Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9510810.26442/20751753.2018.12.000020ArticlesСтатьиResearch ArticleAmyloid heart disease: pathomorphology, diagnostic approaches and treatment optionsАмилоидная кардиопатия: патоморфология, методы диагностики и леченияRameevaA. SРамееваАнна Сергеевна

аспирант каф. внутренних, профессиональных болезней и ревматологии

anna.rameeva@yandex.ruRameevV. VРамеевВилен Вилевич

канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии

vvrameev@mail.ruMoiseevS. VМоисеевСергей Валентинович

д-р мед. наук, проф., зав. каф. внутренних, профессиональных болезней и ревматологии; проф. каф. внутренних болезней

clinpharm@mtu-net.ruTaoP. PТаоПавел Полович

аспирант каф. внутренних, профессиональных болезней и ревматологии

pavel.tao@mail.ruKozlovskayaL. VКозловскаяЛидия Владимировна

д-р мед. наук, проф., проф. каф. внутренних, профессиональных болезней и ревматологии

I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian FederationФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава РоссииM.V.Lomonosov Moscow State UniversityФГБОУ ВО «Московский государственный университет им. М.В.Ломоносова»151220182012VOL 20, NO12 (2018)ТОМ 20, №12 (2018)152228122021Copyright ©; 2018, Consilium MedicumCopyright ©; 2018, ООО "Консилиум Медикум"2018Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95108

Systemic amyloidosis is a relatively rare multisystem disease caused by the deposition of misfolded protein in various tissues and organs. The deposits are derived from several amyloidogenic precursor proteins, and the prognosis of the disease is determined both by the organ(s) involved and the type of amyloid. Cardiac involvement is a leading cause of morbidity and mortality, especially in AL- and ATTR-amyloidosis. The last decade has seen considerable progress in understanding of cardiac amyloidosis. This review focuses on changes in intracardiac hemodynamics and their evaluation using novel diagnostic approaches (strain and speckle tracking imaging, cardiovascular magnetic resonance and cardiac biomarkers). New histological typing techniques and current treatments are discussed

Системный амилоидоз относится к группе редких системных заболеваний и характеризуется накоплением нерастворимых фибриллярных белков в различных органах и тканях. Амилоидные депозиты формируются из различных белков-предшественников, которые определяют тип амилоидоза, характер органного вовлечения и прогноз. Поражение сердца при системном амилоидозе в большинстве случаев является наиболее значимым фактором, определяющим клиническое течение и исход, особенно при AL- и ATTR-амилоидозе. В последнее десятилетие достигнут очевидный успех в понимании амилоидоза в целом и амилоидоза сердца в частности. В представленном обзоре внимание акцентировано на изменениях внутрисердечной гемодинамики при амилоидной кардиопатии, современных высокоинформативных методах диагностики этих изменений с использованием тканевой допплерометрии, strain- и speckle tracking-эхокардиографии, магнитно-резонансной томографии, определением сердечных биомаркеров. В статье рассмотрены новые методы типирования амилоида и современные схемы лечения амилоидной кардиопатии.

amyloidosisheart failureinfiltrative cardiomyopathyimmunoglobulin light chainstransthyretinmyocardial deformationspeckle tracking echocardiographycardiac biomarkerspolyneuropathyамилоидозсердечная недостаточностьинфильтративная кардиопатиялегкие цепи иммуноглобулиновтранстиретиндеформация миокардаspeckle tracking-эхокардиографиясердечные биомаркерыполинейропатияКозловская Л.В., Рамеев В.В. АА- и AL-амилоидоз. Нефрология. Клинические рекомендации. Под ред. Е.М.Шилова, А.В.Смирнова, Н.Л.Козловской. М.: ГЭОТАР-Медиа, 2016: 299-319.Sipe J, Benson M, Buxbaum J et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid 2016; 23 (4): 209-13.Steiner I. The prevalence of isolated atrial amyloid. J Pathol 1987; 153 (4): 395-8.Жданова Е.А., Рамеев В.В., Моисеев С.В. и др. Амилоидоз сердца: клиника, лечение, прогноз. Фарматека. 2012; 9: 10-6.Kyle R.A, Linos A, Beard C.M et al. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood 1992; 79: 1817-22.Pinney J.H, Smith C.J, Taube J.B et al. Systemic amyloidosis in England: an epidemiological study. Br J Haematol 2013; 161: 525-32.Hemminki K, Li X, Försti A et al. Incidence and survival in nonhereditary amyloidosis in Sweden. BMC Public Health 2012; 12: 974.Hemminki K, Li X, Försti A et al. Incidence of hereditary amyloidosis and autoinflammatory diseases in Sweden: endemic and imported diseases. BMC Med Genet 2013; 14: 88.Рамеев В.В., Козловская Л.В. Амилоидоз: современные методы диагностики и лечения. Эффективная фармакотерапия. Урология и нефрология. Спецвып.: Актуальные вопросы нефрологии. 2012; с. 6-15.Kyle R, Gertz M. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995; 32 (1): 45-59.Patel K.S, Hawkins P.N. Cardiac amyloidosis: where are we today? J Intern Med 2015; 278 (2): 126-44.Рамеев В.В. Современные методы диагностики и лечения транстиретинового наследственного амилоидоза. Manage pain. 2018; 1: 20-4.Зиновьева О.Е., Сафиулина Э.И. Транстиретиновая амилоидная полинейропатия: патогенез, клинические особенности, перспективы лечения. Manage pain. 2017; 4: 12-5.Gertz M.A, Merlini G. Definition of organ involvement and response to treatment in AL amyloidosis: an updated consensus opinion. Amyloid 2010; 17 (Suppl. 1): 48-9.Falk R, Alexander K, Liao R, Dorbala S. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. J Am Coll Cardiol 2016; 68 (12): 1323-41.Rapezzi C, Merlini G, Quarta C.C et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation 2009; 120: 1203-12.Dubrey S.W, Cha K, Anderson J et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM 1998; 91: 141-57.Larsen B.T, Mereuta O.M, Dasari S et al. Correlation of histomorphological pattern of cardiac amyloid deposition with amyloid type: a histological and proteomic analysis of 108 cases. Histopathology 2016; 68: 648-56.Shi J, Guan J, Jiang B et al. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a noncanonical p38 MAPK pathway. PNAS 2010; 107: 4188-93.Алехин М.Н. Тканевой допплер в клинической эхокардиографии. М., 2006.Koyama J, Ray-Sequin P.A, Falk R.H. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation 2003; 107: 2446-52.Bellavia D, Pellikka P.A, Abraham T.P et al. Evidence of impaired left ventricular systolic function by Doppler myocardial imaging in patients with systemic amyloidosis and no evidence of cardiac involvement by standard twodimensional and Doppler echocardiography. Am J Cardiol 2008; 101: 1039-45.Belkin R.N, Kupersmith A.C, Khalique O et al. A novel two-dimensional echocardiographic finding in cardiac amyloidosis. Echocardiography 2010; 27: 1171-6.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: 1442-8.Pandey T, Alapati S, Wadhwa V et al. Evaluation of myocardial strain in patients with amyloidosis using cardiac magnetic resonance feature tracking. Curr Probl Diagn Radiol 2017; 46: 288-94.Ternacle J, Bodez D, Guellich A et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging 2016; 9: 126-38.Liu D, Hu K, Nordbeck P et al. Longitudinal strain bull’s eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy. Eur J Med Res. BioMed Central 2016; 21: 21.Никифоров В.С., Никищенкова Ю.В. Cовременные возможности speckle tracking эхокардиографиии в клинической практике. Рациональная фармакотерапия в кардиологии. 2017; 13 (2): 248-55.Phelan D, Thavendiranathan P, Popovic Z 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 Echocardiog 2014; 27: 888-95.Grossman W, Jones D, McLaurin L.P. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975; 56: 56-64.Jiang L, Huang Y, Hunyor S, dos Remedios C.G. Cardiomyocyte apoptosis is associated with increased wall stress in chronic failing left ventricle. Eur Heart J 2003; 24: 742-51.Buchalter M.B, Weiss J.L, Rogers W.J et al. Noninvasive quantification of left ventricular rotation deformation in normal human using magnetic resonance imaging myocardial tagging. Circulation 1990; 81: 1236-44.Torrent-Guasp F. Structure and function of the heart. Rev Esp Cardio 1998; 51: 91-102.Sengupta P.P, Tajik A.J, Chandrasekaran K et al. Twist mechanics of the left ventricle: principles and application. JACC Cardiovasc Imaging 2008; 1: 366-76.Павлюкова Е.Н., Кужель Д.А., Матюшин Г.В. и др. Ротация, скручивание и раскручивание левого желудочка: физиологическая роль и значение в клинической практике. Рациональная фармакотерапия в кардиологии. 2015; 11 (1): 68-78.Nucifora G, Muser D, Morocutti G et al. Disease-specific differences of left ventricular rotational mechanics between cardiac amyloidosis and hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol 2014; 307 (5): H680-8.Nemes A, Földeák D., Domsik P et al. Different patterns of left ventricular rotational mechanics in cardiac amyloidosis - results from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study. Quant Imaging Med Surg 2015; 5 (6): 853-7.Жданова Е.А. Клинические особенности, критерии диагностики и оценки прогноза поражения сердца у больных системным амилоидозом. Автореф. дис.. канд. мед. наук. М., 2014. https: //dlib.rsl.ru/viewer/01005545051#?page=1Синицын В.Е., Мершина Е.А., Ларина О.М. Возможности магнитно-резонансной томографии в диагностике кардиомиопатий. Клин. и эксперимент. хирургия. Журн. им. акад. Б.В.Петровского. 2014; 1: 54-63.Falk R, Quarta C, Dorbala S. How to Image Cardiac Amyloidosis: A Focused Practical Review. Circ Cardiovasc Imaging 2014; 7 (3): 552-62.Maceira A.M, Joshi J, Prasad S.K et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 2005; 111: 186-93.Syed I.S, Glockner J.F, Feng D et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging 2010; 3: 155-64.Roller F.C, Harth S, Schneider C et al. T1, T2 Mapping and Extracellular Volume Fraction (ECV): Application, Value and Further Perspectives in Myocardial Inflammation and Cardiomyopathies. RoFo 2015; 187: 760-70.Karamitsos T.D, Piechnik S.K, Banypersad S.M et al. Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. JACC Cardiovasc Imaging 2013; 6: 488-97.Fontana M, Banypersad S.M, Treibel T.A et al. Native T1 mapping in transthyretin amyloidosis. JACC Cardiovasc Imaging 2014; 7: 157-65.Banypersad S.M, Sado D.M, Flett A.S et al. Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study. Circ Cardiovasc Imaging 2013; 6: 34-9.Bokhari S, Castano A, Pozniakoff T et al. 99mTc-pyrophosphate scintigraphy for differentiating light chain cardac amyloidosis from the transthyret in related familial and senile cardiac amyloidosis. Circ Cardiovasc Imaging 2013; 6 (2): 195-201.Castano A, Grogan M, Johnson G.B et al. Multicenter experience of technetium pyrophosphate scanning for diagnosing TTR cardiac amyloid: a revival in nuclear cardiology. J Card Failure 2015; 21 (8): 85.Rapezzi C, Quarta C.C, Guidalotti P.L et al. Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy. Eur J Nucl Med Mol Imaging 2011; 38: 470-8.Quarta C.C, Obici L, Guidalotti P.L et al. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy. Amyloid 2013; 20: 48-51.Hutt D.F, Quigley A.M, Page J et al. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging 2014; 15: 1289-98.Gillmore J.D, Maurer M.S, Falk R.H et al. Non-biopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 2016; 133: 2404-12.Takemura G, Takatsu Y, Doyama K et al. Expression of atrial and brain natriuretic peptides and their genes in hearts of patients with cardiac amyloidosis. J Am Coll Cardiol 1998; 31: 754-65.Palladini G, Foli A, Milani P et al. Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure. Am J Hematol 2012; 87: 465-71.Dispenzieri A, Kyle R.A, Gertz M.A et al. Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 2003; 361: 1787-9.Dispenzieri A, Gertz M.A, Kyle R.A et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol 2004; 22: 3751-7.Kumar S, Dispenzieri A, Lacy M.Q et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 2012; 30: 989-95.Palladini G, Russo P, Nuvolone M et al. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood 2007; 110: 787-8.Skinner M, Anderson J, Simms R et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicines versus colchicines only. Am J Med 1996; 100 (3): 290-8.Jaccard A, Moreau P, Leblond V et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med 2007; 357 (11): 1083-93.Reece D.E, Hegenbart U, Sanchorawala V et al. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood 2011; 118 (4): 865-73.Gertz M.A, Buadi F.K, Hayman S.R. Treatment of immunoglobulin light chain (primary or AL) amyloidosis. Oncol 2011; 25 (7): 620-6.Comenzo R.L, Vosburgh E, Simms R.W et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients. Blood 1996; 88 (7): 2801-6.Holmgren G, Steen L, Ekstedt J et al. Biochemical eff ect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30). Clin Genet 1991; 40: 242-6.Liepnieks J.J, Benson M.D. Progression of cardiac amyloid deposition in hereditary transthyretin amyloidosis patients aft er liver transplantation. Amyloid 2007; 14 (4): 277-82.Sekijima Y, Dendle M.A, Kelly J.W. Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis. Amyloid 2006; 13 (4): 236-49.Maurer M, Schwartz J, Gundapaneni B. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med 2018; 379: 1007-16.Feng D, Edwards W.D, Oh J.K et al. Intracardiac thrombosis and embolism in patients with cardiac amyloidosis. Circulation 2007; 116: 2420-6.Russo A.M, Stainback R.F, Bailey S.R et al. ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy. J Am Coll Cardiol 2013; 61: 1318-68.2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 2015; 36: 2793-867.Bellavia D, Pellikka P.A, Abraham T.P et al. Hypersynchronisation by tissue velocity imaging in patients with cardiac amyloidosis. Heart 2009; 95: 234-40.Banypersad et al. Cardiac Amyloidosis: A Review. J Am Heart Assoc 2012; 1.Barreiros A, Post F, Hoppe-Lotichius M et al. Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience. Liver Transpl 2010; 16: 314-23.Hamour I.M, Lachmann H.J, Goodman H.J et al. Heart transplantation for homozygous familial transthyretin (TTR) V122I cardiac amyloidosis. Am J Transplant 2008; 8: 1056-9.