Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Review article: Biomedical intelligence

Vol. 154 No. 11 (2024)

Cardiac amyloidosis

DOI
https://doi.org/10.57187/s.4186
Cite this as:
Swiss Med Wkly. 2024;154:4186
Published
14.11.2024

Summary

Cardiac amyloidosis is a disease characterised by the accumulation of amyloid protein in the heart tissue. There are several types of amyloidosis, but the most common types affecting the heart are ATTR amyloidosis (caused by transthyretin protein) and AL amyloidosis (caused by abnormal immunoglobulin light chains). Cardiac amyloidosis causes typical signs and symptoms of heart failure. Diagnosis involves a combination of imaging tests such as echocardiography and cardiac magnetic resonance imaging, as well as nuclear imaging scans and tissue biopsies to confirm the presence of amyloid deposits in the heart. Treatment of cardiac amyloidosis depends on the type and severity of the disease and includes medications to manage symptoms as well as treatments targeting the underlying cause of amyloidosis. Importantly, cardiac amyloidosis is a serious condition requiring specialised care from a multidisciplinary team including cardiologists and haematologists as well as other specialists familiar with the management of this rare disease. This is crucial, as early diagnosis and treatment are important for improving outcomes.

References

  1. Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CC. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol. 1997 Oct;273(3):729–39. doi: https://doi.org/10.1006/jmbi.1997.1348 DOI: https://doi.org/10.1006/jmbi.1997.1348
  2. Röcken C, Sletten K. Amyloid in surgical pathology. Virchows Arch. 2003 Jul;443(1):3–16. doi: https://doi.org/10.1007/s00428-003-0834-y DOI: https://doi.org/10.1007/s00428-003-0834-y
  3. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995 Jan;32(1):45–59.
  4. Jeyashekar NS, Sadana A, Vo-Dinh T. Protein amyloidose misfolding: mechanisms, detection, and pathological implications. Methods Mol Biol. 2005;300:417–35. doi: https://doi.org/10.1385/1-59259-858-7:417 DOI: https://doi.org/10.1385/1-59259-858-7:417
  5. Nitsche C, Scully PR, Patel KP, Kammerlander AA, Koschutnik M, Dona C, et al. Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis. J Am Coll Cardiol. 2021 Jan;77(2):128–39. doi: https://doi.org/10.1016/j.jacc.2020.11.006 DOI: https://doi.org/10.1016/j.jacc.2020.11.006
  6. Falk RH, Alexander KM, Liao R, Dorbala S. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. J Am Coll Cardiol. 2016 Sep;68(12):1323–41. doi: https://doi.org/10.1016/j.jacc.2016.06.053 DOI: https://doi.org/10.1016/j.jacc.2016.06.053
  7. 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 Mar;30(9):989–95. doi: https://doi.org/10.1200/JCO.2011.38.5724 DOI: https://doi.org/10.1200/JCO.2011.38.5724
  8. Oubari S, Hegenbart U, Schoder R, Steinhardt M, Papathanasiou M, Rassaf T, et al. Daratumumab in first-line treatment of patients with light chain amyloidosis and Mayo stage IIIb improves treatment response and overall survival. Haematologica. 2024 Jan;109(1):220–30. DOI: https://doi.org/10.3324/haematol.2023.283325
  9. Staron A, Zheng L, Doros G, Connors LH, Mendelson LM, Joshi T, et al. Marked progress in AL amyloidosis survival: a 40-year longitudinal natural history study. Blood Cancer J. 2021 Aug;11(8):139. doi: https://doi.org/10.1038/s41408-021-00529-w DOI: https://doi.org/10.1038/s41408-021-00529-w
  10. 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 Aug;39(30):2799–806. doi: https://doi.org/10.1093/eurheartj/ehx589 DOI: https://doi.org/10.1093/eurheartj/ehx589
  11. Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018 May;2(10):1046–53. doi: https://doi.org/10.1182/bloodadvances.2018016402 DOI: https://doi.org/10.1182/bloodadvances.2018016402
  12. Gilstrap LG, Dominici F, Wang Y, El-Sady MS, Singh A, Di Carli MF, et al. Epidemiology of Cardiac Amyloidosis-Associated Heart Failure Hospitalizations Among Fee-for-Service Medicare Beneficiaries in the United States. Circ Heart Fail. 2019 Jun;12(6):e005407. doi: https://doi.org/10.1161/CIRCHEARTFAILURE.118.005407 DOI: https://doi.org/10.1161/CIRCHEARTFAILURE.118.005407
  13. Lauppe R, Liseth Hansen J, Fornwall A, Johansson K, Rozenbaum MH, Strand AM, et al. Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries. ESC Heart Fail. 2022 Aug;9(4):2528–37. doi: https://doi.org/10.1002/ehf2.13961 DOI: https://doi.org/10.1002/ehf2.13961
  14. 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 Oct;38(38):2879–87. doi: https://doi.org/10.1093/eurheartj/ehx350 DOI: https://doi.org/10.1093/eurheartj/ehx350
  15. González-López 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 Oct;36(38):2585–94. doi: https://doi.org/10.1093/eurheartj/ehv338 DOI: https://doi.org/10.1093/eurheartj/ehv338
  16. Marchi F, Kessler C, Distefano D, Terzi di Bergamo L, Fumagalli L, Averaimo M, et al. Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis. Amyloid. 2023 Dec;30(4):416–23. doi: https://doi.org/10.1080/13506129.2023.2230516 DOI: https://doi.org/10.1080/13506129.2023.2230516
  17. Roberts WC, Waller BF. Cardiac amyloidosis causing cardiac dysfunction: analysis of 54 necropsy patients. Am J Cardiol. 1983 Jul;52(1):137–46. doi: https://doi.org/10.1016/0002-9149(83)90084-X DOI: https://doi.org/10.1016/0002-9149(83)90084-X
  18. 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;114(7):1089–93. doi: https://doi.org/10.1016/j.amjcard.2014.07.026 DOI: https://doi.org/10.1016/j.amjcard.2014.07.026
  19. Donnellan E, Wazni OM, Hanna M, Elshazly MB, Puri R, Saliba W, et al. Atrial Fibrillation in Transthyretin Cardiac Amyloidosis: Predictors, Prevalence, and Efficacy of Rhythm Control Strategies. JACC Clin Electrophysiol. 2020 Sep;6(9):1118–27. doi: https://doi.org/10.1016/j.jacep.2020.04.019 DOI: https://doi.org/10.1016/j.jacep.2020.04.019
  20. Garcia-Pavia P, Rapezzi C, Adler Y, Arad M, Basso C, Brucato A, 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;42(16):1554–68. doi: https://doi.org/10.1093/eurheartj/ehab072
  21. Benz DC, Dorbala S. Multimodality imaging of cardiac amyloidosis. Heart. 2023. DOI: https://doi.org/10.1136/heartjnl-2022-321115
  22. Abecasis J, Lopes P, Santos RR, Maltês S, Guerreiro S, Ferreira A, et al. Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement. Eur Heart J Cardiovasc Imaging. 2023 Jul;24(8):1033–42. doi: https://doi.org/10.1093/ehjci/jead032 DOI: https://doi.org/10.1093/ehjci/jead032
  23. Dorbala S, Cuddy S, Falk RH. How to Image Cardiac Amyloidosis: A Practical Approach. JACC Cardiovasc Imaging. 2020 Jun;13(6):1368–83. doi: https://doi.org/10.1016/j.jcmg.2019.07.015 DOI: https://doi.org/10.1016/j.jcmg.2019.07.015
  24. Mongeon FP, Jerosch-Herold M, Coelho-Filho OR, Blankstein R, Falk RH, Kwong RY. Quantification of extracellular matrix expansion by CMR in infiltrative heart disease. JACC Cardiovasc Imaging. 2012 Sep;5(9):897–907. doi: https://doi.org/10.1016/j.jcmg.2012.04.006 DOI: https://doi.org/10.1016/j.jcmg.2012.04.006
  25. Poterucha TJ, Elias P, Ruberg FL, DeLuca A, Kinkhabwala M, Johnson LL, et al. False Positive 99mTc-Pyrophosphate Scanning Leading to Inappropriate Tafamidis Prescriptions. JACC Cardiovasc Imaging. 2021 Oct;14(10):2042–4. doi: https://doi.org/10.1016/j.jcmg.2021.04.006 DOI: https://doi.org/10.1016/j.jcmg.2021.04.006
  26. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016 Jun;133(24):2404–12. doi: https://doi.org/10.1161/CIRCULATIONAHA.116.021612 DOI: https://doi.org/10.1161/CIRCULATIONAHA.116.021612
  27. Condoluci A, Théaudin M, Schwotzer R, Pazhenkottil AP, Arosio P, Averaimo M, et al. Management of transthyretin amyloidosis. Swiss Med Wkly. 2021 Oct;151(4142):w30053. doi: https://doi.org/10.4414/SMW.2021.w30053 DOI: https://doi.org/10.4414/SMW.2021.w30053
  28. Rauf MU, Hawkins PN, Cappelli F, Perfetto F, Zampieri M, Argiro A, et al. Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis. Eur Heart J. 2023 Jun;44(24):2187–98. doi: https://doi.org/10.1093/eurheartj/ehad139 DOI: https://doi.org/10.1093/eurheartj/ehad139
  29. Garcia-Pavia P, Rapezzi C, Adler Y, Arad M, Basso C, Brucato A, 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;42(16):1554–68. doi: https://doi.org/10.1093/eurheartj/ehab072 DOI: https://doi.org/10.1093/eurheartj/ehab072
  30. Roteta Unceta-Barrenechea A, Melero Polo J, Andrés Gracia A, Revilla Martí P, Menao Guillén S, Lahuerta Pueyo C, et al. Coexistence of Positive 99mTc-DPD Scintigraphy and Monoclonal Gammopathy: A Frequent Challenge. Zhonghua Minguo Xinzangxue Hui Zazhi. 2022 Mar;38(2):169–74.
  31. 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 Mar;25(1):62–7. doi: https://doi.org/10.1080/13506129.2018.1436048 DOI: https://doi.org/10.1080/13506129.2018.1436048
  32. Clerc OF, Cuddy SA, Robertson M, Vijayakumar S, Neri JC, Chemburkar V, et al. Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study. JACC Cardiovasc Imaging. 2023 Nov;16(11):1419–32. doi: https://doi.org/10.1016/j.jcmg.2023.07.007 DOI: https://doi.org/10.1016/j.jcmg.2023.07.007
  33. Benz DC, Gräni C, Antiochos P, Heydari B, Gissler MC, Ge Y, et al. Cardiac magnetic resonance biomarkers as surrogate endpoints in cardiovascular trials for myocardial diseases. Eur Heart J. 2023 Dec;44(45):4738–47. doi: https://doi.org/10.1093/eurheartj/ehad510 DOI: https://doi.org/10.1093/eurheartj/ehad510
  34. Ioannou A, Massa P, Patel RK, Razvi Y, Porcari A, Rauf MU, et al. Conventional heart failure therapy in cardiac ATTR amyloidosis. Eur Heart J. 2023 Aug;44(31):2893–907. doi: https://doi.org/10.1093/eurheartj/ehad347 DOI: https://doi.org/10.1093/eurheartj/ehad347
  35. Steinhardt MJ, Cejka V, Chen M, Bäuerlein S, Schäfer J, Adrah A, et al. Safety and Tolerability of SGLT2 Inhibitors in Cardiac Amyloidosis-A Clinical Feasibility Study. J Clin Med. 2024 Jan;13(1):283. doi: https://doi.org/10.3390/jcm13010283 DOI: https://doi.org/10.3390/jcm13010283
  36. Dobner S, Bernhard B, Asatryan B, Windecker S, Stortecky S, Pilgrim T, et al. SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin. ESC Heart Fail. 2023 Feb;10(1):397–404. doi: https://doi.org/10.1002/ehf2.14188 DOI: https://doi.org/10.1002/ehf2.14188
  37. Zampieri M, Argirò A, Allinovi M, Perfetto F, Cappelli F. SGLT2i in patients with transthyretin cardiac amyloidosis, a well-tolerated option for heart failure treatment? Results from a small, real-world, patients series. Intern Emerg Med. 2022 Jun;17(4):1243–5. doi: https://doi.org/10.1007/s11739-022-02944-8 DOI: https://doi.org/10.1007/s11739-022-02944-8
  38. Dale Z, Chandrashekar P, Al-Rashdan L, Kim M, Masri A, Nazer B. Management Strategies for Atrial Fibrillation and Flutter in Patients with Transthyretin Cardiac Amyloidosis. Am J Cardiol. 2021 Oct;157:107–14. doi: https://doi.org/10.1016/j.amjcard.2021.07.028 DOI: https://doi.org/10.1016/j.amjcard.2021.07.028
  39. Muchtar E, Gertz MA, Kumar SK, Lin G, Boilson B, Clavell A, et al. Digoxin use in systemic light-chain (AL) amyloidosis: contra-indicated or cautious use? Amyloid. 2018 Jun;25(2):86–92. doi: https://doi.org/10.1080/13506129.2018.1449744 DOI: https://doi.org/10.1080/13506129.2018.1449744
  40. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec;64(21):e1–76. doi: https://doi.org/10.1016/j.jacc.2014.03.022 DOI: https://doi.org/10.1016/j.jacc.2014.03.022
  41. Laptseva N, Rossi VA, Sudano I, Schwotzer R, Ruschitzka F, Flammer AJ, et al. Arrhythmic Manifestations of Cardiac Amyloidosis: Challenges in Risk Stratification and Clinical Management. J Clin Med. 2023 Mar;12(7):2581. doi: https://doi.org/10.3390/jcm12072581 DOI: https://doi.org/10.3390/jcm12072581
  42. Higgins AY, Annapureddy AR, Wang Y, Minges KE, Lampert R, Rosenfeld LE, et al. Survival Following Implantable Cardioverter-Defibrillator Implantation in Patients With Amyloid Cardiomyopathy. J Am Heart Assoc. 2020 Sep;9(18):e016038. doi: https://doi.org/10.1161/JAHA.120.016038 DOI: https://doi.org/10.1161/JAHA.120.016038
  43. Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, et al.; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct;43(40):3997–4126. doi: https://doi.org/10.1093/eurheartj/ehac262 DOI: https://doi.org/10.1093/eurheartj/ehac262
  44. Porcari A, Rossi M, Cappelli F, Canepa M, Musumeci B, Cipriani A, et al. Incidence and risk factors for pacemaker implantation in light-chain and transthyretin cardiac amyloidosis. Eur J Heart Fail. 2022 Jul;24(7):1227–36. doi: https://doi.org/10.1002/ejhf.2533 DOI: https://doi.org/10.1093/eurheartj/ehac544.1771
  45. 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 Jul;136(1):71–80. doi: https://doi.org/10.1182/blood.2019004460 DOI: https://doi.org/10.1182/blood.2019004460
  46. Damy T, Garcia-Pavia P, Hanna M, Judge DP, Merlini G, Gundapaneni B, et al. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Eur J Heart Fail. 2021 Feb;23(2):277–85. doi: https://doi.org/10.1002/ejhf.2027 DOI: https://doi.org/10.1002/ejhf.2027
  47. Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, et al.; ATTRibute-CM Investigators. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2024 Jan;390(2):132–42. doi: https://doi.org/10.1056/NEJMoa2305434 DOI: https://doi.org/10.1056/NEJMoa2305434
  48. 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 Jul;379(1):11–21. doi: https://doi.org/10.1056/NEJMoa1716153 DOI: https://doi.org/10.1056/NEJMoa1716153
  49. Adams D, Tournev IL, Taylor MS, Coelho T, Planté-Bordeneuve V, Berk JL, et al.; HELIOS-A Collaborators. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023 Mar;30(1):1–9. doi: https://doi.org/10.1080/13506129.2022.2091985 DOI: https://doi.org/10.1080/13506129.2022.2091985
  50. 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 Jul;379(1):22–31. doi: https://doi.org/10.1056/NEJMoa1716793 DOI: https://doi.org/10.1056/NEJMoa1716793
  51. Coelho T, Marques W Jr, Dasgupta NR, Chao CC, Parman Y, França MC Jr, et al.; NEURO-TTRansform Investigators. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 2023 Oct;330(15):1448–58. doi: https://doi.org/10.1001/jama.2023.18688 DOI: https://doi.org/10.1001/jama.2023.18688
  52. Maurer MS, Kale P, Fontana M, Berk JL, Grogan M, Gustafsson F, et al.; APOLLO-B Trial Investigators. Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis. N Engl J Med. 2023 Oct;389(17):1553–65. doi: https://doi.org/10.1056/NEJMoa2300757 DOI: https://doi.org/10.1056/NEJMoa2300757
  53. Fontana M, Berk JL, Gillmore JD, Witteles RM, Grogan M, Drachman B, et al.; HELIOS-B Trial Investigators. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. N Engl J Med. 2024 Aug;NEJMoa2409134. doi: https://doi.org/10.1056/NEJMoa2409134 DOI: https://doi.org/10.1056/NEJMoa2409134
  54. Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med. 2021 Aug;385(6):493–502. doi: https://doi.org/10.1056/NEJMoa2107454 DOI: https://doi.org/10.1056/NEJMoa2107454
  55. Fontana M, Gilbertson J, Verona G, Riefolo M, Slamova I, Leone O, et al. Antibody-Associated Reversal of ATTR Amyloidosis-Related Cardiomyopathy. N Engl J Med. 2023 Jun;388(23):2199–201. doi: https://doi.org/10.1056/NEJMc2304584 DOI: https://doi.org/10.1056/NEJMc2304584
  56. Garcia-Pavia P, Aus dem Siepen F, Donal E, Lairez O, van der Meer P, Kristen AV, et al. Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid. N Engl J Med. 2023 Jul;389(3):239–50. doi: https://doi.org/10.1056/NEJMoa2303765 DOI: https://doi.org/10.1056/NEJMoa2303765
  57. Schwotzer R, Flammer AJ, Gerull S, Pabst T, Arosio P, Averaimo M, et al. Expert recommendation from the Swiss Amyloidosis Network (SAN) for systemic AL-amyloidosis. Swiss Med Wkly. 2020 Dec;150(4950):w20364. doi: https://doi.org/10.4414/smw.2020.20364 DOI: https://doi.org/10.4414/smw.2020.20364
  58. Brouwers S, Heimgartner R, Laptseva N, Aguzzi A, Ehl NF, Fehr T, et al. Historic characteristics and mortality of patients in the Swiss Amyloidosis Registry. Swiss Med Wkly. 2024 Feb;154(2):3485. doi: https://doi.org/10.57187/s.3485 DOI: https://doi.org/10.57187/s.3485

Most read articles by the same author(s)