Grey zones in the supportive treatments of cardiac amyloidosis

Abstract

Recent advances in the diagnosis and treatment of cardiac amyloidosis (CA) have translated into a longer life expectancy of patients and more challenging clinical scenarios. Compared to the past, patients with CA and heart failure (HF) currently encountered in clinical practice are a more heterogeneous population and require tailored strategies. The perception of CA as a treatable disease has opened new possibilities for the management of these patients, but many grey areas remain to be explored. The aim of this review is to provide practical suggestions for daily clinical activity in the management of challenging scenarios in CA, including the effectiveness and tolerability of evidence-based HF medication; rate vs. rhythm control in atrial fibrillation, thromboembolic risk, and anticoagulation therapies; replacement of severe aortic valve stenosis; the impact of implantable cardioverter defibrillator on survival; and the usefulness of cardiac resynchronization therapy.

Keywords

Cardiac amyloidosis / grey areas / clinical management / heart failure / atrial fibrillation / aortic stenosis / arrhythmic risk stratification

References

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

[2] Porcari A,Rapezzi C.Transthyretin amyloid cardiomyopathy: an uncharted territory awaiting discovery.Eur J Intern Med2020;82:7-15 PMCID:PMC7534738

[3] Maurer MS,Damy T.Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis.Circ Heart Fail2019;12:e006075 PMCID:PMC6736650

[4] Emdin M,Rapezzi C.Treatment of cardiac transthyretin amyloidosis: an update.Eur Heart J2019;40:3699-706

[5] Merlo M,Pagura L.A national survey on prevalence of possible echocardiographic red flags of amyloid cardiomyopathy in consecutive patients undergoing routine echocardiography: study design and patients characterization-the first insight from the AC-TIVE Study.Eur J Prev Cardiol2021;zwab127:

[6] Kastritis E,Minnema MC.ANDROMEDA Trial InvestigatorsDaratumumab-based treatment for immunoglobulin light-chain amyloidosis.N Engl J Med2021;385:46-58

[7] Sperry BW,Hachamovitch R.Efficacy of chemotherapy for light-chain amyloidosis in patients presenting with symptomatic heart failure.J Am Coll Cardiol2016;67:2941-8

[8] Maurer MS,Gundapaneni B.ATTR-ACT Study InvestigatorsTafamidis treatment for patients with transthyretin amyloid cardiomyopathy.N Engl J Med2018;379:1007-16

[9] Korosoglou G,André F.Diagnostic work-up of cardiac amyloidosis using cardiovascular imaging: current standards and practical algorithms.Vasc Health Risk Manag2021;17:661-73 PMCID:PMC8550552

[10] Porcari A,Lio V.Cardiac amyloidosis: do not forget to look for it.Eur Heart J Suppl2020;22:E142-7 PMCID:PMC7270903

[11] González-López E,Guzzo-Merello G.Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction.Eur Heart J2015;36:2585-94

[12] Porcari A,Longo F.Prognostic significance of unexplained left ventricular hypertrophy in patients undergoing carpal tunnel surgery.ESC Heart Fail2021;

[13] Castaño A,Hamid N.Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.Eur Heart J2017;38:2879-87 PMCID:PMC5837725

[14] Nietlispach F,Ye J.Pathology of transcatheter valve therapy.JACC Cardiovasc Interv2012;5:582-90

[15] Visser RAB,Ahmed S.Amyloidosis and cardiovascular diseases: a clinical insight.J Card Surg2021;36:522-9

[16] Porcari A,Merlo M.Incidence and characterization of concealed cardiac amyloidosis among unselected elderly patients undergoing post-mortem examination.Front Cardiovasc Med2021;8:1680. PMCID:PMC8649842

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

[18] Koike H.The ultrastructure of tissue damage by amyloid fibrils.Molecules2021;26:4611 PMCID:PMC8347239

[19] Koike H.Transthyretin amyloidosis: update on the clinical spectrum, pathogenesis, and disease-modifying therapies.Neurol Ther2020;9:317-33 PMCID:PMC7500251

[20] Mendes Sousa M, Cardoso I, Fernandes R, Guimarães A, Saraiva MJ. Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy.Am J Pathol2001;159:1993-2000

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

[22] Knight DS,Barcella W.Cardiac structural and functional consequences of amyloid deposition by cardiac magnetic resonance and echocardiography and their prognostic roles.JACC Cardiovasc Imaging2019;12:823-33

[23] Falk RH,Liao R.AL (Light-Chain) cardiac amyloidosis: a review of diagnosis and therapy.J Am Coll Cardiol2016;68:1323-41

[24] Rapezzi C,Longhi S.Cardiac amyloidosis: the great pretender.Heart Fail Rev2015;20:117-24

[25] Canepa M,Musumeci B.Real-world versus trial patients with transthyretin amyloid cardiomyopathy.Eur J Heart Fail2019;21:1479-81

[26] Tini G,Biagini E.Current patterns of beta-blocker prescription in cardiac amyloidosis: an Italian nationwide survey.ESC Heart Fail2021;8:3369-74 PMCID:PMC8318433

[27] Aimo A,Castiglione V,Emdin M.Safety and tolerability of neurohormonal antagonism in cardiac amyloidosis.Eur J Intern Med2020;80:66-72

[28] Aus dem Siepen F, Hein S, Bauer R, Katus HA, Kristen AV. Standard heart failure medication in cardiac transthyretin amyloidosis: useful or harmful?.Amyloid2017;24:132-3

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

[30] Mints YY,Berk JL,Ruberg FL.Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: a systematic review and clinical experience.ESC Heart Fail2018;5:772-9 PMCID:PMC6165925

[31] Donnellan E,Hanna M.Atrial fibrillation in transthyretin cardiac amyloidosis: predictors, prevalence, and efficacy of rhythm control strategies.JACC Clin Electrophysiol2020;6:1118-27

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

[33] Hindricks G,Dagres N.ESC Scientific Document Group2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC.Eur Heart J2021;42:373-498

[34] Rubinow A,Cohen AS.Digoxin sensitivity in amyloid cardiomyopathy.Circulation1981;63:1285-8

[35] Muchtar E,Kumar SK.Digoxin use in systemic light-chain (AL) amyloidosis: contra-indicated or cautious use?.Amyloid2018;25:86-92 PMCID:PMC7433245

[36] Cheung CC,Andrade JG,Davis MK.Arrhythmias in cardiac amyloidosis: challenges in risk stratification and treatment.Can J Cardiol2020;36:416-23

[37] Gertz MA,Connors LH,Cohen AS.Selective binding of nifedipine to amylold fibrils.Am J Cardiol1985;55:1646

[38] Gertz MA,Skinner M,Kyle RA.Worsening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents.Am J Cardiol1985;55:1645

[39] Martinez-Naharro A,Corovic A.High prevalence of intracardiac thrombi in cardiac amyloidosis.J Am Coll Cardiol2019;73:1733-4

[40] El-Am EA,Melduni RM.Direct current cardioversion of atrial arrhythmias in adults with cardiac amyloidosis.J Am Coll Cardiol2019;73:589-97 PMCID:PMC6378685

[41] Loungani RS,Geurink KR.Outcomes following cardioversion for patients with cardiac amyloidosis and atrial fibrillation or atrial flutter.Am Heart J2020;222:26-9

[42] Tan NY,Hodge DO.Catheter ablation for atrial arrhythmias in patients with cardiac amyloidosis.J Cardiovasc Electrophysiol2016;27:1167-73

[43] Barbhaiya CR,Baldinger SH.Electrophysiologic assessment of conduction abnormalities and atrial arrhythmias associated with amyloid cardiomyopathy.Heart Rhythm2016;13:383-90

[44] Gillmore JD,Fontana M.A new staging system for cardiac transthyretin amyloidosis.Eur Heart J2018;39:2799-806

[45] Kusumoto FM,Barrett C.2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines, and the heart rhythm society.J Am Coll Cardiol2019;74:932-87

[46] Donnellan E,Saliba WI.Cardiac devices in patients with transthyretin amyloidosis: impact on functional class, left ventricular function, mitral regurgitation, and mortality.J Cardiovasc Electrophysiol2019;30:2427-32

[47] Dubrey S,Skinner M.Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for atrial electromechanical dissociation.Br Heart J1995;74:541-4 PMCID:PMC484078

[48] Cappelli F,Russo D.Arterial thrombo-embolic events in cardiac amyloidosis: a look beyond atrial fibrillation.Amyloid2021;28:12-8

[49] Yarmohammadi H,Puwanant S.Role of CHADS₂ score in evaluation of thromboembolic risk and mortality in patients with atrial fibrillation undergoing direct current cardioversion (from the ACUTE Trial Substudy).Am J Cardiol2012;110:222-6

[50] Donnellan E,Vakamudi S.No association between CHADS-VASc score and left atrial appendage thrombus in patients with transthyretin amyloidosis.JACC Clin Electrophysiol2019;5:1473-4

[51] Feng D,Martinez M.Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis.Circulation2009;119:2490-7

[52] Santarone M,Tagliagambe LM.Atrial thrombosis in cardiac amyloidosis: diagnostic contribution of transesophageal echocardiography.J Am Soc Echocardiogr1999;12:533-6

[53] Parsons C,Cha S.CHA₂DS₂-VASc score: a predictor of thromboembolic events and mortality in patients with an implantable monitoring device without atrial fibrillation.Mayo Clin Proc2017;92:360-9 PMCID:PMC5641434

[54] Ternacle J,Mohty D.Aortic stenosis and cardiac amyloidosis: JACC review topic of the week.J Am Coll Cardiol2019;74:2638-51

[55] Galat A,Bodez D.Aortic stenosis and transthyretin cardiac amyloidosis: the chicken or the egg?.Eur Heart J2016;37:3525-31

[56] Treibel TA,Gilbertson JA.Occult transthyretin cardiac amyloid in severe calcific aortic stenosis: prevalence and prognosis in patients undergoing surgical aortic valve replacement.Circ Cardiovasc Imaging2016;9:e005066

[57] Sperry BW,Vranian MN,Jaber WA.Recognizing transthyretin cardiac amyloidosis in patients with aortic stenosis: impact on prognosis.JACC Cardiovasc Imaging2016;9:904-6

[58] Clavel MA,Pibarot P.Low-gradient aortic stenosis.Eur Heart J2016;37:2645-57 PMCID:PMC5030681

[59] Monticelli FC,Keller T.Cardiac amyloidosis as a potential risk factor for transapical transcatheter aortic valve implantation.J Card Surg2014;29:623-4

[60] Moreno R,López de Sá E.Cause of complete atrioventricular block after percutaneous aortic valve implantation: insights from a necropsy study.Circulation2009;120:e29-30

[61] Dubrey SW,Anderson J.The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement.QJM1998;91:141-57

[62] Varr BC,Coakley T.Implantable cardioverter-defibrillator placement in patients with cardiac amyloidosis.Heart Rhythm2014;11:158-62

[63] Goldsmith YB,Chou J,Comenzo RL.Frequencies and types of arrhythmias in patients with systemic light-chain amyloidosis with cardiac involvement undergoing stem cell transplantation on telemetry monitoring.Am J Cardiol2009;104:990-4

[64] Palladini G,Cò F.Holter monitoring in AL amyloidosis: prognostic implications.Pacing Clin Electrophysiol2001;24:1228-33

[65] Giancaterino S,Darden D.Management of arrhythmias in cardiac amyloidosis.JACC Clin Electrophysiol2020;6:351-61

[66] Priori SG,Mazzanti A.ESC Scientific Document Group2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the Task Force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European society of cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).Eur Heart J2015;36:2793-867

[67] Al-Khatib SM,Ackerman MJ.2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.Heart Rhythm2018;15:e190-252

[68] Ponikowski P,Anker SD.ESC Scientific Document Group2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur Heart J2016;37:2129-200

[69] Hamon D,Gandjbakhch E.Outcome and incidence of appropriate implantable cardioverter-defibrillator therapy in patients with cardiac amyloidosis.Int J Cardiol2016;222:562-8

[70] Lin G,Kyle R,Brady PA.Implantable cardioverter defibrillators in patients with cardiac amyloidosis.J Cardiovasc Electrophysiol2013;24:793-8

[71] Kristen AV,Hegenbart U.Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death.Heart Rhythm2008;5:235-40

[72] Sayed RH,Khan F.A study of implanted cardiac rhythm recorders in advanced cardiac AL amyloidosis.Eur Heart J2015;36:1098-105

[73] Escher F,Doerler J.When and how do patients with cardiac amyloidosis die?.Clin Res Cardiol2020;109:78-88 PMCID:PMC6952329

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

[75] Donnellan E,Hanna M,Saliba WI.Cardiac resynchronization therapy for transthyretin cardiac amyloidosis.J Am Heart Assoc2020;9:e017335 PMCID:PMC7660724

[76] Aouate D,Bellevre D,Marechaux S.Deleterious effect of right ventricular pacing in patients with cardiac transthyretin amyloidosis: potential clinical benefit of cardiac resynchronization therapy.Eur Heart J Case Rep2020;4:1-5 PMCID:PMC7319833