Cardiac amyloidosis: the pathologist’s point of view

Monica De Gaspari , Nicoletta Finato , Cristina Basso

Vessel Plus ›› 2022, Vol. 6 ›› Issue (1) : 57

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Vessel Plus ›› 2022, Vol. 6 ›› Issue (1) :57 DOI: 10.20517/2574-1209.2022.05
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Cardiac amyloidosis: the pathologist’s point of view

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Abstract

Cardiac amyloidosis is a well-known entity recently recognized as a common etiology of heart failure. This infiltrative disease is caused by the deposition of misfolded proteins within the heart. The most common types of cardiac amyloidosis result from fibrils composed of monoclonal immunoglobulin light chains or transthyretin. Clinical presentation is usually elusive, and this can result in diagnostic delay. Diagnosis can be reached with non-invasive methods, but it often requires tissue sampling with pathological analysis. It is fundamental to determine the type of protein being deposited in order to indicate the specific treatment. In this article, we review the main features of cardiac amyloidosis with a focus on different pathological presentations of this rare disorder.

Keywords

Cardiac amyloidosis / cardiovascular pathology / histology

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Monica De Gaspari, Nicoletta Finato, Cristina Basso. Cardiac amyloidosis: the pathologist’s point of view. Vessel Plus, 2022, 6(1): 57 DOI:10.20517/2574-1209.2022.05

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References

[1]

Benson MD,Eisenberg DS.Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee.Amyloid2018;25:215-9

[2]

Maurer MS,Comenzo R,Rapezzi C.Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis.Circulation2017;135:1357-77 PMCID:PMC5392416

[3]

Virchow, R. Über den Gang der amyloiden Degeneration. Archiv f pathol Anat 1855;8:364–8.

[4]

Kyle RA.Amyloidosis: a convoluted story.Br J Haematol2001;114:529-38

[5]

Soyka J. Über amyloide Degeneration. Prag. med. Wchnschr 165 (1876).

[6]

Sipe JD.Review: history of the amyloid fibril.J Struct Biol2000;130:88-98

[7]

Steensma DP."Congo" red: out of Africa?.Arch Pathol Lab Med2001;125:250-2

[8]

Cohen AS.Electron microscopic observations on a fibrous component in amyloid of diverse origins.Nature1959;183:1202-3

[9]

Pras M,Zucker-Franklin D,Franklin EC.The characterization of soluble amyloid prepared in water.J Clin Invest1968;47:924-33

[10]

Benson MD,Eisenberg DS.Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee.Amyloid2020;27:217-22

[11]

Kyle R,Beard C.Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood 1992;79:1817-22.

[12]

Pinney JH,Taube JB.Systemic amyloidosis in England: an epidemiological study.Br J Haematol2013;161:525-32

[13]

Hemminki K,Försti A,Sundquist K.Incidence and survival in non-hereditary amyloidosis in Sweden.BMC Public Health2012;12:974

[14]

Quock TP,Chang E,Broder MS.Epidemiology of AL amyloidosis: a real-world study using US claims data.Blood Adv2018;2:1046-53

[15]

Wechalekar AD,Hawkins PN.Systemic amyloidosis.The Lancet2016;387:2641-54

[16]

Muchtar E,Magen H.Systemic amyloidosis from A (AA) to T (ATTR): a review.J Intern Med2021;289:268-92

[17]

Liao R,Teller P.Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation 2001;104:1594-7.

[18]

Brenner DA,Pimentel DR.Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress.Circ Res2004;94:1008-10

[19]

Shi J,Jiang B.Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway.Proc Natl Acad Sci U S A2010;107:4188-93

[20]

Bergström J,Hellman U.Amyloid deposits in transthyretin-derived amyloidosis: cleaved transthyretin is associated with distinct amyloid morphology.J Pathol2005;206:224-32

[21]

Suhr OB,Westermark P.One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition.J Intern Med2017;281:337-47

[22]

Rapezzi C,Obici L.Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective.Eur Heart J2013;34:520-8

[23]

Rapezzi C,Riva L.Transthyretin-related amyloidoses and the heart: a clinical overview.Nat Rev Cardiol2010;7:398-408

[24]

Kittleson MM,Ambardekar AV.American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American heart association.Circulation2020;142:e7-e22

[25]

Murtagh B,Gertz MA,Tajik AJ.Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement.Am J Cardiol2005;95:535-7

[26]

Rapezzi C,Guidalotti PL.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 Imaging2011;38:470-8

[27]

Quarta CC,Hutt D.99mTc-DPD scintigraphy in immunoglobulin light chain (AL) cardiac amyloidosis.Eur Heart J Cardiovasc Imaging2021;22:1304-11 PMCID:PMC8527328

[28]

Garcia-Pavia P,Adler Y.Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases.Eur Heart J2021;42:1554-68 PMCID:PMC8060056

[29]

Gameren II, Hazenberg BP, Bijzet J, van Rijswijk MH. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice.Arthritis Rheum2006;54:2015-21

[30]

Fine NM,Dispenzieri A.Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis.Am J Cardiol2014;113:1723-7

[31]

Quarta CC,Gilbertson JA.Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis.Eur Heart J2017;38:1905-8 PMCID:PMC5837229

[32]

Picken MM.Thioflavin T Stain: an easier and more sensitive method for amyloid detection. In: Picken MM, Herrera GA, Dogan A, editors. Amyloid and Related Disorders. Cham: springer International Publishing; 2015. pp. 225-7.

[33]

Pomerance A,McWatt J.Experience with the sodium sulphate-Alcian Blue stain for amyloid in cardiac pathology.J Clin Pathol1976;29:22-6

[34]

Castellani C,Frigo AC.Application of confocal laser scanning microscopy for the diagnosis of amyloidosis.Virchows Arch2017;470:455-63

[35]

Maleszewski JJ.Cardiac amyloidosis: pathology, nomenclature, and typing.Cardiovasc Pathol2015;24:343-50

[36]

Shen K,Sun J.[Classification of amyloidosis by laser micro-dissection and mass spectrometry based proteomic analysis].Zhonghua Xue Ye Xue Za Zhi2015;36:99-102 PMCID:PMC7342159

[37]

Dasari S,Vrana JA.Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidoses.J Proteome Res2014;13:2352-8

[38]

Buja L,Roberts WC.Clinically significant cardiac amyloidosis. The American Journal of Cardiology 1970;26:394-405.

[39]

Roberts WC.Cardiac amyloidosis causing cardiac dysfunction: analysis of 54 necropsy patients. The American Journal of Cardiology 1983;52:137-46.

[40]

Smith TJ,Lie J.Clinical Significance of Histopathologic Patterns of Cardiac Amyloidosis.Mayo Clin Proc1984;59:547-55

[41]

Leone O,Quarta CC.New pathological insights into cardiac amyloidosis: implications for non-invasive diagnosis.Amyloid2012;19:99-105

[42]

Larsen BT,Dasari S.Correlation of histomorphological pattern of cardiac amyloid deposition with amyloid type: a histological and proteomic analysis of 108 cases.Histopathology2016;68:648-56

[43]

Porcari A,Merlo M.Incidence and characterization of concealed cardiac amyloidosis among unselected elderly patients undergoing post-mortem examination.Front Cardiovasc Med2021;8:749523 PMCID:PMC8649842

[44]

Elliott P,Arbustini E.Classification of the cardiomyopathies: a position statement from the european society of cardiology working group on myocardial and pericardial diseases.Eur Heart J2008;29:270-6

[45]

Eliot RS,Blount SG.Cardiac Amyloidosis.Circulation1961;23:613-22

[46]

Dinwoodey DL,Maron MS,Ruberg FL.Light-chain amyloidosis with echocardiographic features of hypertrophic cardiomyopathy.Am J Cardiol2008;101:674-6

[47]

Philippakis AA.Cardiac amyloidosis mimicking hypertrophic cardiomyopathy with obstruction: treatment with disopyramide.Circulation2012;125:1821-4

[48]

Basso C,d'Amati G.Association for European Cardiovascular Pathology. Cardiac hypertrophy at autopsy.Virchows Arch2021;479:79-94 PMCID:PMC8298245

[49]

Feng D,Oh JK.Intracardiac thrombosis and embolism in patients with cardiac amyloidosis.Circulation2007;116:2420-6

[50]

Neben-Wittich MA,Mueller PS,Gertz MA.Obstructive intramural coronary amyloidosis and myocardial ischemia are common in primary amyloidosis.Am J Med2005;118:1287

[51]

Pucci A,Musetti V.Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis.J Am Heart Assoc2021;10:e020358 PMCID:PMC8751897

[52]

Frenzel H,Kuhn H.Cardiac amyloid deposits in endomyocardial biopsies. Light microscopic, ultrastructural, and immunohistochemical studies.Am J Clin Pathol1986;85:674-80

[53]

Sikkink LA.Cytotoxicity of amyloidogenic immunoglobulin light chains in cell culture.Cell Death Dis2010;1:e98

[54]

Mishra S,Plovie E.Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish.Am J Physiol Heart Circ Physiol2013;305:H95-103 PMCID:PMC3727100

[55]

Dittloff KT,Zhong JX,Desai TA.Transthyretin amyloid fibrils alter primary fibroblast structure, function, and inflammatory gene expression.Am J Physiol Heart Circ Physiol2021;321:H149-60 PMCID:PMC8321815

[56]

Siegismund CS,Lassner D.Intramyocardial inflammation predicts adverse outcome in patients with cardiac AL amyloidosis.Eur J Heart Fail2018;20:751-7

[57]

Kotecha T,Treibel TA.Myocardial Edema and Prognosis in Amyloidosis.J Am Coll Cardiol2018;71:2919-31

[58]

Lim HE,Kim YH.Acute myocarditis associated with cardiac amyloidosis manifesting as transient complete atrioventricular block and slow ventricular tachycardia.Int J Cardiol2006;109:395-7

[59]

Basso C,Rizzo S.Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study.Eur Heart J2020;41:3827-35 PMCID:PMC7543528

[60]

Bois MC,Layman AJ.COVID-19-Associated Nonocclusive Fibrin Microthrombi in the Heart.Circulation2021;143:230-43 PMCID:PMC7805556

[61]

Bandera F,Chacko L.Clinical importance of left atrial infiltration in cardiac transthyretin amyloidosis.JACC Cardiovasc Imaging2022;15:17-29 PMCID:PMC8724534

[62]

Lool L.Isolated atrial amyloidosis: a clinicopathologic study indicating increased prevalence in chronic heart disease.Human Pathology1993;24:602-7

[63]

Fayyaz AU,Dasari S.Amyloidosis in surgically resected atrial appendages: a study of 345 consecutive cases with clinical implications.Mod Pathol2020;33:764-74

[64]

Kaye GC,d'Ardenne AJ,Camm AJ.Isolated atrial amyloid contains atrial natriuretic peptide: a report of six cases.Br Heart J1986;56:317-20 PMCID:PMC1236864

[65]

Pucci A,Arbustini E.Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide-like immunoreactivity.J Pathol1991;165:235-41

[66]

Wittich CM,Mueller PS,Edwards WD.Deposition of amyloid proteins in the epicardial coronary arteries of 58 patients with primary systemic amyloidosis.Cardiovasc Pathol2007;16:75-8

[67]

Smith RR.Ischemic heart disease secondary to amyloidosis of intramyocardial arteries.The American Journal of Cardiology1979;44:413-7

[68]

Saffitz JE,Roberts WC.Amyloidosis limited to small arteries causing angina pectoris and sudden death.The American Journal of Cardiology1983;51:1234-5

[69]

Barbour DJ.Frequency of acute and healed myocardial infarcts in fatal cardiac amyloidosis.The American Journal of Cardiology1988;62:1134-5

[70]

Pasotti M,Concardi M,Rapezzi C.Obstructive intramural coronary amyloidosis: a distinct phenotype of cardiac amyloidosis that can cause acute heart failure.Eur Heart J2006;27:1810

[71]

Damy T,Guellich A.Identification of prognostic markers in transthyretin and AL cardiac amyloidosis.Amyloid2016;23:194-202

[72]

Kristen AV,Rapezzi C,Suhr OB.THAOS investigators. Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - report from the Transthyretin Amyloidosis Outcome Survey (THAOS).PLoS One2017;12:e0173086 PMCID:PMC5383030

[73]

Olson LJ,Edwards WD.Senile cardiac amyloidosis with myocardial dysfunction. Diagnosis by endomyocardial biopsy and immunohistochemistry.N Engl J Med1987;317:738-42

[74]

Cornwell GG 3rd,Murdoch W.Senile aortic amyloid. A third distinctive type of age-related cardiovascular amyloid.Am J Pathol1982;108:135-9 PMCID:PMC1916086

[75]

Mucchiano G,Westermark P.Senile aortic amyloid. Evidence for two distinct forms of localized deposits.Am J Pathol1992;140:871-7 PMCID:PMC1886375

[76]

Häggqvist B,Sletten K.Medin: an integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid.Proc Natl Acad Sci U S A1999;96:8669-74 PMCID:PMC17574

[77]

Peng S,Westermark P.Medin-amyloid: a recently characterized age-associated arterial amyloid form affects mainly arteries in the upper part of the body.Amyloid2005;12:96-102

[78]

Goffin Y.Microscopic amyloid deposits in the heart valves: a common local complication of chronic damage and scarring.J Clin Pathol1980;33:262-8 PMCID:PMC1146050

[79]

Cooper JH.Localized dystrophic amyloidosis of heart valves. Human Pathology 1983;14:649-53.

[80]

Ladefoged C.Amyloid deposits in aortic and mitral valves. A clinicopathological investigation of material from 100 consecutive heart valve operations.Virchows Arch A Pathol Anat Histopathol1984;404:301-12

[81]

Kristen AV,Winter B.High prevalence of amyloid in 150 surgically removed heart valves--a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions.Cardiovasc Pathol2010;19:228-35

[82]

Audet A,Couture C.Amyloid substance within stenotic aortic valves promotes mineralization.Histopathology2012;61:610-9

[83]

Iwata T,Nagasawa T.Amyloid deposits in heart valves.Acta Pathol Jpn1982;32:23-9

[84]

Goffin YA,Cornwell GG 3rd.Microdeposits of amyloid in sclerocalcific heart valves: a histochemical and immunofluorescence study.J Clin Pathol1983;36:1342-9 PMCID:PMC498565

[85]

James TN.Pathology of the cardiac conduction system in amyloidosis.Ann Intern Med1966;65:28-36

[86]

Ridolfi RL,Hutchins GM.The conduction system in cardiac amyloidosis.The American Journal of Medicine1977;62:677-86

[87]

Yuda S,Yasui K.Pericardial Effusion and Multiple Organ Involvement Are Independent Predictors of Mortality in Patients with Systemic Light Chain Amyloidosis.Intern Med2015;54:1833-40

[88]

Georgin-Lavialle S,Deux JF,Damy T.Isolated Pericardial Infiltration Without Myocardial Involvement in Light-Chain-Related Amyloidosis.Ann Thorac Surg2017;103:e255-7

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