Pathophysiology
Clinical meaning
Cardiac amyloidosis is a progressive and potentially fatal condition caused by the extracellular deposition of insoluble amyloid fibrils within the myocardium, resulting in increased wall thickness, diastolic dysfunction, and ultimately restrictive cardiomyopathy with heart failure. Amyloidosis encompasses a group of diseases characterized by the misfolding of normally soluble precursor proteins into insoluble beta-pleated sheet fibrillar aggregates that deposit in tissues and progressively disrupt organ architecture and function. In the heart, amyloid fibrils infiltrate the interstitial space between cardiomyocytes, the cardiac conduction system, cardiac valves, and coronary microvasculature, producing a characteristic pattern of disease. The two most common types of cardiac amyloidosis are AL (immunoglobulin light chain) amyloidosis and ATTR (transthyretin) amyloidosis, which differ fundamentally in their precursor protein, pathogenesis, prognosis, and treatment. AL amyloidosis (previously called primary amyloidosis) is caused by a clonal plasma cell dyscrasia (similar to multiple myeloma) in which a monoclonal population of plasma cells in the bone marrow produces excess immunoglobulin light chains (usually lambda light chains) that misfold into amyloid fibrils. These light chain-derived amyloid fibrils have direct cardiotoxic effects beyond their space-occupying properties: they...