Rapidly progressive AA cardiomyopathy

Cardiac involvement may occur with AA amyloidosis, but extensive deposition in the heart is rarely seen. We report a 58-year-old man who on autopsy showed massive cardiac AA amyloid deposition. He did not have history of a chronic inflammatory condition and died suddenly prior to diagnosis of amyloidosis. Autopsy revealed marked left ventricular hypertrophy. Although extensive eosinophilic deposits were present in cardiac and adrenal tissues, the deposits stained weakly with Congo red. Biochemical analysis of fibrils extracted from heart gave a protein sequence showing identity to serum amyloid A. Immunohistochemistry with anti-human AA monoclonal antibody revealed strong staining of amyloid deposits in cardiac and adrenal tissues. Based on these findings, a diagnosis of systemic AA amyloidosis was made. This case highlights the importance of considering AA amyloidosis when the causes of left ventricular hypertrophy are unknown, and demonstrates the usefulness of biochemical analysis for diagnosing amyloid type. Introduction: Systemic reactive amyloid A (AA) amyloidosis is a serious complication of chronic inflammatory diseases. AA amyloid fibrils are derived from the acute-phase reactant serum amyloid A (SAA). AA amyloidosis often affects the kidneys and gastrointestinal tracts. While cardiac involvement may occur with AA amyloidosis, extensive deposition in the heart is rarely seen. Here, we report a 58-yearold man who had no history of chronic inflammation and on autopsy showed massive cardiac AA amyloid deposition. Methods: Case history: A 58-year-old man had histories of type 2 diabetes, hypertension, and hyperlipidemia. The patient had a 4-vessel coronary artery bypass graft in 2003 and was diagnosed with congestive heart failure in June 2008. Echocardiography on 11 June 2008 demonstrated increased interventricular septum thickness (IVS) (14 mm) and left ventricular posterior wall thickness (LVPW) (15 mm). Electrocardiogram showed a marked ST elevation in the right precordial leads, and a history of syncope and family history of cardiac death were noted. Therefore a diagnosis of Brugada syndrome type 1 was made. A cardioverter defibrillator was implanted on 8 July. The patient was admitted to the hospital with abdominal pain and shortness of breath on 28 July 2008. Laboratory investigations at admission revealed increased serum levels of Creactive protein (CRP) (235.5 mg/l) and B-type natriuretic peptide (3758 pg/ml). Total protein, albumin, blood urea nitrogen, and creatinine were 7.5 g/dl, 3.9 g/dl, 27 mg/dl, and 1.0 mg/dl, respectively. There was no proteinuria by urinalysis. The patient died suddenly on 8 August 2008 prior to diagnosis. Autopsy revealed marked left ventricular hypertrophy and a heart weight of 1015 g. His IVS and LVPW were 21 mm and 22 mm, respectively. Amyloid analyses: Tissues sections were analyzed for amyloid by Congo red staining, electron microscopy, and immunohistochemistry using anti-human AA antibody generated in this laboratory. Biochemical analysis was performed on formalin-fixed, paraffin-embedded tissue scraped from slides. Tissues sections were deparaffinized in xylene and then denatured in 8 M guanidine-HCl under reducing conditions. Solubilized material was dialyzed against water and lyophilized. Isolated protein was then subjected to amino acid sequence analysis before and after trypsin digestion. Results and discussion: Cardiac and adrenal tissues contained extensive eosinophilic deposits which stained weakly with Congo red (Figure 1). Figure 1. A: Histology section of cardiac tissue stained with hematoxylin and eosin showing extensive interfiber deposition of amyloid, 6100. B: Histology section of adrenal tissue stained with hematoxylin and eosin showing extensive amyloid deposition, 6100. 203