Auswirkungen der Amyloidose am Herzen – Krankhafte Ablagerungsprozesse durch Stoffwechseldefekte

Amyloidosen sind extrazelluläre Ablagerungen pathologischer unlöslicher, betafibrillärer Proteine, die am Herzen zur Ausbildung einer restriktiven Kardiomyopathie führen. Kein nicht-invasiver Test ist für die kardiale Amyloidose pathognomisch, aber die typische Kombination echokardiografischer Befunde (linksventrikuläre Hypertrophie etc.) mit einer dazu diskrepanten peripheren Niedervoltage im EKG ist hochverdächtig. Leitsymptome sind Belastungsdyspnoe und ein rapider Verlust der Leistungsfähigkeit. In Myokardproben wird die kardiale Amyloidose histologisch diagnostiziert und immunhistochemisch typisiert. Chemotherapien tolerieren viele Patienten mit AL-Amyloidose schlecht. Mehrere Plasmazellklone sind gegenüber einer hoch dosierten Chemotherapie resistent. Die Prognose von Patienten mit Amyloidose ist ungünstig und beträgt bei kardialer Amyloidose im Mittel sechs Monate, da die Erkrankung erst sehr spät (zu spät) diagnostiziert wird. Die Überlebenszeit der hereditären ATTR-Amyloidose beträgt bis zu 15 Jahre, die der AA-Amyloidose ist von der Grunderkrankung abhängig.

Cardiac amyloidosis describes a clinically significant involvement of the heart by amyloid deposition, which may or may not be associated with an involvement of other organs. No single noninvasive test abnormality is pathognomonic for cardiac amyloidosis, but the curious combination of a typical echocardigraphic appearance with left ventricular hypertrophy, normal-sized left ventricle, enlarged atria, regular systolic function, severely impaired diastolic function along with an unsuitable low voltage ECG is highly suggestive of this disease. The cardinal clinical symptoms are dyspnoea and a fast, unexplained rapid loss of exercise capacity mostly within six to nine months. Cardiac amyloidosis can be proven by myocardial biopsies taken during cardiac catheterization. The presence of amyloid in myocardial biopsies is confirmed histologically by characteristic birefringence after Congo Red staining and the mutant protein is identified by immunohistochemical typing. Chemotherapy is indicated in AL amyloidosis, and hence, early diagnosis is crucial because patients with advanced disease are usually too ill for an aggressive chemotherapy and stem cell transplantation. Their life expectancy is limited to three to six months.

Key words

Amyloidosis - cardiac amyloidosis - amyloid deposition - dyspnoea - myocardial biopsies

Literatur

• 1 Butz T, Faber L, Piper C. et al. . Tissue doppler imaging in the differential diagnosis of constrictive pericarditis and restrictive cardiomyopathy.  Dtsch Med Wochenschr. 2008;  133 399-405
• 2 Cooper LT, Baughman KL, Feldman AM. et al. . The role of endomyocardial biopsy in the management of cardiovascular disease. A scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology.  Circulation. 2007;  116 2216-2233
• 3 Dubrey SW, Burke MM, Hawkins PhN. et al. . Cardiac transplantation for amyloid heart disease: the United Kingdom experience.  J Heart Lung Transplant. 2004;  23 1142-1153
• 4 Dubrey SW, Cha K, Anderson J. et al. . The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement.  QJM. 1998;  91 141-157
• 5 Falk RH.. Diagnosis and management of the cardiac amyloidoses.  Circulation. 2005;  112 2047-2060
• 6 Falk RH, Rubinow A, Cohen AS.. Cardiac arrhythmias in systemic amyidosis: correlation with echocardiographic abnormalities.  J Am Coll Cardiol. 1984;  3 107-113
• 7 Feng D, Edwards WD, Oh JK.. Intracardiac thrombosis and embolism in patients with cardiac amyloidosis.  Circulation. 2007;  116 2420-2426
• 8 Goodman HJ, Gillmore JD, Lachmann HJ. et al. . Outcome of autologous stem cell transplantation for AL-amyloidosis in the UK.  Br J Haematol. 2006;  134 417-425
• 9 Hamer JP, Janssen S, van Rijswijk MH. et al. . Amyloid cardiomyopathy in systemic non-hererditary amyloidosis. Clinical, echocardiographic and electrocardiographic findings in 30 patients with AA and 24 patients with AL amyloidosis.  Eur Heart J. 1992;  13 623-627
• 10 Hunstein W.. Epigallocathechin-3-gallate in AL amyloidosis: a new therapeutic option?.  Blood. 2007;  110 2216
• 11 Jaccard A, Moreau PH, Leblond V. et al. . High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis.  N Engl J Med. 2007;  357 1083-1093
• 12 Koyama J, Ray-Sequin PA, Falk RH.. Longitudinal myocardial function assessed by tissue velocity, strain and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis.  Circulation. 2003;  107 2446-2452
• 13 Kyle RA, Gertz MA, Greipp PR. et al. . A trial of three regimens for primary amyloidosis colchicine alone, melphalan and prednisone, and melphalan, prednisone and colchicine.  N Engl J Med. 1997;  336 1202-1207
• 14 Kyle RA, Linos A, Beard CM. et al. . Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989.  Blood. 1992;  79 1817-1822
• 15 Linke RP, Oos R, Wiegel NM. et al. . Classification of amyloidosis: misdiagnosing by way of incomplete immunhistochemistra and how to prevent it.  Acta Histochem. 2006;  108 197-208
• 16 Maceira AM, Joshi J, Prasad SK. et al. . Cardiovascular magnetic resonance in cardiac amyloidosis.  Circulation. 2005;  111 186-193
• 17 Merlini G, Westermark P.. The systemic amyloidoses: clearer understanding of the molecular mechanisms offers hope for more effective therapies.  J Intern Med. 2004;  255 159-178
• 18 Murtagh B, Hammill StC, Gertz AM. et al. . Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement.  Am J Cardiol. 2005;  95 535-537
• 19 Perz JB, Schonland SO, Hundemer M. et al. . High dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study.  Br J Haematol. 2004;  127 543-551
• 20 Piper C, Horstkotte D.. Endomyocardial biopsy.  J Heart Valve Dis. 2003;  12 153-155
• 21 Piper C, Horstkotte D.. State of the art anticoagulation management.  J Heart Valve Dis. 2004;  13 76-80
• 22 Puchtler H, Sweat F, Levine M.. On the binding of Congo red by amyloid.  J Histochem Cytochem. 1962;  10 355-364
• 23 Röcken C, Ernst J, Hund E. et al. . Interdisziplinäre Leitlinien zur Diagnostik und Therapie der extrazerebralen Amyloidosen.  Dtsch Med Wochenschr. 2006;  141 45-66
• 24 Röcken C, Schwotzer E, Linke RP. et al. . The classification of amyloid deposits in clinicopathological pracitce.  Histopathology. 1996;  29 325-335
• 25 Selkoe DJ.. Folding proteins in fatal ways.  Nature. 2003;  426 900-904
• 26 Selvanayagam JB, Hawkins PN, Paul B. et al. . Evaluation and management of the cardiac amyloidosis.  J Am Coll Cardiol. 2007;  50 2101-2110
• 27 Weber DM, Chen CH, Niesviszky R. et al. . Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America.  N Engl J Med. 2007;  357 2133-2142
• 28 Wechalekar AD, Goodman HJB, Lachmann HJ. et al. . Safety and efficacy of risk-adapted cyclophosphamide, thalidomide and dexamethasone in systemic AL amyloidosis.  Blood. 2007;  109 457-464

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