Cardiac amyloidosis is a serious, progressive condition resulting from the heart muscle being infiltrated by abnormal protein deposits. The accumulation of these substances interferes with the heart’s normal function, causing it to become stiff and limiting its ability to pump blood effectively. Because this disorder can significantly impair organ function and is sometimes treated with therapies similar to those used for blood cancers, it is frequently misunderstood. This article clarifies the nature of cardiac amyloidosis and distinguishes it from a true malignant disease.
Defining Cardiac Amyloidosis
Cardiac amyloidosis is classified as an infiltrative cardiomyopathy, a disorder where abnormal material deposits into the heart muscle tissue. The core pathology involves the production of misfolded proteins that aggregate outside of cells in a specific configuration called an amyloid. These protein aggregates link together to form insoluble, non-branching structures known as amyloid fibrils.
The deposition of these fibrils occurs within the interstitial spaces between the heart’s muscle cells. This physical infiltration causes the ventricle walls to thicken and lose their natural elasticity, a state known as restrictive cardiomyopathy. The resulting stiffness prevents the heart from properly relaxing and filling with blood, leading to progressive heart failure and irregular heart rhythms.
Amyloidosis Versus Malignancy
Cardiac amyloidosis is fundamentally a protein deposition disorder, not a form of cancer. The damage it causes stems from the physical obstruction and toxicity created by the accumulated, non-dividing amyloid fibrils. This mechanism is distinct from the biological process that defines a malignancy.
A true cancer is characterized by the uncontrolled division and growth of abnormal cells that invade and destroy surrounding tissues. In contrast, amyloidosis does not involve cellular overgrowth or the formation of a tumor. The abnormal cells that cause amyloidosis are located elsewhere in the body, and the heart disease itself is a consequence of their misproduced protein waste.
The Link Between AL Amyloidosis and Blood Disorders
The confusion between amyloidosis and cancer primarily arises because one of its main types, Amyloid Light-chain (AL) amyloidosis, originates from an underlying hematologic condition. AL amyloidosis is caused by a plasma cell dyscrasia, an abnormality in plasma cells residing in the bone marrow. Plasma cells are white blood cells responsible for producing antibodies.
In AL amyloidosis, a single clone of abnormal plasma cells grows excessively and produces defective components of antibodies called light chains. These free light chain proteins are unstable and misfold, aggregating into the amyloid fibrils that deposit in the heart. While AL amyloidosis is a protein disease, the source—the abnormal plasma cell clone—is related to conditions like Multiple Myeloma or Monoclonal Gammopathy of Undetermined Significance (MGUS). These are classified as blood cancers or pre-malignant conditions. The cardiac disease is therefore a complication of the underlying blood disorder, not a cancer of the heart muscle.
Distinct Treatment Strategies
The therapeutic approaches for cardiac amyloidosis highlight the distinction between protein deposition and malignancy by targeting different biological processes. For AL amyloidosis, treatment aims to eliminate the underlying abnormal plasma cell clone to stop the production of toxic light chains. This often involves chemotherapy regimens, sometimes combined with monoclonal antibodies like daratumumab, adapted from treatments for Multiple Myeloma. The goal is to halt the protein supply, preventing further amyloid buildup and potentially allowing existing deposits to clear.
Treatment for Transthyretin (ATTR) cardiac amyloidosis, the other major type, is different and involves no cancer therapies, as it is not caused by a blood disorder. ATTR amyloidosis treatment focuses on either stabilizing the transthyretin protein to prevent its misfolding, using drugs like tafamidis, or by using gene silencers such as patisiran or vutrisiran to reduce the liver’s production of the protein. These disease-modifying therapies underscore that the primary therapeutic focus in amyloidosis is managing protein structure and supply, not killing rapidly dividing cancer cells.