Infiltrative Cardiomyopathy: Amyloid, Sarcoid and Iron

Infiltrative cardiomyopathies are a group of myocardial diseases characterized by the abnormal deposition of substances within the cardiac interstitium, leading to progressive ventricular stiffness, diastolic dysfunction, and ultimately heart failure with preserved or mildly reduced ejection fraction (HFpEF). The three major subtypes — cardiac amyloidosis, cardiac sarcoidosis, and hemochromatosis (iron overload cardiomyopathy) — share a common hemodynamic phenotype of restrictive physiology but differ fundamentally in their pathogenesis and treatment. Cardiac Amyloidosis: Amyloidosis results from the extracellular deposition of insoluble fibrillar proteins (amyloid) in a cross-beta-pleated sheet configuration that is resistant to proteolytic degradation. Two types predominantly affect the heart. AL (light-chain) amyloidosis occurs when clonal plasma cells in the bone marrow produce immunoglobulin light chains that misfold and deposit as amyloid fibrils in multiple organs including the heart, kidneys, liver, and peripheral nerves. It is associated with multiple myeloma and other plasma cell dyscrasias. ATTR (transthyretin) amyloidosis involves the deposition of transthyretin protein, normally produced by the liver for thyroid hormone and retinol transport. Wild-type ATTR (wtATTR, formerly senile cardiac amyloidosis) is increasingly recognized in elderly patients (predominantly men >65)...