Skip to main content
SpringerLink
Log in

Cardiac Amyloidosis: Diagnosis and Treatment Strategies

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

Abstract

Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

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

  1. Shah KB, Inoue Y, Mehra MR. Amyloidosis and the heart: a comprehensive review. Arch Intern Med. 2006;166(17):1805–13.

    Article  CAS  PubMed  Google Scholar 

  2. Mohammed S, Mirzoyev S, Edwards W, Dogan A, Grogan D, Dunlay S, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2(2):113–22.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Leone O, Longhi S, Quarta C, Ragazzini T, De Giorgi L, Pasquale F, et al. New pathological insights into cardiac amyloidosis: implications for non-invasive diagnosis. Amyloid. 2012;19(2):99–105.

    Article  CAS  PubMed  Google Scholar 

  4. Brenner DA, Jain M, Pimentel DR, Wang B, Connors LH, Skinner M, et al. Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in the cellular oxidant stress. Circulation. 2004;94(8):1008–10.

    Article  CAS  Google Scholar 

  5. Dubrey S, Cha K, Anderson J, Chamarthi B, Reisinger J, Skinner M, et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM. 1998;91(2):141–57.

    Article  CAS  PubMed  Google Scholar 

  6. Dubrey S, Hawkins P, Falk R. Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart. 2011;97(1):75–84.

    Article  CAS  PubMed  Google Scholar 

  7. Castano A, Drachman B, Judge D, Maurer M. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cornwell G, Murdoch W, Kyle R, Westermark P, Pitkanen P. Frequency and distribution of senile cardiovascular amyloid. A clinicopathologic correlation. Am J Med. 1983;75(4):618–23.

    Article  PubMed  Google Scholar 

  9. •• Kristen A, Brokbals E, Aus dem Siepen F, Bauer R, Hein S, Aurich M, et al. Cardiac amyloid load: a prognostic and predictive biomarker in patients with light-chain amyloidosis. J Am Coll Cardiol. 2016;68(1):13–24. Patient with a late diagnosis of cardiac AL amyloidosis after extensive amyloid deposition may not have improvement in outcomes with chemotherapy

    Article  CAS  PubMed  Google Scholar 

  10. Dispenzieri A, Kyle R, Gertz M, Therneau T, Miller W, Chandrasekaran K, et al. Survival in patients with primary systemic amyoidosis and raised serum cardiac troponins. Lancet. 24(361(9371)):1787–9.

  11. Dispenzieri A, Gertz M, Kyle R, Lacy M, Burritt M, Therneau T, 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 

  12. 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;20(30(9)):989–95.

    Article  Google Scholar 

  13. Gertz M, Comenzo R, Falk R, Fermand J, Hazenberg B, Hawkins P, 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 H Hematol. 79(4):319–28.

  14. Dubrey S, Cha K, Skinner M, LaValley M, Falk R. Familial and primary (AL) cardiac amyloidosis: echocardiographically similar diseases with distinctly different clinical outcomes. Heart. 1997;78(1):74–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Siqueira-Filho A, Cunha C, Tajik A, Seward J, Schattenberg T, Giuliani E. M-mode and two-dimensional echocardiographic features in cardiac amyloidosis. Circulation. 1981;63(1):188–96.

    Article  CAS  PubMed  Google Scholar 

  16. Klein A, Hatle L, Burstow D, Seward J, Kyle R, Bailey K. Doppler characterization of left ventricular diastolic function in cardiac amyloidosis. J Am Coll Cardiol. 1989;13:1017–26.

    Article  CAS  PubMed  Google Scholar 

  17. Koyama J, Ray-Sequin PA, Falk RH. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation. 2003;107(19):2446–52.

    Article  PubMed  Google Scholar 

  18. Liu D, Niemann M, Hu K, Herrmann S, Stork S, Knop S, et al. Echocardiographic evaluation of systolic and diastolic function in patients with cardiac amyloidosis. Am J Cardiol. 2015;108(4):591–8.

    Article  Google Scholar 

  19. Ternacle J, Bodez D, Guellich A, Audureau E, Rappeneau S, Lim P, et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging. 2016;9(2):126–38.

    Article  PubMed  Google Scholar 

  20. •• Phelan D, Collier P, Thavendiranathan P, Popovic Z, Hanna M, Plana J, 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. Relatively preserved apical strain in the setting of significantly abnormal basal and mid ventricular strain is both a sensitive and specific finding for cardiac amyloidosis

    Article  PubMed  Google Scholar 

  21. Liu D, Hu K, Niemann M, Herrmann S, Cikes M, Stork S, et al. Effect of combined systolic and diastolic functional parameter assessment for differentiation of cardiac amyloidosis from other causes of concentric left ventricular hypertrophy. Circ Cardiovasc Imaging. 2013;6(6):1066–72.

    Article  PubMed  Google Scholar 

  22. Klein A, Hatle L, Taliercio C, Oh J, Kyle R, Gertz M. Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis: a Doppler echocardiography study. Circulation. 1991;83:808–16.

    Article  CAS  PubMed  Google Scholar 

  23. Kristen A, Perz J, Schonland S, Schnabel P, Kristen J, Goldschmidt H, et al. Non-invasive predictors of survival in cardiac amyloidosis. Eur J Heart Fail. 2007;9(6–7):617–24.

    Article  CAS  PubMed  Google Scholar 

  24. Koyama J, Falk R. Prognostic significance of strain Doppler imaging in light-chain amyloidosis. JACC Cardiovasc Imaging. 2010;3:333–42.

    Article  PubMed  Google Scholar 

  25. Buss S, Emami M, Mereles D, Korosoglou G, Kristen A, Voss A. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical biochemical markers. J Am Coll Cardiol. 2012;60:1067–76.

    Article  PubMed  Google Scholar 

  26. Bhatti S, Watts E, Syed F, Vallurupatti S, Pandey T, Jambekar K, et al. Clinical and prognostic utility of cardiovascular magnetic resonance imaging in myeloma patients with suspected cardiac amyloidosis. Eur Heart J Cardiovasc Imaging. 2016;17(9):970–7.

    Article  PubMed  Google Scholar 

  27. Maceira A, Joshi H, Prasad S, Moon J, Perugini E, Harding I, et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2005;18:186–93.

    Article  Google Scholar 

  28. Minutoli F, Di Bella G, Mazzeo A, Donato R, Russo M, Scribano E, et al. Comparison between (99m)Tc-diphosphonate imaging and MRI with late gadolinium enhancement in evaluating cardiac involvement in patients with transthyretin familial amyloid polyneuropathy. AJR Am J Roentgenol. 2013;200(3):W256–65.

    Article  PubMed  Google Scholar 

  29. Deux J, Damy T, Rahmouni A, Mayer J, Plante-Bordeneuve V. Noninvasive detection of cardiac involvement in patients with hereditary transthyretin associated amyloidosis using cardiac magnetic resonance imaging: a prospective study. Amyloid. 2014;21(4):246–55.

    Article  PubMed  Google Scholar 

  30. Fontana M, Pica S, Reant P, Abdel-Gadir A, Treibel T, Banypersad S, et al. Prognostic value of late gadolinium enhancement cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2015;132(16):1570–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. •• Dungu J, Valencia O, Pinney J, Gibbs S, Rowczenio D, Gilbertson J, et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. JACC Cardiovasc Imaging. 2014;7(2):133–42. Transmural LGE is more common in ATTR, and the Query Amyloid Late Enhancement (QALE) score, which represents the degree of LGE in the right and left ventricle, may help differentiate between AL and ATTR amyloidosis.

    Article  PubMed  Google Scholar 

  32. Austin B, Tang W, Rodriguez E, Tan C, Flamm S, Taylor D, et al. Delayed hyper-enhancement magnetic resonance imaging provides incremental diagnostic and prognostic utility in suspected cardiac amyloidosis. JACC Cardiovasc Imaging. 2009;2(12):1369–77.

    Article  PubMed  Google Scholar 

  33. Maceira A, Prasad S, Hawkins P, Roughton M, Pennell D. Cardiovascular magnetic resonance and prognosis in cardiac amyloidosis. J Cardiovasc Magn Reson. 2008;10:54.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ruberg F, Appelbaum E, Davidoff R, Ozonoff A, Kissinger K, Harrigan C, et al. Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in light-chain cardiac amyloidosis. Am J Cardiol. 2009;103(4):544–9.

    Article  PubMed  Google Scholar 

  35. Aljaroudi W, Desai M, Tang W, Phelan D, Cerqueira M, Jaber W. 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. Rapezzi C, Quarta C, Guidalotti P, Pettinato C, Fanti S, Leone O, et al. Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging. 2011;4(6):659–70.

    Article  PubMed  Google Scholar 

  37. Perugini E, Guidalotti P, Salvi F, Cooke R, 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 

  38. •• Rapezzi C, Quarta C, Guidalotti P, Longhi S, Pettinato C, Leone O, et al. Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy. Eur J Nucl Med Mol Imaging. 2011;38(3):470–8. Nuclear imaging with radiotracer 99m Tc-DPD can help differentiate ATTR versus AL cardiac amyloidosis although the diagnostic accuracy is best when there is either no uptake or intense uptake.

    Article  PubMed  Google Scholar 

  39. Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer M. (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 

  40. Dorbala S, Vangala D, Semer J, Strader C, Bruyere J, Di Carli M, et al. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. 2014;41(9):1652–62.

    Article  CAS  PubMed  Google Scholar 

  41. Brigham and Women’s Hospital. Imaging cardiac amyloidosis: a pilot study using F-18 florbetapir positron emission tomography. 2012 Sep; Available from: https://clinicaltrials.gov/ct2/show/study/NCT01683825.

  42. Perugini E, Rapezzi C, Piva T, Leone O, Bacchi-Reggiani L, Riva L, et al. Non-invasive evaluation of the myocardial substrate of cardiac amyloidosis by gadolinium cardiac magnetic resonance. Heart. 2006;92(3):343–9.

    Article  CAS  PubMed  Google Scholar 

  43. Mathew V, Olson L, Gertz M, Hayes D. Symptomatic conduction system disease in cardiac amyloidosis. Am J Cardiol. 1997;80(11):1491–2.

    Article  CAS  PubMed  Google Scholar 

  44. Lin G, Dispenzieri A, Kyle R, Grogan M, Brady P. Implantable cardioverter defibrillators in patients with cardiac amyloidosis. J Cardiovasc Electrophysiol. 2013;24(7):793–8.

    Article  PubMed  Google Scholar 

  45. Kristen A, Dengler T, Hegenbart U, Schonland S, Goldschmidt H, Sack F, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008;5(2):235–40.

    Article  PubMed  Google Scholar 

  46. DePasquale E, Nasir K, Jacoby D. Outcomes of adults with restrictive cardiomyopathy after heart transplantation. J Heart Lung Transplant. 2012;31(12):1269–75.

    Article  PubMed  Google Scholar 

  47. Kpodonu J, Massad M, Caines A, Geha A. Outcome of heart transplantation in patients with amyloid cardiomyopathy. J Heart Lung Transpl. 2005;24:1763–5.

    Article  Google Scholar 

  48. Davis M, 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;15:650–8.

    Article  CAS  PubMed  Google Scholar 

  49. Bulawa C, Connelly S, Devit M, Wang L, Weigel C, Fleming J, et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc Natl Acad Sci. 2012;109(24):9629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Said G, Grippon S, Kirkpatrick P. Tafamidis. Nat Rev Drug Discov. 2012;11(3):185–6.

    Article  CAS  PubMed  Google Scholar 

  51. Coelho T, Adams D, Silva A, Lozeron P, Hawkins P, Mant T, et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. NEJM. 2013;369(9):819–29.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA

    Mirela Tuzovic, Eric H. Yang & Gabriel Vorobiof

  2. Ahmanson-UCLA Cardiomyopathy Center, Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA

    Arnold S. Baas, Eugene C. Depasquale, Mario C. Deng & Daniel Cruz

  3. Cardiovascular Center, 100 Medical Plaza, Suite 545, 100 UCLA Medical Plaza, Los Angeles, CA, 90095, USA

    Gabriel Vorobiof

Authors
  1. Mirela Tuzovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric H. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arnold S. Baas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eugene C. Depasquale
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mario C. Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriel Vorobiof
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriel Vorobiof.

Ethics declarations

Conflict of Interest

Mirela Tuzovic, Eric H. Yang, Arnold S. Baas, Eugene C. Depasquale, Mario C. Deng, Daniel Cruz, and Gabriel Vorobiof declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

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

Additional information

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

Electronic Supplementary Material

Video 1

Transthoracic echocardiography, apical four chamber view corresponding to the image in Fig. 1A. (MOV 1716 kb)

Video 2

Transthoracic echocardiography, apical four chamber view with strain measurement corresponding to the image in Fig. 3A. (MOV 857 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tuzovic, M., Yang, E.H., Baas, A.S. et al. Cardiac Amyloidosis: Diagnosis and Treatment Strategies. Curr Oncol Rep 19, 46 (2017). https://doi.org/10.1007/s11912-017-0607-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-017-0607-4

Keywords

Search

Navigation