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Cardiac Amyloidosis for the Primary Care Provider: A Practical Review to Promote Earlier Recognition of Disease

Published:January 11, 2021DOI:https://doi.org/10.1016/j.amjmed.2020.11.031

      Abstract

      Cardiac amyloidosis is increasingly recognized as an underdiagnosed cause of heart failure. Diagnostic delays of up to 3 years from symptom onset may occur, and patients may be evaluated by more than 5 specialists prior to receiving the correct diagnosis. Newly available therapies improve clinical outcomes by preventing amyloid fibril deposition and are usually more effective in early stages of disease, making early diagnosis essential. Better awareness among primary care providers of the clinical presentation and modern treatment landscape is essential to improve timely diagnosis and early treatment of this disease. In this review, we provide practical guidance on the epidemiology, clinical manifestations, diagnostic evaluation, and treatment of transthyretin and light chain cardiac amyloidosis to promote earlier disease recognition among primary care providers.

      Keywords

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      References

        • Zhang KW
        • Stockerl-Goldstein KE
        • Lenihan DJ.
        Emerging therapeutics for the treatment of light chain and transthyretin amyloidosis.
        JACC Basic Trans Sci. 2019; 4: 1-11https://doi.org/10.1016/j.jacbts.2019.02.002
        • Mohammed SF
        • Mirzoyev SA
        • Edwards WD
        • et al.
        Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction.
        JACC Heart Fail. 2014; 2: 113-122https://doi.org/10.1016/j.jchf.2013.11.004
        • González-López E
        • Gallego-Delgado M
        • Guzzo-Merello G
        • et al.
        Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction.
        Eur Heart J. 2015; 36: 2585-2594https://doi.org/10.1093/eurheartj/ehv338
        • Scully PR
        • Patel KP
        • Treibel TA
        • et al.
        Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation.
        Eur Heart J. 2020; 41: 2759-2767https://doi.org/10.1093/eurheartj/ehaa170
        • Milandri A
        • Farioli A
        • Gagliardi C
        • et al.
        Carpal tunnel syndrome in cardiac amyloidosis: implications for early diagnosis and prognostic role across the spectrum of aetiologies.
        Eur J Heart Fail. 2020; 22: 507-515https://doi.org/10.1002/ejhf.1742
        • Bishop E
        • Brown EE
        • Fajardo J
        • Barouch LA
        • Judge DP
        • Halushka MK.
        Seven factors predict a delayed diagnosis of cardiac amyloidosis.
        Amyloid. 2018; 25: 174-179https://doi.org/10.1080/13506129.2018.1498782
        • Lousada I
        • Comenzo RL
        • Landau H
        • Guthrie S
        • Merlini G.
        Light chain amyloidosis: patient experience survey from the Amyloidosis Research Consortium.
        Adv Ther. 2015; 32: 920-928https://doi.org/10.1007/s12325-015-0250-0
        • Maurer MS
        • Hanna M
        • Grogan M
        • et al.
        Genotype and phenotype of transthyretin cardiac amyloidosis in the United States: The Transthyretin Amyloid Outcome Survey (THAOS).
        J Am Coll Cardiol. 2017; 68: 161-172https://doi.org/10.1016/j.jacc.2016.03.596.Genotype
        • Sperry BW
        • Reyes BA
        • Ikram A
        • et al.
        Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release.
        J Am Coll Cardiol. 2018; 72: 2040-2050https://doi.org/10.1016/j.jacc.2018.07.092
        • Buxbaum JN
        • Ruberg FL.
        Transthyretin V122I (pV142I)∗ cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans.
        Genet Med. 2017; 19: 733-742https://doi.org/10.1038/gim.2016.200
        • 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; 2: 1046-1053https://doi.org/10.1182/bloodadvances.2018016402
        • Kyle RA
        • Larson DR
        • Therneau TM
        • et al.
        Long-term follow-up of monoclonal gammopathy of undetermined significance.
        N Engl J Med. 2018; 378: 241-249https://doi.org/10.1056/NEJMoa1709974
        • Lee Chuy K
        • Drill E
        • Yang JC
        • et al.
        Incremental value of global longitudinal strain for predicting survival in patients with advanced AL amyloidosis.
        JACC CardioOncol. 2020; 2: 223-231https://doi.org/10.1016/j.jaccao.2020.05.012
        • Yanagisawa A
        • Ueda M
        • Sueyoshi T
        • et al.
        Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis.
        Mod Pathol. 2015; 28: 201-207https://doi.org/10.1038/modpathol.2014.102
        • Maurer MS
        • Hanna M
        • Grogan M
        • et al.
        Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey).
        J Am Coll Cardiol. 2016; 68: 161-172https://doi.org/10.1016/j.jacc.2016.03.596
        • Palladini G
        • Campana C
        • Klersy C
        • et al.
        Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis.
        Circulation. 2003; 107: 2440-2445https://doi.org/10.1161/01.CIR.0000068314.02595.B2
        • Zhang KW
        • Miao J
        • Mitchell JD
        • et al.
        Plasma hepatocyte growth factor for diagnosis and prognosis in light chain and transthyretin cardiac amyloidosis.
        JACC CardioOncol. 2020; 2: 56-66https://doi.org/10.1016/j.jaccao.2020.01.006
        • Reisinger J
        • Dubrey SW
        • Lavalley M
        • Skinner M
        • Falk RH.
        Electrophysiologic abnormalities in AL (primary) amyloidosis with cardiac involvement.
        J Am Coll Cardiol. 1997; 30: 1046-1051https://doi.org/10.1016/S0735-1097(97)00267-2
        • Mussinelli R
        • Salinaro F
        • Alogna A
        • et al.
        Diagnostic and prognostic value of low QRS voltages in cardiac AL amyloidosis.
        Ann Noninvasive Electrocardiol. 2013; 18: 271-280https://doi.org/10.1111/anec.12036
        • Cheng Z
        • Zhu K
        • Tian Z
        • Zhao D
        • Cui Q
        • Fang Q.
        The findings of electrocardiography in patients with cardiac amyloidosis.
        Ann Noninvasive Electrocardiol. 2013; 18: 157-162https://doi.org/10.1111/anec.12018
        • El-Am EA
        • Dispenzieri A
        • Melduni RM
        • et al.
        Direct current cardioversion of atrial arrhythmias in adults with cardiac amyloidosis.
        J Am Coll Cardiol. 2019; 73: 589-597https://doi.org/10.1016/j.jacc.2018.10.079
        • Martinez-Naharro A
        • Gonzalez-Lopez E
        • Corovic A
        • et al.
        High prevalence of intracardiac thrombi in cardiac amyloidosis.
        J Am Coll Cardiol. 2019; 73: 1733-1734https://doi.org/10.1016/j.jacc.2019.01.035
        • Boldrini M
        • Cappelli F
        • Chacko L
        • et al.
        Multiparametric echocardiography scores for the diagnosis of cardiac amyloidosis.
        JACC Cardiovasc Imaging. 2020; 13: 909-920https://doi.org/10.1016/j.jcmg.2019.10.011
        • Maceira AM
        • Joshi J
        • Prasad SK
        • et al.
        Cardiovascular magnetic resonance in cardiac amyloidosis.
        Circulation. 2005; 111: 186-193https://doi.org/10.1161/01.CIR.0000152819.97857.9D
        • Vogelsberg H
        • Mahrholdt H
        • Deluigi CC
        • et al.
        Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis. noninvasive imaging compared to endomyocardial biopsy.
        J Am Coll Cardiol. 2008; 51: 1022-1030https://doi.org/10.1016/j.jacc.2007.10.049
        • Banypersad SM
        • Sado DM
        • Flett AS
        • et al.
        Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study.
        Circ Cardiovasc Imaging. 2013; 6: 34-39https://doi.org/10.1161/CIRCIMAGING.112.978627
        • Baggiano A
        • Boldrini M
        • Martinez-Naharro A
        • et al.
        Noncontrast magnetic resonance for the diagnosis of cardiac amyloidosis.
        JACC Cardiovasc Imaging. 2020; 13: 69-80https://doi.org/10.1016/j.jcmg.2019.03.026
        • Sethi S
        • Vrana JA
        • Theis JD
        • et al.
        Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis.
        Kidney Int. 2012; 82: 226-234https://doi.org/10.1038/ki.2012.108
        • Gillmore JD
        • Maurer MS
        • Falk RH
        • et al.
        Nonbiopsy diagnosis of cardiac transthyretin amyloidosis.
        Circulation. 2016; 133: 2404-2412https://doi.org/10.1161/CIRCULATIONAHA.116.021612
        • Quarta CC
        • Gonzalez-Lopez E
        • Gilbertson JA
        • et al.
        Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis.
        Eur Heart J. 2017; 38: 1905-1908https://doi.org/10.1093/eurheartj/ehx047
        • Li T
        • Huang X
        • Cheng S
        • et al.
        Utility of abdominal skin plus subcutaneous fat and rectal mucosal biopsy in the diagnosis of AL amyloidosis with renal involvement.
        PLoS One. 2017; 12: 1-10https://doi.org/10.1371/journal.pone.0185078
        • Grogan M
        • Scott CG
        • Kyle RA
        • et al.
        Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system.
        J Am Coll Cardiol. 2016; 68: 1014-1020https://doi.org/10.1016/j.jacc.2016.06.033
        • Wechalekar AD
        • Schonland SO
        • Kastritis E
        • et al.
        A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis.
        Blood. 2013; 121: 3420-3427https://doi.org/10.1182/blood-2012-12-473066
        • Barrett CD
        • Alexander KM
        • Zhao H
        • et al.
        Outcomes in patients with cardiac amyloidosis undergoing heart transplantation.
        JACC Heart Fail. 2020; 8: 461-468https://doi.org/10.1016/j.jchf.2019.12.013
        • Miroy GJ
        • Lai Z
        • Lashuel Ha
        • Peterson Sa
        • Strang C
        • Kelly JW.
        Inhibiting transthyretin amyloid fibril formation via protein stabilization.
        Proc Natl Acad Sci U S A. 1996; 93: 15051-15056https://doi.org/10.1073/pnas.93.26.15051
        • Maurer MS
        • Schwartz JH
        • Gundapaneni B
        • et al.
        Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy.
        N Engl J Med. 2018; 379: 1007-1016https://doi.org/10.1056/NEJMoa1805689
        • Benson MD
        • Waddington-Cruz M
        • Berk JL
        • et al.
        Inotersen treatment for patients with hereditary transthyretin amyloidosis.
        N Engl J Med. 2018; 379: 22-31https://doi.org/10.1056/NEJMoa1716793
        • Adams D
        • Gonzalez-Duarte A
        • O'Riordan WD
        • et al.
        Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis.
        N Engl J Med. 2018; 379: 11-21https://doi.org/10.1056/NEJMoa1716153
        • Sidiqi MH
        • Aljama MA
        • Buadi FK
        • et al.
        Stem cell transplantation for light chain amyloidosis: decreased early mortality over time.
        J Clin Oncol. 2018; 36: 1323-1329https://doi.org/10.1200/JCO.2017.76.9554
        • Wechalekar AD
        • Whelan C.
        Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis.
        Blood Cancer J. 2017; 7: 89-91https://doi.org/10.1038/bcj.2017.26
        • Pitt B
        • Pfeffer MA
        • Assmann SF
        • et al.
        Spironolactone for heart failure with preserved ejection fraction.
        N Engl J Med. 2014; 370: 1383-1392https://doi.org/10.1056/NEJMoa1313731
        • Lin G
        • Dispenzieri A
        • Kyle R
        • Grogan M
        • Brady PA.
        Implantable cardioverter defibrillators in patients with cardiac amyloidosis.
        J Cardiovasc Electrophysiol. 2013; 24: 793-798https://doi.org/10.1111/jce.12123
        • Kim E-J
        • Holmes BB
        • Huang S
        • et al.
        Outcomes in patients with cardiac amyloidosis and implantable cardioverter-defibrillator.
        EP Eur. 2020; 22: 1216-1223.https://doi.org/10.1093/europace/euaa094