Bir Olgu Üzerinden Kardiyak Amiloidoza Yaklaşım
Özet
Kardiyak amiloidoz, miyokard dokusunda ekstraselüler amiloid fibrillerinin birikimiyle karakterize, sistemik amiloidozlar arasında en kötü prognoza sahip multisistemik bir hastalıktır. Geçmişte nadir bir durum olarak değerlendirilse de kardiyak manyetik rezonans görüntüleme, ekokardiyografi ve radyonüklid görüntüleme teknolojilerindeki güncel ilerlemeler sayesinde klinik farkındalığı artmış ve tanı oranları yükselmiştir. Bu sayede endomiyokardiyal biyopsi gibi girişimsel tanı yöntemlerine olan gereksinim azalmıştır. Hastalık genellikle korunmuş ejeksiyon fraksiyonlu kalp yetmezliği, ileti bozuklukları ve atrial fibrilasyon gibi çeşitli klinik tablolarla prezante olur. Tedavi yaklaşımı, konjesyonu hafifletmeye yönelik semptomatik diüretik tedavisi ile amiloid birikimini durdurmayı hedefleyen TTR stabilizatörleri (tafamidis), gen susturucuları ve kemoterapi gibi amiloid spesifik stratejilerden oluşur. Sunulan 85 yaşındaki erkek olgu örneğinde olduğu gibi, rutin pratikte sık görülen kalp yetmezliği bulgularına sahip hastalarda kardiyak amiloidoz olasılığının akılda tutulması ve erken aşamada klinik şüphe duyulması hayati önem taşır. Günümüzde geliştirilen yeni spesifik tedavi seçenekleri sayesinde, amiloidoz artık yönetilebilir ve tedavi şansı olan bir patoloji olarak kabul edilmektedir.
Cardiac amyloidosis is a multisystemic disease characterized by the extracellular deposition of amyloid fibrils within the myocardium, carrying the worst prognosis among systemic amyloidoses. Although previously considered a rare condition, its clinical recognition and diagnosis rates have significantly increased in recent years due to advancements in cardiac magnetic resonance imaging, echocardiography, and radionuclide imaging. These non-invasive diagnostic techniques have effectively reduced the need for interventional procedures like endomyocardial biopsy. The disease typically presents with diverse clinical manifestations, including heart failure with preserved ejection fraction, conduction disturbances, and atrial fibrillation. Management involves symptomatic diuretic therapy to alleviate congestion, combined with amyloid-specific strategies aimed at halting fibril accumulation, such as TTR stabilizers (tafamidis), gene silencers, and chemotherapy. As demonstrated in the presented case of an 85-year-old male patient, maintaining clinical suspicion in individuals with common heart failure symptoms is the most critical step for timely diagnosis. Thanks to emerging and promising specific therapeutic developments, cardiac amyloidosis is now recognized as a manageable condition with viable treatment opportunities.
Referanslar
Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. Taylor & Francis; 2020;27(4): 217–222. doi:10.1080/13506129.2020.1835263
Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: A position statement of the ESC Working Group on Myocardial and Pericardial Diseases. European Heart Journal. Oxford University Press; 2021;42(16): 1554–1568. doi:10.1093/eurheartj/ehab072
Dungu JN, Anderson LJ, Whelan CJ, et al. Cardiac transthyretin amyloidosis. Heart. 2012;98(21): 1546. doi:10.1136/heartjnl-2012-301924
Mohty D, Damy T, Cosnay P, et al. Cardiac amyloidosis: Updates in diagnosis and management. [Online] Archives of Cardiovascular Diseases. 2013. doi:10.1016/j.acvd.2013.06.051
Kitaoka H, Izumi C, Izumiya Y, et al. JCS 2020 guideline on diagnosis and treatment of cardiac amyloidosis. Circulation Journal. 2020;84(9): 1610–1671. doi:10.1253/circj.CJ-20-0110
Coelho T, Maurer MS, Suhr OB. THAOS – The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Current Medical Research and Opinion. Taylor & Francis; 2013;29(1): 63–76. doi:10.1185/03007995.2012.754348
Kristen A v, Maurer MS, Rapezzi C, et al. Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis-Report from the Transthyretin Amyloidosis Outcome Survey (THAOS) Thibaud Damy 6 , on behalf of the THAOS investigators. 2017; doi:10.1371/journal.pone.0173086
Hahn VS, Yanek LR, Vaishnav J, et al. Endomyocardial Biopsy Characterization of Heart Failure With Preserved Ejection Fraction and Prevalence of Cardiac Amyloidosis. JACC: Heart Failure. 2020;8(9): 712–724. doi:https://doi.org/10.1016/j.jchf.2020.04.007
Arvanitis M, Simon S, Chan G, et al. Retinol binding protein 4 (RBP4) concentration identifies V122I transthyretin cardiac amyloidosis. Amyloid. Taylor & Francis; 2017;24(sup1): 120–121. doi:10.1080/13506129.2017.1295371
Agrawal T, Nagueh SF. Echocardiographic assessment of cardiac amyloidosis. Heart Failure Reviews. 2021; doi:10.1007/s10741-021-10165-y
Habib G, Bucciarelli-Ducci C, Caforio ALP, 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. European Heart Journal - Cardiovascular Imaging. 2017;18(10): 1090–1121. doi:10.1093/ehjci/jex034
Bhandari AK, Nanda NC. Myocardial texture characterization by two-dimensional echocardiography. American Journal of Cardiology. Elsevier; 1983;51(5): 817–825. doi:10.1016/S0002-9149(83)80139-8
Austin BA, Duffy B, Tan C, et al. Comparison of Functional Status, Electrocardiographic, and Echocardiographic Parameters to Mortality in Endomyocardial-Biopsy Proven Cardiac Amyloidosis. American Journal of Cardiology. Elsevier; 2009;103(10): 1429–1433. doi:10.1016/j.amjcard.2009.01.361
Tendler A, Helmke S, Teruya S, et al. The myocardial contraction fraction is superior to ejection fraction in predicting survival in patients with AL cardiac amyloidosis. Amyloid. Taylor & Francis; 2015;22(1): 61–66. doi:10.3109/13506129.2014.994202
Quarta CC, Solomon SD, Uraizee I, et al. Left Ventricular Structure and Function in Transthyretin-Related Versus Light-Chain Cardiac Amyloidosis. Circulation. American Heart Association; 2014;129(18): 1840–1849. doi:10.1161/CIRCULATIONAHA.113.006242
Phelan D, Collier P, Thavendiranathan P, 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(19): 1442. doi:10.1136/heartjnl-2012-302353
Liu D, Hu K, Niemann M, et al. Effect of Combined Systolic and Diastolic Functional Parameter Assessment for Differentiation of Cardiac Amyloidosis From Other Causes of Concentric Left Ventricular Hypertrophy. Circulation: Cardiovascular Imaging. American Heart Association; 2013;6(6): 1066–1072. doi:10.1161/CIRCIMAGING.113.000683
Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 1 of 2—Evidence Base and Standardized Methods of Imaging. Journal of Cardiac Failure. Elsevier Inc.; 2019;25(11): e1–e39. doi:10.1016/j.cardfail.2019.08.001
Bellavia D. Comparison of right ventricular longitudinal strain imaging, tricuspid annular plane systolic excursion, and cardiac biomarkers for early diagnosis of cardiac involvement and risk stratification in primary systematic (AL) amyloidosis: a 5-year cohort study. doi:10.1093/ehjci/jes009
Karamitsos TD, Piechnik SK, Banypersad SM, et al. Noncontrast T1 Mapping for the Diagnosis of Cardiac Amyloidosis. JACC: Cardiovascular Imaging. Elsevier; 2013;6(4): 488–497. doi:10.1016/J.JCMG.2012.11.013
Fontana M, Banypersad SM, Treibel TA, et al. Native T1 Mapping in Transthyretin Amyloidosis. JACC: Cardiovascular Imaging. Elsevier; 2014;7(2): 157–165. doi:10.1016/J.JCMG.2013.10.008
Syed IS, Glockner JF, Feng DL, et al. Role of Cardiac Magnetic Resonance Imaging in the Detection of Cardiac Amyloidosis. JACC: Cardiovascular Imaging. Elsevier; 2010;3(2): 155–164. doi:10.1016/J.JCMG.2009.09.023
Messroghli DR, Moon JC, Ferreira VM, et al. Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI). Journal of Cardiovascular Magnetic Resonance. 2017;19: 75. doi:10.1186/s12968-017-0389-8
Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. American Heart Association; 2016;133(24): 2404–2412. doi:10.1161/CIRCULATIONAHA.116.021612
Castano A, Haq M, Narotsky DL, et al. Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for Patients With ATTR Cardiac Amyloidosis. JAMA Cardiology. 2016;1(8): 880–889. doi:10.1001/jamacardio.2016.2839
Perugini E, Guidalotti PL, Salvi F, et al. Noninvasive Etiologic Diagnosis of Cardiac Amyloidosis Using 99mTc-3,3-Diphosphono-1,2-Propanodicarboxylic Acid Scintigraphy. Journal of the American College of Cardiology. Elsevier; 2005;46(6): 1076–1084. doi:10.1016/J.JACC.2005.05.073
Hutt DF, Quigley A-M, Page J, et al. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. European Heart Journal - Cardiovascular Imaging. 2014;15(11): 1289–1298. doi:10.1093/ehjci/jeu107
Maurer MS, Hanna M, Grogan M, et al. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). Journal of the American College of Cardiology. 2016;68(2): 161–172. doi:10.1016/j.jacc.2016.03.596
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2021;42(36): 3599–3726. doi:10.1093/eurheartj/ehab368
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. American Heart Association; 2022;145(18): e895–e1032. doi:10.1161/CIR.0000000000001063
Donnellan E, Elshazly MB, Vakamudi S, et al. No Association Between CHADS-VASc Score and Left Atrial Appendage Thrombus in Patients With Transthyretin Amyloidosis. JACC: Clinical Electrophysiology. Elsevier; 2019;5(12): 1473–1474. doi:10.1016/J.JACEP.2019.10.013
Stern LK, Patel J. Cardiac Amyloidosis Treatment. [Online] Methodist DeBakey cardiovascular journal. NLM (Medline); 2022. p. 59–72. doi:10.14797/mdcvj.1050
Donnellan E, Wazni O, Kanj M, et al. Atrial fibrillation ablation in patients with transthyretin cardiac amyloidosis. EP Europace. 2020;22(2): 259–264. doi:10.1093/europace/euz314
Towbin JA, McKenna WJ, Abrams DJ, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. Elsevier; 2019;16(11): e301–e372. doi:10.1016/j.hrthm.2019.05.007
Donnellan E, Wazni OM, Saliba WI, et al. Cardiac devices in patients with transthyretin amyloidosis: Impact on functional class, left ventricular function, mitral regurgitation, and mortality. Journal of Cardiovascular Electrophysiology. John Wiley & Sons, Ltd; 2019;30(11): 2427–2432. doi:https://doi.org/10.1111/jce.14180
Kristen A v, Dengler TJ, Hegenbart U, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. Elsevier; 2008;5(2): 235–240. doi:10.1016/j.hrthm.2007.10.016
Palladini G, Milani P, Merlini G. Management of AL amyloidosis in 2020. Blood. 2020;136(23): 2620–2627. doi:10.1182/blood.2020006913
Sidiqi MH, Aljama MA, Buadi FK, et al. Stem Cell Transplantation for Light Chain Amyloidosis: Decreased Early Mortality Over Time. Journal of Clinical Oncology. Wolters Kluwer; 2018;36(13): 1323–1329. doi:10.1200/JCO.2017.76.9554
Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. New England Journal of Medicine. Massachusetts Medical Society; 2021;385(1): 46–58. doi:10.1056/NEJMoa2028631
Meshitsuka S, Shingaki S, Hotta M, et al. Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis. International Journal of Hematology. 2017;105(3): 295–308. doi:10.1007/s12185-016-2112-1
Ward JE, Ren R, Toraldo G, et al. Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis. Blood. 2011;118(25): 6610–6617. doi:10.1182/blood-2011-04-351643
Solomon SD, Adams D, Kristen A, et al. Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis. Circulation. American Heart Association; 2019;139(4): 431–443. doi:10.1161/CIRCULATIONAHA.118.035831
Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. New England Journal of Medicine. Massachusetts Medical Society; 2018;379(1): 22–31. doi:10.1056/NEJMoa1716793
Dasgupta NR, Rissing SM, Smith J, et al. Inotersen therapy of transthyretin amyloid cardiomyopathy. Amyloid. Taylor & Francis; 2020;27(1): 52–58. doi:10.1080/13506129.2019.1685487
Gillmore JD, Gane E, Taubel J, et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. New England Journal of Medicine. Massachusetts Medical Society; 2021;385(6): 493–502. doi:10.1056/NEJMoa2107454
Wixner J, Westermark P, Ihse E, et al. The Swedish open-label diflunisal trial (DFNS01) on hereditary transthyretin amyloidosis and the impact of amyloid fibril composition. Amyloid. Taylor & Francis; 2019;26(sup1): 39–40. doi:10.1080/13506129.2019.1593133
Rosenblum H, Castano A, Alvarez J, et al. TTR (Transthyretin) Stabilizers Are Associated With Improved Survival in Patients With TTR Cardiac Amyloidosis. Circulation: Heart Failure. American Heart Association; 2018;11(4): e004769. doi:10.1161/CIRCHEARTFAILURE.117.004769
Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. New England Journal of Medicine. Massachusetts Medical Society; 2018;379(11): 1007–1016. doi:10.1056/NEJMoa1805689
Kristen A v, Lehrke S, Buss S, et al. Green tea halts progression of cardiac transthyretin amyloidosis: an observational report. Clinical Research in Cardiology. 2012;101(10): 805–813. doi:10.1007/s00392-012-0463-z
Cardoso I, Martins D, Ribeiro T, et al. Synergy of combined Doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models. Journal of Translational Medicine. 2010;8(1): 74. doi:10.1186/1479-5876-8-74
Karlstedt E, Jimenez-Zepeda V, Howlett JG, et al. Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis. Journal of Cardiac Failure. Elsevier; 2019;25(3): 147–153. doi:10.1016/j.cardfail.2019.01.006
Richards DB, Cookson LM, Berges AC, et al. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. New England Journal of Medicine. Massachusetts Medical Society; 2015;373(12): 1106–1114. doi:10.1056/NEJMoa1504942
