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Heart Failure Reviews

Open Access 22-09-2023 | Cardiac Amyloidosis

Valvular heart disease in patients with cardiac amyloidosis

Authors: Alberto Aimo, Lara Camerini, Iacopo Fabiani, Paolo Morfino, Giorgia Panichella, Andrea Barison, Angela Pucci, Vincenzo Castiglione, Giuseppe Vergaro, Gianfranco Sinagra, Michele Emdin

Published in: Heart Failure Reviews

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Abstract

Cardiac amyloidosis (CA) is an underdiagnosed condition caused by the deposition of misfolded proteins, namely immunoglobulin light chains and transthyretin, in the extracellular spaces of the heart. Any cardiovascular structure can be affected by amyloid infiltration, including the valves. Amyloid accumulation within the cardiac valves may lead to their structural and functional impairment, with a profound impact on patients’ prognosis and quality of life. The most common forms of valvular disease in CA are aortic stenosis (AS), mitral regurgitation (MR), and tricuspid regurgitation (TR). CA and AS share similar risk factors, disease mechanisms, and remodeling patterns, which make their diagnosis particularly challenging. Patients with both CA and AS experience worse outcomes than CA or AS alone, and transcatheter aortic valve replacement may represent a useful therapeutic strategy in this population. Data on MR and TR are quite limited and mainly coming from case reports or small series. This review paper will summarize our current understanding on the epidemiology, disease mechanisms, echocardiographic features, clinical implications, and therapeutic options of AS, MR, and TR in patients with CA.
Literature
1.
Maurizi N, Rella V, Fumagalli C, Salerno S, Castelletti S, Dagradi F et al (2020) Prevalence of cardiac amyloidosis among adult patients referred to tertiary centres with an initial diagnosis of hypertrophic cardiomyopathy. Int J Cardiol 300:191–5 PubMedCrossRef
2.
Emdin M, Aimo A, Rapezzi C, Fontana M, Perfetto F, Seferović PM et al (2019) Treatment of cardiac transthyretin amyloidosis: an update. Eur Heart J 40(45):3699–706 PubMedCrossRef
3.
Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A et al (2016) Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 133(24):2404–12 PubMedCrossRef
4.
Fontana M, Chung R, Hawkins PN, Moon JC (2015) Cardiovascular magnetic resonance for amyloidosis. Heart Fail Rev 20(2):133–44 PubMed
5.
Quarta CC, Fontana M, Damy T, Catini J, Simoneau D, Mercuri M et al (2022) Changing paradigm in the treatment of amyloidosis: from disease-modifying drugs to anti-fibril therapy. Front Cardiovasc Med 9:1073503 PubMedPubMedCentralCrossRef
6.
Rapezzi C, Aimo A, Barison A, Emdin M, Porcari A, Linhart A et al (2022) Restrictive cardiomyopathy: definition and diagnosis. Eur Heart J 43(45):4679–93 PubMedPubMedCentralCrossRef
7.
Coffey S, Cox B, Williams MJ (2014) The prevalence, incidence, progression, and risks of aortic valve sclerosis: a systematic review and meta-analysis. J Am Coll Cardiol 63(25 Pt A):2852–2861 PubMedCrossRef
8.
Peskó G, Jenei Z, Varga G, Apor A, Vágó H, Czibor S et al (2019) Coexistence of aortic valve stenosis and cardiac amyloidosis: echocardiographic and clinical significance. Cardiovasc Ultrasound 17(1):32 PubMedPubMedCentral
9.
Castaño A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A et al (2017) Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J 38(38):2879–87 PubMedPubMedCentralCrossRef
10.
Scully PR, Treibel TA, Fontana M, Lloyd G, Mullen M, Pugliese F et al (2018) Prevalence of cardiac amyloidosis in patients referred for transcatheter aortic valve replacement. J Am Coll Cardiol 71(4):463–4 PubMedPubMedCentralCrossRef
11.
12.
Longhi S, Lorenzini M, Gagliardi C, Milandri A, Marzocchi A, Marrozzini C et al (2016) Coexistence of degenerative aortic stenosis and wild-type transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging 9(3):325–7 PubMedCrossRef
13.
Singal AK, Bansal R, Singh A, Dorbala S, Sharma G, Gupta K et al (2021) Concomitant transthyretin amyloidosis and severe aortic stenosis in elderly Indian population: a pilot study. JACC CardioOncology. 3(4):565–76 PubMedPubMedCentralCrossRef
14.
Ternacle J, Krapf L, Mohty D, Magne J, Nguyen A, Galat A et al (2019) Aortic stenosis and cardiac amyloidosis: JACC review topic of the week. J Am Coll Cardiol 74(21):2638–51 PubMed
15.
Aimo A, Merlo M, Porcari A, Georgiopoulos G, Pagura L, Vergaro G et al (2022) Redefining the epidemiology of cardiac amyloidosis a systematic review and meta-analysis of screening studies. Eur Heart J Fail 24(12):2342–2351 CrossRef
16.
Nitsche C, Aschauer S, Kammerlander AA, Schneider M, Poschner T, Duca F et al (2020) Light-chain and transthyretin cardiac amyloidosis in severe aortic stenosis: prevalence, screening possibilities, and outcome. Eur J Heart Fail 22(10):1852–62 PubMedCrossRef
17.
Nitsche C, Scully PR, Patel KP, Kammerlander AA, Koschutnik M, Dona C et al (2021) Prevalence and outcomes of concomitant aortic stenosis and cardiac amyloidosis. J Am Coll Cardiol 77(2):128–39 PubMedPubMedCentral
18.
Marcoux J, Mangione PP, Porcari R, Degiacomi MT, Verona G, Taylor GW et al (2015) A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis. EMBO Mol Med 7(10):1337–49 PubMedPubMedCentralCrossRef
19.
20.
Sud K, Narula N, Aikawa E, Arbustini E, Pibarot P, Merlini G et al (2023) The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis. Nat Rev Cardiol 20(6):418–428. https://​doi.​org/​10.​1038/​s41569-022-00818-2. Epub 2023 Jan 9. Erratum in: Nat Rev Cardiol. 2023 Feb 17;: PMID: 36624274; PMCID: PMC10199673.
21.
Maurer MS, Bokhari S, Damy T, Dorbala S, Drachman BM, Fontana M et al (2019) Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail 12(9):e006075 PubMedPubMedCentralCrossRef
22.
Merlini G, Dispenzieri A, Sanchorawala V, Schönland SO, Palladini G, Hawkins PN et al (2018) Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers 4(1):38 PubMedCrossRef
23.
Vergaro G, Castiglione V, Aimo A, Prontera C, Masotti S, Musetti V et al (2023) N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T hold diagnostic value in cardiac amyloidosis. Eur J Heart Fail 25(3):335–46 PubMedCrossRef
24.
Tang CX, Petersen SE, Sanghvi MM, Lu GM, Zhang LJ (2019) Cardiovascular magnetic resonance imaging for amyloidosis: the state-of-the-art. Trends Cardiovasc Med 29(2):83–94 PubMedCrossRef
25.
Garcia-Pavia P, Rapezzi C, Adler Y, Arad M, Basso C, Brucato A et al (2021) Diagnosis and treatment of cardiac amyloidosis. A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur J Heart Fail 23(4):512–526 PubMedCrossRef
26.
Oike F, Usuku H, Yamamoto E, Marume K, Takashio S, Ishii M et al (2022) Utility of left atrial and ventricular strain for diagnosis of transthyretin amyloid cardiomyopathy in aortic stenosis. ESC Heart Fail 9(3):1976–86 PubMedPubMedCentralCrossRef
27.
Robin G, Cognet T, Bouisset F, Cariou E, Méjean S, Pradel S et al (2021) Value of longitudinal strain to identify wild-type transthyretin amyloidosis in patients with aortic stenosis. Circulation journal : Official journal of the Japanese Circulation Society 85(9):1494–504 PubMedCrossRef
28.
Cersosimo A, Bonelli A, Lombardi CM, Moreo A, Pagnesi M, Tomasoni D et al (2023) Multimodality imaging in the diagnostic management of concomitant aortic stenosis and transthyretin-related wild-type cardiac amyloidosis. Front Cardiovasc Med 10:1108696 PubMedPubMedCentralCrossRef
29.
Scully PR, Bastarrika G, Moon JC, Treibel TA (2018) Myocardial extracellular volume quantification by cardiovascular magnetic resonance and computed tomography. Curr Cardiol Rep 20(3):15 PubMedPubMedCentralCrossRef
30.
Frangogiannis NG (2017) The extracellular matrix in myocardial injury, repair, and remodeling. J Clin Investig 127(5):1600–12 PubMedPubMedCentral
31.
Scully PR, Patel KP, Saberwal B, Klotz E, Augusto JB, Thornton GD et al (2020) Identifying cardiac amyloid in aortic stenosis: ECV quantification by CT in TAVR patients. JACC Cardiovasc Imaging 13(10):2177–89 PubMedPubMedCentralCrossRef
32.
Tavoosi A, Brito JBO, El Mais H, Small TD, Crean AM, Chow BJW et al (2023) Dual versus single energy cardiac CT to measure extra cellular volume in cardiac amyloidosis: correlations with cardiac MRI. IJC Heart Vasc 44
33.
Gama F, Rosmini S, Bandula S, Patel KP, Massa P, Tobon-Gomez C et al (2022) Extracellular volume fraction by computed tomography predicts long-term prognosis among patients with cardiac amyloidosis. JACC Cardiovasc Imaging 15(12):2082–94 PubMedCrossRef
34.
Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J et al (2022) 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 43(7):561–632 PubMedCrossRef
35.
Hussain M, Hanna M, Griffin BP, Conic J, Patel J, Fava AM, Watson C, Phelan DM, Jellis C, Grimm RA, Rodriguez LL, Schoenhagen P, Hachamovitch R, Jaber WA, Cremer PC, Collier P (2020) Aortic valve calcium in patients with transthyretin cardiac amyloidosis: a propensity-matched analysis. Circ Cardiovasc Imaging 13(10):e011433. https://​doi.​org/​10.​1161/​CIRCIMAGING.​120.​011433. Epub 2020 Sep 23. PMID: 32967445.
36.
Hussain M, Hanna M, Rodriguez L, Griffin B, Watson C, Phelan D et al (2020) Subthreshold aortic valve calcium scores in severe aortic stenosis and transthyretin cardiac amyloidosis. JACC Case Rep 2(14):2205–9 PubMedPubMedCentralCrossRef
37.
38.
Ho JS, Kor Q, Kong WK, Lim YC, Chan MY, Syn NL et al (2022) Prevalence and outcomes of concomitant cardiac amyloidosis and aortic stenosis: a systematic review and meta-analysis. Hellenic J Cardiol: HJC = Hellenike Kardiologike Epitheorese 64:67–76 PubMedCrossRef
39.
Ricci F, Ceriello L, Khanji MY, Dangas G, Bucciarelli-Ducci C, Di Mauro M et al (2021) Prognostic significance of cardiac amyloidosis in patients with aortic stenosis: a systematic review and meta-analysis. JACC Cardiovasc Imaging 14(1):293–5 PubMedCrossRef
40.
Myasoedova VA, Conte M, Valerio V, Moschetta D, Massaiu I, Petraglia L et al (2022) Red flags, prognostic impact, and management of patients with cardiac amyloidosis and aortic valve stenosis: a systematic review and meta-analysis. Front Med 9:858281 CrossRef
41.
Cannata F, Chiarito M, Pinto G, Villaschi A, Sanz-Sánchez J, Fazzari F et al (2022) Transcatheter aortic valve replacement in aortic stenosis and cardiac amyloidosis: a systematic review and meta-analysis. ESC Heart Fail 9(5):3188–97 PubMedPubMedCentralCrossRef
42.
Scully PR, Patel KP, Treibel TA, Thornton GD, Hughes RK, Chadalavada S et al (2020) Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation. Eur Heart J 41(29):2759–67 PubMedPubMedCentralCrossRef
43.
de Campos D, Saleiro C, Botelho A, Costa M, Gonçalves L, Teixeira R (2022) Aortic valve intervention for aortic stenosis and cardiac amyloidosis: a systematic review and meta-analysis. Future Cardiol 18(6):477–86 PubMedCrossRef
44.
Nitsche C, Koschutnik M, Donà C, Radun R, Mascherbauer K, Kammerlander A et al (2022) Reverse remodeling following valve replacement in coexisting aortic stenosis and transthyretin cardiac amyloidosis. Circ Cardiovasc Imaging 15(7):e014115 PubMedCrossRef
45.
Garcia-Pavia P, Rapezzi C, Adler Y, Arad M, Basso C, Brucato A et al (2021) Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J 42(16):1554–68 PubMedPubMedCentralCrossRef
46.
Donà C, Nitsche C, Koschutnik M, Heitzinger G, Mascherbauer K, Kammerlander AA et al (2022) Unveiling cardiac amyloidosis, its characteristics, and outcomes among patients with MR undergoing transcatheter edge-to-edge MV repair. JACC Cardiovasc Interv 15(17):1748–58 PubMedCrossRef
47.
Mohty D, Pradel S, Magne J, Fadel B, Boulogne C, Petitalot V et al (2017) Prevalence and prognostic impact of left-sided valve thickening in systemic light-chain amyloidosis. Clinical research in cardiology : official journal of the German Cardiac Society. 106(5):331–40 PubMedCrossRef
48.
Kristen AV, Schnabel PA, Winter B, Helmke BM, Longerich T, Hardt S et al (2010) High prevalence of amyloid in 150 surgically removed heart valves–a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 19(4):228–35 PubMedCrossRef
49.
Yokota T, Okabayashi H, Ishihara T, Kawano H, Wakabayashi F, Miyamoto AT et al (1994) Immunohistochemical and pathological characteristics of dystrophic amyloid in surgically excised cardiac valves. Pathol Int 44(3):182–5 PubMed
50.
Smith TJ, Kyle RA, Lie JT (1984) Clinical significance of histopathologic patterns of cardiac amyloidosis. Mayo Clin Proc 59(8):547–55 PubMedCrossRef
51.
Nemes A, Földeák D, Kormányos Á, Domsik P, Kalapos A, Borbényi Z et al (2017) Cardiac amyloidosis associated with enlargement and functional impairment of the mitral annulus: insights from the three-dimensional speckle tracking echocardiographic MAGYAR-path study. J Heart Valve Dis 26(3):304–8 PubMed
52.
Nishi H, Mitsuno M, Ryomoto M, Miyamoto Y (2008) Severe mitral regurgitation due to cardiac amyloidosis–a rare reason for ruptured chordae. Interact Cardiovasc Thorac Surg 7(6):1199–200 PubMedCrossRef
53.
Aimo A, Fabiani I, Maccarana A, Vergaro G, Chubuchny V, Pasanisi EM, Petersen C, Poggianti E, Giannoni A, Spini V, Taddei C, Castiglione V, Passino C, Fontana M, Emdin M, Venneri L (2023) Valve disease in cardiac amyloidosis: an echocardiographic score. Int J Cardiovasc Imaging. https://​doi.​org/​10.​1007/​s10554-023-02901-2. Epub ahead of print. PMID: 37341947.
54.
Chacko L, Karia N, Venneri L, Bandera F, Passo BD, Buonamici L et al (2022) Progression of echocardiographic parameters and prognosis in transthyretin cardiac amyloidosis. Eur J Heart Fail 24(9):1700–12 PubMedCrossRef
55.
Lane T, Fontana M, Martinez-Naharro A, Quarta CC, Whelan CJ, Petrie A et al (2019) Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis. Circulation. 140(1):16–26 PubMedCrossRef
56.
Bandera F, Martone R, Chacko L, Ganesananthan S, Gilbertson JA, Ponticos M et al (2022) Clinical importance of left atrial infiltration in cardiac transthyretin amyloidosis. JACC Cardiovasc Imaging 15(1):17–29 PubMedPubMedCentralCrossRef
57.
58.
Volz MJ, Pleger ST, Weber A, Geis NA, Hamed S, Mereles D et al (2021) Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis. Eur J Clin Invest 51(6):e13473 PubMed
59.
Thakker RA, Elbadawi A, Albaeni A, Hasan SM, Suthar KH, Modi SA et al (2022) Percutaneous mitral valve repair in cardiac amyloidosis and severe mitral regurgitation. Curr Probl Cardiol 47(9):100881 PubMed
60.
Fagot J, Lavie-Badie Y, Blanchard V, Fournier P, Galinier M, Carrié D et al (2021) Impact of tricuspid regurgitation on survival in patients with cardiac amyloidosis. ESC Heart Fail 8(1):438–46 PubMedCrossRef
61.
Nemes A, Rácz G, Kormányos Á, Földeák D, Borbényi Z (2022) The tricuspid annulus in amyloidosis with cardiac involvement: detailed analysis from the three-dimensional speckle tracking echocardiographic MAGYAR-Path Study. Int J Cardiol Heart Vasc 40:101026 PubMedPubMedCentral
62.
Tomasoni D, Adamo M, Porcari A, Aimo A, Bonfioli GB, Castiglione V, Franzini M, Inciardi RM, Khalil A, Lombardi CM, Lupi L, Nardi M, Oriecuia C, Pagnesi M, Panichella G, Rossi M, Saccani N, Specchia C, Vergaro G, Merlo M, Sinagra G, Emdin M, Metra M (2023) Right ventricular to pulmonary artery coupling and outcome in patients with cardiac amyloidosis. Eur Heart J Cardiovasc Imaging jead145. https://​doi.​org/​10.​1093/​ehjci/​jead145. Epub ahead of print. PMID: 37379445.
63.
Hoerbrand IA, Volz MJ, Aus dem Siepen F, Aurich M, Schlegel P, Geis NA et al (2023) Initial experience with transcatheter tricuspid valve repair in patients with cardiac amyloidosis. ESC Heart Fail 10(2):1003–10012 PubMedCrossRef
64.
Merlo M, Pagura L, Porcari A, Cameli M, Vergaro G, Musumeci B et al (2022) Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey. Eur J Heart Fail 24(8):1377–86 PubMedCrossRef
65.
Emdin M, Morfino P, Crosta L, Aimo A, Vergaro G, Castiglione V (2023) Monoclonal antibodies and amyloid removal as a therapeutic strategy for cardiac amyloidosis. European Heart Journal Supplements : Journal of the European Society of Cardiology 25(Suppl B):B79-b84 PubMedCrossRef
66.
Garcia-Pavia P, Aus dem Siepen F, Donal E, Lairez O, van der Meer P, Kristen AV et al (2023) Phase 1 trial of antibody NI006 for depletion of cardiac transthyretin amyloid. New Engl J Med 389(3):239–250 PubMedCrossRef
67.
Nietlispach F, Webb JG, Ye J, Cheung A, Lichtenstein SV, Carere RG et al (2012) Pathology of transcatheter valve therapy. JACC Cardiovasc Interv 5(5):582–90 PubMedCrossRef
68.
Cavalcante JL, Rijal S, Abdelkarim I, Althouse AD, Sharbaugh MS, Fridman Y et al (2017) Cardiac amyloidosis is prevalent in older patients with aortic stenosis and carries worse prognosis. Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance 19(1):98 PubMedCrossRef
69.
Xu B, Godoy Rivas C, Rodriguez ER, Tan C, Gillinov AM, Harb S et al (2019) Unrecognized cardiac amyloidosis at the time of mitral valve surgery: incidence and outcomes. Cardiology 142(4):253–8 PubMedCrossRef
Metadata
Title
Valvular heart disease in patients with cardiac amyloidosis
Authors
Alberto Aimo
Lara Camerini
Iacopo Fabiani
Paolo Morfino
Giorgia Panichella
Andrea Barison
Angela Pucci
Vincenzo Castiglione
Giuseppe Vergaro
Gianfranco Sinagra
Michele Emdin
Publication date
22-09-2023
Publisher
Springer US
Published in
Heart Failure Reviews
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-023-10350-1
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