Amyloidosis is a rare and complex group of disorders in which abnormal proteins called amyloids build up in various tissues and organs throughout the body.

These amyloids are insoluble and form fibrils that accumulate in different organs, disrupting their normal function and causing severe damage over time. One of the most affected organs by amyloidosis is the heart. When amyloidosis affects the heart, it is known as cardiac amyloidosis.

Transthyretin-related amyloidosis (ATTR) is a subcategory of amyloidosis that specifically involves the transthyretin protein.

Transthyretin is produced primarily by the liver and plays a crucial role in transporting thyroxine and retinol throughout the body. However, in ATTR, the transthyretin protein misfolds and forms amyloid fibrils that accumulate in the heart and other tissues.

There are two main types of transthyretin-related amyloidosis: hereditary and wild-type.

Hereditary transthyretin-related amyloidosis (hATTR) is caused by genetic mutations in the transthyretin gene.

These mutations lead to the production of abnormal transthyretin protein, which forms amyloid fibrils and accumulates in various organs, including the heart. The age of onset, severity, and organs affected can vary depending on the specific mutation.

Wild-type transthyretin-related amyloidosis (wtATTR) is not caused by genetic mutations but rather by the natural aging process. As individuals age, the transthyretin protein can undergo changes that cause it to misfold and form amyloid fibrils.

These fibrils can deposit in the heart and other organs, leading to cardiac amyloidosis.

Symptoms and Diagnosis of Cardiac Amyloidosis

The symptoms of cardiac amyloidosis can vary depending on the extent of organ involvement and the specific type of amyloid protein deposited.

However, common symptoms include progressive heart failure, shortness of breath, fatigue, swollen limbs, irregular heartbeat, and weight loss.

Diagnosing cardiac amyloidosis can be challenging, as the symptoms can mimic those of other heart conditions.

It typically involves a combination of medical history evaluation, physical examination, imaging tests (such as echocardiography), and tissue biopsy to confirm the presence of amyloid deposits.

The treatment approach for transthyretin-related cardiac amyloidosis focuses on managing symptoms, slowing disease progression, and improving the patient’s quality of life. Currently, there are several treatment options available:.

1. Medications

Medications such as tafamidis and inotersen can help stabilize transthyretin proteins and prevent their misfolding, slowing down the accumulation of amyloid deposits in the heart and other organs.

These medications have shown promising results in clinical trials and have been approved for the treatment of hATTR amyloidosis.

2. Stem Cell Transplantation

Stem cell transplantation, also known as a bone marrow transplant, can be an option for select patients with hATTR amyloidosis.

This treatment involves replacing the patient’s bone marrow with healthy donor cells, which can produce normal transthyretin proteins and reduce amyloid deposits. However, it is a complex and high-risk procedure, and not all patients are eligible candidates.

3. Supportive Therapies

Supportive therapies aim to manage the symptoms and complications of cardiac amyloidosis.

These may include medications to control blood pressure, diuretics to reduce fluid buildup, antiarrhythmic drugs to stabilize heart rhythm, and heart failure medications to improve cardiac function. In some cases, a heart transplant may be necessary for end-stage cardiac amyloidosis.

Research and Future Perspectives

Advancements in the understanding of transthyretin-related cardiac amyloidosis have led to the development of new treatment approaches and ongoing research studies.

Researchers are exploring the potential of gene-silencing technologies and newer medications to target amyloid deposits directly. Early diagnosis and intervention remain crucial in improving outcomes for patients with cardiac amyloidosis.

Conclusion

Amyloidosis is a complex disorder characterized by the accumulation of abnormal protein fibrils in various organs, including the heart. Transthyretin-related amyloidosis, both hereditary and wild-type, can lead to cardiac amyloidosis.

Diagnosing this condition can be challenging, but advancements in treatment options, such as medication and stem cell transplantation, provide hope for patients. Ongoing research aims to improve early detection and develop more targeted therapies. With further advancements, the prognosis for individuals with transthyretin-related cardiac amyloidosis is expected to improve.