Cardiac amyloidosis is a serious condition resulting from the accumulation of abnormal protein deposits, known as amyloid fibrils, within the heart muscle. When this deposition occurs, it causes the heart walls to become thick and stiff. This structural change impairs the heart’s ability to pump blood effectively, which can progress quickly to severe heart failure. Early identification and subtyping are necessary, as the specific protein type determines the course of treatment and prognosis.
Understanding the Types of Cardiac Amyloidosis
The most common forms of cardiac amyloidosis are caused by two distinct precursor proteins: Light Chain (AL) and Transthyretin (ATTR). The origin of the faulty protein differs significantly for each type, impacting the targeted treatment approach.
In Light Chain Amyloidosis (AL), the abnormal protein is produced by dysfunctional plasma cells, typically located in the bone marrow. These cells overproduce fragments of immunoglobulin light chains that misfold and aggregate into amyloid fibrils. AL amyloidosis deposits rapidly in the heart and other organs.
Transthyretin Amyloidosis (ATTR) involves the transthyretin protein, which is primarily synthesized in the liver. ATTR is categorized into two subtypes: hereditary (variant) and wild-type. Hereditary ATTR results from a genetic mutation that makes the protein unstable, causing deposits. Wild-type ATTR is associated with aging, occurring when the structurally normal protein misfolds over time.
How Amyloid Deposits Affect Heart Function
The presence of amyloid fibrils within the heart muscle causes infiltrative cardiomyopathy. These protein deposits fill the spaces between heart muscle cells, stiffening the walls of the ventricles. This stiffness results in restrictive cardiomyopathy, where the heart’s chambers cannot properly relax between beats.
The inability of the heart muscle to relax, known as diastolic dysfunction, is the primary mechanical issue. Stiffened ventricles resist stretching, preventing them from filling adequately with blood. This impaired filling leads to a backup of pressure, causing symptoms of congestion.
As the condition progresses, the heart walls visibly thicken, though the muscle fibers are displaced by non-contractile amyloid material. This compromises the heart’s ability to pump, reducing cardiac output. Amyloid deposits can also infiltrate the electrical system, interfering with impulse conduction. This results in rhythm disturbances, such as atrial fibrillation or heart block, further impairing performance.
Identifying the Symptoms
The clinical presentation often mimics common congestive heart failure, frequently leading to a delayed diagnosis. Patients experience profound fatigue and a reduced ability to tolerate physical activity. Shortness of breath (dyspnea) is common, especially during exercise or when lying flat at night.
Fluid retention, or edema, is a hallmark symptom, manifesting as noticeable swelling in the legs, ankles, and sometimes the abdomen. This systemic congestion results from the heart’s inability to accept returning blood, causing fluid to accumulate in the tissues. Some individuals may also experience heart palpitations or lightheadedness due to electrical system interference.
Non-cardiac symptoms, particularly in ATTR amyloidosis, can be early indicators of the disease’s systemic nature. These include bilateral carpal tunnel syndrome, often preceding a cardiac diagnosis by several years. Lumbar spinal stenosis (narrowing of the spinal canal) and peripheral neuropathy affecting the limbs are also observed.
Diagnostic Procedures and Targeted Treatment Strategies
Diagnostic Procedures
Confirming cardiac amyloidosis requires advanced imaging and specific laboratory tests to identify the amyloid subtype. Initial evaluation often involves an echocardiogram, which visualizes the thickened, stiffened heart walls. Cardiac Magnetic Resonance Imaging (MRI) provides detailed tissue characterization, revealing a specific pattern of late gadolinium enhancement suggestive of amyloid infiltration.
A unique, non-invasive tool for Transthyretin amyloidosis is the technetium-99m pyrophosphate (D-PYP) nuclear scan. This scan uses a radioactive tracer that binds specifically to ATTR deposits in the heart. This often allows for diagnosis without an invasive biopsy, provided AL amyloidosis is ruled out. Tissue biopsy, either of the heart or a less invasive site like the abdominal fat pad, remains the gold standard for definitive confirmation and accurate protein typing.
Targeted Treatment Strategies
Treatment for cardiac amyloidosis depends entirely on the identified protein type. For AL amyloidosis, the strategy focuses on eliminating the source of the misfolded protein by targeting the abnormal plasma cells. This is achieved through chemotherapy regimens, similar to those used for multiple myeloma, and sometimes an autologous stem cell transplant. The goal is to stop the production of toxic light chains.
The treatment approach for ATTR amyloidosis involves stabilizing or silencing the faulty transthyretin protein. Stabilizers, such as Tafamidis, bind to the protein to prevent it from breaking apart and forming new fibrils. Silencers or inhibitors reduce the production of the transthyretin protein by the liver. Supportive care, including diuretics to manage fluid retention and medications to control heart rhythms, is implemented to alleviate heart failure symptoms regardless of the subtype.