Journal of Rare Cardiovascular Diseases

Amyloidosis is a rare disorder which can affect multiple organs, with cardiac amyloidosis (CA) being one of its main clinical manifestations. CA has 2 distinct subtypes, AL amyloidosis and transthyretin amyloidosis (ATTR), with different histopathological appearances and subsequently different treatment strategies. The diagnostic methods available include multiple modalities to properly detect CA, ranging from the surface electrocardiogram and simple 2D‐echocardiography to more sophisticated methods such as specific biomarkers, speckle tracking echocardiography, or even bone scintigraphy with radioisotopes. However, the definitive diagnosis is reached with an endomyocardial biopsy or a biopsy from peripheral tissue. CA is a particularly challenging disorder in terms of patient management, which ranges from symptomatic treatment for heart failure symptoms to special medication and multiple drug regimens. For AL amyloidosis, a 3‐drug regimen is used as a first‐line therapy including cyclophosphamide, a proteasome inhibitor, and dexamethasone. For ATTR amyloidosis, specific medications are used such as Tafamidis, depending on the specific stage of the disease. Clinical trials of new drugs are pending with the ultimate goal of improving treatment rates and quality of life in patients with any type of CA. JRCD 2019; 4 (2): 34–41

rare disease; cardiac disease; electrocardiography; echocardiography; scintigraphy; endomyocardial biopsy; specific treatment; quality of life

References

Glenn K. Lee, DaLi Feng, Martha Grogan, et al. Cardiac Amyloidosis: Typing, Diagnosis, Prognosis and Management. In: Intech Open, Amyloidosis, ed: DaLi Feng, 2013, pp: 1240 – 1598.

Reixach N, Deechongkit S, Jiang X, et al. Tissue damage in the amyloidosis: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc Natl Acad Sci U S A 2004; 101(9):2817-22.

Baker ΚR, and Rice L. The Amyloidoses: Clinical Features, Diagnosis and Treatment. Methodist Debakey Cardiovasc J. 2012; 8(3): 3–7.

McCausland KL, White MK, Guthrie SD, et al. Light Chain (AL) Amyloidosis: The Journey to Diagnosis. Patient 2018; 11(2): 207–216.

Hasan SM, Ahmed NN, Ahmed Z, et al .Response of Bortezomib Chemotherapy in Hepatic Amyloidosis. J Investig Med High Impact Case Rep. 2018; 6:2324709618760079.

Chen R, Chen CP, Preston JE. Effects of transthyretin on thyroxine and β-amyloid removal from cerebrospinal fluid in mice. Clin Exp Pharmacol Physiol. 2016;43(9):844-50.

Coelho T, Merlini G, Bulawa CE, et al. Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis. Neurol Ther. 2016; 5(1):1-25.

Ruberg FL, Berk JL. Transthyretin (TTR) Cardiac Amyloidosis. Circulation 2012; 126(10):1286-300.

Banypersad SM, Moon JC, Whelan C, et al. Updates in cardiac amyloidosis: a review. J Am Heart Assoc. 2012; 1(2):e000364.

Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med. 2017; 84(12 Suppl 3):12-26.

Martinez-Naharro A, Hawkins PN, Fontana M. Cardiac amyloidosis. Clin Med (Lond). 2018; 18(Suppl 2):s30–s35.

Singh A, Geller HI, Falk RH. Val122Ile mt-ATTR Has a Worse Survival Than wt-ATTR Cardiac Amyloidosis. J Am Coll Cardiol. 2017; 69(6):757-758.

Adams D., Hawkins P., Schmidt H. Abstracts from the First European Meeting for ATTR Amyloidosis for Doctors and Patients. Orphanet J Rare Dis. 2017; 12(Suppl 1):165.

Squier TC. Oxidative stress and protein aggregation during biological aging. Exp Gerontol. 2001; 36(9):1539-50.

Hassan W, Al- Sergani H, Mourad W, et al. Amyloid Heart Disease: New Frontiers and Insights in Pathophysiology, Diagnosis, and Management. Tex Heart Inst J. 2005; 32(2):178-84.

Sertaç Ç. Cardiac amyloidosis and aortic stenosis: Great masquerader back again! J Thorac and Cardiovasc Surg. 2018; 156(1):104-105.

Metzler M, Duerr S, Granata R, et al. Neurogenic orthostatic hypotension: pathophysiology, evaluation, and management. J Neurol. 2013; 260(9):2212-9.

Bjerrum OW, Rygaard-Olsen C, Dahlerup B, et al. The carpal tunnel syndrome and amyloidosis. A clinical and histological study. Clin Neurol Neorosurg. 1984; 86(1):29-32.

Westermark P, Westermark GT, Suhr OB, et al. Transthyretin-derived amyloidosis: Probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014; 119(3):223-8.

Banypersad SM, Moon JC, Whelan C, et al. Updates in cardiac amyloidosis: a review. J Am Heart Assoc. 2012;1(2):e000364.

García-Pavía P, Tomé-Esteban MT, Rapezzi C. Amyloidosis. Also a heart disease. Rev Esp Cardiol. 2011; 64(9):797-808.

Sun JP, Stewart WJ, Yang XS, et al. Differentiation of hypertrophic cardiomyopathy and cardiac amyloidosis from other causes of Ventricular Wall thickening by two-dimensional strain imaging echocardiography. Am J Cardiol. 2009; 103(3):411–415.

Quarta CC, Solomon SD, Uraizee I, et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation 2014;129(18):1840–1849.

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;10(3): e005588.

Migrino RQ, Harmann L, Woods T, et al. Intraventricular dyssynchrony in light chain amyloidosis: a new mechanism of systolic dysfunction assessed by 3-dimensional echocardiography. Cardiovasc Ultrasound. 2008;6:40.

Syed IS, Glockner JF, Feng D, et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging. 2010;3(2):155–164.

Izumiya Y, Takashio S, Oda S, et al. Recent advances in diagnosis and treatment of cardiac amyloidosis. J Cardiol. 2018; 71(2):135-143.

Fontana M, Banypersad SM, Treibel TA, et al. Native T1 mapping in transthyretin amyloidosis. JACC Cardiovasc Imaging. 2014;7(2):157–165.

Karamitsos TD, Piechnik SK, Banypersad SM, et al. Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. JACC Cardiovasc Imaging 2013;6(4):488–497.

Bhogal S, Ladia V, Sitwala P, et al. Cardiac Amyloidosis: An Updated Review with Emphasis on Diagnosis and Future Directions. Curr Probl Cardiol. 2018 Jan;43(1):10-34.

Kyriakou P, Mouselimis D, Tsarouchas A, et al. Diagnosis of cardiac amyloidosis: a systematic review on the role of imaging and biomarkers. BMC Cardiovasc Disord. 2018; 18: 221.

Qian G, Wu C, Zhang Y, et al. Prognostic value of high-sensitivity cardiac troponin T in patients with endomyocardial-biopsy proven cardiac amyloidosis. J Geriatr Cardiol. 2014;11(2):136–140.

Palladini G, Dispenzieri A, Gertz MA, 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. 2012;30(36):4541–4549.

Arvanitis M, Simon S, Chan G, et al. Retinol binding protein 4 (RBP4) concentration identifies V122I transthyretin cardiac amyloidosis. Amyloid. 2017;24(sup1):120-121.

Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation 2005; 112(13):2047–2060.

Castaño A, Drachman BM, Judge D, et al. 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.

Rubinow Α., Skinner Μ., Cohen A.S. Digoxin sensitivity in amyloid cardiomyopathy. Circulation 1981;63(6):1285-8.

Feng D, Syed IS, Martinez M, et al. Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis. Circulation 2009; 119(18):2490–2497.

Gertz MA. Immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment. Am J Hematol. 2016; 91(9):947–956.

Alexander KM, Singh A, Falk RH. Novel pharmacotherapies for cardiac amyloidosis. Pharmacol Ther. 2017; 180:129–138.

Sanchorawala V, Palladini G, Kukreti V, et al. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood 2017; 130(5):597–605.

Gertz MA, Landau H, Comenzo RL, et al. First-in-human phase I/II study of NEOD001 in patients with light chain amyloidosis and persistent organ dysfunction. J Clin Oncol. 2016; 34(10):1097–1103.

Pepys MB, Herbert J, Hutchinson WL, et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 2002; 417(6886):254–259.

Hanna M. Novel drugs targeting transthyretin amyloidosis. Curr Heart Fail Rep. 2014; 11(1):50–57.

Castaño A, Helmke S, Alvarez J, et al. Diflunisal for ATTR cardiac amyloidosis. Congest Heart Fail. 2012; 18(6):315–319.

Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.

Cardoso I, Martins D, Ribeiro T, et al. Synergy of combined doxycycline/TUDCA treatment in lowering transthyretin deposition and associated biomarkers: studies in FAP mouse models. J Transl Med. 2010; 8:74.

Kristen AV, Lehrke S, Buss S, et al. Green tea halts progression of cardiac transthyretin amyloidosis: An observational report. Clin Res Cardiol. 2012; 101(10):805–813.

Higaki JN, Chakrabartty A, Galant NJ, et al. Novel conformation specific monoclonal antibodies against amyloidogenic forms of forms of transthyretin. Amyloid 2016; 23(2):86–97.

Sousa M, Monohan G, Rajagopalan N, et al. Heart transplantation in cardiac amyloidosis. Heart Fail Rev. 2017; 22(3):317–327.