77(2):128139. doi: 10.1016/j.jacc.2020.11.006
  39. Takashio S, Yamamuro M, Izumiya Y, et al. Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis. ESC Heart Fail. 2018 Feb;5(1):2735. doi: 10.1002/ehf2.12203
  40. Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med. 2017 Dec;84(12 Suppl 3):1226. doi: 10.3949/ccjm.84.s3.02
  41. Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System. J Am Coll Cardiol. 2016 Sep 6;68(10):101420. doi: 10.1016/j.jacc.2016.06.033
  42. Kreusser MM, Volz MJ, Knop B, et al. A novel risk score to predict survival in advanced heart failure due to cardiac amyloidosis. Clin Res Cardiol. 2020 Jun;109(6):700713. doi: 10.1007/s00392-019-01559-y
  43. Dispenzieri A, Gertz MA, Kyle RA, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004 Sep 15;22(18):37517. doi: 10.1200/JCO.2004.03.029
  44. Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018 Aug 7;39(30):27992806. doi: 10.1093/eurheartj/ehx589
  45. Bonderman D, Pölzl G, Ablasser K, et al. Diagnosis and treatment of cardiac amyloidosis: an interdisciplinary consensus statement. Wien Klin Wochenschr. 2020 Dec;132(23–24):742761. doi: 10.1007/s00508-020-01781-z
  46. Palladini G, Russo P, Bosoni T, 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 Mar;55(3):499504. doi: 10.1373/clinchem.2008.117143
  47. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 Jun 11;73(22):28722891. doi: 10.1016/j.jacc.2019.04.003
  48. Phull P, Sanchorawala V, Connors LH, et al. Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR). Amyloid. 2018 Mar;25(1):6267. doi: 10.1080/13506129.2018.1436048
  49. Singh G. Serum Free Light Chain Assay and κ/λ Ratio Performance in Patients Without Monoclonal Gammopathies: High False-Positive Rate. Am J Clin Pathol. 2016 Aug;146(2):20714. doi: 10.1093/ajcp/aqw099
  50. Abadie JM, van Hoeven KH, Wells JM. Are renal reference intervals required when screening for plasma cell disorders with serum free light chains and serum protein electrophoresis? Am J Clin Pathol. 2009 Feb;131(2):16671. doi: 10.1309/AJCPR2M4EUYNHLGM
  51. Marshall G, Tate J, Mollee P. Borderline high serum free light chain kappa/lambda ratios are seen not only in dialysis patients but also in non-dialysis-dependent renal impairment and inflammatory states. Am J Clin Pathol. 2009 Aug;132(2):309. doi: 10.1309/AJCP8VOT5TVLAQBQ
  52. Hanson JLS, Arvanitis M, Koch CM, et al. Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin. Circ Heart Fail. 2018 Feb;11(2):e004000. doi: 10.1161/CIRCHEARTFAILURE.117.004000
  53. Saith SE, Gamino D, Teruya S, et al. Factors associated with changes in serum transthyretin after treatment with tafamidis and outcomes in transthyretin cardiac amyloidosis. Amyloid. 2021 Dec;28(4):267268. doi: 10.1080/13506129.2021.1904390
  54. Arvanitis M, Koch CM, Chan GG, et al. Identification of Transthyretin Cardiac Amyloidosis Using Serum Retinol-Binding Protein 4 and a Clinical Prediction Model. JAMA Cardiol. 2017 Mar 1;2(3):305313. doi: 10.1001/jamacardio.2016.5864
  55. Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016 Jun 14;133(24):240412. doi: 10.1161/CIRCULATIONAHA.116.021612
  56. Brownrigg J, Lorenzini M, Lumley M, Elliott P. Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta-analysis. ESC Heart Fail. 2019 Oct;6(5):10411051. doi: 10.1002/ehf2.12511
  57. Pucci A, Aimo A, Musetti V, et al. Amyloid Deposits and Fibrosis on Left Ventricular Endomyocardial Biopsy Correlate With Extracellular Volume in Cardiac Amyloidosis. J Am Heart Assoc. 2021 Oct 19;10(20):e020358. doi: 10.1161/JAHA.120.020358
  58. Maceira AM, Joshi J, Prasad SK. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2005 Jan 18;111(2):18693. doi: 10.1161/01.CIR.0000152819.97857.9D
  59. Baggiano A, Boldrini M, Martinez-Naharro A, et al. Noncontrast Magnetic Resonance for the Diagnosis of Cardiac Amyloidosis. JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 1):6980. doi: 10.1016/j.jcmg.2019.03.026
  60. Martinez-Naharro A, Treibel TA, Abdel-Gadir A, et al. Magnetic Resonance in Transthyretin Cardiac Amyloidosis. J Am Coll Cardiol. 2017 Jul 25;70(4):466477. doi: 10.1016/j.jacc.2017.05.053
  61. Dorbala S, Ando Y, Bokhari S, 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. Circ Cardiovasc Imaging. 2021 Jul;14(7):e000030. doi: 10.1161/HCI.0000000000000029
  62. Bokhari S, Castaño 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 Mar 1;6(2):195201. doi: 10.1161/CIRCIMAGING.112.000132
  63. Poterucha TJ, Elias P, Bokhari S, et al. Diagnosing Transthyretin Cardiac Amyloidosis by Technetium Tc 99m Pyrophosphate: A Test in Evolution. JACC Cardiovasc Imaging. 2021 Jun;14(6):12211231. doi: 10.1016/j.jcmg.2020.08.027
  64. Alexander KM, Masri A. Recipe for Success in Transthyretin Cardiomyopathy: Monoclonal Protein Rule Out, SPECT Imaging, and Genetic Testing. JACC Cardiovasc Imaging. 2021 Jun;14(6):12321234. doi: 10.1016/j.jcmg.2020.09.009
  65. Masri A, Bukhari S, Ahmad S, et al. Efficient 1-Hour Technetium-99 m Pyrophosphate Imaging Protocol for the Diagnosis of Transthyretin Cardiac Amyloidosis. Circ Cardiovasc Imaging. 2020 Feb;13(2):e010249. doi: 10.1161/CIRCIMAGING.119.010249
  66. Duvall WL, Godoy Rivas C, Elsadany M, Hobocan M, Mcmahon S. The use of a novel method for SPECT/CT quantification of 99m-Tc-PYP uptake in the evaluation of ATTR cardiac amyloidosis. Eur Heart J Cardiovasc Imaging. 2021 Jul 20;22(Suppl 3). doi: 10.1093/ehjci/jeab111.075
  67. Dasari S, Theis JD, Vrana JA, et al. Amyloid Typing by Mass Spectrometry in Clinical Practice: a Comprehensive Review of 16,175 Samples. Mayo Clin Proc. 2020 Sep;95(9):18521864. doi: 10.1016/j.mayocp.2020.06.029
  68. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):1121. doi: 10.1056/NEJMoa1716153
  69. Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):2231. doi: 10.1056/NEJMoa1716793
DOI: https://doi.org/10.14797/mdcvj.1061 | Journal eISSN: 1947-6108
Language: English
Page range: 36 - 46
Submitted on: Nov 12, 2021
Accepted on: Feb 10, 2022
Published on: Mar 14, 2022
Published by: Houston Methodist DeBakey Heart & Vascular Center
In partnership with: Paradigm Publishing Services

© 2022 Sajan S. Gill, Eric Fellin, Lisa Stampke, Yuanzi Zhao, Ahmad Masri, published by Houston Methodist DeBakey Heart & Vascular Center
This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 License.