Cardiovascular Complications in Patients with AL Amyloidosis

Amyloidosis is a disease characterized by aberrant precursor molecules whose misfolded intermediate forms aggregate and are deposited as interstitial fibrils. The most common type of systemic amyloidosis is immunoglobulin light-chain amyloidosis (AL). Less common types of systemic amyloidosis are the transthyretin (ATTR) types caused by either mutant (hereditary) variants or wild-type ("senile systemic") transthyretin. Although rare in developed countries secondary amyloidosis is associated with autoimmune or inflammatory diseases, chronic infections and malignancies. Different precursor proteins can coexist in the same patient as in the African-American population, which has a 4% incidence of an hereditary ATTR variant (Val122Ile) and a significant incidence of monoclonal gammopathy (1, 2). The amyloids are highly ordered cross-┚ sheet protein with extra cellular deposition in single or multiple organs. Cardiac deposition, leading to an infiltrative/restrictive cardiomyopathy, is a common feature and may be present at the diagnosis or discovered while investigating a patient presenting with non-cardiac amyloidosis. AL amyloidosis, is associated with clinical cardiac involvement in about half of all cases, although subclincal involvement may be detected in almost every case at autopsy on endomyocardial biopsy. Laser micro dissection with mass spectrometry assessing the constituents of the Congophilic deposits is now the gold standard for amyloid typing, obtaining protein type identification in over 98% of cases (3). Evaluation for cardiac involvement is a critical step of the initial staging of amyloidosis. Criteria for the assessment of organ involvement at baseline and after treatment have been standardized (4). In systemic AL amyloidosis the extent of cardiac involvement has prognostic indications, with a median survival of 6 months for untreated or non-responding patients (5, 6).