Abstract
Amyloidosis is a term used to describe a group of rare heterogeneous diseases that
ultimately result in the deposition and accumulation of misfolded proteins. These
misfolded proteins, known as amyloids, are associated with a variety of precursor
proteins that have amyloidogenic potential. Ultimately, the specific type of amyloidosis
is dependent on multiple factors including genetic variability of precursor proteins
and the tissue or organ in which the amyloid accumulates. Several types of amyloid
have a predilection for the heart and thus contribute to cardiac amyloidosis, a major
cause of restrictive cardiomyopathy. Individuals with cardiac amyloidosis present
clinically with heart failure with preserved ejection fraction. Although improved
diagnostics and increased awareness of cardiac amyloidosis have led to a relative
increase in diagnosis, cardiac amyloidosis remains an underrecognized and underdiagnosed
cause of heart failure with preserved ejection fraction. It is essential to properly
identify cases of cardiac amyloidosis and determine the pathology responsible for
the formation of amyloid to appropriately provide management. This review aims to
encourage physician awareness of cardiac amyloidosis by focusing on clinical presentation
and the distinctions between types. Furthermore, epidemiology is central to understanding
the affected demographics and sometimes hereditary nature of the disease. Improved
understanding of cardiac amyloidosis will ideally lead to earlier diagnosis and interventions
to improve patient outcomes.
Résumé
L’amyloïdose est un terme utilisé pour décrire un groupe de maladies hétérogènes rares
qui aboutit au dépôt et à l’accumulation de protéines mal repliées. Ces protéines
mal repliées, appelées amyloïdes, sont associées à de nombreuses protéines précurseurs
qui ont un potentiel amyloïdogène. Finalement, le type spécifique d’amyloïdose dépend
de multiples facteurs, notamment la variabilité génétique des protéines précurseurs,
et le tissu ou l’organe dans lequel l’amyloïde s’accumule. Plusieurs types d’amyloïdes
ont une prédilection pour le cœur et, par conséquent, contribuent à l’amyloïdose cardiaque,
la cause principale de la cardiomyopathie restrictive. Les individus atteints d’amyloïdose
cardiaque montrent sur le plan clinique une insuffisance cardiaque à fraction d’éjection
préservée. Bien que l’amélioration des diagnostics et la sensibilisation accrue à
l’amyloïdose cardiaque aient mené à une augmentation relative du diagnostic, l’amyloïdose
cardiaque demeure une cause non reconnue et sous-diagnostiquée de l’insuffisance cardiaque
à fraction d’éjection préservée. Il est essentiel d’identifier correctement les cas
d’amyloïdose cardiaque et de déterminer la pathologie responsable de la formation
de l’amyloïde pour offrir une prise en charge appropriée. La présente revue vise à
encourager la sensibilisation des médecins à l’amyloïdose cardiaque en se penchant
sur le tableau clinique et les différences entre les types. De plus, l’épidémiologie
est essentielle à la compréhension des caractéristiques démographiques concernées
et parfois de la nature héréditaire de la maladie. Une meilleure compréhension de
l’amyloïdose cardiaque mènera idéalement à un diagnostic et à des interventions plus
précoces pour améliorer l’évolution de l’état de santé des patients.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic and PersonalCorporate R&D ProfessionalsOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Molecular mechanisms of amyloidosis.N Engl J Med. 2003; 349: 583-596
- Amyloid fibrils: abnormal protein assembly.Prion. 2008; 2: 112-117
- Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines.Amyloid. 2016; 23: 209-213
- Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis.Circulation. 2017; 135: 1357-1377
- Natural history and therapy of AL cardiac amyloidosis.Heart Fail Rev. 2015; 20: 155-162
- Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system.J Am Coll Cardiol. 2016; 68: 1014-1020
- A molecular history of the amyloidoses.J Mol Biol. 2012; 421: 142-159
- Diagnosis and management of the cardiac amyloidoses.Circulation. 2005; 112: 2047-2060
- Transthyretin amyloidosis: an under-recognized neuropathy and cardiomyopathy.Clin Sci (Lond). 2017; 131: 395-409
- Trends in hospitalizations and survival of acute decompensated heart failure in four US communities (2005-2014): ARIC study community surveillance.Circulation. 2018; 138: 12-24
- National differences in trends for heart failure hospitalizations by sex and race/ethnicity.Circ Cardiovasc Qual Outcomes. 2017; : 10
- Epidemiology of heart failure.Circ Res. 2013; 113: 646-659
- 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure. a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.J Am Coll Cardiol. 2017; 70: 776-803
- Heart disease and stroke statistics—2017 update: a report from the American Heart Association.Circulation. 2017; 135: e146-e603
- Epidemiology of left ventricular systolic dysfunction and heart failure in the Framingham study: an echocardiographic study over 3 decades.JACC Cardiovasc Imaging. 2018; 11: 1-11
- Inflammatory and molecular pathways in heart failure—ischemia, HFpEF and transthyretin cardiac amyloidosis.Int J Mol Sci. 2019; 20 (E2322)
- Cardiac amyloidosis a rare disease in older adults hospitalized for heart failure?.Circ Heart Fail. 2019; 12 (e006169)
- Restrictive cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy.Circ Res. 2017; 121: 819-837
- Seven factors predict a delayed diagnosis of cardiac amyloidosis.Amyloid. 2018; 25: 174-179
- Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment.Trends Cardiovasc Med. 2018; 28: 10-21
- Diagnosis of cardiac amyloidosis: a systematic review on the role of imaging and biomarkers.BMC Cardiovasc Disord. 2018; 18: 221
- Integrated diagnostic approach to wild-type transthyretin cardiac amyloidosis with the use of high-sensitivity cardiac troponin T measurement and 99mTc-pyrophosphate scintigraphy.J Cardiol. 2020; 75: 12-19
- Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death.Blood. 2017; 129: 2111-2119
- Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments.J Neurol Neurosurg Psychiatry. 2015; 86: 1036-1043
- Guidelines on the diagnosis and investigation of AL amyloidosis.Br J Haemotol. 2015; 168: 207-218
- Systemic AA amyloidosis: epidemiology, diagnosis, and management.Clin Epidemiol. 2014; 6: 369-377
- Systemic amyloidosis: novel therapies and role of biomarkers.Nephrol Dial Transplant. 2016; 32: 770-780
- Apolipoprotein A-1–related amyloidosis: 2 case reports and review of the literature.Medicine (Baltimore). 2017; 96 (e8148)
- Hereditary apolipoprotein AI–associated amyloidosis in surgical pathology specimens: identification of three novel mutations in the APOA1 gene.J Mol Diagn. 2009; 11: 257-262
- Cardiac amyloidosis: a review of the literature and a practical approach for the clinicians.Ital J Med. 2019; 13: 73-90
- Genotype and phenotype of transthyretin cardiac amyloidosis. THAOS (Transthyretin Amyloid Outcome Survey).J Am Coll Cardiol. 2016; 68: 161-172
- Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters and treatment algorithm.Orphanet J Rare Dis. 2018; 13: 6
- Clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma.Mayo Clin Proc. 2010; 85: 232-238
- Differential diagnosis of monoclonal gammopathy of undetermined significance.Hematology Am Soc Hematol Educ Program. 2012; 2012: 595-603
- Light chain (AL) amyloidosis: the journey to diagnosis.Patient. 2018; 11: 207-216
- Light chain amyloidosis: patient experience survey from the Amyloidosis Research Consortium.Adv Ther. 2015; 32: 920-928
- Systemic amyloidosis in E ngland: an epidemiological study.Br J Haematol. 2013; 161: 525-532
- Epidemiology of AL amyloidosis: a real-world study using US claims data.Blood Adv. 2018; 2: 1046-1053
- Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study.Circulation. 2016; 133: 282-290
- Analysis of the TTR gene in the investigation of amyloidosis: a 25-year single UK center experience.Hum Mutat. 2019; 40: 90-96
- Hereditary amyloid cardiomyopathy caused by a variant apolipoprotein A1.Am J Pathol. 1999; 154: 221-227
- Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota 1950 through 1989.Blood. 1992; 79: 1817-1822
- The burden of amyloid light chain amyloidosis on health-related quality of life.Orphanet J Rare Dis. 2017; 12: 15
- Disease burden of systemic light-chain amyloidosis: a systematic literature review.Curr Med Res Opin. 2017; 33: 1017-1031
- Primary systemic amyloidosis: clinical and laboratory features in 474 cases.Semin Hematol. 1995; 32: 45-59
- Clinical characteristics and treatment outcome of Chinese patients with systemic amyloid light-chain amyloidosis: a retrospective single-center analysis.Clin Lymphoma Myeloma Leuk. 2016; 16: 104-110
- Immunoglobulin light-chain amyloidosis: from basics to new developments in diagnosis, prognosis and therapy.Acta Haematol. 2016; 135: 172-190
- Nationwide survey of 741 patients with systemic amyloid light-chain amyloidosis in Japan.Intern Med. 2018; 57: 181-187
- Macroglossia—not always AL amyloidosis.Amyloid. 2011; 18: 83-86
- Cardiac amyloidosis and its new clinical phenotype: heart failure with preserved ejection fraction.Arq Bras Cardiol. 2017; 109: 71-80
- Renal outcomes in patients with AL amyloidosis: prognostic factors, renal response and the impact of therapy.Am J Hematol. 2017; 92: 632-639
- Myocardial infarction with “clean coronaries” caused by amyloid light-chain AL amyloidosis: a case report and literature review.Amyloid. 2011; 18: 160-164
- Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis.JACC Heart Fail. 2014; 2: 358-367
- Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress.Circ Res. 2004; 94: 1008-1010
- Pathophysiology and treatment of cardiac amyloidosis.Nat Rev Cardiol. 2015; 12: 91-102
- Cardiac amyloidosis: pathology, nomenclature, and typing.Cardiovasc Pathol. 2015; 24: 343-350
- Amyloidogenicity and clinical phenotype associated with five novel mutations in apolipoprotein A-I.Am J Pathol. 2011; 179: 1978-1987
- Transthyretin cardiac amyloidosis in older Americans.J Card Fail. 2016; 22: 996-1003
- THAOS—the Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis.Curr Med Res Opin. 2013; 29: 63-76
- Cardiac amyloidosis.Clin Med (Lond). 2018; 18: s30-s35
- Online registry for mutations in hereditary amyloidosis including nomenclature recommendations.Hum Mutat. 2014; 35: E2403-E2412
- Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.Proc Natl Acad Sci U S A. 2018; 115: E6428-E6436
- Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population.Amyloid. 2008; 15: 181-186
- Nomenclature 2014: amyloid fibril proteins and clinical classification of the amyloidosis.Amyloid. 2014; 21: 221-224
- The amyloidogenic V122I transthyretin variant in elderly black Americans.N Engl J Med. 2015; 372: 21-29
- Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African-Americans.Amyloid. 2015; 22: 171-174
- Estimating the prevalence of allelic variants in the transthyretin gene by analysing large-scale sequencing data.Eur J Hum Genet. 2019; 27: 783-791
- Afro-Caribbean heart failure in the United Kingdom: cause, outcomes, and ATTR V122I cardiac amyloidosis.Circ Heart Fail. 2016; : 9
- A molecular mechanism for transthyretin amyloidogenesis.Nat Commun. 2019; 10: 925
- Transthyretin-related amyloidoses and the heart: a clinical overview.Nat Rev Cardiol. 2010; 7: 398
- Clinical presentation, diagnosis and treatment of TTR amyloidosis.J Neuromuscul Dis. 2019; 6: 189-199
- Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), previously known as senile cardiac amyloidosis: clinical presentation, diagnosis, management and emerging therapies.J Thorac Dis. 2018; 10: 2034-2045
- Phenotypic and genotypic heterogeneity in transthyretin-related cardiac amyloidosis: toward tailoring of therapeutic strategies?.Amyloid. 2006; 13: 143-153
- A study of the neuropathy associated with transthyretin amyloidosis (ATTR) in the UK.J Neurol Neurosurg Psychiatry. 2016; 87: 620-627
- Influence of Janus kinase inhibition on interleukin 6-mediated induction of acute-phase serum amyloid A in rheumatoid synovium.J Rheumatol. 2011; 38: 2309-2317
- Serum amyloid-A protein concentration in inflammatory diseases and its relationship to the incidence of reactive systemic amyloidosis.Lancet. 1982; 2: 231-234
- Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a single national referral centre.Amyloid. 2017; 24: 162-166
- Effect of amino acid variations in the central region of human serum amyloid A on the amyloidogenic properties.Biochem Biophys Res Commun. 2014; 444: 92-97
- Pathogenic serum amyloid A 1.1 shows a long oligomer-rich fibrillation lag phase contrary to the highly amyloidogenic nonpathogenic SAA2.2.J Biol Chem. 2013; 288: 2744-2755
- An allele of serum amyloid A1 associated with amyloidosis in both Japanese and Caucasians.Amyloid. 2003; 10: 7-11
- AA amyloidosis associated with a mutated serum amyloid A4 protein.Amyloid. 2009; 16: 84-88
- Clinical characteristics of patients with systemic amyloidosis from 2000-2010.Rev Clin Esp (Barc). 2013; 213: 186-193
- Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy.Br J Rheumatol. 1996; 35: 44-49
- Drawing attention to a neglected injecting-related harm: a systematic review of AA amyloidosis among people who inject drugs.Addiction. 2018; 113: 1790-1801
- Natural history and outcome in systemic AA amyloidosis.N Engl J Med. 2007; 356: 2361-2371
- Gastroparesis in a patient with gastric AL amyloidosis.Case Rep Gastroenterol. 2018; 12: 317-321
- The changing face of AA amyloidosis: a single center experience.Amyloid. 2011; 18: 226-228
- First nationwide survey of 199 patients with amyloid A amyloidosis in Japan.Intern Med. 2018; 57: 3351-3355
- Renal AA amyloidosis: survey of epidemiologic and laboratory data from one nephrology centre.Int Urol Nephrol. 2009; 41: 941-945
- Ten years’ experience of an amyloid clinic—a clinicopathological survey.Q J Med. 1985; 54: 213-227
- A novel apolipoprotein A-1 variant, Arg173Pro, associated with cardiac and cutaneous amyloidosis.Biochem Biophys Res Commun. 1999; 257: 584-588
- The new apolipoprotein A-I variant Leu(174)--> Ser causes hereditary cardiac amyloidosis, and the amyloid fibrils are constituted by the 93-residue N-terminal polypeptide.Am J Pathol. 1999; 155: 695-702
- Two different types of amyloid deposits—apolipoprotein A-IV and transthyretin—in a patient with systemic amyloidosis.Lab Invest. 2004; 84: 981-988
- An N-terminal pro–atrial natriuretic peptide (NT-proANP) “aggregation-prone” segment involved in isolated atrial amyloidosis.FEBS Lett. 2014; 588: 52-57
- Patterns of isolated atrial amyloid: a study of 100 hearts on autopsy.Cardiovasc Pathol. 2006; 15: 287-290
- The association of atrial tachyarrhythmias with isolated atrial amyloid disease: preliminary observations in autopsied heart specimens.Cardiology. 2009; 113: 132-137
- Prevalence of isolated atrial amyloidosis in young patients affected by congestive heart failure.ScientificWorldJournal. 2012; 2012: 293863
- Amyloid deposition as a cause of atrial remodelling in persistent valvular atrial fibrillation.Eur Heart J. 2004; 25: 1237-1241
- Incidence and distribution of isolated atrial amyloid: histologic and immunohistochemical studies of 100 aging hearts.Pathol Int. 1995; 45: 335-342
Article Info
Publication History
Published online: December 17, 2019
Accepted:
December 9,
2019
Received:
August 21,
2019
Footnotes
See page 381 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
