Asuman BİÇER, Mustafa Beğenç TAŞCANOV, Zülkif TANRIVERDİ

Günlük pratikte tanıdan tedaviye amiloid kardiyomiyopati

Amiloidoz; organ ve yumuşak dokuların hücre dışı boşluğunda amiloid fibril birikiminin neden olduğu bir hastalıktır. Öncü proteinin tipine göre amiloidoz sınıflandırması yapılır. Kalp, böbrek, karaciğer, gastrointestinal sistem ve/veya otonom sinir sistemi gibi çeşitli organlarda amiloid birikimi izlenebilmekle birlikte, prognozu en kötü olan organ tutulumu türü kardiyak amiloidozdur. Birçok amiloidoz türleri arasında hemen hemen tüm klinik kardiyak amiloidoz vakalarına, transtiretin amiloidoz (ATTR) veya hafif zincir amiloidoz (AL veya primer sistemik) neden olur. Kardiyak ATTR; kalıtsal (ATTRm) veya doğal tip (ATTRwt) olabilir. Kardiyak tutulum sıklığı ve kardiyomiyopatinin prognozu amiloidoz tipleri arasında değişkenlik gösterir ve klinik belirtiler, organ tutulum paternine bağlı olarak değişir. Değişken klinik fenotip ve genellikle özgül olmayan klinik özellikler, bu hastalıkta tanıda gecikmelere neden olabilir ve tanıda multidisipliner (hematoloji, patoloji, radyoloji, nükleer tıp, nöroloji, nefroloji, kardiyoloji, romatoloji, gastroenteroloji) yaklaşım gerekir. Gelişen tanı yöntemleri klinisyene kardiyak amiloidozda erken tanı olanağını vermektedir. Kardiyak amiloidozdan şüphelenilen hastalarda; görüntüleme yöntemleri ve gerekirse doku biyopsisi ile amiloid birikimi gösterilmelidir. Amiloidoza sebep olan öncü protein saptandıktan sonra, altta yatan hastalığın tedavisi ve semptomatik hastalarda kalp yetmezliğine yönelik tedavi uygulanmaktadır. Erken tanı ve tedavi yaklaşımları ile prognozun düzeltilebildiği gösterilmiştir. Bu derlemede, kardiyak amiloidoz hastalığı hakkında farkındalığın artırılması amaçlanmış olup, günlük pratiğimizde kullanabileceğimiz güncel tanı yöntemleri ve tedavi yaklaşımları ele alınacaktır.

Amyloid cardiomyopathy from diagnosis to treatment in daily practice

Amyloidosis is a disease caused by the accumulation of amyloid fibril in the extracellular space of organs and soft tissues. Amyloidosis classification is made according to the type of precursor protein. Although amyloid accumulation can be observed in various organs such as heart, kidney, liver, gastrointestinal and/or autonomic nervous system; the worst prognosis type of organ involvement is cardiac amyloidosis. Among many types of amyloidosis, almost all clinical cases of cardiac amyloidosis are caused by transtiretin amyloidosis (ATTR) or light chain amyloidosis (AL or primary systemic). Cardiac ATTR can be hereditary (ATTRm) or wild type (ATTRwt). The frequency of cardiac involvement and prognosis of cardiomyopathy varies between the types of amyloidosis and clinical symptoms vary depending on the organ involvement pattern. Variable clinical phenotype and often non-specific clinical features can cause delays in diagnosis and a multidisciplinary (hematology, pathology, radiology, nuclear medicine, neurology, nephrology, cardiology, rheumatology, gastroenterology) approach is required in diagnosis. The developing diagnostic methods give the clinician early diagnosis of cardiac amyloidosis. Amyloid accumulation should be demonstrated by imaging methods and tissue biopsy is necessary in patients with suspected cardiac amyloidosis. Once the precursor protein that causes amyloidosis has been identified, treatment of the underlying disease and heart failure is performed in symptomatic patients. It has been shown that prognosis can be corrected with early diagnosis and treatment approaches. In this review, it is aimed to raise awareness about cardiac amyloidosis disease, current diagnostic methods and treatment approaches that we can use in our daily practice will be discussed.

Keywords:

amyloidosis, cardiac,

PDF

___

1. Fontana M, Corovic A, Scully P, Moon JC. Myocardial amyloidosis: the exemplar interstitial disease. JACC Cardiovasc Imaging. 2019;12:2345-56.
2. Cavusoglu Y, Ozpelit E, Celik A, Ikitimur B, Kayıkcioglu M, Tokgozoglu L et al. [Cardiac amyloidosis: Recent advances in the diagnosis and therapy]. Turk Kardiyol Dern Ars. 2019;47:1-34.
3. Habib G, Bucciarelli-Ducci C, Caforio ALP, Cardim N, Charron P, Cosyns B et al. Multimodality Imaging in Restrictive Cardiomyopathies: An EACVI expert consensus document In collaboration with the “Working Group on myocardial and pericardial diseases” of the European Society of Cardiology Endorsed by The Indian Academy of Echocardiography. Eur Heart J Cardiovasc Imaging. 2017;18:1090-121.
4. Falk RH, Alexander KM, Liao R, Dorbala S. AL (Light-Chain) Cardiac amyloidosis: a review of diagnosis and therapy. J Am Coll Cardiol. 2016;68:1323-41.
5. Gertz MA, Benson MD, Dyck PJ, Grogan M, Coelho T, Cruz M et al. Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J Am Coll Cardiol. 2015;66:2451-66.
6. Sipe JD, Benson MD, Buxbaum JN, Ikeda SI, Merlini G, Saraiva MJM et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification. International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23:209-213.
7. Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126:1286-300.
8. Gonzalez-Lopez E, Gallego-Delgado M, Guzzo- Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36:2585-94.
9. Castano A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017;38:2879-87.
10. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387:2641-54.
11. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583-96.
12. Kyle RA, Linos A, Beard CM, Gertz MA, O'Fallon WM, Kurland LT. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992;79:1817- 22.
13. Dubrey SW, Hawkins PN, Falk RH. Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart. 2011;97:75-84.
14. Liao R, Jain M, Teller P, Connors LH, Ngoy S, Skinner M et al. Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation. 2001;104:1594- 97.
15. Shi J, Guan J, Jiang B, Monte FD, Ward JE, Connors LH et al. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway. Proc Natl Acad Sci U S A. 2010;107:4188-93.
16. Chamarthi B, Dubrey SW, Cha K, Skinner M, Falk RH. Features and prognosis of exertional syncope in light-chain associated AL cardiac amyloidosis. Am J Cardiol 1997; 80:1242-45.
17. Martinez-Naharro A, Gonzalez-Lopez E, Corovic A, Mirelis JG, Baksi AJ, Moon JC et al. High prevalence of intracardiac thrombi in cardiac amyloidosis. J Am Coll Cardiol. 2019;73:1733-34.
18. El-Am EA, Dispenzieri A, Melduni RM, Ammash NM, White RD, Hodge DO et al. Direct current cardioversion of atrial arrhythmias in adults with cardiac amyloidosis. J Am Coll Cardiol. 2019;73:589- 97.
19. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol 2019; 73:2872-91.
20. Treibel TA, Fontana M, Gilbertson JA, Castelletti S, White SK, Scully PR et al. Occult transthyretin cardiac amyloid in severe calcific aortic stenosis: prevalence and prognosis in patients undergoing surgical aortic valve replacement. Circ Cardiovasc Imaging. 2016;9:e005066.
21. Longhi S, Lorenzini M, Gagliardi C, Milandri A, Marzocchi A, Marrozzini C et al. Coexistence of degenerative aortic stenosis and wild-type transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging. 2016;9:325-27.
22. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014;114:1089-93.
23. Mussinelli R, Salinaro F, Alogna A, Boldrini M, Raimondi A, Musca F et al. Diagnostic and prognostic value of low QRS voltages in cardiac AL amyloidosis. Ann Noninvasive Electrocardiol. 2013;18:271-80.
24. Gonzalez-Lopez E, Gagliardi C, Dominguez F, Quarta CC, Moral FJHD, Milandri A et al. Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths. Eur Heart J. 2017;38:1895-1904.
25. Longhi S, Quarta CC, Milandri A, Lorenzini M, Gagliardi C, Manuzzi L et al. Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk factors and prognostic role. Amyloid. 2015;22:147-55.
26. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135:1357-77.
27. Martinez-Naharro A, Treibel TA, Abdel-Gadir A, Bulluck H, Zumbo G, Knight DS et al. Magnetic resonance in transthyretin cardiac amyloidosis. J Am Coll Cardiol. 2017;70:466-77.
28. Knight DS, Zumbo G, Barcella W, Steeden JA, Muthurangu V, Naharro AM et al. Cardiac structural and functional consequences of amyloid deposition by cardiac magnetic resonance and echocardiography and their prognostic roles. JACC Cardiovasc Imaging. 2019;12:823-33.
29. Phelan D, Collier P, Thavendiranathan P, Popoviv ZB, Hanna M, Plana JC et al. Relative apical sparing of longitudinal strain using two-dimensional speckle- tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98:1442-48.
30. Phelan D, Thavendiranathan P, Popovic Z, Collier P, Griffin B, Thomas JD et al. Application of a parametric display of two-dimensional speckle- tracking longitudinal strain to improve the etiologic diagnosis of mild to moderate left ventricular hypertrophy. J Am Soc Echocardiogr. 2014;27:888- 95.
31. Brownrigg J, Lorenzini M, Lumley M, Elliott P. Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta-analysis. ESC Heart Fail. 2019;6:1041-51.
32. Dorbala S, Cuddy S, Falk RH. How to image cardiac amyloidosis: a practical approach. JACC Cardiovasc Imaging. 2020;13:1368-83.
33. Zhao L, Tian Z, Fang Q. Diagnostic accuracy of cardiovascular magnetic resonance for patients with suspected cardiac amyloidosis: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2016;16:129.
34. Syed IS, Glockner JF, Feng D, Araoz PA, Martinez MW, Edwards WD et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging. 2010;3:155- 64.
35. Vogelsberg H, Mahrholdt H, Deluigi CC, Yilmaz A, Kispert EM, Greulich S et al. Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy. J Am Coll Cardiol. 2008;51:1022-30.
36. Austin BA, Tang WH, Rodriguez ER, Tan C, Flamm SD, Taylor DO et al. Delayed hyper-enhancement magnetic resonance imaging provides incremental diagnostic and prognostic utility in suspected cardiac amyloidosis. JACC Cardiovasc Imaging. 2009;2:1369- 77.
37. Ruberg FL, Appelbaum E, Davidoff R, Ozonoff A, Kissinger KV, Harrigan C et al. Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in light-chain cardiac amyloidosis. Am J Cardiol. 2009;103:544-49.
38. Syed IS, Glockner JF, Feng D, Araoz PA, Martinez MW, Edwards WD et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging. 2010;3:155- 64.
39. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133:2404- 12.
40. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS et al. Transthyretin amyloid cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73:2872-91.
41. Ponikowski P, Voors AA, Anker SD et al. 2016 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 J Heart Fail. 2016;18:891-975.
42. Elliot PM, Anastasakis A, Borger MA et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2733-79.
43. Griffiths BE, Hughes P, Dowdle R, Stephens MR. Cardiac amyloidosis with asymmetrical septal hypertrophy and deterioration after nifedipine. Thorax. 1982;37:711-12.
44. Gertz MA, Skinner M, Connors LH, Falk RH, Cohen AS, Kyle RA. Selective binding of nifedipine to amyloid fibrils. Am J Cardiol. 1985;55:1646.
45. Pollak A, Falk RH. Left ventricular systolic dysfunction precipitated by verapamil in cardiac amyloidosis. Chest. 1993;104:618-20.
46. Feng D, Syed IS, Martinez M, Oh JK, Jaffe AS, Grogan M et al. Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis. Circulation. 2009;119:2490-97.
47. Lin G, Dispenzieri A, Kyle R, Grogan M, Brady PA. Implantable cardioverter defibrillators in patients with cardiac amyloidosis. J Cardiovasc Electrophysiol. 2013;24:793-98.
48. Davis MK, Kale P, Liedtke M, Schrier S, Arai S, Wheeler M et al. Outcomes after heart transplantation for amyloid cardiomyopathy in the modern era. Am J Transplant. 2015;15:650-58.
49. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M et al. ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-16.
50. Fuchs U, Zittermann A, Suhr O, Holmgren G, Tenderich G, Minami K et al. Heart transplantation in a 68-year-old patient with senile systemic amyloidosis. Am J Transplant. 2005;5:1159-62.
51. Careddu L, Zanfi C, Pantaleo A, Loforte A, Ercolani G, Cescon M et al. Combined heart-liver transplantation: a single-center experience. Transpl Int. 2015;28:828-34.
52. Raichlin E, Daly RC, Rosen CB, McGregor CG, Charlton MR, Frantz RP et al. Combined heart and liver transplantation: a single-center experience. Transplantation. 2009;88:219-25.