Amyloidosis : incidence, prognosis, investigation and management

• Main Author: Pinney, J. H.
• Published: University College London (University of London) 2013
• Subjects: 610
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.594381

Background: Amyloidosis is a rare disorder of protein folding in which a variety of proteins deposit as fibrils in the extracellular space. The two most commonly affected organs are the kidneys and heart. Deposition of amyloid in these two critical organs is of major prognostic importance. Aims: To identify the burden of systemic amyloidosis in the English population. To characterise the phenotype and diagnostic features of wild type transthyretin amyloidosis and identify the type and frequency of arrhythmic activity in cardiac amyloidosis. To evaluate outcome in renal amyloidosis, and assess the role of renal replacement therapy. Results and Conclusions: Amyloidosis was mentioned in 0.58/1000 deaths in England between 2000 and 2008. Sensitivity of death certificates in identifying patients with amyloidosis was 79%. The estimated true incidence of the disease is ~1/100000 population in England. Wild type transthyretin amyloidosis (ATTRwt) is increasingly diagnosed in the UK. Age of the patient at diagnosis and N T-proB N P level can aid in distinguishing ATTRwt from cardiac AL amyloidosis. Median survival is significantly better in ATTRwt than in cardiac AL amyloidosis. A positive troponin T, a pacemaker and NYHA class IV symptoms are all associated with worse outcome. Complex ventricular arrhythmias are seen more frequently on Holter monitoring in patients with transthyretin cardiac amyloidosis compared to cardiac AL which are in turn more frequent than patients without myocardial amyloid infiltration. There does not appear to be an association between the frequency of complex ventricular arrhythmi as and disease severity in cardiac amyl oi dosi s. Renal and overall outcome in AL amyl oi dosi s are both strongly associated with FLC response and are best among patients who achieve >90% suppression of the monoclonal component of the FLC. Survival on dialysis is improving. Outcome following renal transplantation is dependent on the amyloid fibril type and suppression of the precursor protein.